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In JoVE (1)
Other Publications (16)
- Physical Review Letters
- Physical Review Letters
- European Heart Journal
- EMBO Molecular Medicine
- Physical Review Letters
- Physical Review Letters
- Physical Review Letters
- Physical Review Letters
- Physical Review Letters
- Physical Review Letters
- Physical Review Letters
- The International Journal of Neuropsychopharmacology / Official Scientific Journal of the Collegium Internationale Neuropsychopharmacologicum (CINP)
- Liver Transplantation : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society
- Journal of Clinical Bioinformatics
- Journal Der Deutschen Dermatologischen Gesellschaft = Journal of the German Society of Dermatology : JDDG
- PloS One
Articles by Conrad T. Pfeiffer in JoVE
JoVE General
Solid Phase Synthesis of a Functionalized Bis-Peptide Using "Safety Catch" Methodology
College of Science and Technology, Temple University
The efficient solid-phase peptide synthesis of a functionalized bis-peptide trimer utilizing a "safety catch" cleavage procedure from HMBA resin is described.
Other articles by Conrad T. Pfeiffer on PubMed
Measurement of the Inclusive Jet Cross Section in Pp Collisions at Sqrt[s]=7  TeV
The inclusive jet cross section is measured in pp collisions with a center-of-mass energy of 7 TeV at the Large Hadron Collider using the CMS experiment. The data sample corresponds to an integrated luminosity of 34  pb^{-1}. The measurement is made for jet transverse momenta in the range 18-1100 GeV and for absolute values of rapidity less than 3. The measured cross section extends to the highest values of jet p_{T} ever observed and, within the experimental and theoretical uncertainties, is generally in agreement with next-to-leading-order perturbative QCD predictions.
Anomalous Robustness of the ν=5/2 Fractional Quantum Hall State Near a Sharp Phase Boundary
We report magnetotransport measurements in wide GaAs quantum wells with a tunable density to probe the stability of the fractional quantum Hall effect at a filling factor of ν=5/2 in the vicinity of the crossing between Landau levels (LLs) belonging to the different (symmetric and antisymmetric) electric subbands. When the Fermi energy (E_{F}) lies in the excited-state LL of the symmetric subband, the 5/2 quantum Hall state is surprisingly stable and gets even stronger near this crossing, and then suddenly disappears and turns into a metallic state once E_{F} moves to the ground-state LL of the antisymmetric subband. The sharpness of this disappearance suggests a first-order transition.
Optimal Timing of Invasive Angiography in Stable Non-ST-elevation Myocardial Infarction: the Leipzig Immediate Versus Early and Late PercutaneouS Coronary Intervention TriAl in NSTEMI (LIPSIA-NSTEMI Trial)
AimsThe optimal timing of intervention in non-ST-elevation myocardial infarction (NSTEMI) remains uncertain. The aim of this multicentre trial was to assess whether an immediate invasive approach is superior to an early invasive or a selective invasive approach with respect to reduction of large infarction.Methods and resultsPatients with NSTEMI were randomized to either an immediate (<2 h after randomization; n= 201), an early (10-48 h after randomization; n= 200), or a selective invasive approach with high invasive percentage (n= 201). The primary outcome was the peak creatine kinase (CK)-myocardial band (MB) activity during index hospitalization; key secondary clinical endpoints were the composite of (i) death and non-fatal infarction; (ii) death, non-fatal infarction, and refractory ischaemia; (iii) death, non-fatal infarction, refractory ischaemia, and rehospitalization for unstable angina within 6 months.The median time from randomization to angiography was 1.1 h in the immediate vs. 18.6 h in the early and 67.2 h in the selective invasive group (P< 0.001). There was no significant difference in the peak CK-MB activity between groups. The key secondary clinical endpoints were similar between groups at 6-month follow-up: death and infarction: 21.0 vs. 16.0 vs. 14.5%; P= 0.17; death, infarction, refractory ischaemia: 20.9 vs. 21.5 vs. 22.0%; P= 0.98; death, infarction, refractory ischaemia, rehospitalization: 26.0 vs. 26.5 vs. 24.5%; P= 0.91, respectively.ConclusionsIn NSTEMI patients, an immediate invasive approach does not offer an advantage over an early or a selective invasive approach with respect to large myocardial infarctions as defined by peak CK-MB levels, which is supported by similar clinical outcomes.ClinicalTrials.gov NCT00402675.
Dantrolene Rescues Arrhythmogenic RYR2 Defect in a Patient-specific Stem Cell Model of Catecholaminergic Polymorphic Ventricular Tachycardia
Coordinated release of calcium (Ca(2+) ) from the sarcoplasmic reticulum (SR) through cardiac ryanodine receptor (RYR2) channels is essential for cardiomyocyte function. In catecholaminergic polymorphic ventricular tachycardia (CPVT), an inherited disease characterized by stress-induced ventricular arrhythmias in young patients with structurally normal hearts, autosomal dominant mutations in RYR2 or recessive mutations in calsequestrin lead to aberrant diastolic Ca(2+) release from the SR causing arrhythmogenic delayed after depolarizations (DADs). Here, we report the generation of induced pluripotent stem cells (iPSCs) from a CPVT patient carrying a novel RYR2 S406L mutation. In patient iPSC-derived cardiomyocytes, catecholaminergic stress led to elevated diastolic Ca(2+) concentrations, a reduced SR Ca(2+) content and an increased susceptibility to DADs and arrhythmia as compared to control myocytes. This was due to increased frequency and duration of elementary Ca(2+) release events (Ca(2+) sparks). Dantrolene, a drug effective on malignant hyperthermia, restored normal Ca(2+) spark properties and rescued the arrhythmogenic phenotype. This suggests defective inter-domain interactions within the RYR2 channel as the pathomechanism of the S406L mutation. Our work provides a new in vitro model to study the pathogenesis of human cardiac arrhythmias and develop novel therapies for CPVT.
Search for B(s)(0) †’ μ+ μ- and B(0) †’ μ+ μ- Decays in Pp Collisions at Sqrt[s] = 7 TeV
A search for the rare decays B(s)(0) → μ+ μ- and B(0) → μ+ μ- is performed in pp collisions at sqrt[s] = 7 TeV, with a data sample corresponding to an integrated luminosity of 1.14 fb(-1), collected by the CMS experiment at the LHC. In both cases, the number of events observed after all selection requirements is consistent with expectations from background and standard-model signal predictions. The resulting upper limits on the branching fractions are B(B(s)(0) → μ+ μ-) < 1.9 × 10(-8) and B(B(0) → μ+ μ-)<4.6 × 10(-9), at 95% confidence level.
Search for New Physics with a Monojet and Missing Transverse Energy in Pp Collisions at Sqrt[s]=7  TeV
A study of events with missing transverse energy and an energetic jet is performed using pp collision data at a center-of-mass energy of 7 TeV. The data were collected by the CMS detector at the LHC, and correspond to an integrated luminosity of 36  pb^{-1}. An excess of these events over standard model contributions is a signature of new physics such as large extra dimensions and unparticles. The number of observed events is in good agreement with the prediction of the standard model, and significant extension of the current limits on parameters of new physics benchmark models is achieved.
Search for Supersymmetry at the LHC in Events with Jets and Missing Transverse Energy
A search for events with jets and missing transverse energy is performed in a data sample of pp collisions collected at sqrt[s]=7  TeV by the CMS experiment at the LHC. The analyzed data sample corresponds to an integrated luminosity of 1.14  fb^{-1}. In this search, a kinematic variable α_{T} is used as the main discriminator between events with genuine and misreconstructed missing transverse energy. No excess of events over the standard model expectation is found. Exclusion limits in the parameter space of the constrained minimal supersymmetric extension of the standard model are set. In this model, squark masses below 1.1 TeV are excluded at 95% C.L. Gluino masses below 1.1 TeV are also ruled out at 95% C.L. for values of the universal scalar mass parameter below 500 GeV.
Evolution of the 7/2 Fractional Quantum Hall State in Two-subband Systems
We report the evolution of the fractional quantum Hall state (FQHS) at a total Landau level (LL) filling factor of ν=7/2 in wide GaAs quantum wells in which electrons occupy two electric subbands. The data reveal subtle and distinct evolutions as a function of density, magnetic field tilt angle, or symmetry of the charge distribution. At intermediate tilt angles, for example, we observe a strengthening of the ν=7/2 FQHS. Moreover, in a well with asymmetric change distribution, there is a developing FQHS when the LL filling factor of the symmetric subband ν_{S} equals 5/2 while the antisymmetric subband has a filling factor of 1<ν_{A}<2.
Search for a Vectorlike Quark with Charge 2/3 in T+Z Events from Pp Collisions at Sqrt[s]=7  TeV
A search for pair-produced heavy vectorlike charge-2/3 quarks, T, in pp collisions at a center-of-mass energy of 7 TeV, is performed with the CMS detector at the LHC. Events consistent with the flavor-changing-neutral-current decay of a T quark to a top quark and a Z boson are selected by requiring two leptons from the Z-boson decay, as well as an additional isolated charged lepton. In a data sample corresponding to an integrated luminosity of 1.14  fb^{-1}, the number of observed events is found to be consistent with the standard model background prediction. Assuming a branching fraction of 100% for the decay T→tZ, a T quark with a mass less than 475  GeV/c^{2} is excluded at the 95% confidence level.
Search for Signatures of Extra Dimensions in the Diphoton Mass Spectrum at the Large Hadron Collider
A search for signatures of extra spatial dimensions in the diphoton invariant-mass spectrum has been performed with the CMS detector at the LHC. No excess of events above the standard model expectation is observed using a data sample collected in proton-proton collisions at √s=7 TeV corresponding to an integrated luminosity of 2.2 fb(-1). In the context of the large-extra-dimensions model, lower limits are set on the effective Planck scale in the range of 2.3-3.8 TeV at the 95% confidence level. These limits are the most restrictive bounds on virtual-graviton exchange to date. The most restrictive lower limits to date are also set on the mass of the first graviton excitation in the Randall-Sundrum model in the range of 0.86-1.84 TeV, for values of the associated coupling parameter between 0.01 and 0.10.
Search for the Standard Model Higgs Boson in the Decay Channel H→ZZ→4â„“ in Pp Collisions at ˆšs=7 TeV
A search for a Higgs boson in the four-lepton decay channel H→ZZ, with each Z boson decaying to an electron or muon pair, is reported. The search covers Higgs boson mass hypotheses in the range of 110
A Variant of the Neuronal Amino Acid Transporter SLC6A15 is Associated with ACTH and Cortisol Responses and Cognitive Performance in Unipolar Depression
Major depressive disorder (MDD) is accompanied by both cognitive impairments and a hyperactivity of the hypothalamic-pituitary-adrenocortical (HPA) system, resulting in an enhanced glucocorticoid secretion. Cortisol acts via mineralocorticoid and glucocorticoid receptors densely located in the hippocampus, a brain area that is important regarding cognitive functions and especially memory functions. Recently, a variant (rs1545843) affecting transcription of the human SLC6A15 gene has been associated with depression in a genome-wide association study. In an animal model, the neuronal amino acid transporter SLC6A15 was found to be decreased in stress-susceptible mice. Against the background of stress impacting on the activity of the HPA axis, we have investigated alterations of adrenocorticotropic hormone (ACTH) and cortisol secretion in the combined dexamethasone/corticotrophin-releasing hormone (Dex/CRH) test as well as memory and attention performance in a sample of 248 patients with unipolar depression and 172 healthy control subjects genotyped for rs1545843. MDD patients carrying the depression-associated AA genotype showed enhanced maximum and area under the curve ACTH and cortisol answers (p=0.03) as well as an impaired memory and impaired sustained attention performance (p=0.04) compared to carriers of at least one G allele. No effects of the SLC6A15 variant were found in the healthy control group. Our findings argue for a role of the SLC6A15 gene in ACTH and cortisol secretion during the Dex/CRH test and furthermore in the occurrence of cognitive impairments in unipolar depression.
Early Viral Load and Recipient IL28B Rs12979860 Genotype Are Predictors for Progression of Hepatitis C After Liver Transplantation
There have been few studies of detailed viral kinetics following liver transplantation (LT) and conflicting data have been reported on viral load and severity of recurrent hepatitis C virus (HCV) disease. This long-term study aimed to examine (1) the impact of HCV RNA levels at specific points in time within the first year and (2) the influence of IL28B genotype on patient outcome and severity of recurrent HCV disease. Viral load was measured at week 2, 4, 12, 24 and 48 following LT and recipient / donor IL28B genotypes of 164 patients were determined. Cox-regression analysis showed that viral load at week 2 was an independent negative predictor of recipient outcome. A week 2 viral load of = 6.0 log(10) IU/mL was significantly associated with reduced patient survival. After a mean follow-up of 6.5 years 21 patients (12.2%) developed either a cholestatic type of HCV recurrence and/or rapid progression to cirrhosis within one year. Multivariate binary regression analysis showed that HCV viremia at week 2 and a non C/C recipient IL28B genotype were independent risk factors for cholestatic recurrent hepatitis C. No predictive factors could be found for the occurrence of recurrent liver cirrhosis at 5- and 10 years following LT. Our study shows that HCV RNA levels at week 2 and recipient IL28B genotype are independent, statistically significant risk factors for post-LT cholestatic hepatitis C emphasizing the importance of viral load monitoring and of IL28B genotyping to identify HCV recipients at risk for severe hepatitis C recurrence. © 2012 American Association for the Study of Liver Diseases.
A Distinct Metabolic Signature Predicts Development of Fasting Plasma Glucose
ABSTRACT: BACKGROUND: High blood glucose and diabetes are amongst the conditions causing the greatest losses in years of healthy life worldwide. Therefore, numerous studies aim to identify reliable risk markers for development of impaired glucose metabolism and type 2 diabetes. However, the molecular basis of impaired glucose metabolism is so far insufficiently understood. The development of so called `omics' approaches in the recent years promises to identify molecular markers and to further understand the molecular basis of impaired glucose metabolism and type 2 diabetes. Although univariate statistical approaches are often applied, we demonstrate here that the application of multivariate statistical approaches is highly recommended to fully capture the complexity of data gained using high-throughput methods. METHODS: We took blood plasma samples from 172 subjects who participated in the prospective Metabolic Syndrome Berlin Potsdam follow-up study (MESY-BEPO Follow-up). We analysed these samples using Gas Chromatography coupled with Mass Spectrometry (GC-MS), and measured 286 metabolites. Furthermore, fasting glucose levels were measured using standard methods at baseline, and after an average of six years. We did correlation analysis and built linear regression models as well as Random Forest regression models to identify metabolites that predict the development of fasting glucose in our cohort. RESULTS: We found a metabolic pattern consisting of nine metabolites that predicted fasting glucose development with an accuracy of 0.47 in tenfold cross-validation using Random Forest regression. We also showed that adding established risk markers did not improve the model accuracy. However, external validation is eventually desirable. Although not all metabolites belonging to the final pattern are identified yet, the pattern directs attention to amino acid metabolism, energy metabolism and redox homeostasis. CONCLUSIONS: We demonstrate that metabolites identified using a high-throughput method (GC-MS) perform well in predicting the development of fasting plasma glucose over several years. Notably, not single, but a complex pattern of metabolites propels the prediction and therefore reflects the complexity of the underlying molecular mechanisms. This result could only be captured by application of multivariate statistical approaches. Therefore, we highly recommend the usage of statistical methods that seize the complexity of the information given by high-throughput methods.
Diagnostics of Autoimmune Bullous Diseases in German Dermatology Departments
No consistent data are available on the currently employed diagnostic tools for autoimmune bullous diseases in Germany. The aim of this survey was to describe currently performed diagnostic methods for bullous autoimmune diseases in German dermatology departments.
A Genome-wide Association Search for Type 2 Diabetes Genes in African Americans
African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
