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As the urgency to limit global warming has intensified, negative emissions technology such as direct air capture and carbon sequestration are increasingly considered in climate mitigation scenarios. When Iceland opened the commercial-grade direct air carbon capture and storage (DACCS) facility in 2021, this marked a breakthrough for DACCS technology as a scalable climate mitigation solution. This study investigates the adoption of DACCS in Iceland and the potential for diffusion into other contexts as a global decarbonization solution. We implement expert interviews to analyze the adoption of technology, and to identify the various requirements of scaling DACCS into local and global contexts. Using inductive thematic analysis, we characterize the diverging perspectives on the role of carbon dioxide removal as a climate mitigation solution and also identify pathways toward technology upscaling at national, regional, and global scales. Despite the successful technology demonstration of DACCS, we find that experts hold different mental models of climate mitigation generally, characterized as "nature vs. technology." We also find that experts clearly articulate the necessary conditions for the diffusion of DACCS more broadly, including explicit regulatory measures as guardrails against a "license to pollute" as well as bilateral governance structures that include financial investment. Finally, we find that the importance of public acceptance of the technology was noted among all expert groups. Limited data exist on the acceptance of DACCS paired with renewable energy and this is a future research recommendation. [ABSTRACT FROM AUTHOR]

KCNQ1, the major component of the slow-delayed rectifier potassium channel, is responsible for repolarization of cardiac action potential. Mutations in this channel can lead to a variety of diseases, most notably long QT syndrome. It is currently unknown how many of these mutations change channel function and structure on a molecular level. Since tetramerization is key to proper function and structure of the channel, it is likely that mutations modify the stability of KCNQ1 oligomers. Presently, the C-terminal domain of KCNQ1 has been noted as the driving force for oligomer formation. However, truncated versions of this protein lacking the C-terminal domain still tetramerize. Therefore, we explored the role of native cysteine residues in a truncated construct of human KCNQ1, amino acids 100–370, by blocking potential interactions of cysteines with a nitroxide based spin label. Mobility of the spin labels was investigated with continuous wave electron paramagnetic resonance (CW-EPR) spectroscopy. The oligomerization state was examined by gel electrophoresis. The data provide information on tetramerization of human KCNQ1 without the C-terminal domain. Specifically, how blocking the side chains of native cysteines residues reduces oligomerization. A better understanding of tetramer formation could provide improved understanding of the molecular etiology of long QT syndrome and other diseases related to KCNQ1. • Exploration of oligomerization of Kv channels without C-terminal domain. • Nitroxide based spin labeling of native cysteine residues alters oligomerization. • C214 plays a role in the stability and or formation of KCNQ1 tetramers. [ABSTRACT FROM AUTHOR]

Extensive portions of the human genome have unknown function, including those derived from transposable elements. One such element, the DNA transposon Hsmar1, entered the primate lineage approximately 50 million years ago leaving behind terminal inverted repeat (TIR) sequences and a single intact copy of the Hsmar1 transposase, which retains its ancestral TIR-DNA-binding activity, and is fused with a lysine methyltransferase SET domain to constitute the chimeric SETMAR gene. Here, we provide a structural basis for recognition of TIRs by SETMAR and investigate the function of SETMAR through genome-wide approaches. As elucidated in our 2.37 Å crystal structure, SETMAR forms a dimeric complex with each DNA-binding domain bound specifically to TIRDNA through the formation of 32 hydrogen bonds. We found that SETMAR recognizes primarily TIR sequences (-5000 sites) within the human genome as assessed by chromatin immunoprecipitation sequencing analysis. In two SETMAR KO cell lines, we identified 163 shared differentially expressed genes and 233 shared alternative splicing events. Among these genes are several pre-mRNA-splicing factors, transcription factors, and genes associated with neuronal function, and one alternatively spliced primate-specific gene, TMEM14B, which has been identified as a marker for neocortex expansion associated with brain evolution. Taken together, our results suggest a model in which SETMAR impacts differential expression and alternative splicing of genes associated with transcription and neuronal function, potentially through both its TIR-specific DNA-binding and lysine methyltransferase activities, consistent with a role for SETMAR in simian primate development. [ABSTRACT FROM AUTHOR]

Abstract: An overview is presented of some of the recent results concerning the suitability of Czochralski silicon to High Energy Physics (HEP) radiation detectors. It has been shown that an elevated oxygen concentration within the bulk silicon of detectors offers increased radiation hardness to charged particle radiation. Silicon produced using the Czochralski growth method has an intrinsically higher concentration of oxygen than the standard silicon growth method, float zone, which is extensively used in HEP radiation detectors. The research reviewed in this paper aims to understand the microscopic and macroscopic behaviour of Czochralski and compares the performance to standard silicon radiation detectors. The majority of this work has been performed in the framework of the RD50 collaboration. [Copyright &y& Elsevier]

The VErtex LOcator (VELO) is the silicon microstrip vertexing and triggering sub-detector of the LHCb experiment. It consists of a series of forward disks with the active region ex- tending to just 8 mm from the LHC beams. The current status of the VELO is presented. Due to the high radiation environment, the VELO may have to be replaced after some years, possibly with new materials. A candidate material is Czochralski silicon. We present here promising new results on the first test beam of a large, high resistivity Czochralski microstrip silicon detector read out with LHC speed electronics. The performance was studied before and after irradiation with high energy protons. A signal to noise of over 20:1 was obtained from the detector and significant charge collection efficiencies were measured at relatively modest voltages after a fluence of 4.3 × 1014 1 MeV neutron equivalents (neq) per cm². Studies using the Transient Current Technique probed the electric field within MCz test detectors and proved that MCz silicon does not type invert up until a radiation level of at least 5 × 1014 24 GeV/c p/cm². This would mean the VELO could possibly replace, in a potential upgrade, n+ -on-n DOFZ sensors and the complicated processing involved, for standard p+ -on-n processing with MCz. [ABSTRACT FROM AUTHOR]

Abstract: Magnetic Czochralski (MCz) silicon has recently become a promising material for the development of radiation tolerant detectors for future high-luminosity HEP experiments. A thorough study of 24GeV/c proton-irradiated p+-in-n Float Zone (FZ) , Diffusion Oxygenated Float Zone (DOFZ) and MCz silicon detectors has been conducted using the standard radiation damage characterization tools IV and CV, the Transient Current Technique (TCT) and annealing studies. The first systematic study on the effective trapping time in MCz silicon has been performed. The results show that the introduction rate for the traps responsible for the degradation of the effective trapping time for MCz material agrees with the introduction rate for FZ and DOFZ silicon. From the behaviour of the depletion voltage as a function of proton fluence and through the TCT technique, it has been shown that by a radiation fluence of 5×1014 p/cm2 the depletion voltage has passed its minimum value without type inversion. An annealing study compares the evolution of the effective trapping time, the effective space charge density and the current-related damage parameters for MCz and DOFZ silicon. [Copyright &y& Elsevier]

Background and Purpose. Hemispherectomy is performed to help control intractable seizures, yet little research quantifies and projects the clinical course of the impairments, functional limitations, and disabilities of patients who have undergone the procedure. This case report describes the physical therapist preoperative and postoperative examination, evaluation, and intervention during the acute hospitalization of an adult who underwent a right hemispherectomy. Case Description. The patient was a 27-year-old man who had intractable seizures despite having tried multiple drug regimens and undergoing several surgical interventions after a brain injury at age 5 years. He underwent a right functional hemispherectomy and then had 9 postoperative physical therapy sessions during his acute hospitalization. Outcomes. The patient made rapid gains, surpassing all initial goals. At discharge, the patient had distal left-sided sensorimotor impairments, but he was able to ambulate 121.9 m (400 ft) with assistance to maintain his balance. Discussion. The patient's posthemispherectomy recovery was rapid. His brain injury at a young age may have triggered preoperative transfer of function to the unaffected left hemisphere. The prognosis for this patient's improvements of impairments and functional limitations was better than initially expected, perhaps because of the redundant features and plasticity of the central nervous system. [Bates AL, Zadai CC. Acute care physical therapist evaluation and intervention for an adult after right hemispherectomy. Phys Ther. 2003;83:567-580.] [ABSTRACT FROM AUTHOR]

The possibility of substantial offshore wind energy development in the United States (U.S.) is rapidly advancing. Several offshore wind projects have been proposed proximate to federally-recognized tribal territory. Historically marginalized, indigenous communities have for centuries experienced injustices during the expansion of the U.S. energy system. Few studies have systematically examined the responses of indigenous communities to offshore wind, and little is known about the ways that indigenous concerns are leveraged by non-members to advance a position advocating for or against offshore development. In this study, we examine the discourses that surround indigenous communities through legally mandated decision-making processes for two proposed offshore wind projects in the northeast U.S. We show that narratives surrounding indigenous stakeholders in the offshore wind scoping process can be thematically identified as: 1. religious, cultural, and spiritual value , 2. land and identity , and 3. process and procedures. However, the concerns and perspectives of indigenous communities are mostly brought forth by non-group members, and were found to be leveraged or diminished by non-indigenous individuals pushing anti- or pro-offshore wind sentiment. This reveals the finding that indigenous concerns are being co-opted or sidelined through formal and legal decision-making processes in the U.S. The results indicate that the formal consultation process failed to meet standards of energy justice by inadvertently giving outsize voice to lesser impacted communities. Therefore, our study cautions that energy justice is not achieved solely through "inclusive" processes and decision-makers should be diligent in considering the multi-faceted aspects of justice. [ABSTRACT FROM AUTHOR]

The article focuses on the reasons behind the rejection of papers submitted to the Journal of Mental Health, highlighting the increasing number of submissions and the rigorous review process. Topics include the importance of meeting submission criteria, considerations during the scientific evaluation process, and specific guidelines for different types of studies, such as prioritizing international importance and avoiding redundant research on topics like COVID-19.

Hsp90s are ATP-dependent chaperones that collaborate with co-chaperones and Hsp70s to remodel client proteins. Grp94 is the ER Hsp90 homolog essential for folding multiple secretory and membrane proteins. Grp94 interacts with the ER Hsp70, BiP, although the collaboration of the ER chaperones in protein remodeling is not well understood. Grp94 undergoes large-scale conformational changes that are coupled to chaperone activity. Within Grp94, a region called the pre-N domain suppresses ATP hydrolysis and conformational transitions to the active chaperone conformation. In this work, we combined in vivo and in vitro functional assays and structural studies to characterize the chaperone mechanism of Grp94. We show that Grp94 directly collaborates with the BiP chaperone system to fold clients. Grp94's pre-N domain is not necessary for Grp94-client interactions. The folding of some Grp94 clients does not require direct interactions between Grp94 and BiP in vivo, suggesting that the canonical collaboration may not be a general chaperone mechanism for Grp94. The BiP co-chaperone DnaJB11 promotes the interaction between Grp94 and BiP, relieving the pre-N domain suppression of Grp94's ATP hydrolysis activity. In structural studies, we find that ATP binding by Grp94 alters the ATP lid conformation, while BiP binding stabilizes a partially closed Grp94 intermediate. Together, BiP and ATP push Grp94 into the active closed conformation for client folding. We also find that nucleotide binding reduces Grp94's affinity for clients, which is important for productive client folding. Alteration of client affinity by nucleotide binding may be a conserved chaperone mechanism for a subset of ER chaperones. [ABSTRACT FROM AUTHOR]

KCNQ1 (Kv7.1 or KvLQT1) is a voltage-gated potassium ion channel that is involved in the ventricular repolarization following an action potential in the heart. It forms a complex with KCNE1 in the heart and is the pore forming subunit of slow delayed rectifier potassium current (I ks). Mutations in KCNQ1, leading to a dysfunctional channel or loss of activity have been implicated in a cardiac disorder, long QT syndrome. In this study, we report the overexpression, purification, biochemical characterization of human KCNQ1 100 – 370 , and lipid bilayer dynamics upon interaction with KCNQ1 100 – 370. The recombinant human KCNQ1 was expressed in Escherichia coli and purified into n-dodecylphosphocholine (DPC) micelles. The purified KCNQ1 100 – 370 was biochemically characterized by SDS-PAGE electrophoresis, western blot and nano-LC-MS/MS to confirm the identity of the protein. Circular dichroism (CD) spectroscopy was utilized to confirm the secondary structure of purified protein in vesicles. Furthermore, 31P and 2H solid-state NMR spectroscopy in DPPC/POPC/POPG vesicles (MLVs) indicated a direct interaction between KCNQ 100 – 370 and the phospholipid head groups. Finally, a visual inspection of KCNQ1 100 – 370 incorporated into MLVs was confirmed by transmission electron microscopy (TEM). The findings of this study provide avenues for future structural studies of the human KCNQ1 ion channel to have an in depth understanding of its structure-function relationship. [Display omitted] • Purification of KCNQ1 potassium ion channel • Probing the interaction of KCNQ1 with the membrane using solid-state NMR spectroscopic techniques • Secondary structural characteristics of KCNQ1 [ABSTRACT FROM AUTHOR]

Telomere dysfunction has been strongly implicated in the initiation of genomic instability and is suspected to be an early event in the carcinogenesis of human solid tumors. Recent findings have established the presence of telomere fusions in human breast and prostate malignancies; however, the onset of this genomic instability mechanism during progression of other solid cancers is not well understood. Herein, we explored telomere dynamics in patient-derived epithelial ovarian cancers (OC), a malignancy characterized by multiple distinct subtypes, extensive molecular heterogeneity, and widespread genomic instability. We discovered a high frequency of telomere fusions in ovarian tumor tissues; however, limited telomere fusions were detected in normal adjacent tissues or benign ovarian samples. In addition, we found relatively high levels of both telomerase activity and hTERT expression, along with anaphase bridges in tumor tissues, which were notably absent in adjacent normal ovarian tissues and benign lesions. These results suggest that telomere dysfunction may occur early in ovarian carcinogenesis and, importantly, that it may play a critical role in the initiation and progression of the disease. Recognizing telomere dysfunction as a pervasive feature of this heterogeneous malignancy may facilitate the future development of novel diagnostic tools and improved methods of disease monitoring and treatment. [ABSTRACT FROM AUTHOR]

We report DNA- and RNA-like systems built from eight nucleotide “letters” (hence the name “hachimoji”) that form four orthogonal pairs. These synthetic systems meet the structural requirements needed to support Darwinian evolution, including a polyelectrolyte backbone, predictable thermodynamic stability, and stereoregular building blocks that fit a Schrödinger aperiodic crystal. Measured thermodynamic parameters predict the stability of hachimoji duplexes, allowing hachimoji DNA to increase the information density of natural terran DNA. Three crystal structures show that the synthetic building blocks do not perturb the aperiodic crystal seen in the DNA double helix. Hachimoji DNA was then transcribed to give hachimoji RNA in the form of a functioning fluorescent hachimoji aptamer. These results expand the scope of molecular structures that might support life, including life throughout the cosmos. [ABSTRACT FROM AUTHOR]

Several studies have been performed in the last three decades to assess the impacts of marine biofouling on offshore wind turbines (OWTs) substructures. Marine biofouling generally refers to the settlement and growth of aquatic organisms on human-made structures situated in marine and estuarine environments. OWTs continue to demonstrate significant energy extraction potential and their performance in the ocean is a promising area of research. Most wind turbine installations are in shallow water depths of less than 100 m. At these depths, biofouling can be seen on a large section of cylindrical structures, including mooring lines or power cables, with considerable roughness. This paper provides a review of biofouling phenomena in the context of offshore/marine cylindrical structures. The ecological and social implications of biofouling are reviewed alongside the technical parameters of what is considered to be undesired growth among engineers. The review specifically highlights various marine fouling parameters and laboratory approaches employed by past researchers in modelling biofouling, and the latter's effects on hydrodynamic loading from wave and current excitation. This paper explores challenges in modelling biofouling caused by its intrinsic randomness and uncertainty, as well as suggestions for many studies on marine fouling that are currently absent. • Study of the effect of surface roughness is done under the premise of hard biofouling. • Only a few studies have investigated the impact of soft and lengthy flapping biofouling. • Dependence of biofouling only on surface roughness remains a debated topic. • Ecological effects of biofouling and social preferences for artificial reefs complicate antifouling designs. • Most research rarely considers the effects of fatigue environmental conditions on OWTs substructures. [ABSTRACT FROM AUTHOR]

In mammalian cells, specific aminoacyl-transfer RNA (tRNA) synthetases have cytokine functions that require interactions with partners outside of the translation apparatus. Little is known about these interactions and how they facilitate expanded functions that link protein translation to other cellular pathways. For example, an alternative splice fragment of tryptophanyl-tRNA synthetase (TrpRS) and a similar natural proteolytic fragment are potent angiostatic factors that act through the vascular endothelial-cadherin receptor and Akt signaling pathway. Here we demonstrate mobilization of TrpRS for exocytosis from endothelial cells and the potential for plasmin to activate the cytokine function of the extracellular synthetase. Direct physical evidence showed that the annexin II-S100A10 complex, which regulates exocytosis, forms a ternary complex with TrpRS. Functional studies demonstrate that both annexin II and S100A10 regulate trafficking of TrpRS. Thus, complexes of mammalian tRNA synthetases with seemingly disparate proteins may in general be relevant to understanding how their expanded functions are implemented. [ABSTRACT FROM AUTHOR]

Summary: Disease-causing mutations occur in genes for aminoacyl tRNA synthetases. That some mutations are dominant suggests a gain of function. Native tRNA synthetases, such as tyrosyl-tRNA synthetase (TyrRS) and tryptophanyl-tRNA synthetase, catalyze aminoacylation and are also procytokines that are activated by natural fragmentation. In principle, however, gain-of-function phenotypes could arise from mutational activation of synthetase procytokines. From crystal structure analysis, we hypothesized that a steric block of a critical Glu-Leu-Arg (ELR) motif in full-length TyrRS suppresses the cytokine activity of a natural fragment. To test this hypothesis, we attempted to uncover ELR in the procytokine by mutating a conserved tyrosine (Y341) that tethers ELR. Site-specific proteolytic cleavage and small-angle X-ray scattering established subtle opening of the structure by the mutation. Strikingly, four different assays demonstrated mutational activation of cytokine functions. The results prove the possibilities for constitutive gain-of-function mutations in tRNA synthetases. [Copyright &y& Elsevier]

Colorectal cancer (CRC) is the fourth leading cause of cancer-related deaths worldwide. Liver metastasis is the major cause of CRC patient mortality, occurring in 60% patients with no effective therapies. Although studies have indicated the role of miRNAs in CRC, an in-depth miRNA expression analysis is essential to identify clinically relevant miRNAs and understand their potential in targeting liver metastasis. Here we analyzed miRNA expressions in 405 patient tumors from publicly available colorectal cancer genome sequencing project database. Our analyses showed miR-132, miR-378f, miR-605 and miR-1976 to be the most significantly downregulated miRNAs in primary and CRC liver metastatic tissues, and CRC cell lines. Observations in CRC cell lines indicated that ectopic expressions of miR-378f, -605 and -1976 suppress CRC cell proliferation, anchorage independent growth, metastatic potential, and enhance apoptosis. Consistently, CRC patients with higher miR-378f and miR-1976 levels exhibited better survival. Together, our data suggests an anti-tumorigenic role of these miRNAs in CRC and warrant future in vivo evaluation of the molecules for developing biomarkers or novel therapeutic strategies. [ABSTRACT FROM AUTHOR]