Mol. Cell. Proteomics

Chemical cross-linking in combination with mass spectrometric analysis offers the potential to obtain low-resolution structural information from proteins and protein complexes. Identification of peptides connected by a cross-link provides direct evidence for the physical interaction of amino acid side chains, information that can be used for computational modeling purposes. Despite impressive advances that were made in recent years, the number of experimentally observed cross-links still falls below the number of possible contacts of cross-linkable side chains within the span of the cross-linker. Here, we propose two complementary experimental strategies to expand cross-linking data sets. First, enrichment of cross-linked peptides by size exclusion chromatography selects cross-linked peptides based on their higher molecular mass, thereby depleting the majority of unmodified peptides present in proteolytic digests of cross-linked samples. Second, we demonstrate that the use of proteases in addition to trypsin, such as Asp-N, can additionally boost the number of observable cross-linking sites. The benefits of both SEC enrichment and multiprotease digests are demonstrated on a set of model proteins and the improved workflow is applied to the characterization of the 20S proteasome from rabbit and Schizosaccharomyces pombe

Temperature in One-Dimensional Bosonic Mott insulators

The Mott insulating phase of a one-dimensional bosonic gas trapped in optical lattices is described by a Bose-Hubbard model. A continuous unitary transformation is used to map this model onto an effective model conserving the number of elementary excitations. We obtain quantitative results for the kinetics and for the spectral weights of the low-energy excitations for a broad range of parameters in the insulating phase. By these results, recent Bragg spectroscopy experiments are explained. Evidence for a significant temperature of the order of the microscopic energy scales is found.Comment: 8 pages, 7 figure

Systematic Mapping of the Hubbard Model to the Generalized t-J Model

The generalized t-J model conserving the number of double occupancies is constructed from the Hubbard model at and in the vicinity of half-filling at strong coupling. The construction is realized by a self-similar continuous unitary transformation. The flow equation is closed by a truncation scheme based on the spatial range of processes. We analyze the conditions under which the t-J model can be set up and we find that it can only be defined for sufficiently large interaction. There, the parameters of the effective model are determined.Comment: 16 pages, 13 figures included. v2: Order of sections changed. Calculation and discussion of apparent gap in Section IV.A correcte

Performance of Different Diagnostic PD-L1 Clones in Head and Neck Squamous Cell Carcinoma

Background: The approval of immune checkpoint inhibitors in combination with specific diagnostic biomarkers presents new challenges to pathologists as tumor tissue needs to be tested for expression of programmed death-ligand 1 (PD-L1) for a variety of indications. As there is currently no requirement to use companion diagnostic assays for PD-L1 testing in Germany different clones are used in daily routine. While the correlation of staining results has been tested in various entities, there is no data for head and neck squamous cell carcinomas (HNSCC) so far. Methods: We tested five different PD-L1 clones (SP263, SP142, E1L3N, 22-8, 22C3) on primary HNSCC tumor tissue of 75 patients in the form of tissue microarrays. Stainings of both immune and tumor cells were then assessed and quantified by pathologists to simulate real-world routine diagnostics. The results were analyzed descriptively and the resulting staining pattern across patients was further investigated by principal component analysis and non-negative matrix factorization clustering. Results: Percentages of positive immune and tumor cells varied greatly. Both the resulting combined positive score as well as the eligibility for certain checkpoint inhibitor regimens was therefore strongly dependent on the choice of the antibody. No relevant co-clustering and low similarity of relative staining patterns across patients was found for the different antibodies. Conclusions: Performance of different diagnostic anti PD-L1 antibody clones in HNSCC is less robust and interchangeable compared to reported data from other tumor entities. Determination of PD-L1 expression is critical for therapeutic decision making and may be aided by back-to-back testing of different PD-L1 clones

An SU(N) Mott insulator of an atomic Fermi gas realized by large-spin Pomeranchuk cooling

The Hubbard model, containing only the minimum ingredients of nearest neighbor hopping and on-site interaction for correlated electrons, has succeeded in accounting for diverse phenomena observed in solid-state materials. One of the interesting extensions is to enlarge its spin symmetry to SU(N>2), which is closely related to systems with orbital degeneracy. Here we report a successful formation of the SU(6) symmetric Mott insulator state with an atomic Fermi gas of ytterbium (173Yb) in a three-dimensional optical lattice. Besides the suppression of compressibility and the existence of charge excitation gap which characterize a Mott insulating phase, we reveal an important difference between the cases of SU(6) and SU(2) in the achievable temperature as the consequence of different entropy carried by an isolated spin. This is analogous to Pomeranchuk cooling in solid 3He and will be helpful for investigating exotic quantum phases of SU(N) Hubbard system at extremely low temperatures.Comment: 20 pages, 6 figures, to appear in Nature Physic

Strong-coupling expansion and effective hamiltonians

When looking for analytical approaches to treat frustrated quantum magnets, it is often very useful to start from a limit where the ground state is highly degenerate. This chapter discusses several ways of deriving {effective Hamiltonians} around such limits, starting from standard {degenerate perturbation theory} and proceeding to modern approaches more appropriate for the derivation of high-order effective Hamiltonians, such as the perturbative continuous unitary transformations or contractor renormalization. In the course of this exposition, a number of examples taken from the recent literature are discussed, including frustrated ladders and other dimer-based Heisenberg models in a field, as well as the mapping between frustrated Ising models in a transverse field and quantum dimer models.Comment: To appear as a chapter in "Highly Frustrated Magnetism", Eds. C. Lacroix, P. Mendels, F. Mil

Comparison of two DNA targets for the diagnosis of Toxoplasmosis by real-time PCR using fluorescence resonance energy transfer hybridization probes

BACKGROUND: Toxoplasmosis is an infectious disease caused by the parasitic protozoan Toxoplasma gondii. It is endemic worldwide and, depending on the geographic location, 15 to 85% of the human population are asymptomatically infected. Routine diagnosis is based on serology. The parasite has emerged as a major opportunistic pathogen for immunocompromised patients, in whom it can cause life-threatening disease. Moreover, when a pregnant woman develops a primary Toxoplasma gondii infection, the parasite may be transmitted to the fetus and cause serious damnage. For these two subpopulations, a rapid and accurate diagnosis is required to initiate treatment. Serological diagnosis of active infection is unreliable because reactivation is not always accompanied by changes in antibody levels, and the presence of IgM does not necessarily indicate recent infection. Application of quantitative PCR has evolved as a sensitive, specific, and rapid method for the detection of Toxoplasma gondii DNA in amniotic fluid, blood, tissue samples, and cerebrospinal fluid. METHODS: Two separate, real-time fluorescence PCR assays were designed and evaluated with clinical samples. The first, targeting the 35-fold repeated B1 gene, and a second, targeting a newly described multicopy genomic fragment of Toxoplasma gondii. Amplicons of different intragenic copies were analyzed for sequence heterogeneity. RESULTS: Comparative LightCycler experiments were conducted with a dilution series of Toxoplasma gondii genomic DNA, 5 reference strains, and 51 Toxoplasma gondii-positive amniotic fluid samples revealing a 10 to 100-fold higher sensitivity for the PCR assay targeting the newly described 529-bp repeat element of Toxoplasma gondii. CONCLUSION: We have developed a quantitative LightCycler PCR protocol which offer rapid cycling with real-time, sequence-specific detection of amplicons. Results of quantitative PCR demonstrate that the 529-bp repeat element is repeated more than 300-fold in the genome of Toxoplasma gondii. Since individual intragenic copies of the target are conserved on sequence level, the high copy number leads to an ultimate level of analytical sensitivity in routine practice. This newly described 529-bp repeat element should be preferred to less repeated or more divergent target sequences in order to improve the sensitivity of PCR tests for the diagnosis of toxoplasmosis

Relationship between foot pronation and rotation of the tibia and femur during walking

ABSTRACT The purpose of this study was to test the hypothesis that the magnitude and timing of peak foot pronation would be predictive of the magnitude and timing of peak rotation of tibia and femur. Thirty subjects who demonstrated a wide range of pronation participated. Threedimensional kinematics of the foot, tibia, and femur segments were recorded during self-selected free walking trials using a six-camera VICON motion analysis system. Regression analysis demonstrated that the magnitude and timing of peak pronation was not predictive of the magnitude and timing of tibial and femoral rotation. The lack of a relationship between peak foot pronation and the rotation of the tibia and femur is contrary to the clinical hypothesis that increased pronation results in greater lower extremity rotation. It would seem, therefore, that the relationship between foot pronation and rotation of the lower extremity segments should be assessed on a patient-by-patient basis

Measurement of the top quark mass and top-antitop production cross section from dilepton events at the Collider Detector at Fermilab

We present an analysis of dilepton events originating from top-antitop production in proton-antiproton collisions at sqrt{s}=1.8 TeV at the Fermilab Tevatron Collider. The sample corresponds to an integrated luminosity of 109+-7 pb^{-1}. We observe 9 candidate events, with an estimated background of 2.4+-0.5 events. We determine the mass of the top quark to be M_top = 161+-17(stat.)+-10(syst.) GeV/c^2. In addition we measure a top-antitop production cross section of 8.2+4.4-3.4 pb (where M_top = 175 GeV/c^2 has been assumed for the acceptance estimate).Comment: 6 pages of text, 3 figure