The Functional Genomics Experiment model (FuGE): an extensible framework for standards in functional genomics

Nature Biotechnology 25, 1127 - 1133 (2007) Published online: 5 October 2007 doi:10.1038/nbt1347
The Functional Genomics Experiment model (FuGE): an extensible framework for standards in functional genomics
Andrew R Jones1,2,16, Michael Miller3, Ruedi Aebersold4,5, Rolf Apweiler6, Catherine A Ball7, Alvis Brazma6, James DeGreef8, Nigel Hardy9, Henning Hermjakob6, Simon J Hubbard2, Peter Hussey10, Mark Igra10, Helen Jenkins9, Randall K Julian, Jr11, Kent Laursen11, Stephen G Oliver2, Norman W Paton1, Susanna-Assunta Sansone6, Ugis Sarkans6, Christian J Stoeckert, Jr12, Chris F Taylor6, Patricia L Whetzel12, Joseph A White13, Paul Spellman14 & Angel Pizarro15,16
The Functional Genomics Experiment data model (FuGE) has been developed to facilitate convergence of data standards for high-throughput, comprehensive analyses in biology. FuGE models the components of an experimental activity that are common across different technologies, including protocols, samples and data. FuGE provides a foundation for describing entire laboratory workflows and for the development of new data formats. The Microarray Gene Expression Data society and the Proteomics Standards Initiative have committed to using FuGE as the basis for defining their respective standards, and other standards groups, including the Metabolomics Standards Initiative, are evaluating FuGE in their development efforts. Adoption of FuGE by multiple standards bodies will enable uniform reporting of common parts of functional genomics workflows, simplify data-integration efforts and ease the burden on researchers seeking to fulfill multiple minimum reporting requirements. Such advances are important for transparent data management and mining in functional genomics and systems biology.
read more click here
Download full text PDF here

Effects of Torcetrapib in Patients at High Risk for Coronary Events

Philip J. Barter, M.D., Ph.D., Mark Caulfield, M.D., M.B., B.S., Mats Eriksson, M.D., Ph.D., Scott M. Grundy, M.D., Ph.D., John J.P. Kastelein, M.D., Ph.D., Michel Komajda, M.D., Jose Lopez-Sendon, M.D., Ph.D., Lori Mosca, M.D., M.P.H., Ph.D., Jean-Claude Tardif, M.D., David D. Waters, M.D., Charles L. Shear, Dr.P.H., James H. Revkin, M.D., Kevin A. Buhr, Ph.D., Marian R. Fisher, Ph.D., Alan R. Tall, M.B., B.S., Bryan Brewer, M.D., Ph.D., for the ILLUMINATE Investigators
Background Inhibition of cholesteryl ester transfer protein (CETP) has been shown to have a substantial effect on plasma lipoprotein levels. We investigated whether torcetrapib, a potent CETP inhibitor, might reduce major cardiovascular events. The trial was terminated prematurely because of an increased risk of death and cardiac events in patients receiving torcetrapib.
Methods We conducted a randomized, double-blind study involving 15,067 patients at high cardiovascular risk. The patients received either torcetrapib plus atorvastatin or atorvastatin alone. The primary outcome was the time to the first major cardiovascular event, which was defined as death from coronary heart disease, nonfatal myocardial infarction, stroke, or hospitalization for unstable angina.
Results At 12 months in patients who received torcetrapib, there was an increase of 72.1% in high-density lipoprotein cholesterol and a decrease of 24.9% in low-density lipoprotein cholesterol, as compared with baseline (P<0.001 for both comparisons), in addition to an increase of 5.4 mm Hg in systolic blood pressure, a decrease in serum potassium, and increases in serum sodium, bicarbonate, and aldosterone (P<0.001 for all comparisons). There was also an increased risk of cardiovascular events (hazard ratio, 1.25; 95% confidence interval [CI], 1.09 to 1.44; P=0.001) and death from any cause (hazard ratio, 1.58; 95% CI, 1.14 to 2.19; P=0.006). Post hoc analyses showed an increased risk of death in patients treated with torcetrapib whose reduction in potassium or increase in bicarbonate was greater than the median change.
Conclusions Torcetrapib therapy resulted in an increased risk of mortality and morbidity of unknown mechanism. Although there was evidence of an off-target effect of torcetrapib, we cannot rule out adverse effects related to CETP inhibition. ( number, NCT00134264 [] .)
Evidence supporting the proposition that high-density lipoprotein (HDL) cholesterol should be considered as a therapeutic target includes experimental models of atherosclerosis,1 an inverse relationship to the risk of cardiovascular disease in humans,2 clinical trials of drugs for which raising HDL cholesterol levels is a primary pharmacologic effect,3 and the residual risk of cardiovascular disease associated with a low HDL cholesterol level after effective statin therapy.4
Cholesteryl ester transfer protein (CETP) promotes the transfer of cholesteryl esters from HDL to other lipoproteins; the inhibition of this protein raises HDL cholesterol levels and decreases low-density lipoprotein (LDL) cholesterol levels. There is evidence supporting CETP inhibition as a therapeutic approach to the prevention of major cardiovascular events, although there is also evidence to the contrary.5,6,7
Torcetrapib is an inhibitor of CETP that has been shown to inhibit the development of atherosclerosis in rabbits.8 In early-phase studies in humans, the drug increased HDL cholesterol by 60 to 100% at the same time that it lowered LDL cholesterol by up to 20%.9,10 Torcetrapib was subsequently investigated in three large trials with the use of ultrasonography and other imaging techniques and was found to have no significant effect on coronary atheroma burden11 or carotid intima–media thickness.12,13 Concurrent with these imaging studies, the Investigation of Lipid Level Management to Understand its Impact in Atherosclerotic Events (ILLUMINATE) trial tested the proposition that torcetrapib would decrease the risk of clinical cardiovascular events. This trial was terminated prematurely on December 2, 2006, in a decision made by the sponsor on the basis of the recommendation of the trial's independent steering committee, which was acting on advice from the independent data and safety monitoring board.14 This report describes the main results of the ILLUMINATE trial.
Study Design
We conducted a prospective, randomized, multicenter, double-blind clinical trial, using a centralized randomization strategy with a block size of four. The trial was designed by an independent steering committee in collaboration with the sponsor, Pfizer. Data were collected by PharmaNet Development Group and analyzed independently by the Statistical Data Analysis Center at the University of Wisconsin, Madison; representatives of these organizations vouch for the completeness and veracity of the data and the analyses, respectively. An institutional review board at each center approved the protocol, and patients provided written informed consent. The original protocol was amended on November 28, 2006, a change that had not yet received institutional review board approval at the time of the trial's termination. The amendment included the addition of hospitalization for unstable angina to the primary outcome to increase the number of events and thus increase the statistical power to reject the null hypothesis.
Men and women between the ages of 45 and 75 years were eligible to participate in the study if they had a history of cardiovascular disease (including myocardial infarction, stroke, acute coronary syndrome, unstable angina, peripheral vascular disease, and cardiac revascularization) 30 days to 5 years before screening. Patients with type 2 diabetes without previous cardiovascular disease who met American Diabetes Association criteria or were receiving hypoglycemic agents were also eligible. Patients were excluded if they had evidence of an unstable medical condition, a life expectancy of less than 5 years, or an LDL cholesterol level of less than 100 mg per deciliter (2.6 mmol per liter) if the patient was not receiving a lipid-altering drug. Patients were also excluded if they had had a cardiovascular event during the run-in period or uncontrolled hypertension (defined as a systolic blood pressure of >140 mm Hg or a diastolic blood pressure of >90 mm Hg) or if the LDL cholesterol target level had not been reached at the end of the run-in period.
During a run-in period of 4 to 10 weeks, patients underwent lifestyle counseling and also received atorvastatin titrated (if needed) at 2-week intervals to achieve an LDL cholesterol level of less than 100 mg per deciliter. A variability tolerance of +15 mg per deciliter (0.4 mmol per liter) was allowed. Patients whose LDL level met the target were randomly assigned to receive either atorvastatin (at a dose established during the run-in period) plus 60 mg of torcetrapib or atorvastatin plus placebo. After termination of the trial, the sponsor maintained support for independent oversight during the trial's closeout (which involved four of the academic authors) with continuing support from the Statistical Data Analysis Center, which performed the primary statistical analyses.
Study Outcomes
Patients' visits were scheduled at 1, 3, 6, 9, and 12 months after randomization. Thereafter, patients were to be seen twice yearly. An increase or decrease in the dose of atorvastatin was allowed at the 12-month visit on the basis of predefined LDL cholesterol levels. The level of HDL cholesterol was determined through enzyme analysis with the use of polyethylene glycol–modified cholesterol esterase, cholesterol oxidase, and dextran sulfate to generate peroxide that was measured calorimetrically. Total cholesterol and triglyceride levels were determined by standard enzymatic techniques. LDL cholesterol was quantified by the Friedewald formula, except when the triglyceride level was more than 400 mg per deciliter (4.5 mmol per liter), in which case the level was measured by direct beta quantification. Apolipoproteins A-I and B-100 were measured by means of immunoturbidimetric assay. High-sensitivity C-reactive protein (CRP) was measured with the use of a particle-enhanced immunoturbidimetric assay. All measurements were performed at a central laboratory (MDS). Blood pressure was measured in triplicate at each visit with the use of a standard calibrated measuring device with the patient seated after 5 minutes of rest. The first reading was not used, and the latter two readings were averaged for the visit measurement. The estimated glomerular filtration rate was calculated as described previously.15
The QT interval was calculated with the use of Bazett's correction. A decision to measure aldosterone was made after termination of the trial after investigators observed a pattern of change in serum electrolytes and blood pressure. Stored serum samples that had been obtained from patients at baseline and at 3 months were used, with measurements made by means of liquid chromatography–tandem mass spectrometry (Mayo Central Laboratory for Clinic Trials).
Efficacy Measures
The primary outcome was the time to the first occurrence of a major cardiovascular event, a composite that included four components: death from coronary heart disease (defined as fatal myocardial infarction excluding procedure-related events, fatal heart failure, sudden cardiac death, or other cardiac death), nonfatal myocardial infarction (excluding procedure-related events), stroke, and hospitalization for unstable angina.
Secondary outcomes were the time to the first occurrence of each individual component of the primary outcome, the time to death from any cause, and the change from baseline in LDL and HDL cholesterol levels. Tertiary outcomes included further breakdowns in categories and composites of secondary outcomes.
Members of a central committee who were unaware of study-group assignments adjudicated potential outcomes as reported by the investigators. Adjudicated outcomes are not included in totals of adverse events and serious adverse events.
Statistical Analysis
The original design assumed a sample size of 13,000 patients (6500 per treatment group) to yield 551 primary outcomes in the atorvastatin-only group (8.48%) and 433 in the group receiving both atorvastatin and torcetrapib (6.66%) after an average of 4.5 years of follow-up — in other words, an absolute reduction of 1.82 percentage points or a relative reduction of 21% in the cumulative incidence. This number of patients would provide a statistical power of 90% to detect a treatment difference in the primary efficacy analysis at the two-sided level of 0.05 with the use of a log-rank test. A total of 15,067 patients underwent randomization, with overenrollment owing to an increase in screening activity after notification of an upcoming closure in enrollment at each site. On the basis of the modified primary outcome in the amended protocol and on the increased number of patients, the number of primary outcomes at an average follow-up of 4.5 years was expected to be 1820.
The prespecified safety-monitoring boundary (a P value <0.01, unadjusted for multiple comparisons) was based on a log-rank test for death from any cause. An efficacy-monitoring boundary (to be implemented after approximately 50% of the expected number of events had occurred in the primary outcome) was prespecified, but the requisite event count was never reached.
All treatment comparisons were performed with the use of an intention-to-treat analysis. All data were censored for the primary analyses on December 2, 2006, when the trial was terminated. Events occurring after that date, in the period between termination of the study and the end of data collection, are also reported. These events were captured either at a final visit after the discontinuation of a study drug (active surveillance) or as a result of instructions to patients to report serious adverse events (passive surveillance). The last adjudicated outcome reported during this observation period occurred on July 15, 2007.
P values for continuous and ordered categorical data were computed with the use of a nonparametric Wilcoxon test. Pearson's chi-square test (without continuity correction) was used for dichotomous and unordered categorical data. The log-rank test was used for time-to-event analyses. Post hoc exploratory analyses were also performed; only descriptive statistics were used to identify patterns of association, since these analyses were not inferential in nature. No adjustments have been made for multiple comparisons.
Between August 23, 2004, and December 28, 2005, a total of 15,067 patients underwent randomization at 260 centers in seven countries. Of these patients, 7534 were assigned to receive atorvastatin plus placebo (atorvastatin-only group), and 7533 were assigned to receive torcetrapib plus atorvastatin (torcetrapib group) (Figure 1). At the end of the study on December 2, 2006, the median follow-up in each group was 550 days. Earlier discontinuation of treatment had occurred in 831 patients in the atorvastatin-only group (11.0%) and in 1008 patients in the torcetrapib group (13.4%). Higher rates of discontinuation owing to nonfatal adverse events in the torcetrapib group were associated mainly with a higher frequency of hypertension, nonspecific gastrointestinal symptoms, and headache. Follow-up was 99.7% complete, with 20 patients in the atorvastatin-only group and 19 patients in the torcetrapib group who were not followed until December 2, 2006. Baseline demographic and clinical characteristics of the two groups are presented in Table 1. Patients with a history of diabetes but no evidence of cardiovascular disease at study entry represented 18.8% of the atorvastatin-only group and 17.9% of the torcetrapib group (data not shown).

The "Bad Bug Book"

This handbook provides basic facts regarding foodborne pathogenic microorganisms and natural toxins. It brings together in one place information from the Food & Drug Administration, the Centers for Disease Control & Prevention, the USDA Food Safety Inspection Service, and the National Institutes of Health.
Some technical terms have been linked to the National Library of Medicine's Entrez glossary. Recent articles from Morbidity and Mortality Weekly Reports have been added to selected chapters to update the handbook with information on later outbreaks or incidents of foodborne disease. At the end of selected chapters on pathogenic microorganisms, hypertext links are included to relevant Entrez abstracts and GenBank genetic loci. A more complete description of the handbook may be found in the Preface.
Salmonella spp.
Clostridium botulinum
Staphylococcus aureus
Campylobacter jejuni
Yersinia enterocolitica and Yersinia pseudotuberculosis
Listeria monocytogenes
Vibrio cholerae O1
Vibrio cholerae non-O1
Vibrio parahaemolyticus and other vibrios
Vibrio vulnificus
Clostridium perfringens
Bacillus cereus
Aeromonas hydrophila and other spp.
Plesiomonas shigelloides
Shigella spp.
Miscellaneous enterics
Escherichia coli - enterotoxigenic (ETEC)
Escherichia coli - enteropathogenic (EPEC)
Escherichia coli O157:H7 enterohemorrhagic (EHEC)
Escherichia coli - enteroinvasive (EIEC)
Giardia lamblia
Entamoeba histolytica
Cryptosporidium parvum
Cyclospora cayetanensis
Anisakis sp. and related worms
Diphyllobothrium spp.
Nanophyetus spp.
Eustrongylides sp.
Acanthamoeba and other free-living amoebae
Ascaris lumbricoides and Trichuris trichiura
Hepatitis A virus
Hepatitis E virus
Norwalk virus group
Other viral agents
Ciguatera poisoning
Shellfish toxins (PSP, DSP, NSP, ASP)
Scombroid poisoning
Tetrodotoxin (Pufferfish)
Mushroom toxins
Pyrrolizidine alkaloids
Phytohaemagglutinin (Red kidney bean poisoning)
Grayanotoxin (Honey intoxication)
Infective dose
Epidemiology summary table
Factors affecting microbial growth in foods
Foodborne Disease Outbreaks, United States 1988-1992
Additional Foodborne Disease Outbreak Articles and Databases.

Free Full Text adalah wesite yang mengumpulkan berbagai macam alamat jurnal ilmiah yang bisa diakses secara gratis. Alamat jurnal-jurnal tersebut tersusun berdasarkan alphabetic, jadi bisa mempremudah kita dalam mencari jurnal yang kita inginkan. Silahkan buktikan sendiri di link ini

Artikel-artikel Biologi Molekuler

Jurnal ini memuat berbagai informasi hasil penelitian terbaru di bidang biologi molekuler, untuk edisi 1 November 2007 sendiri ada beberapa isu terberu di bidang tersebut. Sayangnya jurnal ini The EMBO Journal tidak gratis, so cuma bisa membaca Abstraknya aja. Tapi untuk sekedar pengetahuan sudah cukup bagus...
Isu-isu terbaru 1 November 2007 antara lain :
Multifunctional class I transcription in Trypanosoma brucei depends on a novel protein complex
Jens Brandenburg, Bernd Schimanski, Everson Nogoceke, Tu N Nguyen, Júlio C Padovan, Brian T Chait, George A M Cross and Arthur Günzl The EMBO Journal advance online publication 1 November 2007;doi: 10.1038/sj.emboj.7601905
The vector-borne, protistan parasite Trypanosoma brucei is the only known eukaryote with a multifunctional RNA polymerase I that, in addition to ribosomal genes, transcribes genes encoding the parasite's major cell-surface proteins—the variant surface glycoprotein (VSG) and procyclin. In the mammalian bloodstream, antigenic variation of the VSG coat is the parasite's means to evade the immune response, while procyclin is necessary for effective establishment of trypanosome infection in the fly. Moreover, the exceptionally high efficiency of mono-allelic VSG expression is essential to bloodstream trypanosomes since its silencing caused rapid cell-cycle arrest in vitro and clearance of parasites from infected mice. Here we describe a novel protein complex that recognizes class I promoters and is indispensable for class I transcription; it consists of a dynein light chain and six polypeptides that are conserved only among trypanosomatid parasites. In accordance with an essential transcriptional function of the complex, silencing the expression of a key subunit was lethal to bloodstream trypanosomes and specifically affected the abundance of rRNA and VSG mRNA. The complex was dubbed class I transcription factor A.
Keywords: class I transcription factor, DYNLL1, procyclin, Tryponosoma brucei, VSG
A role for cytochrome c and cytochrome c peroxidase in electron shuttling from Erv1
Deepa V Dabir1, 6, Edward P Leverich1, 6, Sung-Kun Kim2, 5, Frederick D Tsai1, Masakazu Hirasawa2, David B Knaff2 and Carla M Koehler1, 3, 4 1 Department of Chemistry and Biochemistry, University of California at Los Angeles, Los Angeles, CA, USA2 Department of Chemistry and Biochemistry, Center for Biotechnology and Genomics, Texas Tech University, Lubbock, TX, USA3 Molecular Biology Institute, University of California at Los Angeles, Los Angeles, CA, USA4 Jonsson Comprehensive Cancer Center, University of California at Los Angeles, Los Angeles, CA, USA5 Department of Chemistry and Biochemistry, Baylor University, Waco, TX, USATo whom correspondence should be addressedCarla M Koehler, Department of Chemistry and Biochemistry, Molecular Biology Institute, Jonsson Comprehensive Cancer Center, Box 951569, University of California at Los Angeles, Los Angeles, CA 90095, USA. Tel.: +1 310 794 4834; Fax: +1 310 206 4038; E-mail:
Erv1 is a flavin-dependent sulfhydryl oxidase in the mitochondrial intermembrane space (IMS) that functions in the import of cysteine-rich proteins. Redox titrations of recombinant Erv1 showed that it contains three distinct couples with midpoint potentials of -320, -215, and -150 mV. Like all redox-active enzymes, Erv1 requires one or more electron acceptors. We have generated strains with erv1 conditional alleles and employed biochemical and genetic strategies to facilitate identifying redox pathways involving Erv1. Here, we report that Erv1 forms a 1:1 complex with cytochrome c and a reduced Erv1 can transfer electrons directly to the ferric form of the cytochrome. Erv1 also utilized molecular oxygen as an electron acceptor to generate hydrogen peroxide, which is subsequently reduced to water by cytochrome c peroxidase (Ccp1). Oxidized Ccp1 was in turn reduced by the Erv1-reduced cytochrome c. By coupling these pathways, cytochrome c and Ccp1 function efficiently as Erv1-dependent electron acceptors. Thus, we propose that Erv1 utilizes diverse pathways for electron shuttling in the IMS.
Keywords: mitochondria, protein import, protein translocation, redox chemistry
Semoga bermanfaa ....

Balasan buat mas wayan

Salam kenal juga buat Mas Wayan.
Sebenarnya untuk memberi ide Mas Wayan, aku belum mampu. Coz basic keilmuanku bukan management. Tapi untuk sekedar berbagi informasi, mungkin bisa....
Ada beberapa artikel yang cukup bagus yang membahas " Manajemen Proyek". Smoga saja artikel-artikel ini bisa bermanfaat buat mas wayan.
Artike-artikel ini saya peroleh dari Websitenya Drs. Azhari, SN., MT. Beliau adalah staff pengajar Universitas Gadjah Mada Yogyakarta. Mas Wayan kunjungi aja websitnya di di situ banyak artike-artikel yang membahas Manajemen Proyek.
Dah yo... semoga sukses.