CiteULike: Author Brunner

NMR Spectroscopic Study of Noble Gas Binding into the Engineered Cavity of HPr(I14A) from Staphylococcus carnosus

L Nisius — 2008-08-20T10:37:29-00:00

J. Phys. Chem. B, Vol. 109, No. 38. (29 September 2005), pp. 17795-17798.

Abstract: Xenon binding into preexisting cavities in proteins is a well-known phenomenon. Here we investigate the interaction of helium, neon, and argon with hydrophobic cavities in proteins by NMR spectroscopy. 1H and 15N chemical shifts of the I14A mutant of the histidine-containing phosphocarrier protein (HPr(I14A)) from Staphylococcus carnosus are analyzed by chemical shift mapping. Total noble gas induced chemical shifts, , are calculated and compared with the corresponding values obtained using xenon as a probe atom. This comparison reveals that the same cavity is detected with both argon and xenon. Measurements using the smaller noble gases helium and neon as probe atoms do not result in comparable effects. The dependence of amide proton and nitrogen chemical shifts on the argon concentration is investigated in the range from 10 mM up to 158 mM. The average dissociation constant for argon binding into the engineered cavity is determined to be about 90 mM.

Inflammation, Insulin Resistance, and Diabetes-Mendelian Randomization Using CRP Haplotypes Points Upstream.

Eric J Brunner — 2008-08-17T23:13:21-00:00

PLoS medicine, Vol. 5, No. 8. (12 August 2008)

BACKGROUND: Raised C-reactive protein (CRP) is a risk factor for type 2 diabetes. According to the Mendelian randomization method, the association is likely to be causal if genetic variants that affect CRP level are associated with markers of diabetes development and diabetes. Our objective was to examine the nature of the association between CRP phenotype and diabetes development using CRP haplotypes as instrumental variables. METHODS AND FINDINGS: We genotyped three tagging SNPs (CRP + 2302G > A; CRP + 1444T > C; CRP + 4899T > G) in the CRP gene and measured serum CRP in 5,274 men and women at mean ages 49 and 61 y (Whitehall II Study). Homeostasis model assessment-insulin resistance (HOMA-IR) and hemoglobin A1c (HbA1c) were measured at age 61 y. Diabetes was ascertained by glucose tolerance test and self-report. Common major haplotypes were strongly associated with serum CRP levels, but unrelated to obesity, blood pressure, and socioeconomic position, which may confound the association between CRP and diabetes risk. Serum CRP was associated with these potential confounding factors. After adjustment for age and sex, baseline serum CRP was associated with incident diabetes (hazard ratio = 1.39 [95% confidence interval 1.29-1.51], HOMA-IR, and HbA1c, but the associations were considerably attenuated on adjustment for potential confounding factors. In contrast, CRP haplotypes were not associated with HOMA-IR or HbA1c (p = 0.52-0.92). The associations of CRP with HOMA-IR and HbA1c were all null when examined using instrumental variables analysis, with genetic variants as the instrument for serum CRP. Instrumental variables estimates differed from the directly observed associations (p = 0.007-0.11). Pooled analysis of CRP haplotypes and diabetes in Whitehall II and Northwick Park Heart Study II produced null findings (p = 0.25-0.88). Analyses based on the Wellcome Trust Case Control Consortium (1,923 diabetes cases, 2,932 controls) using three SNPs in tight linkage disequilibrium with our tagging SNPs also demonstrated null associations. CONCLUSIONS: Observed associations between serum CRP and insulin resistance, glycemia, and diabetes are likely to be noncausal. Inflammation may play a causal role via upstream effectors rather than the downstream marker CRP.

Optical pumping of a single hole spin in a quantum dot.

BD Gerardot — 2008-08-15T20:21:55-00:00

Nature, Vol. 451, No. 7177. (24 January 2008), pp. 441-444.

The spin of an electron is a natural two-level system for realizing a quantum bit in the solid state. For an electron trapped in a semiconductor quantum dot, strong quantum confinement highly suppresses the detrimental effect of phonon-related spin relaxation. However, this advantage is offset by the hyperfine interaction between the electron spin and the 10(4) to 10(6) spins of the host nuclei in the quantum dot. Random fluctuations in the nuclear spin ensemble lead to fast spin decoherence in about ten nanoseconds. Spin-echo techniques have been used to mitigate the hyperfine interaction, but completely cancelling the effect is more attractive. In principle, polarizing all the nuclear spins can achieve this but is very difficult to realize in practice. Exploring materials with zero-spin nuclei is another option, and carbon nanotubes, graphene quantum dots and silicon have been proposed. An alternative is to use a semiconductor hole. Unlike an electron, a valence hole in a quantum dot has an atomic p orbital which conveniently goes to zero at the location of all the nuclei, massively suppressing the interaction with the nuclear spins. Furthermore, in a quantum dot with strong strain and strong quantization, the heavy hole with spin-3/2 behaves as a spin-1/2 system and spin decoherence mechanisms are weak. We demonstrate here high fidelity (about 99 per cent) initialization of a single hole spin confined to a self-assembled quantum dot by optical pumping. Our scheme works even at zero magnetic field, demonstrating a negligible hole spin hyperfine interaction. We determine a hole spin relaxation time at low field of about one millisecond. These results suggest a route to the realization of solid-state quantum networks that can intra-convert the spin state with the polarization of a photon.

Inside discrete-event simulation software: how it works and why it matters

TJ Schriber — 2006-06-19T07:31:27-00:00

Winter Simulation Conference, 2005 Proceedings of the (2005), 11 pp..

This paper provides simulation practitioners and consumers with a grounding in how discrete event simulation software works. Topics include discrete event systems; entities, resources, control elements and operations; simulation runs; entity states; entity lists; and entity list management. The implementation of these generic ideas in AutoMod, SLX, and Extend is described. The paper concludes with several examples of "why it matters" for modelers to know how their simulation software works, including coverage of SIMAN (Arena), ProModel, and GPSS/H as well as the other three tools.

Identifying sources and estimating glandular output of salivary TIMP-1.

L Holten-Andersen — 2008-08-01T08:44:57-00:00

Scandinavian journal of clinical and laboratory investigation (15 February 2008), pp. 1-7.

Objective. Tissue inhibitor of metalloproteinases 1 (TIMP-1) has been identified as a potential biomarker in diseases such as cancer, cardiovascular diseases and diabetes. Since TIMP-1 resides in most tissues and bodily fluids, we evaluated the potential of using saliva to obtain reproducible TIMP-1 measurements in a non-invasive manner. Material and methods. Samples of unstimulated and stimulated whole saliva and saliva collected from individual glands were analysed for TIMP-1 content. A TIMP-1 ELISA was validated for use in saliva testing and the most optimal sampling and handling procedures for reproducible measurements identified. Western blotting and MALDI-TOF mass spectrometry were used for confirmatory analyses. Results. The TIMP-1 ELISA was found suitable for saliva measurements. All saliva secretions contained TIMP-1, but in different concentrations ranging from 2.81 ng/mL in submandibular/sublingual saliva to 173.88 ng/mL in parotid saliva. TIMP-1 concentrations were influenced to a varying degree by fluctuations in flow. We found the lowest output in submandibular/sublingual saliva stimulated with 0.5 % citric acid (3.56 ng/min) and highest output in chewing-stimulated whole saliva (267.01 ng/min). Conclusion. This study shows that saliva contains authentic TIMP-1, the concentration of which was found to depend on gland type and salivary flow. Stimulated whole saliva is suggested as a reliable and easily accessible source for TIMP-1 determinations in bodily fluids.

Unfairness and the social gradient of metabolic syndrome in the Whitehall II Study

Roberto De Vogli — 2008-07-31T01:18:10-00:00

Journal of Psychosomatic Research, Vol. 63, No. 4. (October 2007), pp. 413-419.

Objectives Little work has investigated the relationship between unfairness and risk factors for heart disease. We examine the role of unfairness in predicting the metabolic syndrome and explaining the social gradient of the metabolic syndrome.Methods The design is a prospective study with an average follow-up of 5.8 years. Participants were 4128 males and 1715 females of 20 civil service departments in London (Whitehall II study). Sociodemographics, unfairness, employment grade, behavioral risk factors, and other psychosocial factors were measured at baseline (Phase 3, 1991-1993). Waist circumference, triglycerides, high-density lipoprotein (HDL) cholesterol, fasting glucose, and hypertension were used to define metabolic syndrome at follow-up (Phase 5, 1997-2000), according to the National Cholesterol Education Program/Adult Treatment Panel III guidelines.Results Unfairness is positively associated with waist circumference, hypertension, triglycerides, and fasting glucose and negatively associated with serum HDL cholesterol. High levels of unfairness are also associated with the metabolic syndrome [odds ratio (OR)=1.72, 95% CI=1.31-2.25], after adjustment for age and gender. After additional adjustment for employment grade, behavioral risk factors, and other psychosocial factors, the relationship between high unfairness and metabolic syndrome weakened but remained significant (OR=1.37, 95% CI=1.00-1.93). When adjusting for unfairness, the social gradient of metabolic syndrome was reduced by approximately 10%.Conclusion Unfairness may be a risk factor for the metabolic syndrome and its components. Future research is needed to study the biological mechanisms linking unfairness and the metabolic syndrome.

Effects of plantarflexion on pelvis and lower limb kinematics

R Brunner — 2008-02-26T04:04:47-00:00

Gait & Posture, Vol. In Press, Corrected Proof

Modelling the effect of soleus and gastrocnemius contractions against the floor resistance in a forward dynamics simulation revealed that hip flexion, internal rotation and adduction together with external pelvic rotation could be attributed to a direct, but distant effect of triceps surae contraction. Knee flexion smoothed out the effect. To validate this clinically relevant biomechanical observation, ankle plantar flexion was correlated with hip and pelvic rotation retrospectively in children with spastic cerebral palsy. In 49 children with spastic hemiplegia, plantar flexion showed a significant correlation with increased pelvic retraction and hip internal rotation. In contrast, in 47 children with spastic diplegia no significant effect of the triceps surae on hip and pelvis kinematics was found. Bilateral hip and knee flexion in diplegia appeared to prevent the proximal effect of the triceps surae seen in the hemiplegics. In diplegia triceps surae overactivity did not appear to be a significant cause of internal rotation gait.

Dagstuhl seminar on disruption tolerant networking

Marcus Brunner — 2006-06-28T09:52:05-00:00

SIGCOMM Comput. Commun. Rev., Vol. 35, No. 3. (July 2005), pp. 69-72.

Reconstitution of a microtubule plus-end tracking system in vitro

Peter Bieling — 2007-12-03T17:41:00-00:00

Nature (02 December 2007)

Bayeswatch: an overview of Bayesian statistics.

PC Austin — 2007-09-16T05:04:14-00:00

J Eval Clin Pract, Vol. 8, No. 2. (May 2002), pp. 277-286.

Increasingly, clinical research is evaluated on the quality of its statistical analysis. Traditionally, statistical analyses in clinical research have been carried out from a 'frequentist' perspective. The presence of an alternative paradigm - the Bayesian paradigm - has been relatively unknown in clinical research until recently. There is currently a growing interest in the use of Bayesian statistics in health care research. This is due both to a growing realization of the limitations of frequentist methods and to the ability of Bayesian methods explicitly to incorporate prior expert knowledge and belief into the analyses. This is in contrast to frequentist methods, where prior experience and beliefs tend to be incorporated into the analyses in an ad hoc fashion. This paper outlines the frequentist and Bayesian paradigms. Acute myocardial infarction mortality data are then analysed from both a Bayesian and a frequentist perspective. In some analyses, the two methods are seen to produce comparable results; in others, they produce different results. It is noted that in this example, there are clinically relevant questions that are more easily addressed from a Bayesian perspective. Finally, areas in clinical research where Bayesian ideas are increasingly common are highlighted.

The XMM-Newton Serendipitous Survey. VI. The Second XMM-Newton Serendipitous Source Catalogue

MG Watson — 2008-07-08T15:37:40-00:00

(7 Jul 2008)

Aims: Pointed observations with XMM-Newton provide the basis for creating catalogues of X-ray sources detected serendipitously in each field. This paper describes the creation and characteristics of the 2XMM catalogue. Methods: The 2XMM catalogue has been compiled from a new processing of the XMM-Newton EPIC camera data. The main features of the processing pipeline are described in detail. Results: The catalogue, the largest ever made at X-ray wavelengths, contains 246,897 detections drawn from 3491 public XMM-Newton observations over a 7-year interval, which relate to 191,870 unique sources. The catalogue fields cover a sky area of more than 500 sq.deg. The non-overlapping sky area is ~360 sq.deg. (~1% of the sky) as many regions of the sky are observed more than once by XMM-Newton. The catalogue probes a large sky area at the flux limit where the bulk of the objects that contribute to the X-ray background lie and provides a major resource for generating large, well-defined X-ray selected source samples, studying the X-ray source population and identifying rare object types. The main characteristics of the catalogue, including its photometric and astrometric properties are presented.

Overexpression of RPGR Leads to Male Infertility in Mice Due to Defects in Flagellar Assembly.

Sandra Brunner — 2008-07-01T12:41:35-00:00

Biology of reproduction (25 June 2008)

Male infertility is one possible consequence of a group of disorders arising from dysfunction of cilia. Ciliopathies include primary ciliary dyskinesia (PCD), polycystic kidney disease (PKD), Usher syndrome, nephronophthisis, Bardet-Biedl syndrome (BBS), Alstrom syndrome and Meckel-Gruber syndrome as well as some forms of retinal degenerations. Mutations in the retinitis pigmentosa GTPase regulator gene (RPGR) are best known for leading to retinal degeneration, but have also been associated with ciliary dysfunctions affecting other tissues. To further study the involvement of RPGR in ciliopathies, transgenic mouse lines overexpressing RPGR were generated. Animals carrying the transgene in varying copy number were investigated. We found that infertility due to aberrant spermatozoa correlated with increased copy numbers. In animals with moderately increased gene copies of Rpgr, structural disorganization in the flagellar midpiece, outer dense fibers, and fibrous sheath was apparent. In contrast, in animals with high copy numbers condensed sperm heads were present but the flagellum was absent in the vast majority of spermatozoa although early steps of flagellar biogenesis were observed. This complexity of defects in flagellar assembly suggests a role of RPGR in intraflagellar transport (IFT) processes.

Predicting disease genes using protein-protein interactions.

M Oti — 2007-08-22T12:18:45-00:00

J Med Genet, Vol. 43, No. 8. (August 2006), pp. 691-698.

BACKGROUND: The responsible genes have not yet been identified for many genetically mapped disease loci. Physically interacting proteins tend to be involved in the same cellular process, and mutations in their genes may lead to similar disease phenotypes. OBJECTIVE: To investigate whether protein-protein interactions can predict genes for genetically heterogeneous diseases. METHODS: 72,940 protein-protein interactions between 10,894 human proteins were used to search 432 loci for candidate disease genes representing 383 genetically heterogeneous hereditary diseases. For each disease, the protein interaction partners of its known causative genes were compared with the disease associated loci lacking identified causative genes. Interaction partners located within such loci were considered candidate disease gene predictions. Prediction accuracy was tested using a benchmark set of known disease genes. RESULTS: Almost 300 candidate disease gene predictions were made. Some of these have since been confirmed. On average, 10% or more are expected to be genuine disease genes, representing a 10-fold enrichment compared with positional information only. Examples of interesting candidates are AKAP6 for arrythmogenic right ventricular dysplasia 3 and SYN3 for familial partial epilepsy with variable foci. CONCLUSIONS: Exploiting protein-protein interactions can greatly increase the likelihood of finding positional candidate disease genes. When applied on a large scale they can lead to novel candidate gene predictions.

Conserved co-expression for candidate disease gene prioritization

Martin Oti — 2008-04-24T19:51:08-00:00

BMC Bioinformatics, Vol. 9 (23 April 2008), 208.

Solution of perfect foresight saddlepoint problems: a simple method and applications

Martin Brunner — 2008-06-23T04:26:00-00:00

Journal of Economic Dynamics and Control, Vol. 26, No. 5. (May 2002), pp. 737-753.

The paper proposes a method to compute adjustment dynamics that occur in infinite time horizon problems of deterministic optimal control. Without loss of accuracy, this method is easier to implement than existing ones. Discussed applications are the standard neoclassical growth model and the general two-sector growth model with cyclical adjustment on a two-dimensional manifold.

Dietary advice for reducing cardiovascular risk.

EJ Brunner — 2008-06-13T02:04:15-00:00

Cochrane database of systematic reviews (Online), No. 4. (2007)

BACKGROUND: Changes in population diet are likely to reduce cardiovascular disease and cancer, but the effect of dietary advice is uncertain. OBJECTIVES: To assess the effects of providing dietary advice to achieve sustained dietary changes or improved cardiovascular risk profile among healthy adults. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials, DARE and HTA databases on The Cochrane Library (Issue 4 2006), MEDLINE (1966 to December 2000, 2004 to November 2006) and EMBASE (1985 to December 2000, 2005 to November 2006). Additional searches were done on CAB Health (1972 to December 1999), CVRCT registry (2000), CCT (2000) and SIGLE (1980 to 2000). Dissertation abstracts and reference lists of articles were checked and researchers were contacted. SELECTION CRITERIA: Randomised studies with no more than 20% loss to follow-up, lasting at least 3 months involving healthy adults comparing dietary advice with no advice or minimal advice. Trials involving children, trials to reduce weight or those involving supplementation were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Study authors were contacted for additional information. MAIN RESULTS: Thirty-eight trials with 46 intervention arms (comparisons) comparing dietary advice with no advice were included in the review. 17,871 participants/clusters were randomised. Twenty-six of the 38 included trials were conducted in the USA. Dietary advice reduced total serum cholesterol by 0.16 mmol/L (95% CI 0.06 to 0.25) and LDL cholesterol by 0.18 mmol/L (95% CI 0.1 to 0.27) after 3-24 months. Mean HDL cholesterol levels and triglyceride levels were unchanged. Dietary advice reduced blood pressure by 2.07 mmHg systolic (95% CI 0.95 to 3.19) and 1.15 mmHg diastolic (95% CI 0.48 to 1.85) and 24-hour urinary sodium excretion by 44.2 mmol (95% CI 33.6 to 54.7) after 3-36 months. Three trials reported plasma antioxidants where small increases were seen in lutein and beta-cryptoxanthin, but there was heterogeneity in the trial effects. Self-reported dietary intake may be subject to reporting bias, and there was significant heterogeneity in all the following analyses. Compared to no advice, dietary advice increased fruit and vegetable intake by 1.25 servings/day (95% CI 0.7 to 1.81). Dietary fibre intake increased with advice by 5.99 g/day (95% CI 1.12 to 10.86), while total dietary fat as a percentage of total energy intake fell by 4.49 % (95% CI 2.31 to 6.66) with dietary advice and saturated fat intake fell by 2.36 % (95% CI 1.32 to 3.39). AUTHORS' CONCLUSIONS: Dietary advice appears to be effective in bringing about modest beneficial changes in diet and cardiovascular risk factors over approximately 10 months but longer term effects are not known.

Targeting, Insertion, and Localization of Escherichia coli YidC

Malene Urbanus — 2008-06-12T15:13:14-00:00

J. Biol. Chem., Vol. 277, No. 15. (5 April 2002), pp. 12718-12723.

YidC was recently shown to play an important role in the assembly of inner membrane proteins (IMPs) both in conjunction with and separate from the Sec-translocon. Little is known about the biogenesis and structural and functional properties of YidC, itself a polytopic IMP. Here we analyze the targeting and membrane integration of YidC using in vivo and in vitro approaches. The combined data indicate that YidC is targeted by the signal recognition particle and inserts at the SecAYEG-YidC translocon early during biogenesis, unlike its mitochondrial homologue Oxa1p. In addition, YidC is shown to be relatively abundant compared with other components involved in IMP assembly and is predominantly localized at the poles of the cell. 10.1074/jbc.M200311200

Interplay of signal recognition particle and trigger factor at L23 near the nascent chain exit site on the Escherichia coli ribosome.

RS Ullers — 2008-06-10T10:51:58-00:00

The Journal of cell biology, Vol. 161, No. 4. (26 May 2003), pp. 679-684.

As newly synthesized polypeptides emerge from the ribosome, they interact with chaperones and targeting factors that assist in folding and targeting to the proper location in the cell. In Escherichia coli, the chaperone trigger factor (TF) binds to nascent polypeptides early in biosynthesis facilitated by its affinity for the ribosomal proteins L23 and L29 that are situated around the nascent chain exit site on the ribosome. The targeting factor signal recognition particle (SRP) interacts specifically with the signal anchor (SA) sequence in nascent inner membrane proteins (IMPs). Here, we have used photocross-linking to map interactions of the SA sequence in a short, in vitro-synthesized, nascent IMP. Both TF and SRP were found to interact with the SA with partially overlapping binding specificity. In addition, extensive contacts with L23 and L29 were detected. Both purified TF and SRP could be cross-linked to L23 on nontranslating ribosomes with a competitive advantage for SRP. The results suggest a role for L23 in the targeting of IMPs as an attachment site for TF and SRP that is close to the emerging nascent chain.

The active site of ICP47, a herpes simplex virus-encoded inhibitor of the major histocompatibility complex (MHC)-encoded peptide transporter associated with antigen processing (TAP), maps to the NH2-terminal 35 residues.

B Galocha — 2008-06-09T10:46:01-00:00

The Journal of experimental medicine, Vol. 185, No. 9. (5 May 1997), pp. 1565-1572.

The herpes simplex virus (HSV) immediate early protein ICP47 inhibits the transporter associated with antigen processing (TAP)-dependent peptide translocation. As a consequence, empty major histocompatibility complex (MHC) class I molecules are retained in the endoplasmic reticulum and recognition of HSV-infected cells by cytotoxic T lymphocytes is abolished. We chemically synthesized full-length ICP47 (sICP47) and show that sICP47 inhibits TAP-dependent peptide translocation in human cells. Its biological activity is indistinguishable from that of recombinant ICP47 (rICP47). By using synthetic peptides, we mapped the core sequence of ICP47 minimally required for TAP inhibition to residues 2-35. This segment is located within the region of the molecule conserved between ICP47 from HSV-1 and HSV-2. Through alanine scanning substitution we identified three segments within this region that are critical for the ability to inhibit TAP function. The interaction of ICP47 with TAP is unlikely to mimic precisely that of the transported peptides, as deduced from differential labeling of the TAP1 and TAP2 subunits using sICP47 fragments with chemical cross-linkers.

Sex-lethal, the master sex-determining gene in Drosophila, is not sex-specifically regulated in Musca domestica

M Meise — 2008-06-09T08:03:18-00:00

Development, Vol. 125, No. 8. (1 April 1998), pp. 1487-1494.

The Genome of Black Cottonwood, Populus trichocarpa (Torr. & Gray)

GA Tuskan — 2008-02-07T09:25:26-00:00

Science, Vol. 313, No. 5793. (15 September 2006), pp. 1596-1604.

We report the draft genome of the black cottonwood tree, Populus trichocarpa. Integration of shotgun sequence assembly with genetic mapping enabled chromosome-scale reconstruction of the genome. More than 45,000 putative protein-coding genes were identified. Analysis of the assembled genome revealed a whole-genome duplication event; about 8000 pairs of duplicated genes from that event survived in the Populus genome. A second, older duplication event is indistinguishably coincident with the divergence of the Populus and Arabidopsis lineages. Nucleotide substitution, tandem gene duplication, and gross chromosomal rearrangement appear to proceed substantially more slowly in Populus than in Arabidopsis. Populus has more protein-coding genes than Arabidopsis, ranging on average from 1.4 to 1.6 putative Populus homologs for each Arabidopsis gene. However, the relative frequency of protein domains in the two genomes is similar. Overrepresented exceptions in Populus include genes associated with lignocellulosic wall biosynthesis, meristem development, disease resistance, and metabolite transport. 10.1126/science.1128691

Testing the Dimension of Hilbert Spaces

Nicolas Brunner — 2008-06-02T13:54:48-00:00

Physical Review Letters, Vol. 100, No. 21. (2008)

Given a set of correlations originating from measurements on a quantum state of unknown Hilbert space dimension, what is the minimal dimension d necessary to describe such correlations? We introduce the concept of dimension witness to put lower bounds on d. This work represents a first step in a broader research program aiming to characterize Hilbert space dimension in various contexts related to fundamental questions and quantum information applications.

Accelerating Scientific Applications with Reconfigurable Computing: Getting Started

Volodymyr Kindratenko — 2008-06-02T08:05:43-00:00

Computing in Science & Engineering, Vol. 9, No. 5. (2007), pp. 70-77.

Cytokine storm in a phase 1 trial of the anti-CD28 monoclonal antibody TGN1412.

G Suntharalingam — 2008-05-26T14:49:46-00:00

The New England journal of medicine, Vol. 355, No. 10. (7 September 2006), pp. 1018-1028.

Six healthy young male volunteers at a contract research organization were enrolled in the first phase 1 clinical trial of TGN1412, a novel superagonist anti-CD28 monoclonal antibody that directly stimulates T cells. Within 90 minutes after receiving a single intravenous dose of the drug, all six volunteers had a systemic inflammatory response characterized by a rapid induction of proinflammatory cytokines and accompanied by headache, myalgias, nausea, diarrhea, erythema, vasodilatation, and hypotension. Within 12 to 16 hours after infusion, they became critically ill, with pulmonary infiltrates and lung injury, renal failure, and disseminated intravascular coagulation. Severe and unexpected depletion of lymphocytes and monocytes occurred within 24 hours after infusion. All six patients were transferred to the care of the authors at an intensive care unit at a public hospital, where they received intensive cardiopulmonary support (including dialysis), high-dose methylprednisolone, and an anti-interleukin-2 receptor antagonist antibody. Prolonged cardiovascular shock and acute respiratory distress syndrome developed in two patients, who required intensive organ support for 8 and 16 days. Despite evidence of the multiple cytokine-release syndrome, all six patients survived. Documentation of the clinical course occurring over the 30 days after infusion offers insight into the systemic inflammatory response syndrome in the absence of contaminating pathogens, endotoxin, or underlying disease.

Health technology assessment in Switzerland.

R Cranovsky — 2008-05-26T12:15:24-00:00

International journal of technology assessment in health care, Vol. 16, No. 2. (2000), pp. 576-590.

Switzerland has a mixed public and private healthcare system. All citizens are enrolled in compulsory basic health insurance. A 1996 law allows people to choose among different sickness funds and managed care plans. The federal government is empowered to act on important health issues, but the 26 cantons have prime responsibility in health care and social welfare. They have their own laws on health care, hygiene, hospitals, and social welfare. These laws are not harmonized. The system is complex, with a mix of public (mainly hospitals) and private (mainly doctors' offices) providers. The health services are decentralized. Ambulatory care was traditionally provided in doctors' offices, but the last decade has seen the development of centers for day surgery, group practices, and managed care plans. Decisions on placement, location, and extension of services are decentralized. The payment system is very complex. Current trends include global budgets, cost analyses, and prices related to patient categories. However, coverage policy is developed centrally and includes both traditionally established services and new technologies. New technologies are added to the list only after evaluation by the Federal Coverage Committee. The coverage process integrates health technology assessment (HTA). Coverage can be granted in stages, including limited coverage and temporary coverage. Technologies and coverage can be reevaluated on the basis of registries or assessment information. The structure of the Swiss healthcare system does not lend itself to the establishment of a national HTA program. However, recent moves include the development of a coordinating mechanism for HTA in Switzerland.

Accelerating Scientific Applications with Reconfigurable Computing: Getting Started

VV Kindratenko — 2008-05-26T12:14:42-00:00

Computing in Science & Engineering, Vol. 9, No. 5. (2007), pp. 70-77.

High-performance reconfigurable computing combines the advantages of the coarse-grain parallel processing provided in conventional multiprocessor systems with the fine-grain parallel processing available in field-programmable gate arrays.

Detection of apoptosis in vivo using antibodies against caspase-induced neo-epitopes.

S Jakob — 2008-05-11T14:37:02-00:00

Methods (San Diego, Calif.), Vol. 44, No. 3. (March 2008), pp. 255-261.

Cell death induction by apoptosis is an important process in the maintenance of tissue homeostasis as well as tissue destruction during various pathological processes. Consequently, detection of apoptotic cells in situ represents an important technique to assess the extent and impact of cell death in the respective tissue. While scoring of apoptosis by histological assessment of apoptotic cells is still a widely used method, it is likely biased by sensitivity problems and observed-based variations. The availability of caspase-mediated neo-epitope-specific antibodies offers new tools for the detection of apoptosis in situ. Here, we discuss the use of immunohistochemical detection of cleaved caspase 3 and lamin A for the assessment of apoptotic cells in paraffin-embedded liver tissue. Furthermore, we evaluate the effect of tissue pretreatment and antigen retrieval on the sensitivity of apoptosis detection, background staining and maintenance of tissue morphology.

Nonradiative relaxation times in diagonal transition Si/SiGe quantum cascade structures

I Bormann — 2008-05-07T06:33:59-00:00

Applied Physics Letters, Vol. 83, No. 26. (2003), pp. 5371-5373.

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Enhancement of erbium photoluminescence by substitutional C alloying of Si

M Markmann — 2008-05-07T06:10:38-00:00

Applied Physics Letters, Vol. 75, No. 17. (1999), pp. 2584-2586.

Phenome connections

Martin Oti — 2008-03-03T15:17:05-00:00

Trends in Genetics, Vol. 24, No. 3. (March 2008), pp. 103-106.

Human phenomics is about to come of age with studies that systematically assess the overlap and relationships among all human genetic diseases. A recent study by Andrey Rzhetsky and colleagues illustrates the power of phenomics by revealing links between conditions that were thought to be distinct, suggesting that they share a genetic basis. Their results imply that the human phenome can be viewed as a landscape of interrelated diseases, reflecting overlapping molecular causation.

The Schizosaccharomyces pombe EB1 homolog Mal3p binds and stabilizes the microtubule lattice seam.

L Sandblad — 2007-07-02T09:55:41-00:00

Cell, Vol. 127, No. 7. (29 December 2006), pp. 1415-1424.

End binding 1 (EB1) proteins are highly conserved regulators of microtubule dynamics. Using electron microscopy (EM) and high-resolution surface shadowing we have studied the microtubule-binding properties of the fission yeast EB1 homolog Mal3p. This allowed for a direct visualization of Mal3p bound on the surface of microtubules. Mal3p particles usually formed a single line on each microtubule along just one of the multiple grooves that are formed by adjacent protofilaments. We provide structural data showing that the alignment of Mal3p molecules coincides with the microtubule lattice seam as well as data suggesting that Mal3p not only binds but also stabilizes this seam. Accordingly, Mal3p stabilizes microtubules through a specific interaction with what is potentially the weakest part of the microtubule in a way not previously demonstrated. Our findings further suggest that microtubules exhibit two distinct reaction platforms on their surface that can independently interact with target structures such as microtubule-associated proteins, motors, kinetochores, or membranes.

Crosslinkers and motors organize dynamic microtubules to form stable bipolar arrays in fission yeast.

ME Janson — 2007-06-10T09:45:22-00:00

Cell, Vol. 128, No. 2. (26 January 2007), pp. 357-368.

Microtubule (MT) nucleation not only occurs from centrosomes, but also in large part from dispersed nucleation sites. The subsequent sorting of short MTs into networks like the mitotic spindle requires molecular motors that laterally slide overlapping MTs and bundling proteins that statically connect MTs. How bundling proteins interfere with MT sliding is unclear. In bipolar MT bundles in fission yeast, we found that the bundler ase1p localized all along the length of antiparallel MTs, whereas the motor klp2p (kinesin-14) accumulated only at MT plus ends. Consequently, sliding forces could only overcome resistant bundling forces for short, newly nucleated MTs, which were transported to their correct position within bundles. Ase1p thus regulated sliding forces based on polarity and overlap length, and computer simulations showed these mechanisms to be sufficient to generate stable bipolar bundles. By combining motor and bundling proteins, cells can thus dynamically organize stable regions of overlap between cytoskeletal filaments.

Sloan Digital Sky Survey: Early Data Release

C Stoughton — 2008-04-27T14:02:07-00:00

Astron. J., Vol. 123 (January 2002), pp. 485-548.

The Sloan Digital Sky Survey (SDSS) is an imaging and spectroscopic survey that will eventually cover approximately one-quarter of the celestial sphere and collect spectra of ~10<SUP>6</SUP> galaxies, 100,000 quasars, 30,000 stars, and 30,000 serendipity targets. In 2001 June, the SDSS released to the general astronomical community its early data release, roughly 462 deg<SUP>2</SUP> of imaging data including almost 14 million detected objects and 54,008 follow-up spectra. The imaging data were collected in drift-scan mode in five bandpasses (u, g, r, i, and z); our 95% completeness limits for stars are 22.0, 22.2, 22.2, 21.3, and 20.5, respectively. The photometric calibration is reproducible to 5%, 3%, 3%, 3%, and 5%, respectively. The spectra are flux- and wavelength-calibrated, with 4096 pixels from 3800 to 9200 Å at R~1800. We present the means by which these data are distributed to the astronomical community, descriptions of the hardware used to obtain the data, the software used for processing the data, the measured quantities for each observed object, and an overview of the properties of this data set.

The Emerging Risk Factors Collaboration: analysis of individual data on lipid, inflammatory and other markers in over 1.1 million participants in 104 prospective studies of cardiovascular diseases.

2008-04-18T11:17:41-00:00

European journal of epidemiology, Vol. 22, No. 12. (2007), pp. 839-869.

Many long-term prospective studies have reported on associations of cardiovascular diseases with circulating lipid markers and/or inflammatory markers. Studies have not, however, generally been designed to provide reliable estimates under different circumstances and to correct for within-person variability. The Emerging Risk Factors Collaboration has established a central database on over 1.1 million participants from 104 prospective population-based studies, in which subsets have information on lipid and inflammatory markers, other characteristics, as well as major cardiovascular morbidity and cause-specific mortality. Information on repeat measurements on relevant characteristics has been collected in approximately 340,000 participants to enable estimation of and correction for within-person variability. Re-analysis of individual data will yield up to approximately 69,000 incident fatal or nonfatal first ever major cardiovascular outcomes recorded during about 11.7 million person years at risk. The primary analyses will involve age-specific regression models in people without known baseline cardiovascular disease in relation to fatal or nonfatal first ever coronary heart disease outcomes. This initiative will characterize more precisely and in greater detail than has previously been possible the shape and strength of the age- and sex-specific associations of several lipid and inflammatory markers with incident coronary heart disease outcomes (and, secondarily, with other incident cardiovascular outcomes) under a wide range of circumstances. It will, therefore, help to determine to what extent such associations are independent from possible confounding factors and to what extent such markers (separately and in combination) provide incremental predictive value.

TurfNet: An Architecture for Dynamically Composable Networks

S Schmid — 2007-01-23T13:39:06-00:00

Lecture Notes in Computer Science - Autonomic Communication (2005), pp. 94-114.

The Internet architecture is based on design principles such as end-to-end addressing and global routeability. It suits relatively static, well-managed and flat network hierarchies. Recent years have shown, however, that the Internet is evolving beyond what the current architecture can support. The Internet architecture struggles to support increasingly conflicting requirements from groups with competing interests, such as network, content and application service providers, or end-users of fixed, mobile and ad hoc access networks. This paper describes a new internetworking architecture, called TurfNet. It provides autonomy for individual network domains, or Turfs, through a novel inter-domain communication mechanism that does not require global network addressing or a common network protocol. By minimizing inter-domain dependencies, TurfNet provides a high degree of independence, which in turn facilitates autonomic communications. Allowing network domains to fully operate in isolation maximizes the scope of autonomic management functions. To accomplish this, TurfNet integrates the emerging concept of dynamic network composition with other recent architectural concepts such as decoupling locators from identifiers and establishing end-to-end communication across heterogeneous domains.

A parametric analysis of ordinal quality-of-life data can lead to erroneous results.

E Kahler — 2008-04-14T04:19:19-00:00

Journal of clinical epidemiology, Vol. 61, No. 5. (May 2008), pp. 475-480.

OBJECTIVE: Measurements from health-related quality-of-life (HRQoL) studies, although usually of an ordered categorical nature, are typically treated as continuous variables, allowing the calculation of mean values and the administration of parametric statistics, such as t-tests. We investigated whether parametric, compared to nonparametric, analyses of ordered categorical data may lead to different conclusions. STUDY DESIGN AND SETTING: HRQoL data were obtained from patients with a diagnosis of asthma (n=192) and chronic obstructive pulmonary disease (COPD; n=88) at two time points. The impact of the group factor (asthma vs. COPD) and the time factor (t1 vs. t2) on HRQoL was analyzed with a metric approach (repeated measures ANOVA) and two ordinal approaches (each with a nonparametric repeated measures ANOVA). RESULTS: Using the metric approach, a significant effect of "group" (P=0.0061) and "time" (P=0.0049) on HRQoL was found. The first ordinal approach (ranked total score) still showed a significant effect for "group" (P=0.0033) with a worse HRQoL for patients suffering from COPD. In the second approach (ranks for each HRQoL item and summed ranks), there were no significant effects. CONCLUSION: Applying simple parametric methods to ordered categorical HRQoL scores led to different results from those obtained with nonparametric methods. In these cases, an ordinal approach will prevent inappropriate conclusions.

Knowing your enemies: seasonal dynamics of hostsocial parasite recognition

Dettorre — 2006-05-18T17:58:43-00:00

Naturwissenschaften, Vol. 91, No. 12. (December 2004), pp. 594-597.

Female suicide bombers - Male suicide bombing? looking for Gender in reporting the suicide bombings of the Israeli-Palestinian conflict

Claudia Brunner — 2005-01-26T15:21:58-00:00

Global Society, Vol. 19, No. 1. (January 2005), 29.

Genes for control of plant stature and form

Busov — 2008-01-31T12:16:31-00:00

New Phytologist, Vol. 177, No. 3. (February 2008), pp. 589-607.

Simulation of partial entanglement with no-signaling resources

Nicolas Brunner — 2008-03-18T13:01:51-00:00

(16 Mar 2008)

With the goal of gaining a deeper understanding of quantum non-locality, we decompose quantum correlations into more elementary non-local correlations. In particular we present two models for simulating the correlations of partially entangled states of two qubits without communication, hence using only non-signaling resources. The crucial role of the quantum marginals is discussed.

Gene duplication and exon shuffling by helitron-like transposons generate intraspecies diversity in maize.

Michele Morgante — 2005-08-03T12:52:00-00:00

Nat Genet (31 July 2005)

We report a whole-genome comparison of gene content in allelic BAC contigs from two maize inbred lines. Genic content polymorphisms involve as many as 10,000 sequences and are mainly generated by DNA insertions. The termini of eight of the nine genic insertions that we analyzed shared the structural hallmarks of helitron rolling-circle transposons. DNA segments defined by helitron termini contained multiple gene-derived fragments and had a structure typical of nonautonomous helitron-like transposons. Closely related insertions were found in multiple genomic locations. Some of these produced transcripts containing segments of different genes, supporting the idea that these transposition events have a role in exon shuffling and the evolution of new proteins. We identified putative autonomous helitron elements and found evidence for their transcription. Helitrons in maize seem to continually produce new nonautonomous elements responsible for the duplicative insertion of gene segments into new locations and for the unprecedented genic diversity. The maize genome is in constant flux, as transposable elements continue to change both the genic and nongenic fractions of the genome, profoundly affecting genetic diversity.

Origins, genetic organization and transcription of a family of non-autonomous helitron elements in maize

Stephan Brunner — 2005-09-09T11:45:44-00:00

The Plant Journal, Vol. 43, No. 6. (September 2005), pp. 799-810.

Explorations in the use of semantic web technologies for product information management

Jean-Sébastien Brunner — 2007-07-20T15:36:14-00:00

WWW (2007), pp. 747-756.

Master data refers to core business entities a company uses repeatedly across many business processes and systems (such as lists or hierarchies of customers, suppliers, accounts, products, or organizational units). Product information is the most important kind of master data and product information management (PIM) is becoming critical for modern enterprises because it provides a rich business context for various applications. Existing PIM systems are less flexible and scalable for on-demand business, as well as too weak to completely capture and use the semantics of master data. This paper explores how to use semantic web technologies to enhance a collaborative PIM system by simplifying modeling and representation while preserving enough dynamic flexibility. Furthermore, we build a semantic PIM system using one of the state-of-art ontology repositories and summarize the challenges we encountered based on our experimental results, especially on performance and scalability. We believe that our study and experiences are valuable for both semantic web community and master data management community.

Multiple Splice Variants of Lactate Dehydrogenase C Selectively Expressed in Human Cancer ,

Michael Koslowski — 2008-03-13T13:55:44-00:00

Cancer Res, Vol. 62, No. 22. (15 November 2002), pp. 6750-6755.

We applied a combined data mining and experimental validation Approach for the discovery of germ cell-specific genes aberrantly expressed in cancer. Six of 21 genes with confirmed germ cell specificity were detected in tumors, indicating that ectopic activation of testis-specific genes in cancer is a frequent phenomenon. Most surprisingly one of the genes represented lactate dehydrogenase C (LDHC), the germ cell-specific member of the lactate dehydrogenase family. LDHC escapes from transcriptional repression, resulting in significant expression levels in virtually all tumor types tested. Moreover, we discovered aberrant splicing of LDHC restricted to cancer cells, resulting in four novel tumor-specific variants displaying structural alterations of the catalytic domain. Expression of LDHC in tumors is neither mediated by gene promotor demethylation, as previously described for other germ cell-specific genes activated in cancer, nor induced by hypoxia as demonstrated for enzymes of the glycolytic pathway. LDHC represents the first lactate dehydrogenase isoform with restriction to tumor cells. In contrast to other LDH isoenzymes, LDHC has a preference for lactate as a substrate. Thus LDHC activation in cancer may provide a metabolic rescue pathway in tumor cells by exploiting lactate for ATP delivery.

Anti-Intuitionism and Paraconsistency

Andreas Brunner — 2007-03-17T14:01:35-00:00

This paper aims to help to elucidate some questions on the duality between the intuitionistic and the paraconsistent paradigms of thought, proposing some new classes of anti-intuitionistic propositional logics and investigating their relationships with the original intuitionistic logics. It is shown here that anti-intuitionistic logics are paraconsistent, and in particular we develop a first anti-intuitionistic hierarchy starting with Johansson 's dual calculus and ending up with Godel's...

Properties and applications of MBE grown AlGaN

M Stutzmann — 2008-03-03T02:35:44-00:00

Materials Science and Engineering B, Vol. 50, No. 1-3. (18 December 1997), pp. 212-218.

AlGaN epitaxial films have been grown on sapphire by plasma-induced molecular beam epitaxy (MBE) over the entire composition range from GaN to AlN. Structural and optical properties of the alloys have been investigated by X-ray diffraction (XRD), transmission electron and atomic force microscopy, Raman scattering, ellipsometry, optical transmission, and subgap absorption spectroscopy. Electron spin resonance has been used to study the dependence of intrinsic paramagnetic defects on Al mole fraction. N- and p-type doping with Si and Mg, respectively is found to become increasingly difficult with increasing Al content because of a continuous shift of the donor and acceptor levels deeper into the bandgap. Apart from the use of AlGaN as cladding layers in light emitting diodes, applications in MODFET transistors, solar blind photodetectors, surface acoustic wave devices and Bragg reflectors appear interesting and will be discussed briefly.

Computational disease gene identification: a concert of methods prioritizes type 2 diabetes and obesity candidate genes.

N Tiffin — 2006-11-06T15:55:15-00:00

Nucleic Acids Res, Vol. 34, No. 10. (2006), pp. 3067-3081.

Genome-wide experimental methods to identify disease genes, such as linkage analysis and association studies, generate increasingly large candidate gene sets for which comprehensive empirical analysis is impractical. Computational methods employ data from a variety of sources to identify the most likely candidate disease genes from these gene sets. Here, we review seven independent computational disease gene prioritization methods, and then apply them in concert to the analysis of 9556 positional candidate genes for type 2 diabetes (T2D) and the related trait obesity. We generate and analyse a list of nine primary candidate genes for T2D genes and five for obesity. Two genes, LPL and BCKDHA, are common to these two sets. We also present a set of secondary candidates for T2D (94 genes) and for obesity (116 genes) with 58 genes in common to both diseases.