Investigations into the Elemental Composition of Earthenware Vessels from the Guthe Collection using Instrumental Neutron Activation Analysis

This study undertakes an elemental compositional analysis of Philippine earthenware vessels from the Guthe collection using Instrumental Neutron Activation Analysis (INAA). Unlike foreign trade ceramics, earthenware vessels were locally produced goods but which also played a part in the development of Philippine chiefdoms as an item traded between inland and coastal groups. Thus, the detection of compositional groups within earthenware vessels may help identify patterns of production and exchange. It is also hoped that the results from this pilot study can contribute to the future development of an elemental database for earthenware vessels

Critical Behavior and Fractality in Shallow One-Dimensional Quasiperiodic Potentials

Quasiperiodic systems offer an appealing intermediate between long-range ordered and genuine disordered systems, with unusual critical properties. One-dimensional models that break the so-called self-dual symmetry usually display a mobility edge, similarly as truly disordered systems in dimension strictly higher than two. Here, we determine the critical localization properties of single particles in shallow, one-dimensional, quasiperiodic models and relate them to the fractal character of the energy spectrum. On the one hand, we determine the mobility edge and show that it separates the localized and extended phases, with no intermediate phase. On the other hand, we determine the critical potential amplitude and find the universal critical exponent $\nu \simeq 1/3$. We also study the spectral Hausdorff dimension and show that it is nonuniversal but always smaller than unity, hence showing that the spectrum is nowhere dense. Finally, applications to ongoing studies of Anderson localization, Bose-glass physics, and many-body localization in ultracold atoms are discussed

Health systems strengthening, dissemination, and implementation science in Africa: quo vadis?

Implementing health-system strengthening policies remains a challenge in Africa. Past successes, predictable but unanticipated flaws, underutilization of health services, traditional medicine, global inequity and poor practice by local stakeholders are some of the reasons many African countries have made little progress towards attaining global health goals. As a result, Africa has the highest disease burden despite multiple efforts from the global health community. These raise the question: what has to change so that health systems strengthening efforts in Africa are successful

Computational design of a red fluorophore ligase for site-specific protein labeling in living cells

Chemical fluorophores offer tremendous size and photophysical advantages over fluorescent proteins but are much more challenging to target to specific cellular proteins. Here, we used Rosetta-based computation to design a fluorophore ligase that accepts the red dye resorufin, starting from Escherichia coli lipoic acid ligase. X-ray crystallography showed that the design closely matched the experimental structure. Resorufin ligase catalyzed the site-specific and covalent attachment of resorufin to various cellular proteins genetically fused to a 13-aa recognition peptide in multiple mammalian cell lines and in primary cultured neurons. We used resorufin ligase to perform superresolution imaging of the intermediate filament protein vimentin by stimulated emission depletion and electron microscopies. This work illustrates the power of Rosetta for major redesign of enzyme specificity and introduces a tool for minimally invasive, highly specific imaging of cellular proteins by both conventional and superresolution microscopies.National Institutes of Health (U.S.) (Grant DP1 OD003961)National Institutes of Health (U.S.) (R01 GM072670)American Chemical Societ

Clinical Study Restoration of Central Programmed Movement Pattern by Temporal Electrical Stimulation-Assisted Training in Patients with Spinal Cerebellar Atrophy

Disrupted triphasic electromyography (EMG) patterns of agonist and antagonist muscle pairs during fast goal-directed movements have been found in patients with hypermetria. Since peripheral electrical stimulation (ES) and motor training may modulate motor cortical excitability through plasticity mechanisms, we aimed to investigate whether temporal ES-assisted movement training could influence premovement cortical excitability and alleviate hypermetria in patients with spinal cerebellar ataxia (SCA). The EMG of the agonist extensor carpi radialis muscle and antagonist flexor carpi radialis muscle, premovement motor evoked potentials (MEPs) of the flexor carpi radialis muscle, and the constant and variable errors of movements were assessed before and after 4 weeks of ESassisted fast goal-directed wrist extension training in the training group and of general health education in the control group. After training, the premovement MEPs of the antagonist muscle were facilitated at 50 ms before the onset of movement. In addition, the EMG onset latency of the antagonist muscle shifted earlier and the constant error decreased significantly. In summary, temporal ES-assisted training alleviated hypermetria by restoring antagonist premovement and temporal triphasic EMG patterns in SCA patients. This technique may be applied to treat hypermetria in cerebellar disorders. (This trial is registered with NCT01983670.

CTdatabase: a knowledge-base of high-throughput and curated data on cancer-testis antigens

The potency of the immune response has still to be harnessed effectively to combat human cancers. However, the discovery of T-cell targets in melanomas and other tumors has raised the possibility that cancer vaccines can be used to induce a therapeutically effective immune response against cancer. The targets, cancer-testis (CT) antigens, are immunogenic proteins preferentially expressed in normal gametogenic tissues and different histological types of tumors. Therapeutic cancer vaccines directed against CT antigens are currently in late-stage clinical trials testing whether they can delay or prevent recurrence of lung cancer and melanoma following surgical removal of primary tumors. CT antigens constitute a large, but ill-defined, family of proteins that exhibit a remarkably restricted expression. Currently, there is a considerable amount of information about these proteins, but the data are scattered through the literature and in several bioinformatic databases. The database presented here, CTdatabase (http://www.cta.lncc.br), unifies this knowledge to facilitate both the mining of the existing deluge of data, and the identification of proteins alleged to be CT antigens, but that do not have their characteristic restricted expression pattern. CTdatabase is more than a repository of CT antigen data, since all the available information was carefully curated and annotated with most data being specifically processed for CT antigens and stored locally. Starting from a compilation of known CT antigens, CTdatabase provides basic information including gene names and aliases, RefSeq accession numbers, genomic location, known splicing variants, gene duplications and additional family members. Gene expression at the mRNA level in normal and tumor tissues has been collated from publicly available data obtained by several different technologies. Manually curated data related to mRNA and protein expression, and antigen-specific immune responses in cancer patients are also available, together with links to PubMed for relevant CT antigen article

Molecules with ALMA at Planet-forming Scales (MAPS). VIII. CO gap in AS 209-gas depletion or chemical processing?

Funding: I.C. was supported by NASA through the NASA Hubble Fellowship grant HST-HF2-51405.001-A awarded by the Space Telescope Science Institute, which is operated by the Association of Universities for Research in Astronomy, Inc., for NASA, under contract NAS5-26555. J.D.I. acknowledges support from the Science and Technology Facilities Council of the United Kingdom (STFC) under ST/T000287/1. C.W. acknowledges financial support from the University of Leeds, SFTC, and UKRI (grant Nos. ST/R000549/1, ST/T000287/1, and MR/T040726/1).Emission substructures in gas and dust are common in protoplanetary disks. Such substructures can be linked to planet formation or planets themselves. We explore the observed gas substructures in AS 209 using thermochemical modeling with RAC2D and high-spatial-resolution data from the Molecules with ALMA at Planet-forming Scales (MAPS) program. The observations of C18O J = 2-1 emission exhibit a strong depression at 88 au overlapping with the positions of multiple gaps in millimeter dust continuum emission. We find that the observed CO column density is consistent with either gas surface-density perturbations or chemical processing, while C2H column density traces changes in the C/O ratio rather than the H2 gas surface density. However, the presence of a massive planet (>0.2 MJup) would be required to account for this level of gas depression, which conflicts with constraints set by the dust emission and the pressure profile measured by gas kinematics. Based on our models, we infer that a local decrease of CO abundance is required to explain the observed structure in CO, dominating over a possible gap-carving planet present and its effect on the H2 surface density. This paper is part of the MAPS special issue of the Astrophysical Journal Supplement.Publisher PDFPeer reviewe

Phosphorothioate backbone modifications of nucleotide-based drugs are potent platelet activators

Nucleotide-based drug candidates such as antisense oligonucleotides, aptamers, immunoreceptor-activating nucleotides, or (anti)microRNAs hold great therapeutic promise for many human diseases. Phosphorothioate (PS) backbone modification of nucleotide-based drugs is common practice to protect these promising drug candidates from rapid degradation by plasma and intracellular nucleases. Effects of the changes in physicochemical properties associated with PS modification on platelets have not been elucidated so far. Here we report the unexpected binding of PS-modified oligonucleotides to platelets eliciting strong platelet activation, signaling, reactive oxygen species generation, adhesion, spreading, aggregation, and thrombus formation in vitro and in vivo. Mechanistically, the platelet-specific receptor glycoprotein VI (GPVI) mediates these platelet-activating effects. Notably, platelets from GPVI function-deficient patients do not exhibit binding of PS-modified oligonucleotides, and platelet activation is fully abolished. Our data demonstrate a novel, unexpected, PS backbone-dependent, platelet-activating effect of nucleotide-based drug candidates mediated by GPVI. This unforeseen effect should be considered in the ongoing development programs for the broad range of upcoming and promising DNA/RNA therapeutics