Investigations into Capillary Forces and Capillary Rise in a Three-Finger Microgripper and a Plate: Numerical Simulations and Experimental Validation.

The assembly and position adjustment of micro-components have wide applications in micro-electromechanical systems, wafer packaging and biomedicine. However, current single-finger microgrippers only allow for the pickup and release of micro-components. In the present study, a three-finger capillary microgripper was developed to pick up, release and adjust the position of micro-components.

Evolution of myeloid-mediated immunotherapy resistance in prostate cancer.

Patients with advanced metastatic castration-resistant prostate cancer (mCRPC) are refractory to immune checkpoint inhibitors (ICIs), partly because there are immunosuppressive myeloid cells in tumours. However, the heterogeneity of myeloid cells has made them difficult to target, making blockade of the colony stimulating factor-1 receptor (CSF1R) clinically ineffective. Here we use single-cell profiling on patient biopsies across the disease continuum and find that a distinct population of tumour-associated macrophages with elevated levels of SPP1 transcripts (SPP1-TAMs) becomes enriched with the progression of prostate cancer to mCRPC.

Sialylated glycoproteins suppress immune cell killing by binding to Siglec-7 and Siglec-9 in prostate cancer.

Prostate cancer is the second leading cause of male cancer death in the U.S. Current immune checkpoint inhibitor-based immunotherapies have improved survival for many malignancies; however, they have failed to prolong survival for prostate cancer.

NAIR: Network Analysis of Immune Repertoire.

T cells represent a crucial component of the adaptive immune system and mediate anti-tumoral immunity as well as protection against infections, including respiratory viruses such as SARS-CoV-2. Next-generation sequencing of the T-cell receptors (TCRs) can be used to profile the T-cell repertoire. We developed a customized pipeline for Network Analysis of Immune Repertoire (NAIR) with advanced statistical methods to characterize and investigate changes in the landscape of TCR sequences.

A Predictive Model of Capillary Forces and Contact Diameters between Two Plates Based on Artificial Neural Network.

Many efforts have been devoted to the forecasting of the capillary force generated by capillary adsorption between solids, which is fundamental and essential in the fields of micro-object manipulation and particle wetting. In this paper, an artificial neural network (ANN) model optimized by a genetic algorithm (GA-ANN) was proposed to predict the capillary force and contact diameter of the liquid bridge between two plates. The mean square error () and correlation coefficient () were employed to evaluate the prediction accuracy of the GA-ANN model, theoretical solution method of the Young-Laplace equation and simulation approach based on the minimum energy method.

Circulating monocytes associated with anti-PD-1 resistance in human biliary cancer induce T cell paralysis.

Suppressive myeloid cells can contribute to immunotherapy resistance, but their role in response to checkpoint inhibition (CPI) in anti-PD-1 refractory cancers, such as biliary tract cancer (BTC), remains elusive. We use multiplexed single-cell transcriptomic and epitope sequencing to profile greater than 200,000 peripheral blood mononuclear cells from advanced BTC patients (n = 9) and matched healthy donors (n = 8). Following anti-PD-1 treatment, CD14 monocytes expressing high levels of immunosuppressive cytokines and chemotactic molecules (CD14) increase in the circulation of patients with BTC tumors that are CPI resistant.

Novel Ensemble Feature Selection Approach and Application in Repertoire Sequencing Data.

The T and B cell repertoire make up the adaptive immune system and is mainly generated through somatic V(D)J gene recombination. Thus, the VJ gene usage may be a potential prognostic or predictive biomarker. However, analysis of the adaptive immune system is challenging due to the heterogeneity of the clonotypes that make up the repertoire.

Flexible Magnetic Micropartners for Micromanipulation at Interfaces.

Microrobots working at liquid surfaces have immense potential for micromanipulation in tight and enclosed spaces, whereas constructing agile and functional microrobots with simple structures at liquid surfaces is a great challenge. Herein, a pair of magnetic circular microdisks working as partners at ethylene glycol (EG) surfaces are proposed in order to accomplish flexible locomotion and in situ micromanipulation tasks. The microdisks can be controlled to connect and separate by modulating the orientation of the applied magnetic field.

Capillary Forces between Concave Gripper and Spherical Particle for Micro-Objects Gripping.

The capillary action between two solid surfaces has drawn significant attention in micro-objects manipulation. The axisymmetric capillary bridges and capillary forces between a spherical concave gripper and a spherical particle are investigated in the present study. A numerical procedure based on a shooting method, which consists of double iterative loops, was employed to obtain the capillary bridge profile and bring the capillary force subject to a constant volume condition.

Mutations in Metabotropic Glutamate Receptor 1 Contribute to Natural Short Sleep Trait.

Sufficient and efficient sleep is crucial for our health. Natural short sleepers can sleep significantly shorter than the average population without a desire for more sleep and without any obvious negative health consequences. In searching for genetic variants underlying the short sleep trait, we found two different mutations in the same gene (metabotropic glutamate receptor 1) from two independent natural short sleep families.

Mutant neuropeptide S receptor reduces sleep duration with preserved memory consolidation.

Sleep is a crucial physiological process for our survival and cognitive performance, yet the factors controlling human sleep regulation remain poorly understood. Here, we identified a missense mutation in a G protein-coupled neuropeptide S receptor 1 (NPSR1) that is associated with a natural short sleep phenotype in humans. Mice carrying the homologous mutation exhibited less sleep time despite increased sleep pressure.

A class of circadian long non-coding RNAs mark enhancers modulating long-range circadian gene regulation.

Circadian rhythm exerts its influence on animal physiology and behavior by regulating gene expression at various levels. Here we systematically explored circadian long non-coding RNAs (lncRNAs) in mouse liver and examined their circadian regulation. We found that a significant proportion of circadian lncRNAs are expressed at enhancer regions, mostly bound by two key circadian transcription factors, BMAL1 and REV-ERBα.

Long-Range Chromosome Interactions Mediated by Cohesin Shape Circadian Gene Expression.

Mammalian circadian rhythm is established by the negative feedback loops consisting of a set of clock genes, which lead to the circadian expression of thousands of downstream genes in vivo. As genome-wide transcription is organized under the high-order chromosome structure, it is largely uncharted how circadian gene expression is influenced by chromosome architecture. We focus on the function of chromatin structure proteins cohesin as well as CTCF (CCCTC-binding factor) in circadian rhythm.

Oscillating primary transcripts harbor miRNAs with circadian functions.

The roles of miRNAs as important post-transcriptional regulators in the circadian clock have been suggested in several studies. But the search for circadian miRNAs has led to disparate results. Here we demonstrated that at least 57 miRNA primary transcripts are rhythmically transcribed in mouse liver.

A vacuum microgripping tool with integrated vibration releasing capability.

Pick-and-place of micro-objects is a basic task in various micromanipulation demands. Reliable releasing of micro-objects is usually disturbed due to strong scale effects. This paper focuses on a vacuum micro-gripper with vibration releasing functionality, which was designed and assembled for reliable micromanipulation tasks.