g factor of lithiumlike silicon 28Si11+

The g factor of lithiumlike 28Si11+ has been measured in a triple-Penning trap with a relative uncertainty of 1.1x10^{-9} to be g_exp=2.0008898899(21). The theoretical prediction for this value was calculated to be g_th=2.000889909(51) improving the accuracy to 2.5x10^{-8} due to the first rigorous evaluation of the two-photon exchange correction. The measured value is in excellent agreement with the state-of-the-art theoretical prediction and yields the most stringent test of bound-state QED for the g factor of the 1s^22s state and the relativistic many-electron calculations in a magnetic field

Ocenka effektivnosti sily tolčka pri vypolnenii arabera i bosakova

Provedeno je preliminarno istraživanje udjela i važnost manifestne sile reakcije podloge prilikom odraza u uspješnom izvođenju arabera i bosakova. Uzorak ispitanika obuhvaćao je šest gimnastičarki republičkog i saveznog ranga, u dobi od 13-21 godine, visine od 141-165 cm težine od 34,4 do 56,3 kp te dužine bavljenja sportskom gimnastikom od 4,5 do 9 godina. Mjerena je trokomponentna sila reakcije podloge i davane su ocjene za svaki pojedinačni pokušaj. Na temelju osnovne statističke analize mjernih signala sile došlo se do zaključka da su za uspješno izvođenje arabera i boksova značajni dobra ponljivost signala manifestirane sile reakcije podloge i dobra impulzivnost odraza. Kod izvođenja arabeara mehanizma rotacije tijela oko uzdužne osi inicira se u načelu prilikom odraza.This is a preliminary study of importance of the manifest force of support reaction during jump-off in successful performance of "arber" and "bosakov". The sample consisted of 6 women gymnastics of national reputation, aged 13 to 21, 141 to 165 cm tall and weight from 34,4 to 56,3 kg with an experience in gymnastics from 4,5 to 9 years. The 3 component force of support reaction was measured and each attempt was separately judged. The study was carried out in July 1983. For all 3 components, the values of maximum amplitudes and duration of individual characteristics time segments of force signals were extracted. The basic statistic operations were done on the extracted values; computation of average values, standard deviations and coefficients of variation. The analysis of obtained results and evaluation of achievement suggests: - a successful performance of each element of technique is a result of good training in stereotype movements which is evident in repeatability of morphology of force signals; - a powerful jump, reflected in great measured impulse of the vertical force Fx results, generally speaking, in successfully performed elements; - the transversal component of the reflection force Fy is greater in "araber" than in "bosakov", while for F, stands just the opposite. This means that the rotation of the body around the longitudinal axis starts with the jump, or from the ground (in "arabtr"); -an individual realization of successful movement stereotypes is possible as in the case of gymnasts 1 and 5 who showed an aberration from the former two principles

Induction and characterization of anti-tumor endothelium immunity elicited by ValloVax therapeutic cancer vaccine.

ValloVax is a placental endothelium derived vaccine which induces tissue-nonspecific antitumor immunity by blocking tumor angiogesis. To elucidate mechanisms of action, we showed that production of ValloVax, which involves treating placental endothelial cells with IFN-gamma, results in upregulation of HLA and costimulatory molecules. It was shown that in mixed lymphocyte reaction, ValloVax induces Type I cytokines and allo-proliferative responses. Plasma from ValloVax immunized mice was capable of killing in vitro tumor-like endothelium but not control endothelium. Using defined antigens associated with tumor endothelial cells, specific molecular entities were identified as being targeted by ValloVax induced antibodies. Binding of predominantly IgG antibodies to ValloVax cells was confirmed by flow cytometry. Further suggesting direct killing of tumor endothelial cells was expression of TUNEL positive cells, as well as, reduction in tumor oxygenation. Supporting a role for antibody mediated responses, cell depletion experiments suggested a predominant role of B cells in maintaining an intact anti-tumor endothelial response. Adoptive transfer experiments suggested that infusion of CD3+ T cells from immunized mice was sufficient to transfer tumor protection. Generation of memory T cells selective to tumor endothelial specific markers was observed. Functional confirmation of memory responses was observed in tumor rechallenge experiments. Furthermore, we observed that both PD-1 or CTLA-4 blockade augmented antitumor effects of ValloVax. These data suggest a T cell induced B cell mediated anti-tumor endothelial response and set the framework clinical trials through elucidation of mechanism of action

Macroscopic Dynamics of Multi-Lane Traffic

We present a macroscopic model of mixed multi-lane freeway traffic that can be easily calibrated to empirical traffic data, as is shown for Dutch highway data. The model is derived from a gas-kinetic level of description, including effects of vehicular space requirements and velocity correlations between successive vehicles. We also give a derivation of the lane-changing rates. The resulting dynamic velocity equations contain non-local and anisotropic interaction terms which allow a robust and efficient numerical simulation of multi-lane traffic. As demonstrated by various examples, this facilitates the investigation of synchronization patterns among lanes and effects of on-ramps, off-ramps, lane closures, or accidents.Comment: For related work see http://www.theo2.physik.uni-stuttgart.de/helbing.htm

HIV-1 Broadly Neutralizing Antibody Extracts Its Epitope from a Kinked gp41 Ectodomain Region on the Viral Membrane

SummaryAlthough rarely elicited during natural human infection, the most broadly neutralizing antibodies (BNAbs) against diverse human immunodeficiency virus (HIV)-1 strains target the membrane-proximal ectodomain region (MPER) of viral gp41. To gain insight into MPER antigenicity, immunogenicity, and viral function, we studied its structure in the lipid environment by a combination of nuclear magnetic resonance (NMR), electron paramagnetic resonance (EPR), and surface plasmon resonance (SPR) techniques. The analyses revealed a tilted N-terminal α helix (aa 664–672) connected via a short hinge to a flat C-terminal helical segment (675–683). This metastable L-shaped structure is immersed in viral membrane and, therefore, less accessible to immune attack. Nonetheless, the 4E10 BNAb extracts buried W672 and F673 after initial encounter with the surface-embedded MPER. The data suggest how BNAbs may perturb tryptophan residue-associated viral fusion involving the mobile N-terminal MPER segment and, given conservation of MPER sequences in HIV-1, HIV-2, and SIV, have important implications for structure-guided vaccine design

Magneto-optical study of metamagnetic transitions in the antiferromagnetic phase of α-RuCl3

alpha-RuCl3 is a promising candidate material to realize the so far elusive quantum spin liquid ground state. However, at low temperatures, the coexistence of different exchange interactions couple the effective pseudospins into an antiferromagnetically zigzag (ZZ) ordered state. The low-field evolution of spin structure is still a matter of debate and the magnetic anisotropy within the honeycomb planes is an open and challenging question. Here, we investigate the evolution of the ZZ order parameter by second-order magneto-optical effects, the magnetic linear dichroism and magnetic linear birefringence. Our results clarify the presence and nature of metamagnetic transitions in the ZZ phase of alpha-RuCl3. The experimental observations show the presence of initial magnetic domain repopulation followed by a spin-flop transition for small in-plane applied magnetic fields (approximate to 1.6 T) along specific crystallographic directions. In addition, using a magneto-optical approach, we detected the recently reported emergence of a field-induced intermediate phase before suppressing the ZZ order. The results disclose the details of various angle-dependent in-plane metamagnetic transitions quantifying the bond-anisotropic interactions present in alpha-RuCl3

Four and a Half LIM Protein 1C (FHL1C): A Binding Partner for Voltage-Gated Potassium Channel Kv1.5

Four-and-a-half LIM domain protein 1 isoform A (FHL1A) is predominantly expressed in skeletal and cardiac muscle. Mutations in the FHL1 gene are causative for several types of hereditary myopathies including X-linked myopathy with postural muscle atrophy (XMPMA). We here studied myoblasts from XMPMA patients. We found that functional FHL1A protein is completely absent in patient myoblasts. In parallel, expression of FHL1C is either unaffected or increased. Furthermore, a decreased proliferation rate of XMPMA myoblasts compared to controls was observed but an increased number of XMPMA myoblasts was found in the G0/G1 phase. Furthermore, low expression of Kv1.5, a voltage-gated potassium channel known to alter myoblast proliferation during the G1 phase and to control repolarization of action potential, was detected. In order to substantiate a possible relation between Kv1.5 and FHL1C, a pull-down assay was performed. A physical and direct interaction of both proteins was observed in vitro. In addition, confocal microscopy revealed substantial colocalization of FHL1C and Kv1.5 within atrial cells, supporting a possible interaction between both proteins in vivo. Two-electrode voltage clamp experiments demonstrated that coexpression of Kv1.5 with FHL1C in Xenopus laevis oocytes markedly reduced K+ currents when compared to oocytes expressing Kv1.5 only. We here present the first evidence on a biological relevance of FHL1C

Selective Methyl Labeling of Eukaryotic Membrane Proteins Using Cell-Free Expression

Structural characterization of membrane proteins and other large proteins with NMR relies increasingly on perdeuteration combined with incorporation of specifically protonated amino acid moieties, such as methyl groups of isoleucines, valines, or leucines. The resulting proton dilution reduces dipolar broadening producing sharper resonance lines, ameliorates spectral crowding, and enables measuring of crucial distances between and to methyl groups. While incorporation of specific methyl labeling is now well established for bacterial expression using suitable precursors, corresponding methods are still lacking for cell-free expression, which is often the only choice for producing labeled eukaryotic membrane proteins in mg quantities. Here we show that we can express methyl-labeled human integral membrane proteins cost-effectively by cell-free expression based of crude hydrolyzed ILV-labeled OmpX inclusion bodies. These are obtained in Escherichia coli with very high quantity and represent an optimal intermediate to channel ILV precursors into the eukaryotic proteins

Aging and Replicative Senescence Have Related Effects on Human Stem and Progenitor Cells

The regenerative potential diminishes with age and this has been ascribed to functional impairments of adult stem cells. Cells in culture undergo senescence after a certain number of cell divisions whereby the cells enlarge and finally stop proliferation. This observation of replicative senescence has been extrapolated to somatic stem cells in vivo and might reflect the aging process of the whole organism. In this study we have analyzed the effect of aging on gene expression profiles of human mesenchymal stromal cells (MSC) and human hematopoietic progenitor cells (HPC). MSC were isolated from bone marrow of donors between 21 and 92 years old. 67 genes were age-induced and 60 were age-repressed. HPC were isolated from cord blood or from mobilized peripheral blood of donors between 27 and 73 years and 432 genes were age-induced and 495 were age-repressed. The overlap of age-associated differential gene expression in HPC and MSC was moderate. However, it was striking that several age-related gene expression changes in both MSC and HPC were also differentially expressed upon replicative senescence of MSC in vitro. Especially genes involved in genomic integrity and regulation of transcription were age-repressed. Although telomerase activity and telomere length varied in HPC particularly from older donors, an age-dependent decline was not significant arguing against telomere exhaustion as being causal for the aging phenotype. These studies have demonstrated that aging causes gene expression changes in human MSC and HPC that vary between the two different cell types. Changes upon aging of MSC and HPC are related to those of replicative senescence of MSC in vitro and this indicates that our stem and progenitor cells undergo a similar process also in vivo