Non-volatile hybrid optical phase shifter driven by a ferroelectric transistor

Optical phase shifters are essential elements in photonic integrated circuits (PICs) and function as a direct interface to program the PIC. Non-volatile phase shifters, which can retain information without a power supply, are highly desirable for low-power static operations. Here a non-volatile optical phase shifter is demonstrated by driving a III-V/Si hybrid metal-oxide-semiconductor (MOS) phase shifter with a ferroelectric field-effect transistor (FeFET) operating in the source follower mode. Owing to the various polarization states in the FeFET, multistate non-volatile phase shifts up to 1.25{\pi} are obtained with CMOS-compatible operation voltages and low switching energy up to 3.3 nJ. Furthermore, a crossbar array architecture is proposed to simplify the control of non-volatile phase shifters in large-scale PICs and its feasibility is verified by confirming the selective write-in operation of a targeted FeFET with a negligible disturbance to the others. This work paves the way for realizing large-scale non-volatile programmable PICs for emerging computing applications such as deep learning and quantum computing

Non-volatile optical phase shift in ferroelectric hafnium zirconium oxide

A non-volatile optical phase shifter is a critical component for enabling large-scale, energy-efficient programmable photonic integrated circuits (PICs) on a silicon (Si) photonics platform. While ferroelectric materials like BaTiO3 offer non-volatile optical phase shift capabilities, their compatibility with complementary metal-oxide-semiconductor (CMOS) fabs is limited. Hence, the search for a novel CMOS-compatible ferroelectric material for non-volatile optical phase shifting in Si photonics is of utmost importance. Hafnium zirconium oxide (HZO) is an emerging ferroelectric material discovered in 2011, which exhibits CMOS compatibility due to the utilization of high-k dielectric HfO2 in CMOS transistors. Although extensively studied for ferroelectric transistors and memories, its application in photonics remains relatively unexplored. Here, we show the optical phase shift induced by ferroelectric HZO deposited on a SiN optical waveguide. We observed a negative change in refractive index at a 1.55 um wavelength in the pristine device regardless of the direction of an applied electric filed. We achieved approximately pi phase shift in a 4.5-mm-long device with negligible optical loss. The non-volatile multi-level optical phase shift was confirmed with a persistence of > 10000 s. This phase shift can be attributed to the spontaneous polarization within the HZO film along the external electric field. We anticipate that our results will stimulate further research on optical nonlinear effects, such as the Pockels effect, in ferroelectric HZO. This advancement will enable the development of various devices, including high-speed optical modulators. Consequently, HZO-based programmable PICs are poised to become indispensable in diverse applications, ranging from optical fiber communication and artificial intelligence to quantum computing and sensing

Impact of Baseline ALBI Grade on the Outcomes of Hepatocellular Carcinoma Patients Treated with Lenvatinib: A Multicenter Study

Background: This study investigated the impact of baseline liver function according to the Child–Pugh score and ALBI (albumin-bilirubin) grade on the outcomes of patients with unresectable hepatocellular carcinoma treated with lenvatinib. Methods: A total of 82 lenvatinib treated patients were included. The correlations of baseline liver function according to the Child–Pugh score and ALBI grade with treatment outcomes, including objective response rate per mRECIST (modified Response Evaluation Criteria in the Solid Tumor), time to treatment failure, treatment duration, and likelihood of treatment discontinuation due to adverse events, were assessed in patients with hepatocellular carcinoma treated with lenvatinib. Patients were divided into four groups: (1) Child–Pugh score 5 and ALBI grade 1 (group 1), (2) Child–Pugh score 5 and ALBI grade 2 (group 2), (3) Child–Pugh score 6 (group 3), and (4) Child–Pugh score ≥7 (group 4). Univariate and multivariate analyses were performed to identify the factors contributing to the objective response rate and likelihood of discontinuation due to adverse events. Results: Among the 82 patients analyzed, group 1 had the highest objective response rate (57.1%) and the lowest likelihood of treatment discontinuation because of adverse events (11.1%) among the four groups (p < 0.05 and p < 0.05). Multivariate analysis identified ALBI grade 1 and baseline AFP level <200 ng/mL as the significant predictors of a high objective response rate (p < 0.05 and p < 0.01), and confirmed that patients with ALBI grade 1 had the lowest probability of treatment discontinuation due to adverse events (p < 0.01). Conclusions: Patients with Child–Pugh score of 5 and ALBI grade 1 predicted a higher response rate and lower treatment discontinuation due to adverse events by lenvatinib treatment

Bispectral index-guided propofol sedation during endoscopic ultrasonography

Background/Aims Bispectral index (BIS) monitors process and display electroencephalographic data are used to assess the depth of anesthesia. This study retrospectively evaluated the usefulness of BIS monitoring during endoscopic ultrasonography (EUS). Methods This study included 725 consecutive patients who underwent EUS under sedation with propofol. BIS monitoring was used in 364 patients and was not used in 361. The following parameters were evaluated: (1) median dose of propofol; (2) respiratory and circulatory depression; (3) occurrence of body movements; (4) awakening score >8 at the time; and (5) awakening score 2 hours after leaving the endoscopy room. Results The BIS group received a significantly lower median dose of propofol than the non-BIS group (159.2 mg vs. 167.5 mg; p=0.015) in all age groups. For patients aged ≥75 years, the reduction in heart rate was significantly lower in the BIS group than in the non-BIS group (1.2% vs. 9.1%; p=0.023). Moreover, the occurrence of body movements was markedly lower in the BIS group than in the non-BIS group (8.5% vs. 39.4%; p<0.001). Conclusions During EUS examination, BIS monitoring is useful for maintaining a constant depth of anesthesia, especially in patients 75 years of age or older

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure &lt; 100 mmHg (n = 1127), estimated glomerular filtration rate &lt; 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

AFM analysis of changes in nucleosome wrapping induced by DNA epigenetic modification

Accepted 13 Jun 2014.The wrapping and unwrapping of the nucleosome, which is a fundamental packing unit of chromatin, are tied to the regulation of gene expression. The accessibility of DNA within nucleosomes is controlled not only by chromatin-remodeling molecules, but also by chemical modifications of histones and DNA. Understanding the structural changes of a nucleosome during epigenetic modifications is a key to unravel the mechanisms of gene regulation. Here, we reconstituted nucleosomes using methylcytosine- or hydroxymethylcytosine-substituted DNA, and analyzed their morphological features by atomic force microscopy (AFM). Our results indicate that cytosine methylation induces overwrapping of the DNA around the histone octamer, whereas cytosine hydroxymethylation has a lesser effect on the overwrapping of the DNA. These results suggest that two types of DNA modification yield different wrapping states of nucleosomes, which may contribute to the compaction and relaxation of the chromatin structure