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Factors Affecting Extubation Time in Patients Undergoing Coronary Artery Bypass Grafting Surgery
Ventilatory Differences among ARDS Due to Viral Pneumonia: A Pilot Study
Ventilator Associated Pneumoniaina Medical Intensive Care Unit: Incidence, Risk factors and Mortality
A Prospective Randomised, Double-blinded Study on the Cerebral Haemodynamic Effects of Ketamine Versus Propofol Sedation in Patients with Severe Traumatic Brain Injury Admitted in Trauma Intensive Care
Single-nucleus and spatial signatures of the brainstem in normal brain and mild traumatic brain injury in male mice
The bandgap-detuned excitation regime in photonic-crystal resonators
Abstract Control of nonlinear interactions in microresonators enhances access to classical and quantum field states across nearly limitless bandwidth. A recent innovation has been to leverage coherent scattering of the intraresonator pump field as a control of group-velocity dispersion and nonlinear frequency shifts, which are precursors for the dynamical evolution of new field states. Yet, since nonlinear-resonator phenomena are intrinsically multimode and exhibit complex modelocking, here we demonstrate a new approach to controlling nonlinear interactions with bandgap modes completely separate from the pump laser. We explore this bandgap-detuned excitation regime through generation of benchmark optical parametric oscillators (OPOs) and soliton microcombs. Indeed, we show that mode-locked states are phase matched more effectively in the bandgap-detuned regime in which we directly control the modal Kerr shift with the bandgaps without perturbing the pump field. In particular, bandgap-detuned excitation enables an arbitrary, mode-by-mode control of the backscattering rate as a versatile tool for mode-locked state engineering. Our experiments leverage nanophotonic resonators for phase matching of OPOs and solitons, leading to control over threshold power, conversion efficiency, and emission direction that enable application advances in high-capacity signaling and computing, signal generation, and quantum sensing.
Precision multiplexed base editing in human cells using Cas12a-derived base editors
Abstract Base editors enable the direct conversion of target nucleotides without introducing DNA double strand breaks, making them a powerful tool for creating point mutations in a human genome. However, current Cas9-derived base editing technologies have limited ability to simultaneously edit multiple loci with base-pair level precision, hindering the generation of polygenic phenotypes. Here, we test the ability of six Cas12a-derived base editing systems to process multiple gRNAs from a single transcript. We identify base editor variants capable of multiplexed base editing and improve the design of the respective gRNA array expression cassette, enabling multiplexed editing of 15 target sites in multiple human cell lines, increasing state-of-the-art in multiplexing by three-fold in the field of mammalian genome engineering. To reduce bystander mutations, we also develop a Cas12a gRNA engineering approach that directs editing outcomes towards a single base-pair conversion. We combine these advances to demonstrate that both strategies can be combined to drive multiplex base editing with greater precision and reduced bystander mutation rates. Overcoming these key obstacles of mammalian genome engineering technologies will be critical for their use in studying single nucleotide variant-associated diseases and engineering synthetic mammalian genomes.
Strong association between hypocalcemia and preeclampsia-eclampsia among pregnant women attending at a tertiary referral hospital in Northwestern Tanzania
Cell division protein CdpA organises and anchors the midcell ring in haloarchaea
Tribological properties of hydroxyapatite-coated nanorods on Ti-6Al-4V surfaces
Abstract This paper presents the tribological properties and bioactivity of nanostructured hydroxyapatite (HA) from biowaste sources and coated onto Ti-6Al-4V substrates using a novel pack cementation method. The process introduced HA pillars/nanorods on the surfaces of Ti-6Al-4V to enhance their osseointegration for dental implants. The mechanical and tribological properties were studied with nanoindentation, and pin-on-disk techniques, following the microstructural characterization of the coatings with atomic force microscopy, X-ray diffraction, Raman spectroscopy, scanning electron microscopy, and energy dispersive x-ray spectroscopy. The study also examines the surface bioactivity and elucidates the underlying friction and wear mechanisms of the HA-coated and annealed Ti-6Al-4V surface. The study results show a bone bonding capacity of the biowaste-derived HA-coated substrate with improved hardness and tribological properties. The implications of the study are discussed for the development of nano-structured HA-coated Ti-6Al-4V for dental implants with improved osseointegration for dental and biomedical applications.
Multi-trait genetic analysis of asthma and eosinophils uncovers pleiotropic loci in East Asians
Saliva-based lacosamide monitoring paves the way toward personalized epilepsy pharmacotherapy
The HP1 box of KAP1 organizes HP1α for silencing of endogenous retroviral elements in embryonic stem cells
Abstract Repression of endogenous retroviral elements (ERVs) is facilitated by KAP1 (KRAB-associated protein 1)-containing complexes, however the underlying mechanism remains unclear. Here, we show that binding of KAP1 to the major component of the heterochromatin spreading and maintenance network, HP1α, plays a critical role in silencing of repetitive elements. Structural, biochemical and mutagenesis studies demonstrate that the association of the HP1 box of KAP1 (KAP1Hbox) with the chromoshadow domain of HP1α (HP1αCSD) leads to a symmetrical arrangement of HP1αCSD and multimerization that may promote the closed state of chromatin. The formation of the KAP1Hbox-HP1αCSD complex enhances charge driven DNA binding and phase separation activities of HP1α. ChIP-seq and ATAC-seq analyses using KAP1 knock out mouse embryonic stem cells expressing wild type KAP1 or HP1-deficient KAP1 mutant show that in vivo, KAP1 engagement with HP1 is required for maintaining inaccessible chromatin at ERVs. Our findings provide mechanistic and functional insights that further our understanding of how ERVs are silenced.