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Bone and bone marrow are not only anatomically, but also functionally interdependent. In a systematic review, we examined bone health in patients with hematopoietic disorders and demonstrated that an increased hematopoietic cell proliferation, such as in patients with hemolytic anemias, was associated with bone loss, while bone marrow hypocellularity, such as in patients with chronic myelofibrosis (CMF), was associated with bone gain [Steer K et al. J Bone Miner Res 2017]. Since bone mass in CMF increases at the expense of bone marrow, it contributes to patients' morbidity as it is associated with bone pain, and mortality as it may lead to bone marrow failure. A mouse model with a global knockout of the megakaryocyte (MK) lineage specific inhibitory receptor G6b-B was shown to develop myelofibrosis secondary to aberrant platelet production and function [Mazharian A et al Sci Signal 2012]. Moreover, a group of patients with primary myelofibrosis was identified to have loss-of-function mutations in the G6b-B gene [Hofmann I et al Blood 2018]. The objective of this study was to characterize temporal changes in the skeleton of the G6b-B knockout mice. We examined age- and sex-related changes in 4, 8, 16, and 32 week-old G6b-B+/+, G6b-B-/- female and male mice. Starting from 8 weeks-of-age, spleen progressively increased in female G6b-B-/- mice compared to corresponding G6b-B+/+ mice, reaching 2.9-fold increase at 32 weeks (p < 0.001) (Fig.1A). Micro-computed tomography analysis of femur demonstrated that starting at 8 weeks of age female G6b-B-/- mice had a significantly higher proportion of cortical bone and a respectively lower proportion of marrow (Fig.1B). Starting at 16 weeks of age, female G6b-B-/- mice developed trabecula in the medullary cavity normally occupied by the bone marrow, which by 32 weeks led to a 38-fold increase (p < 0.001) in the proportion of bone to tissue volume compared to G6b-B+/+ (Fig.1C,D). At 32-weeks of age, female G6b-B-/- mice also demonstrated a 7-fold increase in BV/TV (p < 0.001) in the region of metaphysis. While some abnormalities were found in male G6b-B-/- mice, they were considerably less severe compared to females. To establish whether the observed bone phenotype is due to MK and platelet functional defects, we performed microcomputed tomography analysis on femurs of 22 week-old G6b-Bfl/fl;Gp1ba-Cre-/- mice with a MK/platelet-specific knockout of G6b-B. Changes in trabecular bone of G6b-Bfl/fl;Gp1ba-Cre-/- mice recapitulated changes of G6b-B-/- mice. However, periosteal perimeter in male G6b-Bfl/fl;Gp1ba-Cre-/- mice was significantly larger, and in female G6b-Bfl/fl;Gp1ba-Cre-/- mice - significantly smaller than in corresponding control mice, while in global G6b-B-/- mice periosteal perimeter was not affected. Female G6b-B-/- mice demonstrated severe splenomegaly as well as progressive osteosclerosis, which was confirmed in G6b-Bfl/fl;Gp1ba-Cre-/- mice, indicating that trabecular bone gain in G6b-B-/- mice is consequent to a MK disfunction. Dramatic sexual dimorphism suggests that sex-related factors play an important role in the development of osteosclerosis. The differences in cortical bone phenotype between the global and conditional knockout of G6b-B suggest the potential role of G6b-B signaling in osteoclasts or osteoblasts. This study demonstrates that MK-associated myelofibrosis is sufficient to induce osteosclerosis of bone marrow, and that sex hormones play an important role either in protecting male mice from osteosclerosis or in exacerbating osteosclerosis in female mice. Disclosures No relevant conflicts of interest to declare.

Abstract The advancement and availability of technology can be employed to improve our daily lives. One example is Human Activity Recognition (HAR). HAR research has been mainly explored using imagery but is currently evolving to the use of sensors and has the ability to have a positive impact, including individual health monitoring and removing the barrier of healthcare. To reach a marketable HAR device, state-of-the-art classifications and power consumption methods such as convolutional neural network (CNN), data compression and other emerging techniques are reviewed here. The review of the current literature creates a foundation in HAR and addresses the lack of available HAR datasets, recommendation of classification and power reduction techniques, current drawbacks and their respective solutions, as well as future trends in HAR. The lack of publicly available datasets makes it difficult for new users to explore the field of HAR. This paper dedicates a section to publicly available datasets for users to access. Finally, a framework is suggested for HAR applications, which envelopes the current literature and emerging trends in HAR.

Few scientific studies present gender-based analyses on the subject of mistreatment experienced by older women. Nevertheless, women who have lived through such a situation can suffer serious consequences in their daily lives. How do they react when they have been mistreated? How do they express a request for help—or do they ask at all? This chapter presents the findings from research carried out in Quebec (Canada), as part of a doctoral dissertation that uses a phenomenological research design, and that seeks to better understand older women’s experience of mistreatment, the decision-making process that leads them to ask—or not ask—for help in this context, and the significance they attribute to this request for help. The chapter begins with a description of the state of knowledge on mistreatment of older adults and the objectives to, and incentives for, asking for help following an episode of mistreatment. Next, it presents the methodological approach, from data collection through to their analysis using NVivo software, and a sample composed of five women aged between 71 and 77. Semi-directed, qualitative interviews were held with these women. This section is followed by a diagrammatic conceptual framework for the main findings drawn from a review of the literature and an analysis of the data. Finally, avenues are suggested so that more mistreated older women will be encouraged to break the silence about their experiences and share their stories with someone they trust.

The kidney sessions of the 2017 Banff Conference focused on 2 areas: clinical implications of inflammation in areas of interstitial fibrosis and tubular atrophy (i‐IFTA) and its relationship to T cell–mediated rejection (TCMR), and the continued evolution of molecular diagnostics, particularly in the diagnosis of antibody‐mediated rejection (ABMR). In confirmation of previous studies, it was independently demonstrated by 2 groups that i‐IFTA is associated with reduced graft survival. Furthermore, these groups presented that i‐IFTA, particularly when involving >25% of sclerotic cortex in association with tubulitis, is often a sequela of acute TCMR in association with underimmunosuppression. The classification was thus revised to include moderate i‐IFTA plus moderate or severe tubulitis as diagnostic of chronic active TCMR. Other studies demonstrated that certain molecular classifiers improve diagnosis of ABMR beyond what is possible with histology, C4d, and detection of donor‐specific antibodies (DSAs) and that both C4d and validated molecular assays can serve as potential alternatives and/or complements to DSAs in the diagnosis of ABMR. The Banff ABMR criteria are thus updated to include these alternatives. Finally, the present report paves the way for the Banff scheme to be part of an integrative approach for defining surrogate endpoints in next‐generation clinical trials. The Banff consortium presents revisions to the diagnostic criteria for T cell– and antibody‐mediated kidney transplant rejection, including specific criteria for chronic active T cell–mediated rejection, plus prospects for integrative endpoints in clinical trials. See related articles on pages 321, 364, and 377.

Emoji is becoming a ubiquitous language and gaining worldwide popularity in recent years including the field of software engineering (SE). As nonverbal cues, emojis are widely used in user understanding tasks such as sentiment analysis, but few work has been done to study emojis in SE scenarios. This paper presents a large scale empirical study on how GitHub users use emojis in development-related communications. We find that emojis are used by a considerable proportion of GitHub users. In comparison to Internet users, developers show interesting usage characteristics and have their own interpretation of the meanings of emojis. In addition, the usage of emojis reflects a positive and supportive culture of this community. Through a manual annotation task, we find that sentimental usage is a main intention of using emojis in issues, pull requests, and comments, while emojis are mainly used to emphasize important contents in README. These findings not only deepen our understanding about the culture of SE communities, but also provide implications on how to facilitate SE tasks with emojis such as sentiment analysis.

We report on an all-sky search for continuous gravitational waves in the frequency band 20-2000 Hz and with a frequency time derivative in the range of [-1.0,+0.1]×10-8 Hz/s. Such a signal could be produced by a nearby, spinning and slightly nonaxisymmetric isolated neutron star in our Galaxy. This search uses the LIGO data from the first six months of Advanced LIGO's and Advanced Virgo's third observational run, O3. No periodic gravitational wave signals are observed, and 95% confidence-level (C.L.) frequentist upper limits are placed on their strengths. The lowest upper limits on worst-case (linearly polarized) strain amplitude h0 are ∼1.7×10-25 near 200 Hz. For a circularly polarized source (most favorable orientation), the lowest upper limits are ∼6.3×10-26. These strict frequentist upper limits refer to all sky locations and the entire range of frequency derivative values. For a population-averaged ensemble of sky locations and stellar orientations, the lowest 95% C.L. upper limits on the strain amplitude are ∼1.4×10-25. These upper limits improve upon our previously published all-sky results, with the greatest improvement (factor of ∼2) seen at higher frequencies, in part because quantum squeezing has dramatically improved the detector noise level relative to the second observational run, O2. These limits are the most constraining to date over most of the parameter space searched. This work was supported by MEXT, JSPS Leading-edge Research Infrastructure Program, JSPS Grant-in-Aid for Specially Promoted Research 26000005, JSPS Grant-in-Aid for Scientific Research on Innovative Areas 2905: JP17H06358, JP17H06361 and JP17H06364, JSPS Core-to-Core Program A. Advanced Research Networks, JSPS Grant-in-Aid for Scientific Research (S) 17H06133, the joint research program of the Institute for Cosmic Ray Research, University of Tokyo, National Research Foundation (NRF) and Computing Infrastructure Project of KISTI-GSDC in Korea, Academia Sinica (AS), AS Grid Center (ASGC) and the Ministry of Science and Technology (MoST) in Taiwan under grants including ASCDA-105-M06, Advanced Technology Center (ATC) of NAOJ, and Mechanical Engineering Center of KEK Abbott, R. (LIGO Scientific Collaboration, Virgo Collaboration, KAGRA Collaboration)

Abstract Technological advancement is an important instrument for economic and technological development, but most countries receive the benefits of innovation and new technologies through technology transfer. Previous studies typically consider direct linkages in order to understand technological advancement without paying much attention to indirect linkages, such as the inter-connectivity of the recipients of Foreign Direct Investment (FDI). To understand the relationship between FDI and technological advancement and whether recipients’ absorptive capacity matters, we model global FDI networks for the period 2009–2016. We find empirical evidence that the global FDI network has a core-periphery structure, and that core countries are more technologically developed than peripheral countries. We also find empirical evidence that a country’s centrality of position in the global FDI network is positively associated with the technological advancement of a country, and that the absorptive capacity of a country can moderate this relationship. Regression analyses using instrumental variable estimators confirm the robustness of our findings. The most striking finding of our research is the strong moderation effect of knowledge intensity, a constituent of absorptive capacity. This finding provides a nuanced understanding of absorptive capacity, demonstrating the ways a country can benefit from FDI by reshaping the factors related to absorptive capacity.

Made available in DSpace on 2022-04-28T19:46:01Z (GMT). No. of bitstreams: 0 Previous issue date: 2022-01-01 The aim of this study was to determine the association between occurrence and intensity of estrous expression with pregnancy success in recipient lactating dairy cows subjected to embryo transfer (ET). Two observational studies were conducted. Holstein cows were synchronized using the same timed ET protocol, based on estradiol and progesterone in both experiments. At 9 d after the end of the timed ET protocol only animals that had ovulated were implanted with a 7-d embryo [experiment 1 (Exp. 1); n = 1,401 ET events from 1,045 cows, and experiment 2 (Exp. 2); n = 1,147 ET events from 657 cows]. Embryos were produced in vivo (Exp. 1 and Exp. 2) and in vitro (only Exp. 2), then transferred to recipient cows as fresh or frozen-thawed. Pregnancy was confirmed at 29 and 58 d after the end of timed ET protocol. In Exp. 1, animals had their estrous expression monitored through a tail chalk applied on the tail head of the cows and evaluated daily for chalk removal (no estrus: 100% of chalk remaining; estrus: <50% of chalk remaining). In Exp. 2, cows were continuously monitored by a leg-mounted automated activity monitor. Estrous expression was quantified using the relative increase in physical activity at estrus in relation to the days before estrus. Estrous expression was classified as no estrus [<100% relative increase in activity (RI)], weak intensity (100–299% RI), and strong intensity (≥300% RI). Data were analyzed by analysis of variance using mixed linear regression models (GLIMMIX) in SAS (SAS Institute Inc.). A total of 65.2% (914/1,401) and 89.2% (1,019/1,142) of cows from Exp. 1 and Exp. 2, respectively, displayed estrus at the end of the ovulation synchronization protocol. In Exp. 1, cows expressing estrus before to ET had greater pregnancy per ET than those that did not [41.0 ± 2.3% (381/914) vs. 31.5 ± 2.9% (151/487), respectively]. Similarly, in Exp. 2, cows classified in the strong intensity group had greater pregnancy per ET compared with cows in the weak intensity and no estrus groups [41.3 ± 2.2% (213/571) vs. 32.7 ± 2.7% (115/353) vs. 11.3 ± 3.5% (26/218), respectively]. There was no effect of ET type on pregnancy per ET in Exp. 1. However, in Exp. 2, cows that received an in vivo-produced embryo, either fresh or frozen, had greater pregnancy per ET compared with cows that received in vitro-produced embryo. Cows receiving embryos in the early blastocyst and blastocyst stage had greater fertility compared with cows receiving embryos in the morula stage. There was an interaction between the occurrence of estrus and the stage of embryo development on pregnancy per ET, cows which displayed estrus and received a morula or early blastocyst had greater pregnancy per ET than cows that did not display estrus. In conclusion, the occurrence and the intensity of estrous expression improved pregnancy per ET in recipient lactating dairy cows and thus could be used as a tool to assist in the decision making of reproduction strategies in dairy farms. Applied Animal Biology Faculty of Land and Food Systems University of British Columbia Ridgetown Campus University of Guelph Clinic of Animal Reproduction Freie Universitaet Berlin Department of Animal Production São Paulo State University Centre for Genetic Improvement of Livestock University of Guelph Institute of Genetics Vetsuisse Faculty University of Bern Department of Animal Production São Paulo State University

To screen the effect of two compounds, chlorhexidine diacetate (CHX) and epigallocatechin-gallate (EGCG), on the levels of cytokines produced by odontoblast-like cells (MDPC-23).Cells were seeded at 24h and 48h with serial dilution of the compounds to determine cell metabolic activity by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay (n=3). Cells with no compound treatment were used as control (Ctr). For the highest equal non-cytotoxic compound dilution tested at 48h cell treatment, total protein concentration was measured using a Pierce bicinchoninic acid (BCA) assay (n=3), and expression of 23 cytokines was analyzed using the Bio-Plex cytokine assay (n=2). Data were analyzed by one-way ANOVA and Tukey's test (α=5%).The MTT assay revealed that at 24h and 48h, CHX and EGCG did not reduce cell metabolic activity at concentrations of 2.5-20μM (CHX) and 2.5-160μM (EGCG), respectively (p0.05). At 48h, total protein levels were consistent across all groups for 20μM compound dilution (Ctr: 1.04mg/mL; CHX: 0.98mg/mL; and EGCG: 1.06mg/mL). At 20μM dilution, both CHX and EGCG significantly increased the secretion of IL-1β, IL-10, IL-12, KC, MIP-1α, IFN-γ and IL-6 (p0.05). Treatment with CHX significantly increased secretion of IL-4 and RANTES (p0.05).with EGCG significantly increased Eotaxin secretion (p0.05). Both CHX and EGCG significantly decreased secretion of IL-17 (p0.05). GM-CSF and TNF-α did not present significant change in secretion after treatment with either CHX or EGCG (p0.05).Both CHX and EGCG modulate secretion of various inflammatory and anti-inflammatory mediators in odontoblastic cells.

ADTrees (Attack-Defense Trees) are graphical security modeling tools used to logically represent attack scenarios along with their corresponding countermeasures in a user-friendly way. Many researchers nowadays use ADTrees to represent attack scenarios and perform quantitative as well as qualitative security assessment. Among all different existing quantitative security assessment techniques, CTMCs (Continuous Time Markov Chains) have been attractively adopted for ADTrees. ADTrees are usually transformed into CTMCs, where traditional stochastic quantitative analysis approaches can be applied. For that end, the correct transformation of an ADTree to a CTMC requires that each individual element of an ADTree should have its correct and complete representation in the corresponding CTMC. In this paper, we mainly focus on modeling countermeasures in ADTrees using CTMCs. The existing CTMC-model does not provide a precise and complete modeling capability, in particular, when cascaded-countermeasures are used. Cascaded-countermeasures occur when an attacker and a defender in a given ADTree recursively counter each other more than one time in a given branch of the tree. We propose the notion of tokenized-CTMC to construct a new CTMC-model that can precisely model and represent countermeasures in ADTrees. This new CTMC-model allows to handle cascaded-countermeasure scenarios in a more comprehensive way.