The Benefits of Stress: Resolution of the Lifshitz Singularity

Through the AdS/CFT correspondence, Lifshitz spacetimes describe field theories with dynamical scaling ($z \neq 1$). Although curvature invariants are small, the Lifshitz metric exhibits a null singularity in the IR with a large tidal force that excites string oscillator modes. However, Lifshitz is not a vacuum solution of the Einstein equations -- the metric is supported by nontrivial matter content which must be taken into account in analyzing the propagation of test objects. In this paper, we consider the interaction of a string with a D0-brane density in the IR which supports a class of UV-complete $z=2$ Lifshitz constructions. We show that string/D-brane scattering in the Regge limit slows the string significantly, preventing divergent mode production and resolving the would-be singularity in string propagation.Comment: 16 pages; v2: new references adde

Influence of Reducing Agents on Biosafety and Biocompatibility of Gold Nanoparticles

Extensive biomedical applications of nanoparticles are mainly determined by their safety and compatibility in biological systems. The aim of this study was to compare the biosafety and biocompatibility of gold nanoparticles (GNPs) prepared with HEPES buffer, which is popular for cell culture, and sodium citrate, a frequent reducing agent. From experimental results on the body weight and organ coefficients of acute oral toxicity tests, it could be observed that HEPES-prepared GNPs are biologically safer than citric-prepared GNPs at the same dose of 500 μg/kg. The in vitro cell viability was higher for HEPES-prepared GNPs than citric-prepared GNPs at 5.0- and 10.0-ug/mL concentrations. More reactive oxygen species (ROS) were generated in the cell suspension when supplemented with citric-prepared GNPs than HEPES-prepared GNPs when their concentrations were higher than 20 μg/mL. The results stated that HEPES-prepared GNPs had better biosafety and biocompatibility than citric-prepared GNPs. This study not only revealed the influence of reducing agent on biosafety and biocompatibility of nanomaterials but also provided accumulative evidence for nanomaterials in biomedical applications. [Figure: see text

Glycogen synthase kinase 3β inhibition synergizes with PARP inhibitors through the induction of homologous recombination deficiency in colorectal cancer.

Monotherapy with poly ADP-ribose polymerase (PARP) inhibitors results in a limited objective response rate (≤60% in most cases) in patients with homologous recombination repair (HRR)-deficient cancer, which suggests a high rate of resistance in this subset of patients to PARP inhibitors (PARPi). To overcome resistance to PARPi and to broaden their clinical use, we performed high-throughput screening of 99 anticancer drugs in combination with PARPi to identify potential therapeutic combinations. Here, we found that GSK3 inhibitors (GSK3i) exhibited a strong synergistic effect with PARPi in a panel of colorectal cancer (CRC) cell lines with diverse genetic backgrounds. The combination of GSK3β and PARP inhibition causes replication stress and DNA double-strand breaks, resulting in increased anaphase bridges and abnormal spindles. Mechanistically, inhibition or genetic depletion of GSK3β was found to impair the HRR of DNA and reduce the mRNA and protein level of BRCA1. Finally, we demonstrated that inhibition or depletion of GSK3β could enhance the in vivo sensitivity to simmiparib without toxicity. Our results provide a mechanistic understanding of the combination of PARP and GSK3 inhibition, and support the clinical development of this combination therapy for CRC patients

A mouse line for inducible and reversible silencing of specific neurons

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Acknowledgements: We thank Dr. Joseph W. Lynch for sharing the IVMR plasmid, and Dr. Lisa M. Monteggia for sharing the AAV2-Cre plasmid. Rosa-CAG targeting vector was obtained from Addgenes. This work was supported by the Key State Research Program from Ministry of Science and Technology of China (2011CB510005, 2012CB966900, 2013CB835103), National Natural Science Foundation of China (81221001, 81200692, 81101026, 31100788, 31271182, 31030034, 91232724), Science and Technology Commission of Shanghai Municipality (12XD1404800), Shanghai Pujiang Program (12PJ1408800), Key Disciplines Group Construction Project of Pudong Health Bureau of Shanghai (PWZxq2014-04) and Sino-UK Higher Education Research Partnership for PhD Studies.Peer reviewedPublisher PD

Stimulated superconductivity at strong coupling

Stimulating a system with time dependent sources can enhance instabilities, thus increasing the critical temperature at which the system transitions to interesting low-temperature phases such as superconductivity or superfluidity. After reviewing this phenomenon in non-equilibrium BCS theory (and its marginal fermi liquid generalization) we analyze the effect in holographic superconductors. We exhibit a simple regime in which the transition temperature increases parametrically as we increase the frequency of the time-dependent source.Comment: 19 pages, 2 figure. v3: Comments, references and one figure added. Version to appear in JHE

Magnetic criticality-enhanced hybrid nanodiamond-thermometer under ambient conditions

Nitrogen vacancy (NV) centres in diamond are attractive as quantum sensors owing to their superb coherence under ambient conditions. However, the NV centre spin resonances are relatively insensitive to some important parameters such as temperature. Here we design and experimentally demonstrate a hybrid nano-thermometer composed of NV centres and a magnetic nanoparticle (MNP), in which the temperature sensitivity is enhanced by the critical magnetization of the MNP near the ferromagnetic-paramagnetic transition temperature. The temperature susceptibility of the NV center spin resonance reached 14 MHz/K, enhanced from the value without the MNP by two orders of magnitude. The sensitivity of a hybrid nano-thermometer composed of a Cu_{1-x}Ni_{x} MNP and a nanodiamond was measured to be 11 mK/Hz^{1/2} under ambient conditions. With such high-sensitivity, we monitored nanometer-scale temperature variation of 0.3 degree with a time resolution of 60 msec. This hybrid nano-thermometer provides a novel approach to studying a broad range of thermal processes at nanoscales such as nano-plasmonics, sub-cellular heat-stimulated processes, thermodynamics of nanostructures, and thermal remanent magnetization of nanoparticles.Comment: 21 pages, 6 figure

Tgf-b and a specific tgf-b inhibitor regulate pericentrin b and myh9 in glioma cell lines

Los gliomas malignos son tumores vasculares heterogéneos altamente invasivos. El factor de transformación de creci­miento P (TGF-P) es una citoquina multifuncional que es expresada por gliomas de grado III /IV y promueve angiogenesis de tumores, invasión y escape inmunológico. Recientemente se demostró que una pequeña molécula inhibidora (SB-431542) del receptor de TGF-P tipo I (TGF-P-RI), bloquea la señal de transducción mediada por TGF-P, la inducción del factor angiogénico de expresión y la movilidad celular. Ya que las líneas celulares de gliomas mues­tran sensitividad diferencial a TGF-P, se esperaba que también mostrarían impacto diferencial por el bloqueo de la señal de TGF-p. En el presente trabajo se usó un análisis diferencial en gel (DIGE, por sus siglas en inglés: Differential in gel electrophoresis) y espectrometría de masas para determinar los efectos sobre regulación de proteínas por TGF-(3 y SB-431542 en células de gliomas humanos. Se encontró que pericentrina B y miosina no muscular fueron expresa­das diferencialmente en fragmentos, los cuales pueden ser el resultado de la activación de proteasas por el mecanismo de crecimiento del tumor. Estos resultados sugieren que tanto pericentrina B como miosina no muscular, podrían ser usadas como bio-marcadores potenciales de gliomas. Palabras clave: DIGE, proteomica, glioma, TGF-P, espectrometría de masas, miosina no muscular, pericentrina B.Malignant gliomas are heterogeneous, highly invasive vascular tumours. The multifunctional cytokine, transforming growth factor-beta (TGF-P), is expressed by grade III/IV gliomas and promotes tumour angiogenesis, invasión and immune escape. It has been shown previously that a small TGF-P receptor type I (TGF-(3-RI) molecule inhibitor (SB-431542) blocks TGF-(3-mediated signal transduction, induction of angiogenic factor expression and cellular motility. As glioma cell lines display differential sensitivity to TGF-P, it was expected that they would also be differentially impacted by disruption of TGF-P signalling. Differential in gel expression (DIGE) analysis and mass spectrometry was used in this work for determining protein regulation effects of both TGF-P and SB-431542 on human glioma cell lines. It was found that pericentrin B and non muscle myosin were differentially expressed in fragments which likely resulted from protease activation by the tumour growth mechanism. These results suggest that both pericentrin B and non-muscle myosin might be potential glioma biomarkers. Key words: DIGE, proteomics, glioma, TGF-P, mass spectrometry, non muscle myosin, pericentrin B

Association of Aortic Stiffness and Cognitive Decline: A Systematic Review and Meta-Analysis

Background: Increased aortic stiffness has been found to be associated with cognitive function decline, but the evidence is still under debate. It is of great significance to elucidate the evidence in this debate to help make primary prevention decisions to slow cognitive decline in our routine clinical practice.Methods: Electronic databases of PubMed, EMBASE, and Cochrane Library were systematically searched to identify peer-reviewed articles published in English from January 1, 1986, to March 16, 2020, that reported the association between aortic stiffness and cognitive function. Studies that reported the association between aortic pulse wave velocity (PWV) and cognitive function, cognitive impairment, and dementia were included in the analysis.Results: Thirty-nine studies were included in the qualitative analysis, and 29 studies were included in the quantitative analysis. The aortic PWV was inversely associated with memory and processing speed in the cross-sectional analysis. In the longitudinal analysis, the high category of aortic PWV was 44% increased risk of cognitive impairment (OR 1.44; 95% CI 1.24–1.85) compared with low PWV, and the risk of cognitive impairment increased 3.9% (OR 1.039; 95% CI 1.005–1.073) per 1 m/s increase in aortic PWV. Besides, meta-regression analysis showed that age significantly increased the association between high aortic PWV and cognitive impairment risk.Conclusion: Aortic stiffness measured by aortic PWV was inversely associated with memory and processing speed and could be an independent predictor for cognitive impairment, especially for older individuals

LSOTB-TIR:A Large-Scale High-Diversity Thermal Infrared Object Tracking Benchmark

In this paper, we present a Large-Scale and high-diversity general Thermal InfraRed (TIR) Object Tracking Benchmark, called LSOTBTIR, which consists of an evaluation dataset and a training dataset with a total of 1,400 TIR sequences and more than 600K frames. We annotate the bounding box of objects in every frame of all sequences and generate over 730K bounding boxes in total. To the best of our knowledge, LSOTB-TIR is the largest and most diverse TIR object tracking benchmark to date. To evaluate a tracker on different attributes, we define 4 scenario attributes and 12 challenge attributes in the evaluation dataset. By releasing LSOTB-TIR, we encourage the community to develop deep learning based TIR trackers and evaluate them fairly and comprehensively. We evaluate and analyze more than 30 trackers on LSOTB-TIR to provide a series of baselines, and the results show that deep trackers achieve promising performance. Furthermore, we re-train several representative deep trackers on LSOTB-TIR, and their results demonstrate that the proposed training dataset significantly improves the performance of deep TIR trackers. Codes and dataset are available at https://github.com/QiaoLiuHit/LSOTB-TIR.Comment: accepted by ACM Mutlimedia Conference, 202