Anomalous Angular Dependence of the Dynamic Structure Factor near Bragg Reflections: Graphite

The electron energy-loss function of graphite is studied for momentum transfers q beyond the first Brillouin zone. We find that near Bragg reflections the spectra can change drastically for very small variations in q. The effect is investigated by means of first principle calculations in the random phase approximation and confirmed by inelastic x-ray scattering measurements of the dynamic structure factor S(q,\omega). We demonstrate that this effect is governed by crystal local field effects and the stacking of graphite. It is traced back to a strong coupling between excitations at small and large momentum transfers

Linear plasmon dispersion in single-wall carbon nanotubes and the collective excitation spectrum of graphene

We have measured a strictly linear pi-plasmon dispersion along the axis of individualized single wall carbon nanotubes, which is completely different from plasmon dispersions of graphite or bundled single wall carbon nanotubes. Comparative ab initio studies on graphene based systems allow us to reproduce the different dispersions. This suggests that individualized nanotubes provide viable experimental access to collective electronic excitations of graphene, and it validates the use of graphene to understand electronic excitations of carbon nanotubes. In particular, the calculations reveal that local field effects (LFE) cause a mixing of electronic transitions, including the 'Dirac cone', resulting in the observed linear dispersion

Evidence for strong relations between the upper Tagus loess formation (central Iberia) and the marine atmosphere off the Iberian margin during the last glacial period

During glacial times, the North Atlantic region was affected by serious climate changes corresponding to Dansgaard-Oeschger cycles that were linked to dramatic shifts in sea temperature and moisture transfer to the continents. However, considerable efforts are still needed to understand the effects of these shifts on terrestrial environments. In this context, the Iberian Peninsula is particularly interesting because of its close proximity to the North Atlantic, although the Iberian interior lacks paleoenvironmental information so far because suitable archives are rare. Here we provide an accurate impression of the last glacial environmental developments in central Iberia based on comprehensive investigations using the upper Tagus loess record. A multi-proxy approach revealed that phases of loess formation during Marine Isotope Stage (MIS) 2 (and upper MIS 3) were linked to utmost aridity, coldness, and highest wind strengths in line with the most intense Greenland stadials also including Heinrich Events 3–1. Lack of loess deposition during the global last glacial maximum (LGM) suggests milder conditions, which agrees with less-cold sea surface temperatures (SST) off the Iberian margin. Our results demonstrate that geomorphological system behavior in central Iberia is highly sensitive to North Atlantic SST fluctuations, thus enabling us to reconstruct a detailed hydrological model in relation to marine–atmospheric circulation patterns

The Human Minor Histocompatibility Antigen1 Is a RhoGAP

The human minor Histocompatibility Antigen HMHA-1 is a major target of immune responses after allogeneic stem cell transplantation applied for the treatment of leukemia and solid tumors. The restriction of its expression to hematopoietic cells and many solid tumors raised questions regarding its cellular functions. Sequence analysis of the HMHA-1 encoding HMHA1 protein revealed the presence of a possible C-terminal RhoGTPase Activating Protein (GAP) domain and an N-terminal BAR domain. Rho-family GTPases, including Rac1, Cdc42, and RhoA are key regulators of the actin cytoskeleton and control cell spreading and migration. RhoGTPase activity is under tight control as aberrant signaling can lead to pathology, including inflammation and cancer. Whereas Guanine nucleotide Exchange Factors (GEFs) mediate the exchange of GDP for GTP resulting in RhoGTPase activation, GAPs catalyze the low intrinsic GTPase activity of active RhoGTPases, resulting in inactivation. Here we identify the HMHA1 protein as a novel RhoGAP. We show that HMHA1 constructs, lacking the N-terminal region, negatively regulate the actin cytoskeleton as well as cell spreading. Furthermore, we show that HMHA1 regulates RhoGTPase activity in vitro and in vivo. Finally, we demonstrate that the HMHA1 N-terminal BAR domain is auto-inhibitory as HMHA1 mutants lacking this region, but not full-length HMHA1, showed GAP activity towards RhoGTPases. In conclusion, this study shows that HMHA1 acts as a RhoGAP to regulate GTPase activity, cytoskeletal remodeling and cell spreading, which are crucial functions in normal hematopoietic and cancer cells

OSL-dating of the Pleistocene-Holocene climatic transition in loess from China, Europe and North America, and evidence for accretionary pedogenesis

Loess deposits intercalated by paleosols are detailed terrestrial archives of Quaternary climate variability providing information on the global dust cycle and landscape dynamics. Their paleoclimatic significance is often explored by quantifying their mineral magnetic properties due to their sensitivity to local/regional hydroclimate variability. Detailed chronological assessment of such regional proxy records around the climatic transitions allow a better understanding of how regional records react to major global climatic transitions such as the Pleistocene-Holocene climatic transition. Logs of high-resolution magnetic susceptibility and its frequency dependence were used as paleoclimatic proxies to define the environmental transition from the last glacial loess to the current interglacial soil as reflected in nine loess-paleosol sequences across the northern hemisphere, from the Chinese Loess Plateau, the southeastern European loess belt and the central Great Plains, USA. The onset of increase in magnetic susceptibility above typical loess values was used to assess the onset of, and developments during, the Pleistocene-Holocene climatic transition. High-resolution luminescence dating was applied on multiple grain-sizes (4–11 μm, 63–90 μm, 90–125 μm) of quartz extracts from the same sample in order to investigate the timing of Pleistocene-Holocene climatic transition in the investigated sites. The magnetic susceptibility signal shows a smooth and gradual increase for the majority of the sites from the typical low loess values to the interglacial ones. The initiation of this increase, interpreted as recording the initiation of the Pleistocene-Holocene climatic transition at each site, was dated to 14–17.5 ka or even earlier. Our chronological results highlight the need of combining paleoclimatic proxies (magnetic susceptibility) with absolute dating when investigating the Pleistocene-Holocene climatic transition as reflected by the evolution of this proxy in order to avoid chronostratigraphic misinterpretations in loess-paleosol records caused by simple pattern correlation. The detailed luminescence chronologies evidence the continuity of eolian mineral dust accumulation regardless of glacial or interglacial global climatic regimes. Coupled with magnetic susceptibility records this indicates that dust sedimentation and pedogenesis act simultaneously and result in a non-negligible accretional component in the formation of Holocene soils in loess regions across the Northern Hemisphere. The luminescence ages allowed the modeling of accumulation rates for the Holocene soil which are similar for European, Chinese and U.S.A. loess sites investigated and vary from 2 cm ka−1 to 9 cm ka−1. While accretional pedogenesis has often been implicitly or explicitly assumed in paleoclimatic interpretation of loess-paleosol sequences, especially in the Chinese Loess Plateau, our luminescence data add direct evidence for ongoing sedimentation as interglacial soils formed

HSPVdb—the Human Short Peptide Variation Database for improved mass spectrometry-based detection of polymorphic HLA-ligands

T cell epitopes derived from polymorphic proteins or from proteins encoded by alternative reading frames (ARFs) play an important role in (tumor) immunology. Identification of these peptides is successfully performed with mass spectrometry. In a mass spectrometry-based approach, the recorded tandem mass spectra are matched against hypothetical spectra generated from known protein sequence databases. Commonly used protein databases contain a minimal level of redundancy, and thus, are not suitable data sources for searching polymorphic T cell epitopes, either in normal or ARFs. At the same time, however, these databases contain much non-polymorphic sequence information, thereby complicating the matching of recorded and theoretical spectra, and increasing the potential for finding false positives. Therefore, we created a database with peptides from ARFs and peptide variation arising from single nucleotide polymorphisms (SNPs). It is based on the human mRNA sequences from the well-annotated reference sequence (RefSeq) database and associated variation information derived from the Single Nucleotide Polymorphism Database (dbSNP). In this process, we removed all non-polymorphic information. Investigation of the frequency of SNPs in the dbSNP revealed that many SNPs are non-polymorphic “SNPs”. Therefore, we removed those from our dedicated database, and this resulted in a comprehensive high quality database, which we coined the Human Short Peptide Variation Database (HSPVdb). The value of our HSPVdb is shown by identification of the majority of published polymorphic SNP- and/or ARF-derived epitopes from a mass spectrometry-based proteomics workflow, and by a large variety of polymorphic peptides identified as potential T cell epitopes in the HLA-ligandome presented by the Epstein–Barr virus cells

Molecules cooled below the Doppler limit

The ability to cool atoms below the Doppler limit -- the minimum temperature reachable by Doppler cooling -- has been essential to most experiments with quantum degenerate gases, optical lattices and atomic fountains, among many other applications. A broad set of new applications await ultracold molecules, and the extension of laser cooling to molecules has begun. A molecular magneto-optical trap has been demonstrated, where molecules approached the Doppler limit. However, the sub-Doppler temperatures required for most applications have not yet been reached. Here we cool molecules to 50 uK, well below the Doppler limit, using a three-dimensional optical molasses. These ultracold molecules could be loaded into optical tweezers to trap arbitrary arrays for quantum simulation, launched into a molecular fountain for testing fundamental physics, and used to study ultracold collisions and ultracold chemistry

Type II and VI collagen in nasal and articular cartilage and the effect of IL-1α on the distribution of these collagens

The distribution of type II and VI collagen was immunocytochemically investigated in bovine articular and nasal cartilage. Cartilage explants were used either fresh or cultured for up to 4 weeks with or without interleukin 1α (IL-1α). Sections of the explants were incubated with antibodies for both types of collagen. Microscopic analyses revealed that type II collagen was preferentially localized in the interchondron matrix whereas type VI collagen was primarily found in the direct vicinity of the chondrocytes. Treatment of the sections with hyaluronidase greatly enhanced the signal for both types of collagen. Also in sections of explants cultured with IL-1α a higher level of labeling of the collagens was found. This was apparent without any pre-treatment with hyaluronidase. Under the influence of IL-1α the area positive for type VI collagen that surrounded the chondrocytes broadened. Although the two collagens in both types of cartilage were distributed similarly, a remarkable difference was the higher degree of staining of type VI collagen in articular cartilage. Concomitantly we noted that digestion of this type of cartilage hardly occurred in the presence of IL-1α whereas nasal cartilage was almost completely degraded within 18 days of culture. Since type VI collagen is known to be relatively resistant to proteolysis we speculate that the higher level of type VI collagen in articular cartilage is important in protecting cartilage from digestion

A Uniform Genomic Minor Histocompatibility Antigen Typing Methodology and Database Designed to Facilitate Clinical Applications

BACKGROUND: Minor Histocompatibility (H) antigen mismatches significantly influence the outcome of HLA-matched allogeneic stem cell transplantation. The molecular identification of human H antigens is increasing rapidly. In parallel, clinical application of minor H antigen typing has gained interest. So far, relevant and simple tools to analyze the minor H antigens in a quick and reliable way are lacking. METHODOLOGY AND FINDINGS: We developed a uniform PCR with sequence-specific primers (PCR-SSP) for 10 different autosomal minor H antigens and H-Y. This genomic minor H antigen typing methodology allows easy incorporation in the routine HLA typing procedures. DNA from previously typed EBV-LCL was used to validate the methodology. To facilitate easy interpretation for clinical purposes, a minor H database named dbMinor (http://www.lumc.nl/dbminor) was developed. Input of the minor H antigen typing results subsequently provides all relevant information for a given patient/donor pair and additional information on the putative graft-versus-host, graft-versus-tumor and host-versus-graft reactivities. SIGNIFICANCE: A simple, uniform and rapid methodology was developed enabling determination of minor H antigen genotypes of all currently identified minor H antigens. A dbMinor database was developed to interpret the genomic typing for its potential clinical relevance. The combination of the minor H antigen genomic typing methodology with the online dbMinor database and applications facilitates the clinical application of minor H antigens anti-tumor targets after stem cell transplantation