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Guanidine- and thiourea-based complexes have been the subject of extensive study due to their wide range of potential applications, including but not limited to anti-cancer drugs, ion transporters, and sensors. Building upon previous work done in this group, we aimed to demonstrate a new series of organometallic complexes based on functionally diverse guanidine and thiourea ligands. Herein, the synthesis and characterization of new platinum, rhodium, and cobalt complexes is presented. While most of these complexes conformed to properties and behaviours in line with previous work, one complex based on a Pt(II) and guanidine derivative exhibited unusual supramolecular properties, demonstrating a larger self-assembled dimer consisting of six Pt(II) cations.

Background: Ustekinumab, a human immunoglobulin G1 monoclonal antibody that binds to and inhibits interleukin (IL)-12/IL-23, is indicated for multiple immune-mediated diseases. Ustekinumab is actively transported across the placenta and theoretically could impact pregnancy outcomes. Limited data on pregnancy outcomes with ustekinumab exposure are available. Aim: To assess pregnancy outcomes in patients exposed to ustekinumab during pregnancy. Methods: Cumulative data on medically confirmed ustekinumab-exposed pregnancies from the manufacturer's Global Safety Database were summarised. Descriptive data for pregnancy outcomes were presented overall and by patient subgroups. Results: As of 31 August 2020, 408 medically confirmed, prospective, maternal ustekinumab-exposed pregnancies with reported outcomes were identified. The mean maternal age was 31 years. Of the 420 pregnancy outcomes (including 4 sets of twins),a,b 340 (81%) were live births, 51 (12.1%) spontaneous abortions, 25 (6%) elective/induced abortions, 3 (0.7%) stillbirths and 1 (0.2%) ongoing pregnancy with foetal congenital anomaly (CA). Among 340 live births, 33 (9.7%) were born pre-term. The rate of major CAs was similar by indication (Crohn's disease vs psoriasis), ustekinumab dose (45 mg vs 90 mg) and timing and duration of maternal exposure to ustekinumab. Prospective outcomes of pregnancies with paternal periconceptional ustekinumab exposure (n = 87) included 92% live births (1.2% major CA), 5.7% spontaneous abortions and 2.3% elective/induced abortions. Conclusions: Rates of adverse pregnancy outcomes or CAs with ustekinumab exposure were consistent with rates reported for the US general population and do not suggest a higher risk associated with maternal or paternal exposure to ustekinumab.

An indoor visible light positioning system using the received signal strength intensity method and the trilateration technique with user mobility support is proposed for applications, e.g. healthcare. Accurate position information of medical staffs and patients is required for data transmission, tracking, navigation, etc. Seamless data transmission while user is on the move has been conceptualized considering the optical network formed by photosensor (light emitting diode)-based transmitters. Efficiency of these services depends on the position accuracy. To investigate factors contributing to higher position errors in a practical environment, the proposed system is evaluated. Evaluation is done through simulation and experiment for different channel conditions, and the receiver rotation due to user mobility. Simulation results show an average two-dimensional position error of 0.32 m in a channel with a strong background light illumination level of − 60 dBm. Experimental results show that the mean position error is 0.7 m in a normal daytime indoor light condition.

PDF - 1128K, Figure S1. Knockdown of CDK7 and CDK9 can inhibit RNAP II CTD P-Ser2 and P-Ser5. Figure S2. LY2857785 and flavopiridol inhibit MCL-1, XIAP protein expression and induce CASP-3 and cleaved PARP in AML cell MV-4-11. Table S1. LY2857785 inhibits solid tumor cell proliferation and induces apoptosis. Table S2. 261 probsets gene signature in sens and res cell lines. Table S3. LY2857785 inhibits proliferation of normal human hematopoietic cells in vitro.

XLSX - 54K, Table S2. 261 probsets gene signature in sens and res cell lines in Excel format.

DNA-dependent RNA polymerase II (RNAP II) largest subunit RPB1 C-terminal domain (CTD) kinases, including CDK9, are serine/threonine kinases known to regulate transcriptional initiation and elongation by phosphorylating Ser 2, 5, and 7 residues on CTD. Given the reported dysregulation of these kinases in some cancers, we asked whether inhibiting CDK9 may induce stress response and preferentially kill tumor cells. Herein, we describe a potent CDK9 inhibitor, LY2857785, that significantly reduces RNAP II CTD phosphorylation and dramatically decreases MCL1 protein levels to result in apoptosis in a variety of leukemia and solid tumor cell lines. This molecule inhibits the growth of a broad panel of cancer cell lines, and is particularly efficacious in leukemia cells, including orthotopic leukemia preclinical models as well as in ex vivo acute myeloid leukemia and chronic lymphocytic leukemia patient tumor samples. Thus, inhibition of CDK9 may represent an interesting approach as a cancer therapeutic target, especially in hematologic malignancies. Mol Cancer Ther; 13(6); 1442–56. ©2014 AACR.

Urban dwellers’ use of public and private green spaces may have changed during the early years of the Covid-19 pandemic due to movement restriction. A survey was deployed in Brisbane and Sydney, Australia 1 year after the start of Covid-19 restrictions (April 2021) to explore relationships of mental health and wellbeing to different patterns of private yard versus public green space visitation. More frequent yard use during the initial year of Covid-19 was correlated with lower stress, depression, and anxiety and higher wellbeing. However, greater duration of yard visits (week prior to survey) was associated with higher stress, anxiety, and depression scores, potentially because individuals may seek to use nature spaces immediately available for emotional regulation during difficult times. The results highlight the importance of yards for mental health and wellbeing during the Covid-19 pandemic and that relationships between nature interaction and mental health may be context and timeframe dependent.

To check the accuracy of column-average dry air CO2 mole fractions (XCO2) retrieved from Orbiting Carbon Observatory (OCO-2) data, a similar quantity has been measured from the Multi-functional Fiber Laser Lidar (MFLL) aboard aircraft flying underneath OCO-2 as part of the Atmospheric Carbon and Transport (ACT) – America flight campaigns. Here we do a lagged correlation analysis of these MFLL–OCO-2 column CO2 differences and find that their correlation spectrum falls off rapidly at along-track separation distances under 10 km, with a correlation length scale of about 10 km, and less rapidly at longer separation distances, with a correlation length scale of about 20 km. The OCO-2 satellite takes many CO2 measurements with small (∼3 km2) fields of view (FOVs) in a thin ( km wide) swath running parallel to its orbit: up to 24 separate FOVs may be obtained per second (across a ∼6.75 km distance on the ground), though clouds, aerosols, and other factors cause considerable data dropout. Errors in the CO2 retrieval method have long been thought to be correlated at these fine scales, and methods to account for these when assimilating these data into top-down atmospheric CO2 flux inversions have been developed. A common approach has been to average the data at coarser scales (e.g., in 10 s long bins) along-track, then assign an uncertainty to the averaged value that accounts for the error correlations. Here we outline the methods used up to now for computing these 10 s averages and their uncertainties, including the constant-correlation-with-distance error model that was used to summarize the OCO-2 version 9 XCO2 retrievals as part of the OCO-2 flux inversion model intercomparison project. We then derive a new one-dimensional error model using correlations that decay exponentially with separation distance, apply this model to the OCO-2 data using the correlation length scales derived from the MFLL–OCO-2 differences, and compare the results (for both the average and its uncertainty) to those given by the current constant correlation error model. To implement this new model, the data are averaged first across 2 s spans to collapse the cross-track distribution of the real data onto the 1-D path assumed by the new model. Considering correlated errors can cause the average value to fall outside the range of the values averaged; two strategies for preventing this are presented. The correlation lengths over the ocean, which the land-based MFLL data do not clarify, are assumed to be twice those over the land. The new correlation model gives 10 s XCO2 averages that are only a few tenths of 1 ppm different from the constant correlation model. Over land, the uncertainties in the mean are also similar, suggesting that the +0.3 constant correlation coefficient currently used in the model there is accurate. Over the oceans, the twice-the-land correlation lengths that we assume here result in a significantly lower uncertainty on the mean than the +0.6 constant correlation currently gives – measurements similar to the MFLL ones are needed over the oceans to do better. Finally, we show how our 1-D exponential error correlation model may be used to account for correlations in inversion methods that choose to assimilate each XCO2 retrieval individually and also to account for correlations between separate 10 s averages when these are assimilated instead.

Many epithelial compartments undergo constitutive renewal in homeostasis but activate unique regenerative responses following injury. The clear corneal epithelium is crucial for vision and is renewed from limbal stem cells (LSCs). Using single-cell RNA sequencing, we profiled the mouse corneal epithelium in homeostasis, aging, diabetes, and dry eye disease (DED), where tear deficiency predisposes the cornea to recurrent injury. In homeostasis, we capture the transcriptional states that accomplish continuous tissue turnover. We leverage our dataset to identify candidate genes and gene networks that characterize key stages across homeostatic renewal, including markers for LSCs. In aging and diabetes, there were only mild changes with

A survey was conduct to analyze the usage situation of post-exposure prophylaxis(PEP) and related factors among men who have sex with men(MSM) in 6 cities of Shandong Province. Total of 2 620 subjects, the use ratio was 2.98% (78/2 620). Compared with age≤24 years,monthly income5 000 yuan,non-commercial sex, non-DU,non-STD,role for being insert in the anal intercourse,MSM was more likely to use PEP with age≥45 years(对山东省某6个地市招募的2 620名男男性行为者（MSM）进行调查，分析MSM人群HIV暴露后预防（PEP）的使用状况及相关影响因素。MSM人群整体PEP使用比例为2.98%（78/2 620），不同年龄、月收入水平、商业性行为发生状况、吸食新型毒品状况、性病患病状况、性行为角色的MSM人群其PEP使用比例差异具有统计学意义（

Earth is undergoing a devastating extinction crisis caused by human impacts on nature, but only a fraction of society is strongly concerned and acting on the crisis. Understanding what determines people's concern for nature, environmental movement activism, and personal conservation behavior is fundamental if sustainability is to be achieved. Despite its potential importance, the study of the genetic contribution to concern for nature and proenvironmental behaviors has been neglected. Using a twin data set (N = 2312), we show moderate heritability (30%–40%) for concern for nature, environmental movement activism, and personal conservation behavior and high genetic correlations between them (.6–.7), suggesting a partially shared genetic basis. Our results shed light on the individual variation in sustainable behaviors, highlighting the importance of understanding both the environmental and genetic components in the pursuit of sustainability.

Residential yards are a significant component of urban socio‐ecological systems; residential land covers 11% of the United States and is often the dominant land use within urban areas. Residential yards also play an important role in the sustainability of urban socio‐ecological systems, affecting biogeochemical cycles, water and the climate via individual‐ and household‐level behaviours. Spatial contagion has been observed in yard vegetation in several cities, potentially due to social norms that compel neighbours to emulate or conform to specific aesthetic qualities or management regimes. Residents may feel obliged to mow their front yards or prune their trees, creating patterns of spatial autocorrelation in residential neighbourhoods. In this study, we examined the spatial autocorrelation of several yard vegetation characteristics in both front and backyards in Boston, MA, USA. Our study area included 1,027 Census block groups (sub‐neighbourhood areas) and 175,576 parcels with matched front‐backyard pairings (n = 351,152 yards in total) across Boston's metropolitan area. We spatially defined ‘neighbours’ in five ways to better account for the potentially variable nature of how conformity or contagion manifests in empirical terms. We anticipated front yards to have stronger spatial autocorrelation due to the more publicly visible nature of these green spaces. We found positive and significant spatial autocorrelation in all measured vegetation variables, in both front and backyards. Unexpectedly, spatial autocorrelation tended to be higher in backyards for tree canopy variables but higher in front yards for turf grass cover. Among block groups, different socio‐economic variables, such as median household income, predicted spatial autocorrelation of vegetation characteristics. Our results were sensitive to how neighbours were spatially defined. Our results further underscore the importance of backyards as critical areas for sustaining an urban tree canopy, and show that spatial patterns vary across different social groups. The importance of ‘neighbour’ definition indicates opportunities to think carefully about the mechanisms driving spatial autocorrelation and the scales at which patterns develop. The identification of these mechanisms will have important implications for scales of policy and implementation for urban and suburban greening. A free Plain Language Summary can be found within the Supporting Information of this article.

High-fidelity and large-scale hydrological models are increasingly used to investigate the impacts of human activities and climate change on water availability and quality. However, the detailed representations of real-world systems and processes contained in these models inevitably lead to prohibitively high execution times, ranging from minutes to days. Such models become computationally prohibitive or even infeasible when large iterative model simulations are involved. In this study, we propose a generic two-level (i.e., watershed- and subbasin-level) model parallelization schema to reduce the run time of computationally expensive model applications through a combination of model spatial decomposition and the graph-parallel Pregel algorithm. Taking the Soil and Water Assessment Tool (SWAT) as an example, we implemented a generic tool named GP-SWAT, enabling watershed-level and subbasin-level model parallelization on a Spark computer cluster. We then evaluated GP-SWAT in two sets of experiments to demonstrate the ability of GP-SWAT to accelerate single and iterative model simulations and to run in different environments. In each test set, GP-SWAT was applied for the parallel simulation of four synthetic hydrological models with different input/output (I/O) burdens. The single-model parallelization results showed that GP-SWAT can obtain a 2.3–5.8-times speedup. For multiple simulations with subbasin-level parallelization, GP-SWAT yielded a remarkable speedup of 8.34–27.03 times. In both cases, the speedup ratios increased with an increasing computation burden. The experimental results indicate that GP-SWAT can effectively solve the high-computational-demand problems of the SWAT model. In addition, as a scalable and flexible tool, it can be run in diverse environments, from a commodity computer running the Microsoft Windows operating system to a Spark cluster consisting of a large number of computational nodes. Moreover, it is possible to apply this generic tool to other subbasin-based hydrological models or even acyclic models in other domains to alleviate I/O demands and to optimize model computational performance.

Nature-Based Solutions (NBSs) promise a future where natural, human and technical elements help solving many of the issues plaguing cities. Pollution reduction, increased human wellbeing and climate change adaptation are only some of the challenges targeted by NBSs. However, under the warming climate affecting many of the world’s cities, most of modern NBSs will be highly impacted by the same climate factors they hope to mitigate. As in the case of extreme temperatures or altered water availability, these factors can impact and cause the failure in the organisms, technical elements and governance structures that NBSs rely upon, thus decreasing performance, reliability and sustainability of these solutions. In this commentary we propose critical considerations related to designing, building and managing “climate-ready” NBSs – defined as local integrated solutions able to cope with or adapt to climate change. We do so by highlighting examples in heat- and drought-stricken areas across Australian cities as they sit at the global forefront of a hotter world. We discuss in detail i) tolerance and adaptability of NBS to new climates, ii) NBS design for weather extremes and climate-safety margins, iii) NBS trialing and prototyping, and iv) planning for “climate-ready” NBSs. In doing so, we highlight caveats and limitations to propose an implementation framework to make NBSs not only work, but succeed, in a hotter urban world; one that sees 50 °C as a critical limit to sustain urban life and nature.

1. Due to seasonal breeding, geese breeds from Southern China have low egg yield. The genetic makeup underlying performance of local breeds is largely unknown, and few studies have investigated this problem. This study integrated 21 newly generated and 50 publicly existing RNA-seq libraries, representing the hypothalamus, pituitary and testis, to identify candidate genes and importantly related pathways associated with seasonal breeding in male Lion-Head geese.2. In total, 19, 119 and 302 differentially expressed genes (DEGs) were detected in the hypothalamus, pituitary and testis, respectively, of male Lion-Head geese between non-breeding and breeding periods. These genes were significantly involved in the neuropeptide signalling pathway, gland development, neuroactive ligand-receptor interaction, JAK-STAT signalling pathway, cAMP signalling pathway, PI3K-Akt signalling pathway and Foxo signalling pathway.3. By integrating another 50 RNA-seq samples 4, 18 and 40 promising DEGs were confirmed in hypothalamus, pituitary and testis, respectively.4.

High-resolution MRI affords unique image contrasts to non-destructively probe the tissue microstructure, validation of MRI findings with conventional histology is essential to better understand the MRI contrasts. However, the dramatic difference in the spatial resolution and image contrast of these two techniques impede the accurate comparison between MRI metrics and traditional histology. To better validate various MRI metrics, we acquired whole mouse brain multi-gradient recalled-echo (MGRE) and multi-shell diffusion MRI datasets at 25 μm isotropic resolution. The recently developed Allen Mouse Brain Common Coordinate Framework (CCFv3) provides opportunities to integrate multimodal and multiscale datasets of the whole mouse brain in a common 3D space. The T2*, quantitative susceptibility mapping (QSM), diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) parameters were compared with both serial two-photon (STP) tomography images and 3D Nissl staining images in CCFv3 at the same spatial resolution. The correlation between MRI and Nissl staining strongly depends on different metrics and different regions of the brain. Integrating different imaging modalities to the same space may substantially improve our understanding of the complexity of the brain at different scales.

Legal Aid NSW civil lawyers provide community outreach clinics and civil legal assistance to address the civil legal needs of participants in High Intensity Program Units (HIPUs) in prisons in New ...

With the continuous development of smart grids, communication networks carry more and more power services, and at the same time, they are also facing more and more security issues. For example, some malicious software usually uses encryption technology or tunnel technology to bypass firewalls, intrusion detection systems, etc., thereby posing a serious threat to the information security of smart grids. At present, the classification of network traffic mainly depends on the correct extraction of network protocol characteristics. However, the process of extracting network features by some traditional methods is time-consuming and overly dependent on experience. In order to solve the problem of accurate classification of power network traffic, this paper proposes a method of convolutional neural network based on genetic algorithm optimization (GACNN) and data statistical analysis. This method can simultaneously extract the time characteristics between different packet groups and the spatial characteristics in the same packet group. Therefore, it greatly saves manpower and gets rid of the dependence on experience value. The proposed method has been tested and verified on the UNSW-NB15 dataset and the real dataset collected by the power company. The results show that the proposed method can correctly classify abnormal network flows and is much better than traditional machine learning methods. In large-scale real network flow scenarios, the detection rate of the proposed method exceeds 97%, while the traditional method is generally less than 90%.

We point out four mistakes in the symmetry classification of vibrational modes of the CrI3 monolayer at the Γ point in Webster et al.'s paper [PCCP, 2018, 20, 23546]. The discrepancy of Raman activity of A2g mode as well as the misidentification of two optical modes A1u and A2u have been clarified.

Gardening has the potential to improve health and wellbeing, especially during crises. Using an international survey of gardeners (n=3743), this study aimed to understand everyday gardening experiences, perspectives and attitudes during early stages of the COVID-19 pandemic in 2020. Our qualitative reflexive thematic and sentiment analyses show that during the first months of the COVID-19 pandemic, gardening seemed to create a safe and positive space where people could socially connect, learn and be creative. Participants had more time to garden during the pandemic, which led to enhanced connections with family members and neighbours, and the ability to spend time in a safe outdoor environment. More time gardening allowed for innovative and new gardening practices that provided enjoyment for many participants. However, our research also highlighted barriers to gardening (e.g. lack of access to garden spaces and materials). Our results illustrate the multiple benefits of gardening apparent during COVID-19 through a lens of the social-ecological model of health.

Obesity is recognized as a significant risk factor for Alzheimer’s disease (AD). Studies have supported the notion that obesity accelerates AD-related pathophysiology in mouse models of AD. The majority of studies, to date, have focused on the use of early-onset AD models. Here, we evaluate the impact of genetic risk factors on late-onset AD (LOAD) in mice fed with a high fat/high sugar diet (HFD). We focused on three mouse models created through the IU/JAX/PITT MODEL-AD Center. These included a combined risk model with APOE4 and a variant in triggering receptor expressed on myeloid cells 2 (Trem2R47H). We have termed this model, LOAD1. Additional variants including the M28L variant in phospholipase C Gamma 2 (Plcg2M28L) and the 677C > T variant in methylenetetrahydrofolate reductase (Mthfr677C >T) were engineered by CRISPR onto LOAD1 to generate LOAD1.Plcg2M28L and LOAD1.Mthfr677C >T. At 2 months of age, animals were placed on an HFD that induces obesity or a control diet (CD), until 12 months of age. Throughout the study, blood was collected to assess the levels of cholesterol and glucose. Positron emission tomography/computed tomography (PET/CT) was completed prior to sacrifice to image for glucose utilization and brain perfusion. After the completion of the study, blood and brains were collected for analysis. As expected, animals fed a HFD, showed a significant increase in body weight compared to those fed a CD. Glucose increased as a function of HFD in females only with cholesterol increasing in both sexes. Interestingly, LOAD1.Plcg2M28L demonstrated an increase in microglia density and alterations in regional brain glucose and perfusion on HFD. These changes were not observed in LOAD1 or LOAD1.Mthfr677C >T animals fed with HFD. Furthermore, LOAD1.Plcg2M28L but not LOAD1.Mthfr677C >T or LOAD1 animals showed transcriptomics correlations with human AD modules. Our results show that HFD affects the brain in a genotype-specific manner. Further insight into this process may have significant implications for the development of lifestyle interventions for the treatment of AD.

OBJECTIVE: To describe the distribution characteristics of inflammatory bowel disease among permanent residents in Yinzhou District, Ningbo City, and to understand the disease burden and development trend of inflammatory bowel disease in this area. METHODS: Using the retrospective cohort design, we collected the registration information of all permanent residents in the residents' health files of the Yinzhou Regional Health Information Platform from 2010 to 2020, and used electronic medical records to follow up their inflammatory bowel disease visits. A one-year wash-out period was set, and the patients who were diagnosed with the primary diagnosis for the first time after one year of registration were re-garded as new cases. The incidence density and 95% confidence interval (CI) of inflammatory bowel disease were estimated by Poisson distribution. RESULTS: From 2011 to 2020, a total of 1 496 427 permanent residents in Yinzhou District were included, of which 729 996 were male (48.78%). The total follow-up person-years were 8 081 030.82, and the median follow-up person-years were 5.41 [interquartile range (IQR): 5.29]. During the study period, there were 1 217 new cases of inflammatory bowel disease, of which males (624 cases, 51.27%) were more than females (593 cases, 48.73%). The total incidence density was 15.06/100 000 person-years (95%CI: 14.23, 15.93). Among all new cases, there were 1 106 cases (90.88%) of ulcerative colitis, with an incidence density of 13.69 per 100 000 person-years (95%CI: 12.89, 14.52); 70 cases (5.75%) of Crohn's disease, with an incidence density of 0.87 per 100 000 person-years (95%CI: 0.68, 1.09); and 41 cases (3.37%) of indeterminate colitis, with an incidence density of 0.51 per 100 000 person-years (95%CI: 0.36, 0.69). The median age of onset of ulcerative colitis was 50.82 years old (IQR: 18.77), with the highest proportion (15.01%) in the 45-49 years group. The incidence density of ulcerative colitis gradually increased with age, reaching a relatively high level in the 45-49 years group (20.53/100 000 person-years; 95%CI: 17.63, 23.78), followed by a slight increase. And the incidence density in the 65-69 years group was the highest (25.44/100 000 person-years; 95%CI: 20.85, 30.75), with a rapid decrease in the 75-79 years group. The median age of onset of Crohn's disease was 44.34 years (IQR: 33.41), with the highest proportion (12.86%) in the 25-29 years group. Due to the small number of new cases of Crohn's disease, the age distribution fluctuated greatly, with peaks both in young and old people. From 2011 to 2020, the incidence density of inflammatory bowel disease in Yinzhou District was at a low level from 2011 to 2013, and showed a rapid upward trend from 2014 to 2016, reaching a peak of 24.62 per 100 000 person-years in 2016 (95%CI: 21.31, 28.30), and slightly decreased in 2017—2020. CONCLUSION: The incidence density of inflammatory bowel disease in Yinzhou District from 2011 to 2020 was at a relatively high level, and medical institutions and health departments need to pay attention to the burden of disease caused by it.