Parallel measurement of transcriptomes and proteomes from same single cells using nanodroplet splitting.

Single-cell multiomics provides comprehensive insights into gene regulatory networks, cellular diversity, and temporal dynamics. Here, we introduce nanoSPLITS (nanodroplet SPlitting for Linked-multimodal Investigations of Trace Samples), an integrated platform that enables global profiling of the transcriptome and proteome from same single cells via RNA sequencing and mass spectrometry-based proteomics, respectively. Benchmarking of nanoSPLITS demonstrates high measurement precision with deep proteomic and transcriptomic profiling of single-cells.

Safety, tolerability, pharmacokinetics and efficacy of HB0017, a humanized monoclonal antibody that targets interleukin-17A, in healthy participants and patients with moderate-to-severe plaque psoriasis.

Background: Several interleukin (IL)-17 inhibitors have been approved for the treatment of moderate-to-severe plaque psoriasis (PsO). There is still scope for the development of affordable treatments for PsO.

Objectives: To assess, in a phase Ia study, the safety, tolerability and pharmacokinetics (PK) of HB0017, a humanized monoclonal antibody that targets IL-17A, in healthy participants and patients with moderate-to-severe plaque PsO; and, in a phase Ib study, to assess the efficacy of HB0017 in patients with moderate-to-severe plaque PsO.

SPINK1, PRSS1, CTRC, and CFTR Genotypes Influence Disease Onset and Clinical Outcomes in Chronic Pancreatitis.

Objectives: Rare pathogenic variants in the SPINK1, PRSS1, CTRC, and CFTR genes have been strongly associated with a risk of developing chronic pancreatitis (CP). However, their potential impact on the age of disease onset and clinical outcomes, as well as their potential interactions with environmental risk factors, remain unclear. These issues are addressed here in a large Chinese CP cohort.

Structural and kinetic basis for the selectivity of aducanumab for aggregated forms of amyloid-β.

Aducanumab, a human-derived antibody targeting amyloid-β (Aβ), is in Phase 3 clinical trials for the treatment of Alzheimer's disease. Biochemical and structural analyses show that aducanumab binds a linear epitope formed by amino acids 3-7 of the Aβ peptide. Aducanumab discriminates between monomers and oligomeric or fibrillar aggregates based on weak monovalent affinity, fast binding kinetics and strong avidity for epitope-rich aggregates.

First observation of top quark production in the forward region.

Top quark production in the forward region in proton-proton collisions is observed for the first time. The W+b final state with W→μν is reconstructed using muons with a transverse momentum, p_{T}, larger than 25 GeV in the pseudorapidity range 2.0<η<4.

[Effects of cAMP-response element binding protein-1 (CREB-1) on transforming growth factor-b3 (TGFb3) mRNA expression and promoter activity in hepatic stellate cells].

Objective: To investigate the effects of cAMP-response element binding protein-1 (CREB-1) on transforming growth factor-b3 (TGF b3) mRNA expression and promoter activity in hepatic stellate cells (HSCs).

Methods: Freshly isolated HSCs from rats were divided into six groups: CREB-1 expression plasmid transfected group (C), siRNA-CREB-1 plasmid transfected group (S), negative control group (N), forskolin treated group (F), H-89 treated group (H), and blank group (B). Rats in each group were further sub-divided according to whether (+) or not (-) they were exposed to exogenous TGF b3.

Measurement of spin correlation in tt production using a matrix element approach.

We determine the fraction of tt events with spin correlation, assuming that the spin of the top quark is either correlated with the spin of the top antiquark as predicted by the standard model or is uncorrelated. For the first time we use a matrix-element-based approach to study tt spin correlation. We use tt → W+ b W- b → ℓ+ νbℓ- ν b final states produced in pp collisions at a center-of-mass energy sqrt(s)=1.

A sagittally focusing double-multilayer monochromator for ultrafast X-ray imaging applications.

The development of a sagittally focusing double-multilayer monochromator is reported, which produces a spatially extended wide-bandpass X-ray beam from an intense synchrotron bending-magnet source at the Advanced Photon Source, for ultrafast X-ray radiography and tomography applications. This monochromator consists of two W/B(4)C multilayers with a 25 A period coated on Si single-crystal substrates. The second multilayer is mounted on a sagittally focusing bender, which can dynamically change the bending radius of the multilayer in order to condense and focus the beam to various points along the beamline.

Tissue uptake of circulating thrombopoietin is increased in immune-mediated compared with irradiated thrombocytopenic mice.

We have previously demonstrated a significant inverse correlation between circulating thrombopoietin (TPO) levels and peripheral platelet (PLT) counts in patients with thrombocytopenia secondary to megakaryocytic hypoplasia but not in patients with immune thrombocytopenic purpura (ITP; Chang et al, Blood 88:3354, 1996). To test the hypothesis that the differences in the circulating TPO levels in these two types of thrombocytopenia are caused by differences in the total capacity of Mpl receptor-mediated TPO clearance, thrombocytopenia was induced in female CD-1 mice either by sublethal irradiation (irradiated) or rabbit antimouse PLT serum (RAMPS) for 1 day (1 d RAMPS) and 5 days (5 d RAMPS). A well-characterized murine model of autoimmune thrombocytopenic purpura, male (NZW x BXSB) F1 mice (W/B F1), was also included in this study.