Modelling of Surfaces. Part 2: Metallic Alloy Surfaces Using the BFS Method

Using BFS, a new semiempirical method for alloys, we study the surface structure of fcc ordered binary alloys. We concentrate on the calculation of surface energies and surface relaxations for the L1(sub 0) and L1(sub 2) ordered structures. Different terminations of the low-index faces are studied. Also, we present results for the interlayer relaxations for planes close to the surface, revealing different relaxations for atoms of different species producing a rippled surface layer

Conformation-sensitive Antibodies against Alzheimer Amyloid-β by Immunization with a Thioredoxin-constrained B-cell Epitope Peptide

Immunotherapy against the amyloid-beta (Abeta) peptide is a valuable potential treatment for Alzheimer disease (AD). An ideal antigen should be soluble and nontoxic, avoid the C-terminally located T-cell epitope of Abeta, and yet be capable of eliciting antibodies that recognize Abeta fibrils and neurotoxic Abeta oligomers but not the physiological monomeric species of Abeta. We have described here the construction and immunological characterization of a recombinant antigen with these features obtained by tandem multimerization of the immunodominant B-cell epitope peptide Abeta1-15 (Abeta15) within the active site loop of bacterial thioredoxin (Trx). Chimeric Trx(Abeta15)n polypeptides bearing one, four, or eight copies of Abeta15 were constructed and injected into mice in combination with alum, an adjuvant approved for human use. All three polypeptides were found to be immunogenic, yet eliciting antibodies with distinct recognition specificities. The anti-Trx(Abeta15)4 antibody, in particular, recognized Abeta42 fibrils and oligomers but not monomers and exhibited the same kind of conformational selectivity against transthyretin, an amyloidogenic protein unrelated in sequence to Abeta. We have also demonstrated that anti-Trx(Abeta15)4, which binds to human AD plaques, markedly reduces Abeta pathology in transgenic AD mice. The data indicate that a conformational epitope shared by oligomers and fibrils can be mimicked by a thioredoxin-constrained Abeta fragment repeat and identify Trx(Abeta15)4 as a promising new tool for AD immunotherapy

The proton Nuclear Magnetic Resonance spin-lattice relaxation rate of some hydrated synthetic and natural sands

The proton nuclear magnetic resonance (NMR) spin-lattice relaxation rate (R1) of hydrated sands is often used to determine porosity characteristics of near-surface aquifers using magnetic resonance sounding. Large variations in R1 have been reported in laboratory measurements on hydrated sands. To understand these variations, the R1 values of several fully hydrated sands were studied as a function of grain diameter (d) and magnetic field strength (BB0). We conclude the variations are a consequence of trace paramagnetic metals in the sand grains. R1 values from magnetic resonance sounding data should not be used to predict void size in aquifers unless the exact chemical composition of the grains is known

Modulation of nucleosome dynamics in Huntington's disease

Transcriptional dysregulation and aberrant chromatin remodeling are central features in the pathology of Huntington's disease (HD). In order to more fully characterize these pathogenic events, an assessment of histone profiles and associated gene changes were performed in transgenic N171-82Q (82Q) and R6/2 HD mice. Analyses revealed significant chromatin modification, resulting in reduced histone acetylation with concomitant increased histone methylation, consistent with findings observed in HD patients. While there are no known interventions that ameliorate or arrest HD progression, DNA/RNA-binding anthracyclines may provide significant therapeutic potential by correcting pathological nucleosome changes and realigning transcription. Two such anthracyclines, chromomycin and mithramycin, improved altered nucleosome homeostasis in HD mice, normalizing the chromatin pattern. There was a significant shift in the balance between methylation and acetylation in treated HD mice to that found in wild-type mice, resulting in greater acetylation of histone H3 at lysine 9 and promoting gene transcription. Gene expression profiling in anthracycline-treated HD mice showed molecular changes that correlate with disease correction, such that a subset of downregulated genes were upregulated with anthracycline treatment. Improved nucleosomal dynamics were concurrent with a significant improvement in the behavioral and neuropathological phenotype observed in HD mice. These data show the ability of anthracycline compounds to rebalance epigenetic histone modification and, as such, may provide the rationale for the design of human clinical trials in HD patient

An optical coherence tomography study of a biodegradable vs. durable polymer-coated limus-eluting stent: a LEADERS trial sub-study

Aims Incomplete endothelialization has been found to be associated with late stent thrombosis, a rare but devastating phenomenon, more frequent after drug-eluting stent implantation. Optical coherence tomography (OCT) has 10 times greater resolution than intravascular ultrasound and thus appears to be a valuable modality for the assessment of stent strut coverage. The LEADERS trial was a multi-centre, randomized comparison of a biolimus-eluting stent (BES) with biodegradable polymer with a sirolimus-eluting stent (SES) using a durable polymer. This study sought to evaluate tissue coverage and apposition of stents using OCT in a group of patients from the randomized LEADERS trial. Methods and results Fifty-six consecutive patients underwent OCT during angiographic follow-up at 9 months. OCT images were acquired using a non-occlusive technique at a pullback speed of 3 mm/s. Data were analysed using a Bayesian hierarchical random-effects model, which accounted for the correlation of lesion characteristics within patients and implicitly assigned analytical weights to each lesion depending on the number of struts observed per lesion. Primary outcome was the difference in percentage of uncovered struts between BESs and SESs. Twenty patients were included in the analysis in the BES group (29 lesions with 4592 struts) and 26 patients in the SES group (35 lesions with 6476 struts). A total of 83 struts were uncovered in the BES group and 407 out of 6476 struts were uncovered in the SES group [weighted difference −1.4%, 95% confidence interval (CI) −3.7 to 0.0, P = 0.04]. Results were similar after adjustment for pre-procedure lesion length, reference vessel diameter, number of implanted study stents, and presence of stent overlap. There were three lesions in the BES group and 15 lesions in the SES group that had ≥5% of all struts uncovered (difference −33.1%, 95% CI −61.7 to −10.3, P < 0.01). Conclusion Strut coverage at an average follow-up of 9 months appears to be more complete in patients allocated to BESs when compared with SESs. The impact of this difference on clinical outcome and, in particular, on the risk of late stent thrombosis is yet to be determine

Mutant huntingtin's effects on striatal gene expression in mice recapitulate changes observed in human Huntington's disease brain and do not differ with mutant huntingtin length or wild-type huntingtin dosage

To test the hypotheses that mutant huntingtin protein length and wild-type huntingtin dosage have important effects on disease-related transcriptional dysfunction, we compared the changes in mRNA in seven genetic mouse models of Huntington's disease (HD) and postmortem human HD caudate. Transgenic models expressing short N-terminal fragments of mutant huntingtin (R6/1 and R6/2 mice) exhibited the most rapid effects on gene expression, consistent with previous studies. Although changes in the brains of knock-in and full-length transgenic models of HD took longer to appear, 15- and 22-month CHL2Q150/Q150, 18-month HdhQ92/Q92 and 2-year-old YAC128 animals also exhibited significant HD-like mRNA signatures. Whereas it was expected that the expression of full-length huntingtin transprotein might result in unique gene expression changes compared with those caused by the expression of an N-terminal huntingtin fragment, no discernable differences between full-length and fragment models were detected. In addition, very high correlations between the signatures of mice expressing normal levels of wild-type huntingtin and mice in which the wild-type protein is absent suggest a limited effect of the wild-type protein to change basal gene expression or to influence the qualitative disease-related effect of mutant huntingtin. The combined analysis of mouse and human HD transcriptomes provides important temporal and mechanistic insights into the process by which mutant huntingtin kills striatal neurons. In addition, the discovery that several available lines of HD mice faithfully recapitulate the gene expression signature of the human disorder provides a novel aspect of validation with respect to their use in preclinical therapeutic trial

The continuing story of SN IIb 2013df: new optical and IR observations and analysis

This work has been supported by the Hungarian Scientific Research Fund (OTKA) Grants NN107637, K104607, K83790, and K113117. TS is supported by the OTKA Postdoctoral Fellowship PD112325. JCW’s Supernova group at the UT Austin is supported by NSF Grant AST 11-09881 grant. JMS is supported by an NSF Astronomy and Astrophysics Postdoctoral Fellowship under award AST-1302771. KS and AP are supported by the ‘Lend¨ulet-2009’ Young Researchers Program and the LP2012-31 grant of the Hungarian Academy of Sciences, respectively; KS is also supported by the ESA PECS Contract no. 4000110889/14/NL/NDe.SN 2013df is a nearby Type IIb supernova that seems to be the spectroscopic twin of the well-known SN 1993J. Previous studies revealed many, but not all interesting properties of this event. Our goal was to add new understanding of both the early- and late-time phases of SN 2013df. Our spectral analysis is based on six optical spectra obtained with the 9.2 m Hobby-Eberly Telescope during the first month after explosion, complemented by a near-infrared spectrum. We applied the SYNAPPS spectral synthesis code to constrain the chemical composition and physical properties of the ejecta. A principal result is the identification of 'high-velocity' He i lines in the early spectra of SN 2013df, manifest as the blue component of the double-troughed profile at ~5650 Å. This finding, together with the lack of clear separation of H and He lines in velocity space, indicates that both H and He features form at the outer envelope during the early phases. We also obtained ground-based BVRI and g'r'i'z' photometric data up to +45 d and unfiltered measurements with the ROTSE-IIIb telescope up to +168 d. From the modelling of the early-time quasi-bolometric light curve, we find Mej ~ 3.2-4.6 M⊙ and Ekin ~ 2.6-2.8 × 1051 erg for the initial ejecta mass and the initial kinetic energy, respectively, which agree well with the values derived from the separate modelling of the light-curve tail. Late-time mid-infrared excess indicates circumstellar interaction starting ~1 yr after explosion, in accordance with previously published optical, X-ray, and radio data.Publisher PDFPeer reviewe

Short-Term Post-Harvest Stress that Affects Profiles of Volatile Organic Compounds and Gene Expression in Rocket Salad During Early Post-Harvest Senescence

Once harvested, leaves undergo a process of senescence which shares some features with developmental senescence. These include changes in gene expression, metabolites, and loss of photosynthetic capacity. Of particular interest in fresh produce are changes in nutrient content and the aroma, which is dependent on the profile of volatile organic compounds (VOCs). Leafy salads are subjected to multiple stresses during and shortly after harvest, including mechanical damage, storage or transport under different temperature regimes, and low light. These are thought to impact on later shelf life performance by altering the progress of post-harvest senescence. Short term stresses in the first 24 h after harvest were simulated in wild rocket (Diplotaxis tenuifolia). These included dark (ambient temperature), dark and wounding (ambient temperature), and storage at 4 °C in darkness. The effects of stresses were monitored immediately afterwards and after one week of storage at 10 °C. Expression changes in two NAC transcription factors (orthologues of ANAC059 and ANAC019), and a gene involved in isothiocyanate production (thiocyanate methyltransferase, TMT) were evident immediately after stress treatments with some expression changes persisting following storage. Vitamin C loss and microbial growth on leaves were also affected by stress treatments. VOC profiles were differentially affected by stress treatments and the storage period. Overall, short term post-harvest stresses affected multiple aspects of rocket leaf senescence during chilled storage even after a week. However, different stress combinations elicited different responses

Gravitational Waves From Known Pulsars: Results From The Initial Detector Era

We present the results of searches for gravitational waves from a large selection of pulsars using data from the most recent science runs (S6, VSR2 and VSR4) of the initial generation of interferometric gravitational wave detectors LIGO (Laser Interferometric Gravitational-wave Observatory) and Virgo. We do not see evidence for gravitational wave emission from any of the targeted sources but produce upper limits on the emission amplitude. We highlight the results from seven young pulsars with large spin-down luminosities. We reach within a factor of five of the canonical spin-down limit for all seven of these, whilst for the Crab and Vela pulsars we further surpass their spin-down limits. We present new or updated limits for 172 other pulsars (including both young and millisecond pulsars). Now that the detectors are undergoing major upgrades, and, for completeness, we bring together all of the most up-to-date results from all pulsars searched for during the operations of the first-generation LIGO, Virgo and GEO600 detectors. This gives a total of 195 pulsars including the most recent results described in this paper.United States National Science FoundationScience and Technology Facilities Council of the United KingdomMax-Planck-SocietyState of Niedersachsen/GermanyAustralian Research CouncilInternational Science Linkages program of the Commonwealth of AustraliaCouncil of Scientific and Industrial Research of IndiaIstituto Nazionale di Fisica Nucleare of ItalySpanish Ministerio de Economia y CompetitividadConselleria d'Economia Hisenda i Innovacio of the Govern de les Illes BalearsNetherlands Organisation for Scientific ResearchPolish Ministry of Science and Higher EducationFOCUS Programme of Foundation for Polish ScienceRoyal SocietyScottish Funding CouncilScottish Universities Physics AllianceNational Aeronautics and Space AdministrationOTKA of HungaryLyon Institute of Origins (LIO)National Research Foundation of KoreaIndustry CanadaProvince of Ontario through the Ministry of Economic Development and InnovationNational Science and Engineering Research Council CanadaCarnegie TrustLeverhulme TrustDavid and Lucile Packard FoundationResearch CorporationAlfred P. Sloan FoundationAstronom

A First Search for coincident Gravitational Waves and High Energy Neutrinos using LIGO, Virgo and ANTARES data from 2007

We present the results of the first search for gravitational wave bursts associated with high energy neutrinos. Together, these messengers could reveal new, hidden sources that are not observed by conventional photon astronomy, particularly at high energy. Our search uses neutrinos detected by the underwater neutrino telescope ANTARES in its 5 line configuration during the period January - September 2007, which coincided with the fifth and first science runs of LIGO and Virgo, respectively. The LIGO-Virgo data were analysed for candidate gravitational-wave signals coincident in time and direction with the neutrino events. No significant coincident events were observed. We place limits on the density of joint high energy neutrino - gravitational wave emission events in the local universe, and compare them with densities of merger and core-collapse events.Comment: 19 pages, 8 figures, science summary page at http://www.ligo.org/science/Publication-S5LV_ANTARES/index.php. Public access area to figures, tables at https://dcc.ligo.org/cgi-bin/DocDB/ShowDocument?docid=p120000