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In light of Hong Kong's failed attempt to amend the Fugitive Offenders Ordinance in 2019 and China's enactment of the 2020 National Security Law for Hong Kong, many countries have voiced unease about their extradition agreements with China. Some, out of concern over potential adverse impacts on human rights, have even suspended their extradition agreements with Hong Kong. In this article, we investigate factors affecting the signing of extradition agreements between China and other countries. We hypothesize that third countries are more likely to conclude an extradition agreement with China if they are more economically engaged with China or are already cooperating with China in civil and criminal matters. In contrast, countries more strongly committed to the rule of law, or those which maintain a Common Law system, are less likely to sign an extradition agreement with China. Statistical analyses of the 57 Chinese extradition agreements signed between 1993 and 2019 support our hypotheses. [ABSTRACT FROM AUTHOR]

Background: While anti-Müllerian hormone (AMH) predicts quantitative IVF outcomes such as oocyte yield, it is not certain whether AMH predicts markers of oocyte quality such as aneuploidy. Methods: Retrospective case–control analysis of the SART-CORS database, 2014–2016, to determine whether anti-Müllerian hormone (AMH) predicts aneuploidy and live birth in IVF cycles utilizing preimplantation genetic testing for aneuploidy (PGT-A). Results: Of 51,273 cycles utilizing PGT-A for all embryos, 10,878 cycles were included in the final analysis; of these, 2,100 cycles resulted in canceled transfer due to lack of normal embryos and 8,778 cycles resulted in primary FET. AMH levels of cycles with ≥ 1 euploid embryo were greater than those of cycles with no normal embryos, stratifying by number of embryos biopsied (1–2, 3–4, 5–6, and ≥ 7), P < 0.017 for each stratum. Adjusting for age and number of embryos biopsied, AMH was a significant independent predictor of ≥ 1 euploid embryo for all age groups: < 35 yrs (aOR 1.074; 95%CI 1.005–1.163), 35–37 years (aOR 1.085; 95%CI 1.018–1.165) and ≥ 38 years (aOR 1.055; 95%CI 1.020–1.093). In comparative model analysis, AMH was superior to age as a predictor of ≥ 1 euploid embryo for age groups < 35 years and 35–37 years, but not ≥ 38 years. Across all cycles, age (aOR 0.945, 95% CI 0.935–0.956) and number of embryos (aOR 1.144, 95%CI 1.127–1.162) were associated with live birth per transfer, but AMH was not (aOR 0.995, 95%CI 0.983–1.008). In the subset of cycles resulting in ≥ 1 euploid embryo for transfer, neither age nor AMH were associated with live birth. Conclusions: Adjusting for age and number of embryos biopsied, AMH independently predicted likelihood of obtaining ≥ 1 euploid embryo for transfer in IVF PGT-A cycles. However, neither age nor AMH were predictive of live birth once a euploid embryo was identified by PGT-A for transfer. This analysis suggests a predictive role of AMH for oocyte quality (aneuploidy risk), but not live birth per transfer once a euploid embryo is identified following PGT-A. [ABSTRACT FROM AUTHOR]

Postpartum depression (PPD) is a common complication following delivery, though evidence-based treatment options are limited. This study explores the feasibility and efficacy of outpatient PPD treatment with transdermal estradiol (TE). In a pilot, double-blind, placebo-controlled trial, women with PPD were randomized to receive transdermal 17β-estradiol (100 mcg/day) or placebo patch. Over 6 weeks, women completed weekly ratings on the Beck Depression Inventory (BDI), Edinburgh Postnatal Depression Scale (EPDS), and Hamilton Depression Scale (HAM-D). Primary outcome measures were treatment response (> 50% decrease from baseline BDI) and remission (BDI < 10) at 6 weeks, and secondary outcome measures included severity on all scales at weeks 3 and 6. Of 12 recruited women, 6 received TE and 6 received placebo. By week 6, 5 women receiving TE responded to treatment and 4 showed symptom remission, compared to 2 responders and 1 remitter in the placebo group. This difference was not significant (p = 0.24). In a mixed-model of BDI ratings, TE was associated with a 9.2 point decrease at 3 weeks (95%CI − 19.5 to + 1.0, p = 0.074) and a 10.5 point decrease at 6 weeks (95%CI − 21.0–0.0, p = 0.049) compared to placebo, though these differences did not survive multiple comparisons correction. Analogous effects were found for HAM-D but not EPDS scores. Interestingly, no significant difference in plasma estradiol levels existed between groups. We were unable to demonstrate a significant therapeutic benefit of TE compared with placebo in PPD. Although limited by under-recruitment and loss to follow-up, our results suggest TE is a feasible option for outpatient PPD management, with preliminary evidence (based on secondary outcomes) for efficacy. Therapeutic effects may be seen as early as 3 weeks and may not directly depend on peripheral measures of estradiol. [ABSTRACT FROM AUTHOR]

The reported proof of principle study demonstrated the feasibility of local delivery of a c-Met inhibitor (VXc-140) in a subcutaneous xenograft tumor model. VXc-140 was formulated in a wafer delivery system for direct implantation into the tumor. Systemic and local tumor exposure of VXc-140 was analyzed. High tumor exposures coupled with fast release of compound were associated with significant tumor regression and reduction in tumor levels of phosphorylated c-Met. High VXc-140 tumor-to-plasma ratios (∼42 at the tumor periphery) were achieved. The tumor response achieved (7/11 partial response) with VXc-140 with the local delivery in the wafer (4 mg over 15 days) was comparable to the regression observed (11/15 partial response) for VXc-140 in the oral delivery (∼8 mg total administered once a day for 2 weeks). Notably, the plasma levels in animals implanted with VXc-140 wafers ranged from 2 to 4 μM, which, although higher than trough levels achieved with oral administration, were well below oral Cmax levels (∼42 μM) suggesting that toxicities associated with Cmax exposure may be reduced or eliminated by local delivery. The high tumor to plasma exposure of VXc-140 and the efficacy observed with local wafer delivery warrants further exploration into the utility of local delivery. [ABSTRACT FROM AUTHOR]

Endometriosis is a debilitating disease affecting reproductive-aged women. While a broad array of endometriosis treatments exist, optimal regimens are not well-established. We sought to characterize the most common treatment modalities for endometriosis in adolescent and young adult females with biopsy-proven endometriosis. This is a retrospective medical record review of 91 women aged 14-25 who underwent laparoscopy for pelvic pain with biopsy-proven endometriosis at a tertiary hospital system between January 2011 and September 2020. Patients were identified by appropriate CPT and ICD-9/10 codes. Initial and current hormonal treatments (defined as first treatment offered within 6 months of initial presentation, and treatment at most recent follow-up visit, respectively), along with age and BMI were summarized with descriptive statistics. This study was approved by the institutional review board. Oral contraceptives (OCPs) were the most common initial treatment (64%), followed by levonorgestrel IUD (LNG-IUD) (10%). Progestin-only formulations (low- and high-dose norethindrone) were offered to younger patients (age 15.9 ± 2.7 years), compared to those offered OCPs (19.9 ± 3.3 years) and LNG-IUD (21.9 ± 1.7 years). Median follow-up time was 36.7 (IQR 14.9-64.3) months from initial presentation and 17.9 (IQR 4.6-39.1) months from laparoscopy. Current treatments varied widely, and included OCPs (32%), LNG-IUD (18%), oral progestins (low- and high-dose norethindrone, medroxyprogesterone) (14%), elagolix (9%), leuprolide (8%), and one patient who underwent TLH-BSO at age 22. Oral adjuncts to LNG-IUD were common: usually low- or high-dose norethindrone (37% of patients with an LNG-IUD), but also included progesterone, OCPs, and elagolix. There was no apparent association between BMI and initial or current treatments. While 33% of patients had trialed elagolix or leuprolide at some point in their treatment, only 17% were currently taking these medications, suggesting a significant rate of discontinuation. OCPs, LNG-IUD, and oral progestins were the mainstay of initial treatment, with progestin-only formulations offered to younger patients more frequently, likely due to concern of impaired skeletal growth with estrogen-containing therapy. Current treatments varied widely and included OCPs, LNG-IUD, oral progestins, elagolix, and leuprolide. Regimens combining these agents were common. While one third (33%) of patients had tried elagolix or leuprolide at some point in their treatment course, there was a high rate (50%) of discontinuation possibly due to side effects or insurance coverage. This pilot study may help define the spectrum of optimal treatment regimens for endometriosis in adolescent females. [ABSTRACT FROM AUTHOR]

Endometriosis is common among adolescents with chronic pelvic pain but remains underdiagnosed, in part due to a desire to avoid major surgery for young patients. We sought to identify factors affecting time from presentation to laparoscopy (diagnostic delay) in adolescents with biopsy-proven endometriosis. This is a retrospective review of medical records of women aged 14-25 who underwent diagnostic laparoscopy with biopsy-proven endometriosis at a tertiary hospital system between January 2011 and September 2020. Time from initial presentation to laparoscopy was calculated. Multiple regression analysis was used to test the effect of 3 variables on diagnostic delay: specialty of initial OB/GYN provider (community generalist or subspecialist), clinical setting of initial encounter (routine outpatient visit or ED-/hospital-associated visit), and presence of an adnexal mass on initial imaging. Statistical analysis was performed in Prism v.8. This study was approved by the institutional review board. Of 254 adolescents who underwent laparoscopy, 91 (35.8%) had biopsy-proven endometriosis. Of these, 80 had a documented initial encounter prior to laparoscopy and thus included in final analysis. In our sample, median delay to laparoscopy was 5.2 (IQR 2.1-31.8) months. This included 33 (41%) patients who presented to a subspecialist (including via referral from outside providers with no prior records available). For patients presenting to community generalists, median delay was 24.6 (3.5-42.8) months. For women who presented after ED or hospital visit (20%), median delay was 0.6 (0.1-3.7) months, compared to 11.1 (3.3-35.4) in the outpatient setting. If an adnexal mass was found on initial imaging (35%), median delay was 1.6 (0.3-3.7) months, compared to 19.4 (4.7-39.5) without imaging findings. In multiple regression analysis, initial presentation to a subspecialist and presence of an adnexal mass were associated with a shorter time to laparoscopy, with an estimated decrease of 5.2±1.8 months (p=0.005) and 18.6±3.4 months (p<0.0001), respectively. ED visitation was highly correlated with presence of adnexal mass on imaging (Pearson's r=0.62, p<1.2e-9), but not independently associated with shorter diagnostic delay. Patients in the community setting experienced a median time from presentation to definitive diagnosis of over 2 years. Patients with an adnexal mass on initial imaging (35%) experienced a significantly shorter time to laparoscopy (-18.6 months). While presentation to a subspecialist was also associated with a shorter diagnostic delay, the impact of subspecialty referral on access to diagnostic laparoscopy and potential practice differences between generalists and subspecialists requires further study. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the performance of cervical cancer screening algorithms for women living with human immunodeficiency virus (HIV), using primary high-risk human papillomavirus (HPV) testing followed by cytology, visual inspection with acetic acid, or colposcopy.Methods: We conducted a prospective cohort study of women living with HIV in Botswana. All participants underwent high-risk HPV testing. Participants with positive high-risk HPV test results underwent cytology, visual inspection with acetic acid, colposcopy, and biopsy. Participants with negative high-risk HPV test results also underwent cytology. Histopathology was the reference standard for determination of preinvasive cervical disease and cervical cancer. Sensitivity, specificity, positive predictive value (PPV), negative predictive value, and likelihood ratios (LR) of high-risk HPV-based two-stage screening algorithms were calculated.Results: Among 300 women screened, 88 (29%) had a positive high-risk HPV test result, and 29 of the 88 (35%) women who tested positive for high-risk HPV had CIN 2 or higher on histopathology. High-risk HPV followed by colposcopy resulted in a sensitivity of 83%, specificity of 49%, PPV of 47%, LR+ of +1.6, and LR- of -0.4. High-risk HPV followed by visual inspection with acetic acid resulted in a reduced sensitivity of 59%, specificity of 49%, PPV of 39%, LR+ of +1.2, and LR- of -0.8. High-risk HPV testing followed by cytology also resulted in a reduced sensitivity of 62%, specificity of 77%, PPV of 60%, LR+ of +2.7, and LR- of -0.5. Stratification by HPV 16/18/45 did not improve performance of the algorithms.Conclusion: In a high-risk population with HIV, high-risk HPV testing followed by colposcopy demonstrated the highest sensitivity and PPV in detecting high-grade cervical dysplasia. Allocating resources to colposcopy in resource-limited settings may be more effective than other screening strategies. [ABSTRACT FROM AUTHOR]

Peroxisome proliferator-activated receptor-γ (PPARγ) is a member of the nuclear receptor superfamily of ligand-activated transcription factors that plays an important role in the control of gene expression linked to a variety of physiological processes, including cancer. Ligands for PPARγ include naturally occurring fatty acids and the thiazolidinedione class of antidiabetic drugs. Activation of PPARγ in a variety of cancer cells leads to inhibition of growth, decreased invasiveness, reduced production of proinflammatory cytokines, and promotion of a more differentiated phenotype. However, systemic activation of PPARγ has been reported to be protumorigenic in some in vitro systems and in vivo models. Here, we review the available data that implicate PPARγ in lung carcinogenesis and highlight the challenges of targeting PPARγ in lung cancer treatments. [ABSTRACT FROM AUTHOR]

Activation of peroxisome proliferator-activated receptor-γ (PPARγ) inhibits growth of cancer cells including non-small cell lung cancer (NSCLC). Clinically, use of thiazolidinediones, which are pharmacological activators of PPARγ is associated with a lower risk of developing lung cancer. However, the role of this pathway in lung cancer metastasis has not been examined well. The systemic effect of pioglitazone was examined in two models of lung cancer metastasis in immune-competent mice. In an orthotopic model, murine lung cancer cells implanted into the lungs of syngeneic mice metastasized to the liver and brain. As a second model, cancer cells injected subcutaneously metastasized to the lung. In both models systemic administration of pioglitazone increased the rate of metastasis. Examination of tissues from the orthotopic model demonstrated increased numbers of arginase I-positive macrophages in tumors from pioglitazone-treated animals. In co-culture experiments of cancer cells with bone marrow-derived macrophages, pioglitazone promoted arginase I expression in macrophages and this was dependent on the expression of PPARc in the macrophages. To assess the contribution of PPARγ in macrophages to cancer progression, experiments were performed in bone marrow-transplanted animals receiving bone marrow from Lys-M-Cre+/PPARγflox/flox mice, in which PPARγ is deleted specifically in myeloid cells (PPARγ-Macneg), or control PPARγflox/flox mice. In both models, mice receiving PPARγ-Macneg bone marrow had a marked decrease in secondary tumors which was not significantly altered by treatment with pioglitazone. This was associated with decreased numbers of arginase I-positive cells in the lung. These data support a model in which activation of PPARc may have opposing effects on tumor progression, with anti-tumorigenic effects on cancer cells, but pro-tumorigenic effects on cells of the microenvironment, specifically myeloid cells. [ABSTRACT FROM AUTHOR]

Abstract: This paper presents a novel domestic hot water heater model to be used in a multi-objective demand side management program. The model incorporates both the thermal losses and the water usage to determine the temperature of the water in the tank. Water heater loads are extracted from household load data and then used to determine the household water usage patterns. The benefits of the model are: (1) the on/off state of the water heater and temperature of the water in the tank can be accurately predicted, and (2) it enables the development of water usage profiles so that users can be classified based on usage behaviour. As a result, the amount of ancillary services and peak shaving that can be achieved are accurately predictable and can be maximized without adversely affecting users. [Copyright &y& Elsevier]

In this research, a fuzzy logic controller is designed for vision-based autonomous road-following. Because of its high-speed response, portability, and flexibility, a field programmable gate array is applied to implement this control system. Furthermore, a novel hardware/software partitioning method using the genetic algorithm is developed. This method is capable of finding the tradeoff among several evaluation factors under conditions of hard constraints. A small-scaled intelligent vehicle, which is capable of autonomous road-following is built and the proposed controller is tested in the real-world environment. Experiments of hardware implementation and codesign implementation are presented and compared. [ABSTRACT FROM PUBLISHER]

Work from our laboratory and others has demonstrated that activation of the nuclear receptor peroxisome proliferator--activated receptor-γ (PPARγ) inhibits transformed growth of non--small cell lung cancer (NSCLC) cell lines in vitro and in vivo.We have demonstrated that activation of PPARγ promotes epithelial differentiation of NSCLC by increasing expression of E-cadherin, as well as inhibiting expression of COX-2 and nuclear factor-κB. The Snail family of transcription factors, which includes Snail (Snail1), Slug (Snail2), and ZEB1, is an important regulator of epithelial-mesenchymal transition, aswell as cell survival. The goal of this studywas to determine whether the biological responses to rosiglitazone, a memberof the thiazolidinedione family of PPARγ activators, are mediated through the regulation of Snail family members. Our results indicate that, in two independent NSCLC cell lines, rosiglitazone specifically decreased expression of Snail, with no significant effect on either Slug or ZEB1. Suppression of Snail using short hairpin RNA silencing mimicked the effects of PPARγ activation, in inhibiting anchorage-independent growth, promoting acinar formation in three-dimensional culture, and inhibiting invasiveness. This was associated with the increased expression of E-cadherin and decreased expression of COX-2 andmatrixmetaloproteinases. Conversely, overexpression of Snail blocked the biological responses to rosiglitazone, increasing anchorage-independent growth, invasiveness, and promoting epithelial-mesenchymal transition. The suppression of Snail expression by rosiglitazone seemed to be independent of GSK-3 signaling but was rather mediated through suppression of extracellular signal--regulated kinase activity. These findings suggest that selective regulation of Snail may be critical in mediating the antitumorigenic effects of PPARγ activators. [ABSTRACT FROM AUTHOR]

Autonomous road following is one of the major goals in intelligent vehicle applications. The development of an autonomous road following embedded system for intelligent vehicles is the focus of this paper. A fuzzy logic controller (FLC) is designed for vision-based autonomous road following. The stability analysis of this control system is addressed. Lyapunov's direct method is utilized to formulate a class of control laws that guarantee the convergence of the steering error. Certain requirements for the control laws are presented for designers to choose a suitable rule base for the fuzzy controller in order to make the system stable. Stability of the proposed fuzzy controller is guaranteed theoretically and also demonstrated by simulation studies and experiments. Simulations using the model of the four degree of freedom nonholonomic robotic vehicle are conducted to investigate the performance of the fuzzy controller. The proposed fuzzy controller can achieve the desired steering angle and make the robotic vehicle follow the road successfully. Experiments show that the developed intelligent vehicle is able to follow a mocked road autonomously. [ABSTRACT FROM AUTHOR]

The article presents a medical case of a 43-year old Vietnamese-American woman who was referred for evaluation of dyspnea. The patient presented with a 6-month history of progressive dyspnea, a diffusively abnormal chest examination, and normal laboratory data. Pulmonary function tests showed evidence of hyperinflation without evidence of airflow limitation or diffusion defect. radiographic imaging revealed multiple cysts in lungs and kidneys.

In this paper, a framework is proposed for the distributed control and coordination of multiagent systems (MASs). In the proposed framework, the control of MASs is regarded as achieving decentralized control and coordination of agents. Each agent is modeled as a coordinated hybrid agent, which is composed of an intelligent coordination layer and a hybrid control layer. The intelligent coordination layer takes the coordination input, plant input, and workspace input. In the proposed framework, we describe the coordination mechanism in a domain-independent way, i.e., as simple abstract primitives in a coordination rule base for certain dependence relationships between the activities of different agents. The intelligent coordination layer deals with the planning, coordination, decision making, and computation of the agent. The hybrid control layer of the proposed framework takes the output of the intelligent coordination layer and generates discrete and continuous control signals to control the overall process. To verify the feasibility of the proposed framework, experiments for both heterogeneous and homogeneous MASs are implemented. The proposed framework is applied to a multicrane system, a multiple robot system, and a MAS consisting of an overhead crane, a mobile robot, and a robot manipulator. It is demonstrated that the proposed framework can model the three MASs. The agents in these systems are able to cooperate and coordinate to achieve a global goal. In addition, the stability of systems modeled using the proposed framework is also analyzed. [ABSTRACT FROM AUTHOR]

• Hispanic men are more likely to present with non-seminomatous germ cell tumor (NSGCT), at a younger age, and with more advanced disease. • Hispanic men with NSGCT experience significantly worse survival compared to other race/ethnic groups. • Identification of molecular drivers responsible for differences in biologic risk between race/ethnic groups is limited by currently available repositories with small sample sizes. To examine survival outcomes and molecular drivers in testis cancer among Hispanic men using a large national sample and molecular database. We reviewed the SEER registry for testicular cancer from 2000 to 2020. Cox proportional hazards models were used to examine the relationship between race/ethnicity and cancer-specific survival (CSS) by tumor type (seminoma vs. nonseminomatous germ cell tumors [NSGCT]). All models were adjusted for demographic, socioeconomic, and treatment variables. We accessed somatic mutations for testicular cancers through AACR Project GENIE v13.1 and compared mutational frequencies by ethnicity. Our cohort consisted of 43,709 patients (23.3% Hispanic) with median follow-up 106 months (interquartile range: 45-172). Compared to Non-Hispanic Whites (NWH), Hispanics presented at a younger age but with more advanced disease. Hispanics experienced worse CSS for NSGCT (HR 1.7, 95% CI: 1.5-2.0, P < 0.01) but not seminoma. Somatic mutation data was available for 699 patients. KIT and KRAS mutations occurred in 24.2% and 16.9% of seminoma patients (n = 178), respectively. TP53 and KRAS mutations occurred in 12.1% and 7.9% of NSGCT patients (n = 521), respectively. No differences in mutational frequencies were observed between ethnic groups. There was significant heterogeneity in primary ancestral group for Hispanic patients with available data (n = 53); 14 (26.4%) patients had primary Native American ancestry and 30 (56.6%) had primary European ancestry. Cancer-specific survival is worse for Hispanic men with non-seminoma of the testicle. Somatic mutation analysis suggests no differences by ethnicity, though genetic ancestry is heterogeneous among patients identifying as Hispanic. [ABSTRACT FROM AUTHOR]

Background: Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most common cause of familial Parkinson's disease (PD). These mutations elevate the LRRK2 kinase activity, making LRRK2 kinase inhibitors an attractive therapeutic. LRRK2 kinase activity has been consistently linked to specific cell signaling pathways, mostly related to organelle trafficking and homeostasis, but its relationship to PD pathogenesis has been more difficult to define. LRRK2-PD patients consistently present with loss of dopaminergic neurons in the substantia nigra but show variable development of Lewy body or tau tangle pathology. Animal models carrying LRRK2 mutations do not develop robust PD-related phenotypes spontaneously, hampering the assessment of the efficacy of LRRK2 inhibitors against disease processes. We hypothesized that mutations in LRRK2 may not be directly related to a single disease pathway, but instead may elevate the susceptibility to multiple disease processes, depending on the disease trigger. To test this hypothesis, we have previously evaluated progression of α-synuclein and tau pathologies following injection of proteopathic seeds. We demonstrated that transgenic mice overexpressing mutant LRRK2 show alterations in the brain-wide progression of pathology, especially at older ages. Methods: Here, we assess tau pathology progression in relation to long-term LRRK2 kinase inhibition. Wild-type or LRRK2G2019S knock-in mice were injected with tau fibrils and treated with control diet or diet containing LRRK2 kinase inhibitor MLi-2 targeting the IC50 or IC90 of LRRK2 for 3–6 months. Mice were evaluated for tau pathology by brain-wide quantitative pathology in 844 brain regions and subsequent linear diffusion modeling of progression. Results: Consistent with our previous work, we found systemic alterations in the progression of tau pathology in LRRK2G2019S mice, which were most pronounced at 6 months. Importantly, LRRK2 kinase inhibition reversed these effects in LRRK2G2019S mice, but had minimal effect in wild-type mice, suggesting that LRRK2 kinase inhibition is likely to reverse specific disease processes in G2019S mutation carriers. Additional work may be necessary to determine the potential effect in non-carriers. Conclusions: This work supports a protective role of LRRK2 kinase inhibition in G2019S carriers and provides a rational workflow for systematic evaluation of brain-wide phenotypes in therapeutic development. [ABSTRACT FROM AUTHOR]

Simple Summary: High dose acetaminophen (AAP) with N-acetylcysteine (NAC) rescue has demonstrated promising results in pre-clinical and clinical studies. However, the mechanism is not clearly understood. In the present manuscript, we evaluate the effects of high dose AAP/NAC on the tumor immune microenvironment. We demonstrate that high dose AAP inhibits M2 polarization of tumor associated macrophages at the RNA and protein levels. The anti-tumor activity of high dose AAP is lost in macrophage depleted mice, underlining the physiologic relevance of the findings. While at traditional doses AAP is not thought to have anti-inflammatory activity, our study is the first to describe AAP-induced changes on anti-tumor immunity. High-dose acetaminophen (AAP) with N-acetylcysteine (NAC) rescue is among the few treatments that has shown activity in phase I trials without achieving dose-limiting toxicity that has not progressed to evaluation in later line studies. While the anti-tumor effects of AAP/NAC appear not to be mediated by glutathione depletion and free radical injury, the mechanism of anti-tumor effects of AAP/NAC has not been definitively characterized. In vitro, the effects of AAP/NAC were evaluated on bone marrow derived macrophages. Effects of AAP on IL-4/STAT6 (M2) or IFN/LPS/STAT1 (M1) signaling and downstream gene and protein expression were studied. NAC reversed the AAP toxicity in the normal liver but did not reverse AAP cytotoxicity against tumor cells in vitro. AAP/NAC selectively inhibited IL-4-induced STAT6 phosphorylation but not IFN/LPS-induced STAT1 phosphorylation. Downstream, AAP/NAC inhibited IL-4 induction of M2-associated genes and proteins but did not inhibit the IFN/LPS induction of M1-associated genes and proteins. In vivo, AAP/NAC inhibited tumor growth in EF43.fgf4 and 4T1 triple-negative breast tumors. Flow cytometry of tumor-associated macrophages revealed that AAP/NAC selectively inhibited M2 polarization. The anti-tumor activity of high-dose AAP/NAC is lost in macrophage-depleted mouse syngeneic tumor models, suggesting a macrophage-dependent mechanism of action. In conclusion, our study is the first to show that high-dose AAP/NAC has profound effects on the tumor immune microenvironment that facilitates immune-mediated inhibition of tumor growth. [ABSTRACT FROM AUTHOR]

Lung-specific overexpression of prostacyclin synthase (PGIS) decreases tumor initiation in murine lung cancer models. Prostacyclin analogs prevent lung tumor formation in mice and reverse bronchial dysplasia in former smokers. However, the effect of prostacyclin on lung cancer progression has not been well studied. We investigated the effects of pulmonary PGIS overexpression in an orthotopic immunocompetent mouse model of lung cancer using two murine lung cancer cell lines. Pulmonary PGIS overexpression significantly inhibited CMT167 lung tumor growth, increased CXCL9 expression, and increased CD4+ tumor-infiltrating lymphocytes. Immunodepletion of CD4+ T cells abolished the inhibitory effect of pulmonary PGIS overexpression on CMT167 lung tumor growth. In contrast, pulmonary PGIS overexpression failed to inhibit growth of a second murine lung cancer cell line, Lewis Lung Carcinoma (LLC) cells, and failed to increase CXCL9 expression or CD4+ T lymphocytes in LLC lung tumors. Transcriptome profiling of CMT167 cells and LLC cells recovered from tumor-bearing mice demonstrated that in vivo, CMT167 cells but not LLC cells express MHC class II genes and cofactors necessary for MHC class II processing and presentation. These data demonstrate that prostacyclin can inhibit lung cancer progression and suggest that prostacyclin analogs may serve as novel immunomodulatory agents in a subset of lung cancer patients. Moreover, expression of MHC Class II by lung cancer cells may represent a biomarker for response to prostacyclin. [ABSTRACT FROM AUTHOR]

Simple Summary: Lung cancer remains the most commonly diagnosed cancer in the United States, only behind sex-specific cancers such as breast and prostate cancer. While not a sex-specific cancer, lung cancer exhibits sex-specific trends. Males are generally at a higher lifetime risk of developing lung cancer and have a higher mortality than females. There are also differences in therapeutic response between the sexes. As lung cancer is a complex disease, this difference is likely a combination of environmental factors, such as environmental exposures, diet, and smoking status, with inherent biological differences, such as the contribution of sex hormones and differences in immune responses. This narrative review focuses specifically on these biological differences and their contributions to this difference. Gaining a better understanding of the biological reasons behind this sex difference could lead to better treatment and screening decisions in the clinic that take the biological sex of the patient into consideration. Sex disparities in the incidence and mortality of lung cancer have been observed since cancer statistics have been recorded. Social and economic differences contribute to sex disparities in lung cancer incidence and mortality, but evidence suggests that there are also underlying biological differences that contribute to the disparity. This review summarizes biological differences which could contribute to the sex disparity. Sex hormones and other biologically active molecules, tumor cell genetic differences, and differences in the immune system and its response to lung cancer are highlighted. How some of these differences contribute to disparities in the response to therapies, including cytotoxic, targeted, and immuno-therapies, is also discussed. We end the study with a discussion of our perceived future directions to identify the key biological differences which could contribute to sex disparities in lung cancer and how these differences could be therapeutically leveraged to personalize lung cancer treatment to the individual sexes. [ABSTRACT FROM AUTHOR]

miRNAs are some of the most well-characterized regulators of gene expression. Integral to several physiological processes, their aberrant expression often drives the pathogenesis of both benign and malignant diseases. Similarly, DNA methylation represents an epigenetic modification influencing transcription and playing a critical role in silencing numerous genes. The silencing of tumor suppressor genes through DNA methylation has been reported in many types of cancer and is associated with tumor development and progression. A growing body of literature has described the crosstalk between DNA methylation and miRNAs as an additional layer in the regulation of gene expression. Methylation in miRNA promoter regions inhibits its transcription, while miRNAs can target transcripts and subsequently regulate the proteins responsible for DNA methylation. Such relationships between miRNA and DNA methylation serve an important regulatory role in several tumor types and highlight a novel avenue for potential therapeutic targets. In this review, we discuss the crosstalk between DNA methylation and miRNA expression in the pathogenesis of cancer and describe how miRNAs influence DNA methylation and, conversely, how methylation impacts the expression of miRNAs. Finally, we address how these epigenetic modifications may be leveraged as biomarkers in cancer. [ABSTRACT FROM AUTHOR]

Several letters to the editor are presented in response to the article "Dyspnea in a 43-Year-Old Woman With Polycystic Kidney Disease," by H. Y. Li and colleagues in the January 2009 issue.

One promise of synthetic biology is the creation of genetic circuitry that enables the execution of logical programming in living cells. Such 'wet programming' is positioned to transform a wide and diverse swathe of biotechnology ranging from therapeutics and diagnostics to water treatment strategies. Although progress in the development of a library of genetic modules continues apace, a major challenge for their integration into larger circuits is the generation of sufficiently fast and precise communication between modules. An attractive approach is to integrate engineered circuits with host processes that facilitate robust cellular signalling. In this context, recent studies have demonstrated that bacterial protein degradation can trigger a precise response to stress by overloading a limited supply of intracellular proteases. Here we use protease competition to engineer rapid and tunable coupling of genetic circuits across multiple spatial and temporal scales. We characterize coupling delay times that are more than an order of magnitude faster than standard transcription-factor-based coupling methods (less than 1 min compared with ∼20-40 min) and demonstrate tunability through manipulation of the linker between the protein and its degradation tag. We use this mechanism as a platform to couple genetic clocks at the intracellular and colony level, then synchronize the multi-colony dynamics to reduce variability in both clocks. We show how the coupled clock network can be used to encode independent environmental inputs into a single time series output, thus enabling frequency multiplexing (information transmitted on a common channel by distinct frequencies) in a genetic circuit context. Our results establish a general framework for the rapid and tunable coupling of genetic circuits through the use of native 'queueing' processes such as competitive protein degradation. [ABSTRACT FROM AUTHOR]

The article describes the case of in a 61-year-old woman presented with a 4-week history of progressive bilateral leg weakness, bilateral leg pain, and difficulty walking. The patient had a history of breast cancer and was afebrile. Myasthenia gravis was diagnosed clinically and was treated with pyridostigmine, but the patient had no improvement in symptoms. Lambert-Eaton myasthenic syndrome was identified and was treated with carboplatin, etoposide and radiation therapy.

Abstract: The Prior Learning Assessment and Recognition (PLAR) is a labor-intensive process for academic advisors, evaluation services, graduate schools, registrars, learners, and other individuals and organizations responsible for assessment of learner’s credentials and competencies with the purpose of continuing (lifelong) learning. The present paper describes an approach to build an expert system for electronic assessment (e-Assessment) of academic credentials and competencies, which is an e-Learning application intended to essentially help assessors to conduct their work more effective and efficient. The proposed approach uses the semantic web technologies, such as RDFS ontologies and POSL rules to convert academic credentials between educational institutions and make correspondences between the learner’s competencies and credentials. [Copyright &y& Elsevier]

High-dose acetaminophen (AAP) with delayed rescue using n-acetylcysteine (NAC), the FDA-approved antidote to AAP overdose, has demonstrated promising antitumor efficacy in early phase clinical trials. However, the mechanism of action (MOA) of AAP's anticancer effects remains elusive. Using clinically relevant AAP concentrations, we evaluated cancer stem cell (CSC) phenotype in vitro and in vivo in lung cancer and melanoma cells with diverse driver mutations. Associated mechanisms were also studied. Our results demonstrated that AAP inhibited 3D spheroid formation, self-renewal, and expression of CSC markers when human cancer cells were grown in serum-free CSC media. Similarly, anti-CSC activity was demonstrated in vivo in xenograft models - tumor formation following in vitro treatment and ex-vivo spheroid formation following in vivo treatment. Intriguingly, NAC, used to mitigate AAP's liver toxicity, did not rescue cells from AAP's anti-CSC effects, and AAP failed to reduce glutathione levels in tumor xenograft in contrast to mice liver tissue suggesting nonglutathione-related MOA. In fact, AAP mediates its anti-CSC effect via inhibition of STAT3. AAP directly binds to STAT3 with an affinity in the low micromolar range and a high degree of specificity for STAT3 relative to STAT1. These findings have high immediate translational significance concerning advancing AAP with NAC rescue to selectively rescue hepatotoxicity while inhibiting CSCs. The novel mechanism of selective STAT3 inhibition has implications for developing rational anticancer combinations and better patient selection (predictive biomarkers) for clinical studies and developing novel selective STAT3 inhibitors using AAP's molecular scaffold. [ABSTRACT FROM AUTHOR]

Objective: Our study aims to investigate the differences in insomnia between Chinese and Western women during menopause to fill the gaps in the research on menopause in Chinese women, and to examine the premenopausal factors predictive of moderate to severe insomnia during menopause.Study Design: This is a longitudinal cohort study conducted in an urban Chinese community with a total of 458 participants.Main Outcome Measures: Presence of insomnia symptoms (trouble falling asleep, waking up early); vasomotor symptoms; anxiety and depression assessed by the Hospital Anxiety and Depression Scale; and menopausal stages.Results: Multivariable analysis showed that compared with that in premenopause, the prevalence of trouble falling asleep was significantly higher in menopausal transition (P = 0.029) and postmenopause (P < 0.001), and the prevalence of early-morning awakenings also significantly increased in menopausal transition (P = 0.003) and postmenopause (P = 0.011). In multivariable analysis anxiety (P = 0.022) and depression (P = 0.005) were independently and significantly positively associated with trouble falling asleep. Anxiety (P < 0.001), depression (P = 0.018), and levels of follicle stimulating hormone (P-0.031) were independently and significantly positively associated with trouble falling asleep. Women who experienced insomnia in premenopause had a significantly higher risk of moderate to severe insomnia in menopausal transition (P = 0.003) and postmenopause (P = 0.047) than those who did not.Conclusion: This study showed that the prevalence of sleep disturbance significantly increased during and after menopause. Women with anxiety and depression had a higher risk of insomnia. Difficulty in sleep initiation in the premenopausal period was a strong predictor of moderate to severe insomnia at menopausal transition and postmenopause. [ABSTRACT FROM AUTHOR]

MHC class II (MHCII) expression is usually restricted to APC but can be expressed by cancer cells. We examined the effect of cancer cell-specific MHCII (csMHCII) expression in lung adenocarcinoma on T cell recruitment to tumors and response to anti-PD-1 therapy using two orthotopic immunocompetent murine models of non-small cell lung cancer: CMT167 (CMT) and Lewis lung carcinoma (LLC). We previously showed that CMT167 tumors are eradicated by anti-PD1 therapy, whereas LLC tumors are resistant. RNA sequencing analysis of cancer cells recovered from tumors revealed that csMHCII correlated with response to anti-PD1 therapy, with immunotherapy-sensitive CMT167 cells being csMHCII positive, whereas resistant LLC cells were csMHCII negative. To test the functional effects of csMHCII, MHCII expression was altered on the cancer cells through loss- and gain-offunction of CIITA, a master regulator of the MHCII pathway. Loss of CIITA in CMT167 decreased csMHCII and converted tumors from anti-PD-1 sensitive to anti-PD-1 resistant. This was associated with lower levels of Th1 cytokines, decreased T cell infiltration, increased B cell numbers, and decreased macrophage recruitment. Conversely, overexpression of CIITA in LLC cells resulted in csMHCII in vitro and in vivo. Enforced expression of CIITA increased T cell infiltration and sensitized tumors to anti-PD-1 therapy. csMHCII expression was also examined in a subset of surgically resected human lung adenocarcinomas by multispectral imaging, which provided a survival benefit and positively correlated with T cell infiltration. These studies demonstrate a functional role for csMHCII in regulating T cell infiltration and sensitivity to anti-PD-1. [ABSTRACT FROM AUTHOR]

Whole-genome sequencing (WGS) is gaining importance in the analysis of bacterial cultures derived from patients with infectious diseases. Existing computational tools for WGS-based identification have, however, been evaluated on previously defined data relying thereby unwarily on the available taxonomic information. Here, we newly sequenced 846 clinical gram-negative bacterial isolates representing multiple distinct genera and compared the performance of five tools (CLARK, Kaiju, Kraken, DIAMOND/MEGAN and TUIT). To establish a faithful 'gold standard', the expert-driven taxonomy was compared with identifications based on matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS) analysis. Additionally, the tools were also evaluated using a data set of 200 Staphylococcus aureus isolates. CLARK and Kraken (with k=31) performed best with 626 (100%) and 193 (99.5%) correct species classifications for the gramnegative and S. aureus isolates, respectively. Moreover, CLARK and Kraken demonstrated highest mean F-measure values (85.5/87.9% and 94.4/94.7% for the two data sets, respectively) in comparison with DIAMOND/MEGAN (71 and 85.3%), Kaiju (41.8 and 18.9%) and TUIT (34.5 and 86.5%). Finally, CLARK, Kaiju and Kraken outperformed the other tools by a factor of 30 to 170 fold in terms of runtime. We conclude that the application of nucleotide-based tools using k-mers--e.g. CLARK or Kraken--allows for accurate and fast taxonomic characterization of bacterial isolates from WGS data. Hence, our results suggest WGS-based genotyping to be a promising alternative to the MS-based biotyping in clinical settings. Moreover, we suggest that complementary information should be used for the evaluation of taxonomic classification tools, as public databases may suffer from suboptimal annotations. [ABSTRACT FROM AUTHOR]

There are many applications that require mobile robots to autonomously cover an entire area with a sensor or end effector. The vast majority of the literature on this subject is focused on addressing path planning for area coverage under the assumption that the robot’s pose is known or that error is bounded. In this work, we remove this assumption and develop a completely probabilistic representation of coverage. We show that coverage is guaranteed as long as the robot pose estimates are consistent, a much milder assumption than zero or bounded error. After formally connecting robot sensor uncertainty with area coverage, we propose an adaptive sliding window filter pose estimator that provides a close approximation to the full maximum a posteriori estimate with a computation cost that is bounded over time. Subsequently, an adaptive planning strategy is presented that automatically exploits conditions of low vehicle uncertainty to more efficiently cover an area. We further extend this approach to the multi-robot case where robots can communicate through a (possibly faulty and low-bandwidth) channel and make relative measurements of one another. In this case, area coverage is achieved more quickly since the uncertainty over the robots’ trajectories is reduced. We apply the framework to the scenario of mapping an area of seabed with an autonomous underwater vehicle. Experimental results support the claim that our method achieves guaranteed complete coverage notwithstanding poor navigational sensors and that resulting path lengths required to cover the entire area are shortest using the proposed cooperative and adaptive approach. [ABSTRACT FROM AUTHOR]

Most previous studies of cisplatin-induced acute kidney injury (AKI) have been in models of acute, high-dose cisplatin administration that leads to mortality in non-tumor-bearing mice. The aim of the study was to determine whether CD4 T cell knockout protects against AKI and cancer in a clinically relevant model of low-dose cisplatin-induced AKI in mice with cancer. Kidney function, serum neutrophil gelatinase-associated lipocalin (NGAL), acute tubular necrosis (ATN), and tubular apoptosis score were the same in wild-type and CD4 −/− mice with AKI. The lack of protection against AKI in CD4 −/− mice was associated with an increase in extracellular signal-regulated kinase (ERK), p38, CXCL1, and TNF-α, mediators of AKI and fibrosis, in both cisplatin-treated CD4 −/− mice and wild-type mice. The lack of protection was independent of the presence of cancer or not. Tumor size was double, and cisplatin had an impaired therapeutic effect on the tumors in CD4 −/− vs. wild-type mice. Mice depleted of CD4 T cells using the GK1.5 antibody were not protected against AKI and had larger tumors and lesser response to cisplatin. In summary, in a clinically relevant model of cisplatin-induced AKI in mice with cancer, (1) CD4 −/− mice were not protected against AKI; (2) ERK, p38, CXCL1, and TNF-α, known mediators of AKI, and interstitial fibrosis were increased in CD4 −/− kidneys; and (3) CD4 −/− mice had faster tumor growth and an impaired therapeutic effect of cisplatin on the tumors. The data warns against the use of CD4 T cell inhibition to attenuate cisplatin-induced AKI in patients with cancer. Key message: [ABSTRACT FROM AUTHOR]

Macrophages represent an important component of the tumor microenvironment and play a complex role in cancer progression. These cells are characterized by a high degree of plasticity, and they alter their phenotype in response to local environmental cues. Whereas the M1/M2 classification of macrophages has been widely used, the complexity of macrophage phenotypes has not been well studied, particularly in lung cancer. In this study we employed an orthotopic immunocompetent model of lung adenocarcinoma in which murine lung cancer cells are directly implanted into the left lobe of syngeneic mice. Using multimarker flow cytometry, we defined and recovered several distinct populations of monocytes/macrophages from tumors at different stages of progression. We used RNA-seq transcriptional profiling to define distinct features of each population and determine how they change during tumor progression. We defined an alveolar resident macrophage population that does not change in number and expresses multiple genes related to lipid metabolism and lipid signaling. We also defined a population of tumor-associated macrophages that increase dramatically with tumor and selectively expresses a panel of chemokine genes. A third population, which resembles tumor-associated monocytes, expresses a large number of genes involved in matrix remodeling. By correlating transcriptional profiles with clinically prognostic genes, we show that specific monocyte/macrophage populations are enriched in genes that predict outcomes in lung adenocarcinoma, implicating these subpopulations as critical determinants of patient survival. Our data underscore the complexity of monocytes/macrophages in the tumor microenvironment, and they suggest that distinct populations play specific roles in tumor progression. [ABSTRACT FROM AUTHOR]

Finding the minimal set of gene functions needed to sustain life is of both fundamental and practical importance. Minimal gene lists have been proposed by using comparative genomics-based core proteome definitions. A definition of a core proteome that is supported by empirical data, is understood at the systems-level, and provides a basis for computing essential cell functions is lacking. Here, we use a systems biology-based genome-scale model of metabolism and expression to define a functional core proteome consisting of 356 gene products, accounting for 44% of the Escherichia coli proteome by mass based on proteomics data. This systems biology core proteome includes 212 genes not found in previous comparative genomics- based core proteome definitions, accounts for 65% of known essential genes in E. coli, and has 78% gene function overlap with minimal genomes (Buchnera aphidicola andMycoplasma genitalium). Based on transcriptomics data across environmental and genetic backgrounds, the systems biology core proteome is significantly enriched in nondifferentially expressed genes and depleted in differentially expressed genes. Compared with the noncore, core gene expression levels are also similar across genetic backgrounds (two times higher Spearman rank correlation) and exhibit significantly more complex transcriptional and posttranscriptional regulatory features (40% more transcription start sites per gene, 22% longer 5'UTR). Thus, genome-scale systems biology approaches rigorously identify a functional core proteome needed to support growth. This framework, validated by using high-throughput datasets, facilitates a mechanistic understanding of systems-level core proteome function through in silico models; it de facto defines a paleome. [ABSTRACT FROM AUTHOR]

Unmanned aerial vehicles (UAVs) have been widely used in intelligence gathering, psychological operations, laser designation, range finding, and communication. In this paper, the design of a fixed-wing UAV is presented. A target detection and localization method was proposed for the developed UAV. The hardware construction, along with the selection of necessary components, is introduced here. To facilitate modular code development and integration of control laws with simulation and hardware, a hardware-in-the-loop simulator was proposed. The flight control law was developed and tested using the hardware-in-the-loop simulator. WiFi was used for monitoring the state variables of the aircraft. Simulation and experimental results demonstrate the performance of the developed system. [ABSTRACT FROM AUTHOR]

This work addresses the problem of localizing a ground target observed by multiple heterogeneous unmanned vehicles. Specifically, the case of a team of unmanned aerial and ground vehicles is analyzed. Effective collaboration between unmanned aerial and ground vehicles can utilize the strengths of both platforms while mediating their individual weaknesses. In this research, a probabilistic framework is proposed to improve target localization accuracy by utilizing the epipolar geometry and inter-robot localization measurements. A virtual simulation environment is implemented to fully test the proposed methods. Hardware experiments are carried out to validate the proposed methods. [ABSTRACT FROM PUBLISHER]

This work describes a 3D, paper-based assay that can isolate sub-populations of cells based on their invasiveness (i.e., distance migrated in a hydrogel) in a gradient of concentration of oxygen (O 2 ). Layers of paper impregnated with a cell-compatible hydrogel are stacked and placed in a plastic holder to form the invasion assay. In most assays, the stack comprises a single layer of paper containing mammalian cells suspended in a hydrogel, sandwiched between multiple layers of paper containing only hydrogel. Cells in the stack consume and produce small molecules; these molecules diffuse throughout the stack to generate gradients in the stack, and between the stack and the bulk culture medium. Placing the cell-containing layer in different positions of the stack, or modifying the permeability of the holder to oxygen or proteins, alters the profile of the gradients within the stack. Physically separating the layers after culture isolates sub-populations of cells that migrated different distances, and enables their subsequent analysis or culture. Using this system, three independent cell lines derived from A549 cancer cells are shown to produce distinguishable migration behavior in a gradient of oxygen. This result is the first experimental demonstration that oxygen acts as a chemoattractant for cancer cells. [ABSTRACT FROM AUTHOR]

Misexpression of developmental transcription factors occurs often in human cancers, where embryonic programs may be reinstated in a context that promotes or sustains malignant development. In this study, we report the involvement of the kidney development transcription factor Six2 in the metastatic progression of human breast cancer. We found that Six2 promoted breast cancer metastasis by a novel mechanism involving both transcriptional and epigenetic regulation of E-cadherin. Downregulation of E-cadherin by Six2 was necessary for its ability to increase soft agar growth and in vivo metastasis in an immunocompetent mouse model of breast cancer. Mechanistic investigations showed that Six2 represses E-cadherin expression by upregulating Zeb2, in part, through a microRNA-mediated mechanism and by stimulating promoter methylation of the E-cadherin gene (Cdh1). Clinically, SIX2 expression correlated inversely with CDH1 expression in human breast cancer specimens, corroborating the disease relevance of their interaction. Our findings establish Six2 as a regulator of metastasis in human breast cancers and demonstrate an epigenetic function for SIX family transcription factors in metastatic progression through the regulation of E-cadherin. [ABSTRACT FROM AUTHOR]

Navigation in a GPS-denied environment is an essential requirement for increased robotics autonomy. While this is in some sense solved for a single robot, the next challenge is to design algorithms for a team of robots to be able to map and navigate efficiently. The key requirement for achieving this team autonomy is to provide the robots with a collaborative ability to accurately map an environment. This problem is referred to as cooperative simultaneous localization and mapping (SLAM). In this research, the mapping process is extended to multiple robots with a novel occupancy grid map fusion algorithm. Map fusion is achieved by transforming individual maps into the Hough space where they are represented in an abstract form. Properties of the Hough transform are used to find the common regions in the maps, which are then used to calculate the unknown transformation between the maps. Results are shown from tests performed on benchmark datasets and real-world experiments with multiple robotic platforms. [ABSTRACT FROM AUTHOR]

Abstract: Service robotics is an emerging application area for human-centered technologies. The rise of household and personal assistance robots forecasts a human–robot collaborative society. One of the robotics community’s major task is to streamline development trends, work on the harmonization of taxonomies and ontologies, along with the standardization of terms, interfaces and technologies. It is important to keep the scientific progress and public understanding synchronous, through efficient outreach and education. These efforts support the collaboration among research groups, and lead to widely accepted standards, beneficial for both manufacturers and users. This article describes the necessity of developing robotics ontologies and standards focusing on the past and current research efforts. In addition, the paper proposes a roadmap for service robotics ontology development. The IEEE Robotics & Automation Society is sponsoring the working group Ontologies for Robotics and Automation. The efforts of the Working group are presented here, aiming to connect the cutting edge technology with the users of these services—the general public. [Copyright &y& Elsevier]