Prediction of future Alzheimer's disease dementia using plasma phospho-tau combined with other accessible measures

A combination of plasma phospho-tau (P-tau) and other accessible biomarkers might provide accurate prediction about the risk of developing Alzheimer’s disease (AD) dementia. We examined this in participants with subjective cognitive decline and mild cognitive impairment from the BioFINDER (n = 340) and Alzheimer’s Disease Neuroimaging Initiative (ADNI) (n = 543) studies. Plasma P-tau, plasma Aβ42/Aβ40, plasma neurofilament light, APOE genotype, brief cognitive tests and an AD-specific magnetic resonance imaging measure were examined using progression to AD as outcome. Within 4 years, plasma P-tau217 predicted AD accurately (area under the curve (AUC) = 0.83) in BioFINDER. Combining plasma P-tau217, memory, executive function and APOE produced higher accuracy (AUC = 0.91, P < 0.001). In ADNI, this model had similar AUC (0.90) using plasma P-tau181 instead of P-tau217. The model was implemented online for prediction of the individual probability of progressing to AD. Within 2 and 6 years, similar models had AUCs of 0.90–0.91 in both cohorts. Using cerebrospinal fluid P-tau, Aβ42/Aβ40 and neurofilament light instead of plasma biomarkers did not improve the accuracy significantly. The clinical predictions by memory clinic physicians had significantly lower accuracy (4-year AUC = 0.71). In summary, plasma P-tau, in combination with brief cognitive tests and APOE genotyping, might greatly improve the diagnostic prediction of AD and facilitate recruitment for AD trials

Spontaneous time reversal symmetry breaking in the pseudogap state of high-Tc superconductors

When matter undergoes a phase transition from one state to another, usually a change in symmetry is observed, as some of the symmetries exhibited are said to be spontaneously broken. The superconducting phase transition in the underdoped high-Tc superconductors is rather unusual, in that it is not a mean-field transition as other superconducting transitions are. Instead, it is observed that a pseudo-gap in the electronic excitation spectrum appears at temperatures T* higher than Tc, while phase coherence, and superconductivity, are established at Tc (Refs. 1, 2). One would then wish to understand if T* is just a crossover, controlled by fluctuations in order which will set in at the lower Tc (Refs. 3, 4), or whether some symmetry is spontaneously broken at T* (Refs. 5-10). Here, using angle-resolved photoemission with circularly polarized light, we find that, in the pseudogap state, left-circularly polarized photons give a different photocurrent than right-circularly polarized photons, and therefore the state below T* is rather unusual, in that it breaks time reversal symmetry11. This observation of a phase transition at T* provides the answer to a major mystery of the phase diagram of the cuprates. The appearance of the anomalies below T* must be related to the order parameter that sets in at this characteristic temperature .Comment: 11 pages, 4 figure

Ex Situ Characterization of 1T/2H MoS2 and Their Carbon Composites for Energy Applications, a Review

The growing interest in the development of next-generation net zero energy systems has led to the expansion of molybdenum disulfide (MoS2) research in this area. This activity has resulted in a wide range of manufacturing/synthesis methods, controllable morphologies, diverse carbonaceous composite structures, a multitude of applicable characterization techniques, and multiple energy applications for MoS2. To assess the literature trends, 37,347 MoS2 research articles from Web of Science were text scanned to classify articles according to energy application research and characterization techniques employed. Within the review, characterization techniques are grouped under the following categories: morphology, crystal structure, composition, and chemistry. The most common characterization techniques identified through text scanning are recommended as the base fingerprint for MoS2 samples. These include: scanning electron microscopy (SEM), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and Raman spectroscopy. Similarly, XPS and Raman spectroscopy are suggested for 2H or 1T MoS2 phase confirmation. We provide guidance on the collection and presentation of MoS2 characterization data. This includes how to effectively combine multiple characterization techniques, considering the sample area probed by each technique and their statistical significance, and the benefit of using reference samples. For ease of access for future experimental comparison, key numeric MoS2 characterization values are tabulated and major literature discrepancies or currently debated characterization disputes are highlighted

Dijet signals of the Little Higgs model with T-parity

The Littest Higgs model with T-parity (LHT), apart from offering a viable solution to the naturalness problem of the Standard Model, also predicts a set of new fermions as well as a candidate for dark matter. We explore the possibility of discovering the heavy T-odd quark Q_H at the LHC in a final state comprising two hard jets with a large missing transverse momentum. Also discussed is the role of heavy flavor tagging.Comment: Changes in text. Some references adde

Highly efficient catalysis of the Kemp elimination in the cavity of a cubic coordination cage.

The hollow cavities of coordination cages can provide an environment for enzyme-like catalytic reactions of small-molecule guests. Here, we report a new example (catalysis of the Kemp elimination reaction of benzisoxazole with hydroxide to form 2-cyanophenolate) in the cavity of a water-soluble M8L12 coordination cage, with two features of particular interest. First, the rate enhancement is among the largest observed to date: at pD 8.5, the value of kcat/kuncat is 2 × 10(5), due to the accumulation of a high concentration of partially desolvated hydroxide ions around the bound guest arising from ion-pairing with the 16+ cage. Second, the catalysis is based on two orthogonal interactions: (1) hydrophobic binding of benzisoxazole in the cavity and (2) polar binding of hydroxide ions to sites on the cage surface, both of which were established by competition experiments

STRP Screening Sets for the human genome at 5 cM density

BACKGROUND: Short tandem repeat polymorphisms (STRPs) are powerful tools for gene mapping and other applications. A STRP genome scan of 10 cM is usually adequate for mapping single gene disorders. However mapping studies involving genetically complex disorders and especially association (linkage disequilibrium) often require higher STRP density. RESULTS: We report the development of two separate 10 cM human STRP Screening Sets (Sets 12 and 52) which span all chromosomes. When combined, the two Sets contain a total of 782 STRPs, with average STRP spacing of 4.8 cM, average heterozygosity of 0.72, and total sex-average coverage of 3535 cM. The current Sets are comprised almost entirely of STRPs based on tri- and tetranucleotide repeats. We also report correction of primer sequences for many STRPs used in previous Screening Sets. Detailed information for the new Screening Sets is available from our web site: . CONCLUSION: Our new human STRP Screening Sets will improve the quality and cost effectiveness of genotyping for gene mapping and other applications

Colored Resonant Signals at the LHC: Largest Rate and Simplest Topology

We study the colored resonance production at the LHC in a most general approach. We classify the possible colored resonances based on group theory decomposition, and construct their effective interactions with light partons. The production cross section from annihilation of valence quarks or gluons may be on the order of 400 - 1000 pb at LHC energies for a mass of 1 TeV with nominal couplings, leading to the largest production rates for new physics at the TeV scale, and simplest event topology with dijet final states. We apply the new dijet data from the LHC experiments to put bounds on various possible colored resonant states. The current bounds range from 0.9 to 2.7 TeV. The formulation is readily applicable for future searches including other decay modes.Comment: 29 pages, 9 figures. References updated and additional K-factors include

Plasmacytoid dendritic cells orchestrate innate and adaptive anti-tumor immunity induced by oncolytic coxsackievirus A21

Background: The oncolytic virus, coxsackievirus A21 (CVA21), has shown promise as a single agent in several clinical trials and is now being tested in combination with immune checkpoint blockade. Combination therapies offer the best chance of disease control; however, the design of successful combination strategies requires a deeper understanding of the mechanisms underpinning CVA21 efficacy, in particular, the role of CVA21 anti-tumor immunity. Therefore, this study aimed to examine the ability of CVA21 to induce human anti-tumor immunity, and identify the cellular mechanism responsible. Methods: This study utilized peripheral blood mononuclear cells from i) healthy donors, ii) Acute Myeloid Leukemia (AML) patients, and iii) patients taking part in the STORM clinical trial, who received intravenous CVA21; patients receiving intravenous CVA21 were consented separately in accordance with local institutional ethics review and approval. Collectively, these blood samples were used to characterize the development of innate and adaptive anti-tumor immune responses following CVA21 treatment. Results: An Initial characterization of peripheral blood mononuclear cells, collected from cancer patients following intravenous infusion of CVA21, confirmed that CVA21 activated immune effector cells in patients. Next, using hematological disease models which were sensitive (Multiple Myeloma; MM) or resistant (AML) to CVA21-direct oncolysis, we demonstrated that CVA21 stimulated potent anti-tumor immune responses, including: 1) cytokine-mediated bystander killing; 2) enhanced natural killer cell-mediated cellular cytotoxicity; and 3) priming of tumor-specific cytotoxic T lymphocytes, with specificity towards known tumor-associated antigens. Importantly, immune-mediated killing of both MM and AML, despite AML cells being resistant to CVA21-direct oncolysis, was observed. Upon further examination of the cellular mechanisms responsible for CVA21-induced anti-tumor immunity we have identified the importance of type I IFN for NK cell activation, and demonstrated that both ICAM-1 and plasmacytoid dendritic cells were key mediators of this response. Conclusion: This work supports the development of CVA21 as an immunotherapeutic agent for the treatment of both AML and MM. Additionally, the data presented provides an important insight into the mechanisms of CVA21-mediated immunotherapy to aid the development of clinical biomarkers to predict response and rationalize future drug combinations