Palladium-catalyzed difluoromethylation of heteroaryl chlorides, bromides and iodides.

A palladium-catalyzed difluoromethylation of a series of heteroaryl chlorides, bromides and iodides under mild conditions is described. A wide range of heteroaryl halides such as pyridyl, pyrimidyl, pyrazyl, funanyl, thienyl, pyazolyl, imidazolyl, thiazolyl, and oxazolyl halides were efficiently difluoromethylated, thus providing medicinal chemists an alternative choice for the preparation of drug candidates with the difluoromethylated heteroarene unit

The effectiveness and safety of parathyroid hormone in fracture healing: A meta-analysis

The very large economic and social burdens of fracture-related complications make rapid fracture healing a major public health goal. The role of parathyroid hormone (PTH) in treating osteoporosis is generally accepted, but the effect of PTH on fracture healing is controversial. This meta-analysis was designed to investigate the efficacy and safety of PTH in fracture healing. The EMBASE, PubMed, and Cochrane Library databases were systematically searched from the inception dates to April 26, 2018. The primary randomized clinical trials comparing PTH treatment for fracture healing with placebo or no treatment were identified. We did not gain additional information by contacting the authors of the primary studies. Two reviewers independently extracted the data and evaluated study quality. This meta-analysis was executed to determine the odds ratio, mean difference, standardized mean difference, and 95% confidence intervals with random-effects models. In total, 8 randomized trials including 524 patients met the inclusion criteria. There were significant differences in fracture healing time, pain relief and function improvement. There were no significant differences in the fracture healing rate or adverse events, including light-headedness, hypercalcemia, nausea, sweating and headache, except for slight bruising at the injection site. We determined that the effectiveness and safety of PTH in fracture healing is reasonably well established and credible

The Correlation Between Body Mass Index and Computed Tomography Angiography on Vascular Positioning in Anterolateral Thigh Flap Transplantation

Objective: This work aimed to investigate the correlation between body mass index (BMI) and computed tomography angiography (CTA) in the vascular positioning of anterolateral thigh perforator flap (ALT) and to discuss the influence of CTA on the vascular positioning of the ALT by taking BMI as a variable. Methods: A total of 117 patients who admitted to our hospital (Wuxi Ninth People’s Hospital) from January 2017 to May 2019, hospitalized due to limb injury and needed ALT transplantation were collected in this work. According to the BMI, the patients were divided into group A (BMI < 18.5) with 18 cases, group B (18.5 ≤ BMI < 24) with 56 cases, and group C (BMI ≥ 24) with 43 cases. CTA was used to locate the perforator vessels in anterolateral thigh (ALT) flap of the three groups. All surgical and CTA data were collected. Results: There was a significant positive correlation between BMI and CTA positioning (P < 0.05). Conclusion: The larger the BMI, the more accurate the CTA positioning. When the BMI was not less than 18.5, CTA positioning should be the most accurate

Positioning Dispositions in Initial Teacher Education: An Action Research Approach

In spite of debate, ambiguity, and tension around teacher dispositions, in the past over two decades, the place of dispositions in initial teacher education (ITE) has been widely supported among policy makers and researchers. Specifically, debate on whether dispositions are teachable has largely given way to action to foster dispositions. Adopting a two-cycle participatory action research design, this study explored ways to teach the first-year teacher candidates’ dispositions in an early childhood ITE programme in New Zealand. The intervention included eight focus dispositions and corresponding strategies to teach each focus disposition. Data collection methods included student self-assessment surveys, individual and focus group interviews with students and teaching staff, team meetings, and a variety of pedagogical documentation. Ethnographic content analysis generated three themes: legitimacy of the intervention, experiential orientation of the intervention, and effect of the intervention. The study exemplifies how dispositions intervention can be incorporated in ITE programmes

A Locality-based Neural Solver for Optical Motion Capture

We present a novel locality-based learning method for cleaning and solving optical motion capture data. Given noisy marker data, we propose a new heterogeneous graph neural network which treats markers and joints as different types of nodes, and uses graph convolution operations to extract the local features of markers and joints and transform them to clean motions. To deal with anomaly markers (e.g. occluded or with big tracking errors), the key insight is that a marker's motion shows strong correlations with the motions of its immediate neighboring markers but less so with other markers, a.k.a. locality, which enables us to efficiently fill missing markers (e.g. due to occlusion). Additionally, we also identify marker outliers due to tracking errors by investigating their acceleration profiles. Finally, we propose a training regime based on representation learning and data augmentation, by training the model on data with masking. The masking schemes aim to mimic the occluded and noisy markers often observed in the real data. Finally, we show that our method achieves high accuracy on multiple metrics across various datasets. Extensive comparison shows our method outperforms state-of-the-art methods in terms of prediction accuracy of occluded marker position error by approximately 20%, which leads to a further error reduction on the reconstructed joint rotations and positions by 30%. The code and data for this paper are available at https://github.com/non-void/LocalMoCap.Comment: Siggraph Asia 2023 Conference Pape

Improving Negative-Prompt Inversion via Proximal Guidance

DDIM inversion has revealed the remarkable potential of real image editing within diffusion-based methods. However, the accuracy of DDIM reconstruction degrades as larger classifier-free guidance (CFG) scales being used for enhanced editing. Null-text inversion (NTI) optimizes null embeddings to align the reconstruction and inversion trajectories with larger CFG scales, enabling real image editing with cross-attention control. Negative-prompt inversion (NPI) further offers a training-free closed-form solution of NTI. However, it may introduce artifacts and is still constrained by DDIM reconstruction quality. To overcome these limitations, we propose Proximal Negative-Prompt Inversion (ProxNPI), extending the concepts of NTI and NPI. We enhance NPI with a regularization term and reconstruction guidance, which reduces artifacts while capitalizing on its training-free nature. Our method provides an efficient and straightforward approach, effectively addressing real image editing tasks with minimal computational overhead.Comment: Code at https://github.com/phymhan/prompt-to-promp

An assessment of aerosol‐cloud interactions in marine stratus clouds based on surface remote sensing

An assessment of aerosol-cloud interactions (ACI) from ground-based remote sensing under coastal stratiform clouds is presented. The assessment utilizes a long-term, high temporal resolution data set from the Atmospheric Radiation Measurement (ARM) Program deployment at Pt. Reyes, California, United States, in 2005 to provide statistically robust measures of ACI and to characterize the variability of the measures based on variability in environmental conditions and observational approaches. The average ACIN (= dlnNd/dlna, the change in cloud drop number concentration with aerosol concentration) is 0.48, within a physically plausible range of 0–1.0. Values vary between 0.18 and 0.69 with dependence on (1) the assumption of constant cloud liquid water path (LWP), (2) the relative value of cloud LWP, (3) methods for retrieving Nd, (4) aerosol size distribution, (5) updraft velocity, and (6) the scale and resolution of observations. The sensitivity of the local, diurnally averaged radiative forcing to this variability in ACIN values, assuming an aerosol perturbation of 500 c-3 relative to a background concentration of 100 cm-3, ranges betwee-4 and -9 W -2. Further characterization of ACI and its variability is required to reduce uncertainties in global radiative forcing estimates

Graphene quantum dots induce cascadic apoptosis via interaction with proteins associated with anti-oxidation after endocytosis by Trypanosoma brucei

Trypanosoma brucei, the pathogen causing African sleeping sickness (trypanosomiasis) in humans, causes debilitating diseases in many regions of the world, but mainly in African countries with tropical and subtropical climates. Enormous efforts have been devoted to controlling trypanosomiasis, including expanding vector control programs, searching for novel anti-trypanosomial agents, and developing vaccines, but with limited success. In this study, we systematically investigated the effect of graphene quantum dots (GQDs) on trypanosomal parasites and their underlying mechanisms. Ultrasmall-sized GQDs can be efficiently endocytosed by T. brucei and with no toxicity to mammalian-derived cells, triggering a cascade of apoptotic reactions, including mitochondrial disorder, intracellular reactive oxygen species (ROS) elevation, Ca2+ accumulation, DNA fragmentation, adenosine triphosphate (ATP) synthesis impairment, and cell cycle arrest. All of these were caused by the direct interaction between GQDs and the proteins associated with cell apoptosis and anti-oxidation responses, such as trypanothione reductase (TryR), a key protein in anti-oxidation. GQDs specifically inhibited the enzymatic activity of TryR, leading to a reduction in the antioxidant capacity and, ultimately, parasite apoptotic death. These data, for the first time, provide a basis for the exploration of GQDs in the development of anti-trypanosomials

Characterization of the Interaction between the Cohesin Subunits Rad21 and SA1/2

The cohesin complex is responsible for the fidelity of chromosomal segregation during mitosis. It consists of four core subunits, namely Rad21/Mcd1/Scc1, Smc1, Smc3, and one of the yeast Scc3 orthologs SA1 or SA2. Sister chromatid cohesion is generated during DNA replication and maintained until the onset of anaphase. Among the many proposed models of the cohesin complex, the ﾒcoreﾒ cohesin subunits Smc1, Smc3, and Rad21 are almost universally displayed as tripartite ring. However, other than its supportive role in the cohesin ring, little is known about the fourth core subunit SA1/SA2. To gain deeper insight into the function of SA1/SA2 in the cohesin complex, we have mapped the interactive regions of SA2 and Rad21 in vitro and ex vivo. Whereas SA2 interacts with Rad21 through a broad region (301ﾖ750 aa), Rad21 binds to SA proteins through two SA-binding motifs on Rad21, namely N-terminal (NT) and middle part (MP) SA-binding motif, located At 60-81 aa of the N-terminus and 383ﾖ392 aa of the MP of Rad21, respectively. The MP SA-binding motif is a 10 amino acid, a-helical motif. Deletion of these 10 amino acids or mutation of three conserved amino acids (L385, F389, and T390) in this ahelical motif significantly hinders Rad21 from physically interacting with SA1/2. Besides the MP SA-binding motif, the NT SAbinding motif is also important for SA1/2 interaction. Although mutations on both SA-binding motifs disrupt Rad21-SA1/2 interaction, they had no apparent effect on the Smc1-Smc3-Rad21 interaction. However, the Rad21-Rad21 dimerization was reduced by the mutations, indicating potential involvement of the two SA-binding motifs in the formation of the two-ring handcuff for chromosomal cohesion. Furthermore, mutant Rad21 proteins failed to significantly rescue precocious chromosome separation caused by depletion of endogenous Rad21 in mitotic cells, further indicating the physiological significance of the two SA-binding motifs of Rad21

Associations of HLA-DP Variants with Hepatitis B Virus Infection in Southern and Northern Han Chinese Populations: A Multicenter Case-Control Study

) locus has been reported to be associated with hepatitis B virus (HBV) infection in populations of Japan and Thailand. We aimed to examine whether the association can be replicated in Han Chinese populations. = 0.097∼0.697 and 0.198∼0.615 in northern Chinese population, respectively). loci were strongly associated with HBV infection in southern and northern Han Chinese populations, but not with HBV progression