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Spatial Transcriptional Mapping Reveals Site-Specific Pathways Underlying Human Atherosclerotic Plaque Rupture

Background: Atherosclerotic plaque ruptures, triggered by blood flow–associated biomechanical forces, cause most myocardial infarctions and strokes. Objectives: This study aims to investigate the exact location and underlying mechanisms of atherosclerotic plaque ruptures, identifying therapeutic targets against cardiovascular events. Methods: Histology, electron microscopy, bulk and spatial RNA se

Pirtobrutinib targets BTK C481S in ibrutinib-resistant CLL but second-site BTK mutations lead to resistance

Covalent inhibitors of Bruton tyrosine kinase (BTK) have transformed the therapy of chronic lymphocytic leukemia (CLL), but continuous therapy has been complicated by the development of resistance. The most common resistance mechanism in patients whose disease progresses on covalent BTK inhibitors (BTKis) is a mutation in the BTK 481 cysteine residue to which the inhibitors bind covalently. Pirtob

The dark matter of the cancer genome : Aberrations in regulatory elements, untranslated regions, splice sites, non-coding RNA and synonymous mutations

Cancer is a disease of the genome caused by oncogene activation and tumor suppressor gene inhibition. Deep sequencing studies including large consortia such as TCGA and ICGC identified numerous tumor-specific mutations not only in protein-coding sequences but also in non-coding sequences. Although 98% of the genome is not translated into proteins, most studies have neglected the information hidden

M(III) Site-Driven Structural Engineering on Lead-Free Layered Double Perovskite Nanocrystals with Enhanced Photoelectrochemical Activity

Over the past decade, organic–inorganic hybrid perovskites have revolutionized next-generation semiconductors, driving unprecedented advancements in cost-effective optoelectronics. While lead-based perovskite semiconductors exhibit exceptional optoelectronic properties, their inherent toxicity and vulnerability to environmental degradation remain significant barriers to widespread commercializ

A framework for analyzing deployment of solar photovoltaics, with a focus on building-sited grid-connected systems

Policy intervention schemes for increased deployment of solar photovoltaics (PV) have been launched in several countries, with varying success. In order to ensure an efficient deployment of the technology, thorough knowledge is needed about relevant present actors and institutions, and about how a desirable actor base and institutional setup should look like; mere cost reductions are not enough to

Path creation as a process of resource alignment and anchoring : Industry formation for on-site water recycling in Beijing

Where and how new industrial paths emerge are much debated questions in economic geography, especially in light of the recent evolutionary turn. This article contributes to the ongoing debate on path creation with a new analytical framework that specifies the formation of generic resources in embryonic industries. It suggests that path creation processes are not only conditioned by preexisting reg

A Model Analysis of Mechanisms for Radial Microtubular Patterns at Root Hair Initiation Sites

Plant cells have two main modes of growth generating anisotropic structures. Diffuse growth where whole cell walls extend in specific directions, guided by anisotropically positioned cellulose fibers, and tip growth, with inhomogeneous addition of new cell wall material at the tip of the structure. Cells are known to regulate these processes via molecular signals and the cytoskeleton. Mechanical s

The declining spadefoot toad Pelobates fuscus: calling site choice and conservation

We investigated whether local biotic and abiotic conditions could explain the occurrence of calling males of the declining spadefoot toad Pelobates fuscus in 72 ponds in southern Sweden. The ponds covered the entire distribution range of P. fuscus and were monitored during the breeding season in 2000. Calling males were found in 33 ponds. representing ca 50% of all known ponds for the species ill

Calbindin D-28k EF-hand ligand binding and oligomerization: Four high-affinity sites-three modes of action

Calbindin D-28k, a highly conserved protein with Ca2+-sensing and Ca2+-buffering capabilities, is abundant in brain and sensory neurons. This protein contains six EF-hand subdomains, four of which bind Call with high affinity. Calbindin D28k can be reconstituted from six synthetic peptides corresponding to the six EF-hands, indicating a single-domain structure with multiple interactions between th

Synchrotron radiation X-ray absorption fine structure and magnetization improvement of A-site Ce3+ doped LaFeO3

Synchrotron radiation (SR) is an interesting tool for probing the properties of the matter in various domains such as nanotechnology, energy materials, catalysis and the cultural heritage. Herein, we synthesized nanomultiferroic samples La1−xCexFeO3 (0.00 ≤ x ≤ 0.15) using auto combustion method and glycine as a fuel. The magnetic behavior was studied and interrelated with the results of synchrotr

EPR assessment of protein sites for incorporation of Gd(III) MRI contrast labels.

We have engineered apolipoprotein A-I (apoA-I), a major protein constituent of high-density lipoprotein (HDL), to contain DOTA-chelated Gd(III) as an MRI contrast agent for the purpose of imaging reconstituted HDL (rHDL) biodistribution, metabolism and regulation in vivo. This protein contrast agent was obtained by attaching the thiol-reactive Gd[MTS-ADO3A] label at Cys residues replaced at four d

Spatial and temporal dynamics in eddy covariance observations of methane fluxes at a tundra site in northeastern Siberia

In the past two decades, the eddy covariance technique has been used for an increasing number of methane flux studies at an ecosystem scale. Previously, most of these studies used a closed path setup with a tunable diode laser spectrometer (TDL). Although this method worked well, the TDL has to be calibrated regularly and cooled with liquid nitrogen or a cryogenic system, which limits its use in r

Improving a plot-scale methane emission model and its performance at a northeastern Siberian tundra site

In order to better address the feedbacks between climate and wetland methane (CH4) emissions, we tested several mechanistic improvements to the wetland CH4 emission model Peatland-VU with a longer Arctic data set than any other model: (1) inclusion of an improved hydrological module, (2) incorporation of a gross primary productivity (GPP) module, and (3) a more realistic soil-freezing scheme. A lo

Micro-climate determines oviposition site selection and abundance in the butterfly Pyrgus armoricanus at its northern range margin

1. Knowledge about species habitat requirements is important when designing conservation strategies as well as for predicting species distributions. For herbivorous insects, insights in oviposition preferences can provide important information on their habitat requirements. 2. The oviposition preferences of Oberthür's Grizzled Skipper butterfly Pyrgus armoricanus Oberthür at its northern range bou