Sandernelson7908

Raman optical activity (ROA) is effective for studying the conformational structure and behavior of chiral molecules in aqueous solutions and is advantageous over X-ray crystallography and nuclear magnetic resonance spectroscopy in sample preparation and cost performance. However, ROA signals are inherently minuscule; 3-5 orders of magnitude weaker than spontaneous Raman scattering due to the weak chiral light-matter interaction. Localized surface plasmon resonance on metallic nanoparticles has been employed to enhance ROA signals, but suffers from detrimental spectral artifacts due to its photothermal heat generation and inability to efficiently transfer and enhance optical chirality from the far field to the near field. Here we demonstrate all-dielectric chiral-field-enhanced ROA by devising a silicon nanodisk array and exploiting its dark mode to overcome these limitations. Specifically, we use it with pairs of chemical and biological enantiomers to show >100x enhanced chiral light-molecule interaction with negligible artifacts for ROA measurements.Oxygen release and irreversible cation migration are the main causes of voltage fade in Li-rich transition metal oxide cathode. But their correlation is not very clear and voltage decay is still a bottleneck. Herein, we modulate the oxygen anionic redox chemistry by constructing Li2ZrO3 slabs into Li2MnO3 domain in Li1.21Ni0.28Mn0.51O2, which induces the lattice strain, tunes the chemical environment for redox-active oxygen and enlarges the gap between metallic and anionic bands. This modulation expands the region in which lattice oxygen contributes capacity by oxidation to oxygen holes and relieves the charge transfer from anionic band to antibonding metal-oxygen band under a deep delithiation. This restrains cation reduction, metal-oxygen bond fracture, and the formation of localized O2 molecule, which fundamentally inhibits lattice oxygen escape and cation migration. The modulated cathode demonstrates a low voltage decay rate (0.45 millivolt per cycle) and a long cyclic stability.Commonly used for Parkinson's disease (PD), deep brain stimulation (DBS) produces marked clinical benefits when optimized. However, assessing the large number of possible stimulation settings (i.e., programming) requires numerous clinic visits. Here, we examine whether functional magnetic resonance imaging (fMRI) can be used to predict optimal stimulation settings for individual patients. We analyze 3 T fMRI data prospectively acquired as part of an observational trial in 67 PD patients using optimal and non-optimal stimulation settings. Clinically optimal stimulation produces a characteristic fMRI brain response pattern marked by preferential engagement of the motor circuit. Then, we build a machine learning model predicting optimal vs. non-optimal settings using the fMRI patterns of 39 PD patients with a priori clinically optimized DBS (88% accuracy). The model predicts optimal stimulation settings in unseen datasets a priori clinically optimized and stimulation-naïve PD patients. We propose that fMRI brain responses to DBS stimulation in PD patients could represent an objective biomarker of clinical response. Upon further validation with additional studies, these findings may open the door to functional imaging-assisted DBS programming.In living cells, microtubules (MTs) play pleiotropic roles, which require very different mechanical properties. Unlike the dynamic MTs found in the cytoplasm of metazoan cells, the specialized cortical MTs from Toxoplasma gondii, a prevalent human pathogen, are extraordinarily stable and resistant to detergent and cold treatments. Using single-particle cryo-EM, we determine their ex vivo structure and identify three proteins (TrxL1, TrxL2 and SPM1) as bona fide microtubule inner proteins (MIPs). These three MIPs form a mesh on the luminal surface and simultaneously stabilize the tubulin lattice in both longitudinal and lateral directions. Target Protein Ligand chemical Consistent with previous observations, deletion of the identified MIPs compromises MT stability and integrity under challenges by chemical treatments. We also visualize a small molecule like density at the Taxol-binding site of β-tubulin. Our results provide the structural basis to understand the stability of cortical MTs and suggest an evolutionarily conserved mechanism of MT stabilization from the inside.Changes in the sequence of an organism's genome, i.e., mutations, are the raw material of evolution. The frequency and location of mutations can be constrained by specific molecular mechanisms, such as diversity-generating retroelements (DGRs). DGRs have been characterized from cultivated bacteria and bacteriophages, and perform error-prone reverse transcription leading to mutations being introduced in specific target genes. DGR loci were also identified in several metagenomes, but the ecological roles and evolutionary drivers of these DGRs remain poorly understood. Here, we analyze a dataset of >30,000 DGRs from public metagenomes, establish six major lineages of DGRs including three primarily encoded by phages and seemingly used to diversify host attachment proteins, and demonstrate that DGRs are broadly active and responsible for >10% of all amino acid changes in some organisms. Overall, these results highlight the constraints under which DGRs evolve, and elucidate several distinct roles these elements play in natural communities.Spin ice systems display a variety of very nontrivial properties, the most striking being the existence in them of magnetic monopoles. Such monopole states can also have nontrivial electric properties there exist electric dipoles attached to each monopole. A novel situation is encountered in the moment fragmentation (MF) state, in which monopoles and antimonopoles are perfectly ordered, whereas spins themselves remain disordered. We show that such partial ordering strongly modifies the electric activity of such systems the electric dipoles, which are usually random and dynamic, become paired in the MF state in (d, -d) pairs, thus strongly reducing their electric activity. The electric currents existing in systems with noncoplanar spins are also strongly influenced by MF. We also consider modifications in dipole and current patterns in magnetic textures (domain walls, local defects) and at excitations with nontrivial dynamics in a MF state, which show very rich behaviour and which could in principle allow to control them by electric field.All herpesviruses encode a conserved DNA polymerase that is required for viral genome replication and serves as an important therapeutic target. Currently available herpesvirus therapies include nucleoside and non-nucleoside inhibitors (NNI) that target the DNA-bound state of herpesvirus polymerase and block replication. Here we report the ternary complex crystal structure of Herpes Simplex Virus 1 DNA polymerase bound to DNA and a 4-oxo-dihydroquinoline NNI, PNU-183792 (PNU), at 3.5 Å resolution. PNU bound at the polymerase active site, displacing the template strand and inducing a conformational shift of the fingers domain into an open state. These results demonstrate that PNU inhibits replication by blocking association of dNTP and stalling the enzyme in a catalytically incompetent conformation, ultimately acting as a nucleotide competing inhibitor (NCI). Sequence conservation of the NCI binding pocket further explains broad-spectrum activity while a direct interaction between PNU and residue V823 rationalizes why mutations at this position result in loss of inhibition.Non-uniform illumination limits quantitative analyses of fluorescence imaging techniques. In particular, single molecule localization microscopy (SMLM) relies on high irradiances, but conventional Gaussian-shaped laser illumination restricts the usable field of view to around 40 µm × 40 µm. We present Adaptable Scanning for Tunable Excitation Regions (ASTER), a versatile illumination technique that generates uniform and adaptable illumination. ASTER is also highly compatible with optical sectioning techniques such as total internal reflection fluorescence (TIRF). For SMLM, ASTER delivers homogeneous blinking kinetics at reasonable laser power over fields-of-view up to 200 µm × 200 µm. We demonstrate that ASTER improves clustering analysis and nanoscopic size measurements by imaging nanorulers, microtubules and clathrin-coated pits in COS-7 cells, and β2-spectrin in neurons. link2 ASTER's sharp and quantitative illumination paves the way for high-throughput quantification of biological structures and processes in classical and super-resolution fluorescence microscopies.Approximately half of the freshwater discharged from the Greenland and Antarctic Ice Sheets enters the ocean subsurface as a result of basal ice melt, or runoff draining via the grounding line of a deep ice shelf or marine-terminating glacier. Around Antarctica and parts of northern Greenland, this freshwater then experiences prolonged residence times in large cavities beneath floating ice tongues. Due to the inaccessibility of these cavities, it is unclear how they moderate the freshwater associated supply of nutrients such as iron (Fe) to the ocean. Here, we show that subglacial dissolved Fe export from Nioghalvfjerdsbrae (the '79°N Glacier') is decoupled from particulate inputs including freshwater Fe supply, likely due to the prolonged ~162-day residence time of Atlantic water beneath Greenland's largest floating ice-tongue. Our findings indicate that the overturning rate and particle-dissolved phase exchanges in ice cavities exert a dominant control on subglacial nutrient supply to shelf regions.Images of DaTscan (ioflupane [123I] SPECT) have been used as an adjunct to clinical diagnosis to facilitate the differential diagnosis of neurodegenerative (ND) Parkinsonian Syndrome (PS) vs. non-dopamine deficiency aetiologies of Parkinsonism. Despite several systematic reviews having summarised the evidence on diagnostic accuracy, the impact of imaging results on clinical utility has not been systematically assessed. Our objective was to examine the available evidence on the clinical utility of DaTscan imaging in changing diagnosis and subsequent management of patients with suspected PS. We performed a systematic review of published studies of clinical utility from 2000 to 2019 without language restrictions. A meta-analysis of change in diagnosis and management rates reported from each study was performed using a random-effects model and logit transformation. Sub-group analysis, meta-regression and sensitivity analysis was performed to explore heterogeneity. Twenty studies met the inclusion criteria. Thirteen of these contributed to the meta-analyses including 950 and 779 patients with a reported change in management and change in diagnosis, respectively. The use of DaTscan imaging resulted in a change in management in 54% (95% CI 47-61%) of patients. Change in diagnosis occurred in 31% (95% CI 22-42%) of patients. The two pooled analyses were characterised by high levels of heterogeneity. link3 Our systematic review and meta-analysis show that imaging with DaTscan was associated with a change in management in approximately half the patients tested and the diagnosis was modified in one third. Regardless of time from symptom onset to scan results, these changes were consistent. Further research focusing on specific patient subgroups could provide additional evidence on the impact on clinical outcomes.