Thermodynamic and Kinetic Parameters for Calcite Nucleation on Peptoid and Model Scaffolds:A Step toward Nacre Mimicry

The production of novel composite materials, assembled using biomimetic polymers known as peptoids (N-substituted glycines) to nucleate CaCO3, can open new pathways for advanced material design. However, a better understanding of the heterogeneous CaCO3 nucleation process is a necessary first step. We determined the thermodynamic and kinetic parameters for calcite nucleation on self-assembled monolayers (SAMs) of nanosheet-forming peptoid polymers and simpler, alkanethiol analogues. We used nucleation rate studies to determine the net interfacial free energy (γ net) for the peptoid-calcite interface and for SAMs terminated with carboxyl headgroups, amine headgroups, or a mix of the two. We compared the results with γ net determined from dynamic force spectroscopy (DFS) and from density functional theory (DFT), using COSMO-RS simulations. Calcite nucleation has a lower thermodynamic barrier on the peptoid surface than on carboxyl and amine SAMs. From the relationship between nucleation rate (J 0) and saturation state, we found that under low-saturation conditions, i.e. <3.3 (pH 9.0), nucleation on the peptoid substrate was faster than that on all of the model surfaces, indicating a thermodynamic drive toward heterogeneous nucleation. When they are taken together, our results indicate that nanosheet-forming peptoid monolayers can serve as an organic template for CaCO3 polymorph growth

The Western Denmark Cardiac Computed Tomography Registry:a review and validation study

BACKGROUND: As a subregistry to the Western Denmark Heart Registry (WDHR), the Western Denmark Cardiac Computed Tomography Registry (WDHR-CCTR) is a clinical database established in 2008 to monitor and improve the quality of cardiac computed tomography (CT) in Western Denmark. OBJECTIVE: We examined the content, data quality, and research potential of the WDHR-CCTR. METHODS: We retrieved 2008–2012 data to examine the 1) content; 2) completeness of procedure registration using the Danish National Patient Registry as reference; 3) completeness of variable registration comparing observed vs expected numbers; and 4) positive predictive values as well as negative predictive values of 19 main patient and procedure variables. RESULTS: By December 31, 2012, almost 22,000 cardiac CTs with up to 40 variables for each procedure have been registered. Of these, 87% were coronary CT angiography performed in patients with symptoms indicative of coronary artery disease. Compared with the Danish National Patient Registry, the overall procedure completeness was 72%. However, an additional medical record review of 282 patients registered in the Danish National Patient Registry, but not in the WDHR-CCTR, showed that coronary CT angiographies accounted for only 23% of all nonregistered cardiac CTs, indicating >90% completeness of coronary CT angiographies in the WDHR-CCTR. The completeness of individual variables varied substantially (range: 0%–100%), but was >85% for more than 70% of all variables. Using medical record review of 250 randomly selected patients as reference standard, the positive predictive value for the 19 variables ranged from 89% to 100% (overall 97%), whereas the negative predictive value ranged from 97% to 100% (overall 99%). Stratification by center status showed consistently high positive and negative predictive values for both university (96%/99%) and nonuniversity centers (97%/99%). CONCLUSION: WDHR-CCTR provides ongoing prospective registration of all cardiac CTs performed in Western Denmark since 2008. Overall, the registry data have a high degree of completeness and validity, making it a valuable tool for clinical epidemiological research

Clusters of Conserved Beta Cell Marker Genes for Assessment of Beta Cell Phenotype

The aim of this study was to establish a gene expression blueprint of pancreatic beta cells conserved from rodents to humans and to evaluate its applicability to assess shifts in the beta cell differentiated state. Genome-wide mRNA expression profiles of isolated beta cells were compared to those of a large panel of other tissue and cell types, and transcripts with beta cell-abundant and -selective expression were identified. Iteration of this analysis in mouse, rat and human tissues generated a panel of conserved beta cell biomarkers. This panel was then used to compare isolated versus laser capture microdissected beta cells, monitor adaptations of the beta cell phenotype to fasting, and retrieve possible conserved transcriptional regulators.Journal ArticleSCOPUS: ar.jinfo:eu-repo/semantics/publishe

Altered processing of sensory stimuli in patients with migraine

Migraine is a cyclic disorder, in which functional and morphological brain changes fluctuate over time, culminating periodically in an attack. In the migrainous brain, temporal processing of external stimuli and sequential recruitment of neuronal networks are often dysfunctional. These changes reflect complex CNS dysfunction patterns. Assessment of multimodal evoked potentials and nociceptive reflex responses can reveal altered patterns of the brain's electrophysiological activity, thereby aiding our understanding of the pathophysiology of migraine. In this Review, we summarize the most important findings on temporal processing of evoked and reflex responses in migraine. Considering these data, we propose that thalamocortical dysrhythmia may be responsible for the altered synchronicity in migraine. To test this hypothesis in future research, electrophysiological recordings should be combined with neuroimaging studies so that the temporal patterns of sensory processing in patients with migraine can be correlated with the accompanying anatomical and functional changes

Target of Opportunity Observations of Gravitational Wave Events with LSST

The discovery of the electromagnetic counterparts to the binary neutron star merger GW170817 has opened the era of GW+EM multi-messenger astronomy. Exploiting this breakthrough requires increasing samples to explore the diversity of kilonova behaviour and provide more stringent constraints on the Hubble constant, and tests of fundamental physics. LSST can play a key role in this field in the 2020s, when the gravitational wave detector network is expected to detect higher rates of merger events involving neutron stars ($\sim$10s per year) out to distances of several hundred Mpc. Here we propose comprehensive target-of-opportunity (ToOs) strategies for follow-up of gravitational-wave sources that will make LSST the premiere machine for discovery and early characterization for neutron star mergers and other gravitational-wave sources.Comment: White paper for LSST cadence optimization- ToO

Genome-Wide Association Study in BRCA1 Mutation Carriers Identifies Novel Loci Associated with Breast and Ovarian Cancer Risk

BRCA1-associated breast and ovarian cancer risks can be modified by common genetic variants. To identify further cancer risk-modifying loci, we performed a multi-stage GWAS of 11,705 BRCA1 carriers (of whom 5,920 were diagnosed with breast and 1,839 were diagnosed with ovarian cancer), with a further replication in an additional sample of 2,646 BRCA1 carriers. We identified a novel breast cancer risk modifier locus at 1q32 for BRCA1 carriers (rs2290854, P = 2.7×10-8, HR = 1.14, 95% CI: 1.09-1.20). In addition, we identified two novel ovarian cancer risk modifier loci: 17q21.31 (rs17631303, P = 1.4×10-8, HR = 1.27, 95% CI: 1.17-1.38) and 4q32.3 (rs4691139, P = 3.4×10-8, HR = 1.20, 95% CI: 1.17-1.38). The 4q32.3 locus was not associated with ovarian cancer risk in the general population or BRCA2 carriers, suggesting a BRCA1-specific associat

Multi-messenger observations of a binary neutron star merger

On 2017 August 17 a binary neutron star coalescence candidate (later designated GW170817) with merger time 12:41:04 UTC was observed through gravitational waves by the Advanced LIGO and Advanced Virgo detectors. The Fermi Gamma-ray Burst Monitor independently detected a gamma-ray burst (GRB 170817A) with a time delay of ~1.7 s with respect to the merger time. From the gravitational-wave signal, the source was initially localized to a sky region of 31 deg2 at a luminosity distance of 40+8-8 Mpc and with component masses consistent with neutron stars. The component masses were later measured to be in the range 0.86 to 2.26 Mo. An extensive observing campaign was launched across the electromagnetic spectrum leading to the discovery of a bright optical transient (SSS17a, now with the IAU identification of AT 2017gfo) in NGC 4993 (at ~40 Mpc) less than 11 hours after the merger by the One- Meter, Two Hemisphere (1M2H) team using the 1 m Swope Telescope. The optical transient was independently detected by multiple teams within an hour. Subsequent observations targeted the object and its environment. Early ultraviolet observations revealed a blue transient that faded within 48 hours. Optical and infrared observations showed a redward evolution over ~10 days. Following early non-detections, X-ray and radio emission were discovered at the transient’s position ~9 and ~16 days, respectively, after the merger. Both the X-ray and radio emission likely arise from a physical process that is distinct from the one that generates the UV/optical/near-infrared emission. No ultra-high-energy gamma-rays and no neutrino candidates consistent with the source were found in follow-up searches. These observations support the hypothesis that GW170817 was produced by the merger of two neutron stars in NGC4993 followed by a short gamma-ray burst (GRB 170817A) and a kilonova/macronova powered by the radioactive decay of r-process nuclei synthesized in the ejecta