Reliable measurement of elastic modulus of cells by nanoindentation in an atomic force microscope

The elastic modulus of an oral cancer cell line UM1 is investigated by nanoindentation in an atomic force microscope with a flat-ended tip. The commonly used Hertzian method gives apparent elastic modulus which increases with the loading rate, indicating strong effects of viscoelasticity. On the contrary, a rate-jump method developed for viscoelastic materials gives elastic modulus values which are independent of the rate-jump magnitude. The results show that the rate-jump method can be used as a standard protocol for measuring elastic stiffness of living cells, since the measured values are intrinsic properties of the cells. © 2011 Elsevier Ltd.postprin

Reconstruction of primary vertices at the ATLAS experiment in Run 1 proton–proton collisions at the LHC

This paper presents the method and performance of primary vertex reconstruction in proton–proton collision data recorded by the ATLAS experiment during Run 1 of the LHC. The studies presented focus on data taken during 2012 at a centre-of-mass energy of √s=8 TeV. The performance has been measured as a function of the number of interactions per bunch crossing over a wide range, from one to seventy. The measurement of the position and size of the luminous region and its use as a constraint to improve the primary vertex resolution are discussed. A longitudinal vertex position resolution of about 30μm is achieved for events with high multiplicity of reconstructed tracks. The transverse position resolution is better than 20μm and is dominated by the precision on the size of the luminous region. An analytical model is proposed to describe the primary vertex reconstruction efficiency as a function of the number of interactions per bunch crossing and of the longitudinal size of the luminous region. Agreement between the data and the predictions of this model is better than 3% up to seventy interactions per bunch crossing

Unveiling Potential Blood Markers for Endometriosis Through the Integration and Experimental Validation of Immune Cell Traits Genome and Genome-Wide Associated Data

Jie Mei,1– 3,* Xi-Ya Jiang,1,2,* Bin Zhang,4,* Li Wang,5 Ai-Xi Zhang,6 Jie-Jie Li,1– 3 Shun-Xia Chen,1,2 Xiao Xu,1,2 Jing‑Jing Hu,7 Shu-Guang Zhou1– 3 1Department of Gynecology, The Fifth Affiliated Clinical College of Anhui Medical University, Maternal and Child Health Center of Anhui Medical University, Hefei, Anhui, 230001, People’s Republic of China; 2Department of Gynecology, Anhui Women and Children’s Medical Center, Hefei, Anhui, 230001, People’s Republic of China; 3Department of Gynecology, Linquan Maternity and Child Healthcare Hospital, Fuyang, Anhui, 236400, People’s Republic of China; 4Department of Scientific Research, Hefei Maternity and Child Healthcare Hospital, Hefei, Anhui, 230001, People’s Republic of China; 5Department of Clinical Laboratory, Linquan Maternity and Child Healthcare Hospital, Fuyang, Anhui, 236400, People’s Republic of China; 6Department of Public Health, Linquan Maternity and Child Healthcare Hospital, Fuyang, Anhui, 236400, People’s Republic of China; 7Department of reproduction, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, 230032, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shu-Guang Zhou; Jing‑Jing Hu, Email [email protected]; [email protected]: While endometriosis (EM) has been previously associated with multiple immune factors, the causal relationship underlying these associations remains unclear.Objective: In this study, Two-sample Mendelian randomization (MR) method was employed to investigate the causal relationship between 731 immune cell traits and EM based on tabulated data from genome-wide association studies (GWAS).Methods: MR method includes inverse variance weighting (IVW), the weighted median (WM), MR-Egger, the weighted model, and the simple model. IVW is used as the primary method for judging causal effects. Peripheral blood was obtained from EM patients, and the positive immune cell phenotype was confirmed using flow cytometry.Results: After P-value correction, our two-sample MR showed that CD28 on CD28+ DN (CD4-CD8-) had a suggestive causal relationship with EM (β =0.040, 95% CI =1.02– 1.06, P =0.00029, PFDR = 0.1984). The results of the other two main methods were similar: Weighted median (OR =1.031, 95% CI =1.00– 1.07, P =0.082); MR-Egger (OR =1.032, 95% CI =1.10– 1.06, P =0.044). The flow cytometry results indicated that the expression level of CD28 on CD28+ DN (CD4-CD-8) was significantly increased in the ectopic intima of EM patients.Conclusion: Our study demonstrated a causal relationship between immune traits and EM, and the results were verified by clinical samples. The study may provide new biomarkers for the early diagnosis and immunotherapy of EM.Keywords: endometriosis, Mendelian randomization, immune cell traits, flow cytometr

Characteristic classes of proalgebraic varieties and motivic measures

Michael Gromov has recently initiated what he calls ``symbolic algebraic geometry", in which objects are proalgebraic varieties: a proalgebraic variety is by definition the projective limit of a projective system of algebraic varieties. In this paper we introduce characteristic classes of proalgebraic varieties, using Grothendieck transformations of Fulton--MacPherson's Bivariant Theory, modeled on the construction of MacPherson's Chern class transformation of proalgebraic varieties. We show that a proalgebraic version of the Euler--Poincar\'e characteristic with values in the Grothendieck ring is a generalization of the so-called motivic measure.Comment: a revised version of math.AG/040723

Analysis of the impact of broad absorption lines on quasar redshift measurements with synthetic observations

Accurate quasar classifications and redshift measurements are increasingly important to precision cosmology experiments. Broad absorption line (BAL) features are present in 15-20 per cent of all quasars, and these features can introduce systematic redshift errors, and in extreme cases produce misclassifications. We quantitatively investigate the impact of BAL features on quasar classifications and redshift measurements with synthetic spectra that were designed to match observations by the Dark Energy Spectroscopic Instrument (DESI) survey. Over the course of 5 yr, DESI aims to measure spectra for 40 million galaxies and quasars, including nearly three million quasars. Our synthetic quasar spectra match the signal-to-noise ratio and redshift distributions of the first year of DESI observations, and include the same synthetic quasar spectra both with and without BAL features. We demonstrate that masking the locations of the BAL features decreases the redshift errors by about 1 per cent and reduces the number of catastrophic redshift errors by about 80 per cent. We conclude that identifying and masking BAL troughs should be a standard part of the redshift determination step for DESI and other large-scale spectroscopic surveys of quasars

Chapter 3: Pathophysiology

The hallmark pathophysiologic feature of dilated cardiomyopathy is systolic dysfunction. Several pathogenetic mechanisms appear to be operative. These include increased hemodynamic overload, ventricular remodeling, excessive neurohumoral stimulation, abnormal myocyte calcium cycling, excessive or inadequate proliferation of the extracellular matrix, accelerated apoptosis, and genetic mutations. Although beneficial in the early stages of heart failure, these compensatory mechanisms eventually lead to a vicious cycle of worsening heart failure. Genetic causes account for 30\u201340% of DCM and involve genes that encode a heterogeneous group of molecules that participate in force generation, force transmission, sarcomere integrity, cytoskeletal and nuclear architecture, electrolyte homeostasis, mitochondrial function, and transcription. Additional research will improve our understanding of the complex and longitudinal molecular changes that lead from gene mutation to clinical expressio

RhoD regulates cytoskeletal dynamics via the actin nucleation-promoting factor WASp homologue associated with actin Golgi membranes and microtubules

The Rho GTPases have mainly been studied in association with their roles in the regulation of actin filament organization. These studies have shown that the Rho GTPases are essential for basic cellular processes, such as cell migration, contraction, and division. In this paper, we report that RhoD has a role in the organization of actin dynamics that is distinct from the roles of the better-studied Rho members Cdc42, RhoA, and Rac1. We found that RhoD binds the actin nucleation–promoting factor WASp homologue associated with actin Golgi membranes and microtubules (WHAMM), as well as the related filamin A–binding protein FILIP1. Of these two RhoD-binding proteins, WHAMM was found to bind to the Arp2/3 complex, while FILIP1 bound filamin A. WHAMM was found to act downstream of RhoD in regulating cytoskeletal dynamics. In addition, cells treated with small interfering RNAs for RhoD and WHAMM showed increased cell attachment and decreased cell migration. These major effects on cytoskeletal dynamics indicate that RhoD and its effectors control vital cytoskeleton-driven cellular processes. In agreement with this notion, our data suggest that RhoD coordinates Arp2/3-dependent and FLNa-dependent mechanisms to control the actin filament system, cell adhesion, and cell migration

Antitumor activity and mechanisms of action of total glycosides from aerial part of Cimicifuga dahurica targeted against hepatoma

<p>Abstract</p> <p>Background</p> <p>Medicinal plant is a main source of cancer drug development. Some of the cycloartane triterpenoids isolated from the aerial part of <it>Cimicifuga dahurica </it>showed cytotoxicity in several cancer cell lines. It is of great interest to examine the antiproliferative activity and mechanisms of total triterpenoid glycosides of <it>C. dahurica </it>and therefore might eventually be useful in the prevention or treatment of Hepatoma.</p> <p>Methods</p> <p>The total glycosides from the aerial part (TGA) was extracted and its cytotoxicity was evaluated in HepG2 cells and primary cultured normal mouse hepatocytes by an MTT assay. Morphology observation, Annexin V-FITC/PI staining, cell cycle analysis and western blot were used to further elucidate the cytotoxic mechanism of TGA. Implanted mouse H₂₂hepatoma model was used to demonstrate the tumor growth inhibitory activity of TGA <it>in vivo</it>.</p> <p>Results</p> <p>The IC₅₀values of TGA in HepG2 and primary cultured normal mouse hepatocytes were 21 and 105 μg/ml, respectively. TGA induced G₀/G₁cell cycle arrest at lower concentration (25 μg/ml), and triggered G₂/M arrest and apoptosis at higher concentrations (50 and 100 μg/ml respectively). An increase in the ratio of Bax/Bcl-2 was implicated in TGA-induced apoptosis. In addition, TGA inhibited the growth of the implanted mouse H₂₂tumor in a dose-dependent manner.</p> <p>Conclusion</p> <p>TGA may potentially find use as a new therapy for the treatment of hepatoma.</p

The Target-selection Pipeline for the Dark Energy Spectroscopic Instrument

In 2021 May, the Dark Energy Spectroscopic Instrument (DESI) began a 5 yr survey of approximately 50 million total extragalactic and Galactic targets. The primary DESI dark-time targets are emission line galaxies, luminous red galaxies, and quasars. In bright time, DESI will focus on two surveys known as the Bright Galaxy Survey and the Milky Way Survey. DESI also observes a selection of “secondary” targets for bespoke science goals. This paper gives an overview of the publicly available pipeline (desitarget) used to process targets for DESI observations. Highlights include details of the different DESI survey targeting phases, the targeting ID (TARGETID) used to define unique targets, the bitmasks used to indicate a particular type of target, the data model and structure of DESI targeting files, and examples of how to access and use the desitarget code base. This paper will also describe “supporting” DESI target classes, such as standard stars, sky locations, and random catalogs that mimic the angular selection function of DESI targets. The DESI target-selection pipeline is complex and sizable; this paper attempts to summarize the most salient information required to understand and work with DESI targeting data