Dynamic Phase Diagram of Catalytic Surface of Hexagonal Boron Nitride under Conditions of Oxidative Dehydrogenation of Propane.

Partially oxidized surfaces of hexagonal boron nitride (hBN) and several metal borides are unexpectedly excellent catalysts for oxidative dehydrogenation of alkanes to olefins, but the nature of the active site(s) on these B-containing interfaces remains elusive. We characterize the surface of the partially oxidized B-rich hBN surface under reaction conditions from first principles. The interface has thermal access to multiple different stoichiometries and multiple structures of each stoichiometry. The size of the thermal ensemble is composition-dependent. The phase diagram of the interface constructed on the basis of the statistical ensembles of many accessible states is very different from the one based on global minima. Phase boundaries shift and blur, and phases consist of several stoichiometries and structures. The BO layer transiently exposes the reactive -B═O motifs in the metastable states. The fluxionality and structural diversity emerging under reaction conditions must be taken into account in theoretically descriptions of the catalytic interface

Reflections on the Mechanism of DNA Mismatch Repair

Life can be separated from dead organic matter by looking at two characteristics: growth and reproduction. For both of these, cells at some point need to split into two daughter cells. However, before cell division can take place, all the genetic information, encoded in DNA, needs to be copied. This process is called replication. Failure to replicate DNA correctly leads to mutations. These mutations can cause progenitor cells to have defects and die, or can cause cancer in higher organisms. DNA mismatch repair (MMR), the subject of study in this thesis, increases the fidelity of replication by removing mismatches left by the replication machinery. Chapter 1 describes the mechanism of MMR, and implications of mutations that arise when mismatches are left uncorrected. Some of the most prevalent forms of hereditary cancers can be traced back to dysfunction of proteins involved in MMR. In Escherichia coli, MMR is initiated by MutS upon recognition of a DNA mismatch, resulting in ATP-dependent recruitment of MutL and activation of MutH. MutH is an endonuclease that is able to nick hemi-methylated DNA at a GATC motif, which provides an entry point for MMR to remove the strand with the error. The MMR pathway is conserved in most organisms, and MutS and MutL, the initiators of MMR in E. coli, are structurally very similar to their eukaryotic equivalents MutSα and MutLα. This emphasizes the importance of MMR, and sets the stage for consecutive chapters. Chapter 2 deals with strand discrimination and excision during MMR. In E. coli, DNA is methylated by DAM methylase at GATC sites. Transiently hemimethylated GATC sites provide the signal for distinguishing the newly synthesized DNA from the template strand. The efficiency of MMR in vivo depends on the number of GATC sites and the distance between mismatch and nearest GATC site. We quantitatively studied the rate of nicking by MutS, MutL and MutH, and subsequent strand excision by UvrD and ExoI, while varying the number of GATC sites and their distance from a GT mismatch. We find that in vitro, multiple nicks increase the efficiency of excision, while strand discrimination remains efficient over distances of 1 kb. Interestingly, we find a similar mechanism in human MMR. We propose a model where a single activated MMR complex facilitates efficient excision and repair by creating multiple daughter strand nicks. Chapter 3 focuses on the time frame in whic

Triple minima in free energy of semiflexible polymers

We study the free energy of the worm-like-chain model, in the constant-extension ensemble, as a function of the stiffness for finite chains of length L. We find that the polymer properties obtained in this ensemble are "qualitatively" different from those obtained using constant-force ensembles. In particular we find that as we change the stiffness parameter, the polymer makes a transition from the flexible to the rigid phase and there is an intermediate regime of parameter values where the free energy has three minima and both phases are stable. This leads to interesting features in the force-extension curves.Comment: Published version, 4 pages, 5 figures, revte

Exploring Teachers PCK for Computational Thinking in Context

NWOAlgorithms and the Foundations of Software technolog

Entanglement between a diamond spin qubit and a photonic time-bin qubit at telecom wavelength

We report on the realization and verification of quantum entanglement between an NV electron spin qubit and a telecom-band photonic qubit. First we generate entanglement between the spin qubit and a 637 nm photonic time-bin qubit, followed by photonic quantum frequency conversion that transfers the entanglement to a 1588 nm photon. We characterize the resulting state by correlation measurements in different bases and find a lower bound to the Bell state fidelity of F = 0.77 +/- 0.03. This result presents an important step towards extending quantum networks via optical fiber infrastructure

Determine TB-LAM point-of-care tuberculosis assay predicts poor outcomes in outpatients during their first year of antiretroviral therapy in South Africa.

BACKGROUND: Determine TB-LAM is the first point-of-care test (POC) for HIV-associated tuberculosis (TB) and rapidly identifies TB in those at high-risk for short-term mortality. While the relationship between urine-LAM and mortality has been previously described, the outcomes of those undergoing urine-LAM testing have largely been assessed during short follow-up periods within diagnostic accuracy studies. We therefore sought to assess the relationship between baseline urine-LAM results and subsequent hospitalization and mortality under real-world conditions among outpatients in the first year of ART. METHODS: Consecutive, HIV-positive adults with a CD4 count < 100 cells/uL presenting for ART initiation were enrolled. TB diagnoses and outcomes (hospitalization, loss-to-follow and mortality) were recorded during the first year following enrolment. Baseline urine samples were retrospectively tested using the urine-LAM POC assay. Kaplan Meier survival curves were used to assess the cumulative probability of hospitalization or mortality in the first year of follow-up, according to urine-LAM status. Cox regression analyses were performed to determine independent predictors of hospitalization and mortality at  three months and one year of follow-up. RESULTS: 468 patients with a median CD4 count of 59 cells/uL were enrolled. There were 140 patients (29.9%) with newly diagnosed TB in the first year of follow-up of which 79 (56.4%) were microbiologically-confirmed. A total of 18% (n = 84) required hospital admission and 12.2% (n = 57) died within a year of study entry. 38 out of 468 (8.1%) patients retrospectively tested urine-LAM positive - including 19.0% of those with microbiologically-proven TB diagnoses (n = 15/79) and 23.0% (n = 14/61) of those with clinical-only TB diagnoses; 9 of 38 (23.7%) of patients retrospectively testing LAM positive were never diagnosed with TB under routine program conditions. Among all patients (n = 468) in the first year of follow-up, a positive urine-LAM result was strongly associated with all-cause hospitalization and mortality with a corresponding adjusted hazard ratio (aHR) of 3.7 (95%CI, 1.9-7.1) and 2.6 (95%, 1.2-5.7), respectively. CONCLUSIONS: Systematic urine-LAM testing among ART-naïve HIV-positive outpatients with CD4 counts < 100 cells/uL detected TB cases that were missed under routine programme conditions and was highly predictive for subsequent hospitalization and mortality in the first year of ART

Olfactomedin 4 Serves as a Marker for Disease Severity in Pediatric Respiratory Syncytial Virus (RSV) Infection

Funding: Statement of financial support: The study was financially supported by the VIRGO consortium, an Innovative Cluster approved by the Netherlands Genomics Initiative and partially funded by the Dutch Government (BSIK 03012). The authors have indicated they have no personal financial relationships relevant to this article to disclose. Data Availability Statement: The data is accessible at http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE69606.Peer reviewedPublisher PD

Toehold-enchanced lna probes for selective pull down and single-molecule analysis of native chromatin

Biological and Soft Matter Physic