Depth weighted scatter estimators

General depth weighted scatter estimators are introduced and investigated. For general depth functions, we find out that these affine equivariant scatter estimators are Fisher consistent and unbiased for a wide range of multivariate distributions, and show that the sample scatter estimators are strong and \sqrtn-consistent and asymptotically normal, and the influence functions of the estimators exist and are bounded in general. We then concentrate on a specific case of the general depth weighted scatter estimators, the projection depth weighted scatter estimators, which include as a special case the well-known Stahel-Donoho scatter estimator whose limiting distribution has long been open until this paper. Large sample behavior, including consistency and asymptotic normality, and efficiency and finite sample behavior, including breakdown point and relative efficiency of the sample projection depth weighted scatter estimators, are thoroughly investigated. The influence function and the maximum bias of the projection depth weighted scatter estimators are derived and examined. Unlike typical high-breakdown competitors, the projection depth weighted scatter estimators can integrate high breakdown point and high efficiency while enjoying a bounded-influence function and a moderate maximum bias curve. Comparisons with leading estimators on asymptotic relative efficiency and gross error sensitivity reveal that the projection depth weighted scatter estimators behave very well overall and, consequently, represent very favorable choices of affine equivariant multivariate scatter estimators.Comment: Published at http://dx.doi.org/10.1214/009053604000000922 in the Annals of Statistics (http://www.imstat.org/aos/) by the Institute of Mathematical Statistics (http://www.imstat.org

The ∘\circ operation and ∗* operation of Cohen-Macaulay bipartite graphs

Let $G$ be a finite simple graph with the vertex set $V$ and let $I_G$ be its edge ideal in the polynomial ring $S=\mathbb{K}[x_V]$. In this paper, we compute the depth and the Castelnuovo--Mumford regularity of $S/I_G$ when $G=G_1\circ G_2$ or $G=G_1* G_2$ is a graph obtained from Cohen-Macaulay bipartite graphs $G_1$, $G_2$ by $\circ$ operation or $*$ operation, respectively.Comment: arXiv admin note: text overlap with arXiv:2308.0601

Compromised ATP binding as a mechanism of phosphoinositide modulation of ATP-sensitive K+ channels

AbstractInhibition of ATP-sensitive K+ (KATP) channels by ATP, a process presumably initiated by binding of ATP to the pore-forming subunit, Kir6.2, is reduced in the presence of phosphoinositides (PPIs). Previous studies led to the hypothesis that PPIs compromise ATP binding. Here, this hypothesis was tested using purified Kir6.2. We show that PPIs bind purified Kir6.2 in an isomer-specific manner, that biotinylated ATP analogs photoaffinity label purified Kir6.2, and that this labeling is weakened in the presence of PPIs. Patch-clamp measurements confirmed that these ATP analogs inhibited Kir6.2 channels, and that PPIs decreased the level of inhibition. These results indicate that interaction of PPIs with Kir6.2 impedes ATP-binding activity. The PPI regulation of ATP binding revealed in this study provides a putative molecular mechanism that is potentially pivotal to the nucleotide sensitivity of KATP channels

How Practical Phase-shift Errors Affect Beamforming of Reconfigurable Intelligent Surface?

Reconfigurable intelligent surface (RIS) is a new technique that is able to manipulate the wireless environment smartly and has been exploited for assisting the wireless communications, especially at high frequency band. However, it suffers from hardware impairments (HWIs) in practical designs, which inevitably degrades its performance and thus limits its full potential. To address this practical issue, we first propose a new RIS reflection model involving phase-shift errors, which is then verified by the measurement results from field trials. With this beamforming model, various phase-shift errors caused by different HWIs can be analyzed. The phase-shift errors are classified into three categories: (1) globally independent and identically distributed errors, (2) grouped independent and identically distributed errors and (3) grouped fixed errors. The impact of typical HWIs, including frequency mismatch, PIN diode failures and panel deformation, on RIS beamforming ability are studied with the theoretical model and are compared with numerical results. The impact of frequency mismatch are discussed separately for narrow-band and wide-band beamforming. Finally, useful insights and guidelines on the RIS design and its deployment are highlighted for practical wireless systems

The E3 Ubiquitin Ligase AMFR and INSIG1 Bridge the Activation of TBK1 Kinase by Modifying the Adaptor STING

SummaryStimulator of interferon genes (STING, also known as MITA, ERIS, or MPYS) is essential for host immune responses triggered by microbial DNAs. However, the regulatory mechanisms underlying STING-mediated signaling are not fully understood. We report here that, upon cytoplasmic DNA stimulation, the endoplasmic reticulum (ER) protein AMFR was recruited to and interacted with STING in an insulin-induced gene 1 (INSIG1)-dependent manner. AMFR and INSIG1, an E3 ubiquitin ligase complex, then catalyzed the K27-linked polyubiquitination of STING. This modification served as an anchoring platform for recruiting TANK-binding kinase 1 (TBK1) and facilitating its translocation to the perinuclear microsomes. Depletion of AMFR or INSIG1 impaired STING-mediated antiviral gene induction. Consistently, myeloid-cell-specific Insig1−/− mice were more susceptible to herpes simplex virus 1 (HSV-1) infection than wild-type mice. This study uncovers an essential role of the ER proteins AMFR and INSIG1 in innate immunity, revealing an important missing link in the STING signaling pathway

Activation of MET signaling by HDAC6 offers a rationale for a novel ricolinostat and crizotinib combinatorial therapeutic strategy in diffuse large B‐cell lymphoma

Some histone deacetylases (HDACs) promote tumor cell growth and pan‐ or selective HDAC inhibitors are active in some cancers; however, the pivotal HDAC enzyme and its functions in human diffuse large B‐cell lymphoma (DLBCL) remain largely unknown. Using NanoString nCounter assays, we profiled HDAC mRNA expression and identified HDAC6 as an upregulated HDAC family member in DLBCL tissue samples. We then found that HDAC6 plays an oncogenic role in DLBCL, as evidenced by its promotion of cell proliferation in vitro and tumor xenograft growth in vivo. Mechanistically, the interaction between HDAC6 and HR23B downregulated HR23B expression, thereby reducing the levels of casitas B‐lineage lymphoma (c‐Cbl), an E3 ubiquitin ligase for hepatocyte growth factor receptor (MET), which resulted in the inhibition of MET ubiquitination‐dependent degradation. In addition, enhanced HDAC6 expression and decreased HR23B expression were correlated with poor overall survival rates among patients with DLBCL. Taken together, these results establish an HDAC6–HR23B–MET axis and indicate that HDAC6 is a potent promoter of lymphomagenesis in DLBCL. Thus, a therapeutic strategy based on HDAC6 inhibitors in combination with MET inhibitors is promising. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146400/1/path5108_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/146400/2/path5108.pd

Modulation of presynaptic plasticity and learning by the H-ras/extracellular signal-regulated kinase/synapsin I signaling pathway

Molecular and cellular studies of the mechanisms underlying mammalian learning and memory have focused almost exclusively on postsynaptic function. We now reveal an experience-dependent presynaptic mechanism that modulates learning and synaptic plasticity in mice. Consistent with a presynapticfunctionfor endogenous H-ras/extracellular signal-regulated kinase (ERK) signaling, we observed that, under normal physiologic conditions in wild-type mice, hippocampus-dependent learning stimulated the ERK-dependent phosphorylation of synapsin I, and MEK (MAP kinase kinase)/ERK inhibition selectively decreased the frequency of miniature EPSCs. By generating transgenic mice expressing a constitutively active form of H-ras (H-rasG12V), which is abundantly localized in axon terminals, we were able to increase the ERK-dependent phosphorylation of synapsin I. This resulted in several presynaptic changes, including a higher density of docked neurotransmitter vesiclesin glutamatergicterminals, anincreasedfrequency of miniature EPSCs, andincreased paired-pulse facilitation. In addition, we observed facilitated neurotransmitter release selectively during high-frequency activity with consequent increases in long-term potentiation. Moreover, these mice showed dramatic enhancements in hippocampus-dependent learning. Importantly, deletion of synapsin I, an exclusively presynaptic protein, blocked the enhancements of learning, presynaptic plasticity, and long-term potentiation. Together with previous invertebrate studies, these results demonstrate that presynaptic plasticity represents an important evolutionarily conserved mechanism for modulating learning and memory

Using Transcranial Alternating Current Stimulation (tACS) to Improve Romantic Relationships Can Be a Promising Approach

The romantic relationship refers to the specific relationship in which partners are dependent upon each other to obtain satisfactory outcomes and facilitate the pursuit of their most important needs and goals. Satisfying romantic relationships is a strong predictor of better psychological well-being, better physical health, and longer life expectancy. However, romantic relationships are not all smooth-sailing and lovers are often confronted with a variety of unavoidable issues that constantly challenge the stability of their romantic relationships. Dissatisfying romantic relationships are harmful and even destructive. Dyads of lovers engage in a variety of efforts to protect and maintain their romantic relationships based on qualitative research methods including theories- and psychological consultation-based approaches. Unfortunately, those existing approaches do not seem to effectively improve romantic relationships. Thus, it is necessary to seek an efficient approach regulating dyads of lovers in romantic relationships simultaneously. Transcranial alternating current stimulation (tACS) with advantages over existing approaches satisfies this purpose. We discuss the practicability of tACS in detail, as well as why and how tACS can be utilized to improve romantic relationships. In summary, this review firstly introduced the concept of romantic relationship and the necessity of enhancing it. Then, it discussed methods to improve romantic relationships including some existing approaches. This review next discussed the practicability of using tACS to improve romantic relationships. Finally, it shone a spotlight on potential future directions for researches aiming to improve romantic relationships

Establishing Clonal Cell Lines with Endothelial-Like Potential from CD9(hi), SSEA-1(−) Cells in Embryonic Stem Cell-Derived Embryoid Bodies

BACKGROUND: Differentiation of embryonic stem cells (ESCs) into specific cell types with minimal risk of teratoma formation could be efficiently directed by first reducing the differentiation potential of ESCs through the generation of clonal, self-renewing lineage-restricted stem cell lines. Efforts to isolate these stem cells are, however, mired in an impasse where the lack of purified lineage-restricted stem cells has hindered the identification of defining markers for these rare stem cells and, in turn, their isolation. METHODOLOGY/PRINCIPAL FINDINGS: We describe here a method for the isolation of clonal lineage-restricted cell lines with endothelial potential from ESCs through a combination of empirical and rational evidence-based methods. Using an empirical protocol that we have previously developed to generate embryo-derived RoSH lines with endothelial potential, we first generated E-RoSH lines from mouse ESC-derived embryoid bodies (EBs). Despite originating from different mouse strains, RoSH and E- RoSH lines have similar gene expression profiles (r(2) = 0.93) while that between E-RoSH and ESCs was 0.83. In silico gene expression analysis predicted that like RoSH cells, E-RoSH cells have an increased propensity to differentiate into vasculature. Unlike their parental ESCs, E-RoSH cells did not form teratomas and differentiate efficiently into endothelial-like cells in vivo and in vitro. Gene expression and FACS analysis revealed that RoSH and E-RoSH cells are CD9(hi), SSEA-1(−) while ESCs are CD9(lo), SSEA-1(+). Isolation of CD9(hi), SSEA-1(−) cells that constituted 1%–10% of EB-derived cultures generated an E-RoSH-like culture with an identical E-RoSH-like gene expression profile (r(2) = 0.95) and a propensity to differentiate into endothelial-like cells. CONCLUSIONS: By combining empirical and rational evidence-based methods, we identified definitive selectable surface antigens for the isolation and propagation of lineage-restricted stem cells with endothelial-like potential from mouse ESCs