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Abstract Background Accumulated evidence suggest that specific patterns of histone posttranslational modifications (PTMs) and their crosstalks may determine transcriptional outcomes. However, the regulatory mechanisms of these "histone codes" in plants remain largely unknown. Results In this study, we demonstrate for the first time that a salinity stress inducible PHD (plant homeodomain) finger domain containing protein GmPHD5 can read the "histone code" underlying the methylated H3K4. GmPHD5 interacts with other DNA binding proteins, including GmGNAT1 (an acetyl transferase), GmElongin A (a transcription elongation factor) and GmISWI (a chromatin remodeling protein). Our results suggest that GmPHD5 can recognize specific histone methylated H3K4, with preference to di-methylated H3K4. Here, we illustrate that the interaction between GmPHD5 and GmGNAT1 is regulated by the self-acetylation of GmGNAT1, which can also acetylate histone H3. GmGNAT1 exhibits a preference toward acetylated histone H3K14. These results suggest a histone crosstalk between methylated H3K4 and acetylated H3K14. Consistent to its putative roles in gene regulation under salinity stress, we showed that GmPHD5 can bind to the promoters of some confirmed salinity inducible genes in soybean. Conclusion Here, we propose a model suggesting that the nuclear protein GmPHD5 is capable of regulating the crosstalk between histone methylation and histone acetylation of different lysine residues. Nevertheless, GmPHD5 could also recruit chromatin remodeling factors and transcription factors of salt stress inducible genes to regulate their expression in response to salinity stress.

Abstract Background The employment of well characterized test samples prepared from authenticated, high quality medicinal plant materials is key to reproducible herbal research. The present study aims to demonstrate a quality assurance program covering the acquisition, botanical validation, chemical standardization and good manufacturing practices (GMP) production of IBS-20, a 20-herb Chinese herbal formula under study as a potential agent for the treatment of irritable bowel syndrome. Methods Purity and contaminant tests for the presence of toxic metals, pesticide residues, mycotoxins and microorganisms were performed. Qualitative chemical fingerprint analysis and quantitation of marker compounds of the herbs, as well as that of the IBS-20 formula was carried out with high-performance liquid chromatography (HPLC). Extraction and manufacture of the 20-herb formula were carried out under GMP. Chemical standardization was performed with liquid chromatography-mass spectrometry (LC-MS) analysis. Stability of the formula was monitored with HPLC in real time. Results Quality component herbs, purchased from a GMP supplier were botanically and chemically authenticated and quantitative HPLC profiles (fingerprints) of each component herb and of the composite formula were established. An aqueous extract of the mixture of the 20 herbs was prepared and formulated into IBS-20, which was chemically standardized by LC-MS, with 20 chemical compounds serving as reference markers. The stability of the formula was monitored and shown to be stable at room temperature. Conclusion A quality assurance program has been developed for the preparation of a standardized 20-herb formulation for use in the clinical studies for the treatment of irritable bowel syndrome (IBS). The procedures developed in the present study will serve as a protocol for other poly-herbal Chinese medicine studies.

Abstract Background Histone modifications and histone variants are of importance in many biological processes. To understand the biological functions of the global dynamics of histone modifications and histone variants in higher plants, we elucidated the variants and post-translational modifications of histones in soybean, a legume plant with a much bigger genome than that of Arabidopsis thaliana. Results In soybean leaves, mono-, di- and tri-methylation at Lysine 4, Lysine 27 and Lysine 36, and acetylation at Lysine 14, 18 and 23 were detected in HISTONE H3. Lysine 27 was prone to being mono-methylated, while tri-methylation was predominant at Lysine 36. We also observed that Lysine 27 methylation and Lysine 36 methylation usually excluded each other in HISTONE H3. Although methylation at HISTONE H3 Lysine 79 was not reported in A. thaliana, mono- and di-methylated HISTONE H3 Lysine 79 were detected in soybean. Besides, acetylation at Lysine 8 and 12 of HISTONE H4 in soybean were identified. Using a combination of mass spectrometry and nano-liquid chromatography, two variants of HISTONE H3 were detected and their modifications were determined. They were different at positions of A31F41S87S90 (HISTONE variant H3.1) and T31Y41H87L90 (HISTONE variant H3.2), respectively. The methylation patterns in these two HISTONE H3 variants also exhibited differences. Lysine 4 and Lysine 36 methylation were only detected in HISTONE H3.2, suggesting that HISTONE variant H3.2 might be associated with actively transcribing genes. In addition, two variants of histone H4 (H4.1 and H4.2) were also detected, which were missing in other organisms. In the histone variant H4.1 and H4.2, the amino acid 60 was isoleucine and valine, respectively. Conclusion This work revealed several distinct variants of soybean histone and their modifications that were different from A. thaliana, thus providing important biological information toward further understanding of the histone modifications and their functional significance in higher plants.

Substance use disorders (SUD) and drug addiction are major threats to public health, impacting not only the millions of individuals struggling with SUD, but also surrounding families and communities. One of the seminal challenges in treating and studying addiction in human populations is the high prevalence of co-morbid conditions, including an increased risk of contracting a human immunodeficiency virus (HIV) infection. Of the ~15 million people who inject drugs globally, 17% are persons with HIV. Conversely, HIV is a risk factor for SUD because chronic pain syndromes, often encountered in persons with HIV, can lead to an increased use of opioid pain medications that in turn can increase the risk for opioid addiction. We hypothesize that SUD and HIV exert shared effects on brain cell types, including adaptations related to neuroplasticity, neurodegeneration, and neuroinflammation. Basic research is needed to refine our understanding of these affected cell types and adaptations. Studying the effects of SUD in the context of HIV at the single-cell level represents a compelling strategy to understand the reciprocal interactions among both conditions, made feasible by the availability of large, extensively-phenotyped human brain tissue collections that have been amassed by the Neuro-HIV research community. In addition, sophisticated animal models that have been developed for both conditions provide a means to precisely evaluate specific exposures and stages of disease. We propose that single-cell genomics is a uniquely powerful technology to characterize the effects of SUD and HIV in the brain, integrating data from human cohorts and animal models. We have formed the Single-Cell Opioid Responses in the Context of HIV (SCORCH) consortium to carry out this strategy., (© 2024. The Author(s).)

Introduction: Little is known about which conditions seen in primary care are appropriate for video visits. This study evaluated video visits compared to office visits for six conditions: abdominal pain, joint pain, back pain, headache, chest pain, and dizziness., Methods: Six hundred charts of adult patients from our institution's same-day outpatient clinic were reviewed in this study. Charts for video visits evaluating the aforementioned chief complaints that occurred between August and October 2020 were reviewed and compared with charts for office visits that occurred from August to September 2019. Frequencies of 3-week follow-up visits, Emergency Room visits, imaging, and referrals for office and video visits were measured. Reasons for in-person evaluation for patients seen by video were determined by review of clinician notes., Results: Three-week in-person follow-up was more frequent for patients presenting with chest pain (52% vs 18%, p  = 0.0007) and joint pain (24% vs 8%, p  = 0.05) after video evaluation, relative to an office evaluation. Three-week in-person follow-up was also more frequent for patients presenting with dizziness (38% vs 28%) and low back pain (24% vs 14%); however, this difference was not statistically significant. Patients presenting with headache and abdominal pain did not have a higher rate of follow-up., Discussion: Based on the frequency of in-person follow-up, this study suggests that video visits are generally adequate for evaluating headache and abdominal pain. Patients with dizziness and chest pain have the highest frequency of in-person and Emergency Room follow-up within 3 weeks when first seen by video compared to other conditions evaluated and may be less suitable for an initial video visit. Institutions can consider these findings when scheduling and providing guidance to patients on what type of visit is most appropriate for their symptoms., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The safety of human papillomavirus (HPV) vaccines has been evaluated continuously in pre-licensure clinical trials, post-marketing surveillance systems, and observational studies. Most studies have found no significant association between serious adverse events and HPV vaccination. However, these studies have focused on Western populations; similar studies focusing on Asian populations are insufficient. Our retrospective cohort study used the HPV-vaccination records of junior high-school adolescent girls aged 12-15 years between 2013 and 2018 in Taiwan's National Immunization Information System and linked them to a registry for beneficiaries in Taiwan's National Health Insurance Database (NHID) to establish the vaccinated group. We selected 19 serious diseases as serious adverse events. We compared the incidence rates of these serious adverse events between the vaccinated group and girls in the same age group population, and we calculated the standardized incidence ratio (SIR) to evaluate the risk of serious adverse events after HPV vaccination. Because of the onset of different types of diseases, we set three periods after the subjects received HPV vaccination: within 3 months, within 1 year, and during the study period (2013-2018). The results showed the incidence rates and the SIRs of 19 selected adverse events. Among the 19 selected serious adverse events, the disease with the highest incidence rate during the study period was fibromyalgia (73.23 cases per million population), and the disease with the lowest incidence rate during the study period was Crohn's disease (0.15 cases per million population). The results showed no statistically significant increases in the risk of 19 selected serious adverse events and indicated no association between HPV vaccination and serious adverse events. Given the benefits and safety of HPV vaccination, our research can reduce concerns about vaccine side effects, inform health policies and improve public and clinician's acceptance of HPV vaccine policy., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Metabolism and inflammation have been viewed as two separate processes with distinct but critical functions for our survival: metabolism regulates the utilization of nutrients, and inflammation is responsible for defense and repair. Both respond to an organism's stressors to restore homeostasis. The interplay between metabolic status and immune response (immunometabolism) plays an important role in maintaining health or promoting disease development. Understanding these interactions is critical in developing tools for facilitating novel preventative and therapeutic approaches for diseases, including cancer. This trans-National Institutes of Health workshop brought together basic scientists, technology developers, and clinicians to discuss state-of-the-art, innovative approaches, challenges, and opportunities to understand and harness immunometabolism in modulating inflammation and its resolution.

Inflammation is a normal process in our body; acute inflammation acts to suppress infections and support wound healing. Chronic inflammation likely leads to a wide range of diseases, including cancer. Tools to locate and monitor inflammation are critical for developing effective interventions to arrest inflammation and promote its resolution. To identify current clinical needs, challenges, and opportunities in advancing imaging-based evaluations of inflammatory status in patients, the U.S. National Institutes of Health convened a workshop on imaging inflammation and its resolution in health and disease. Clinical speakers described their needs for image-based capabilities that could help determine the extent of inflammatory conditions in patients to guide treatment planning and undertake necessary interventions. The imaging speakers showcased the state-of-the-art in vivo imaging techniques for detecting inflammation in different disease areas. Many imaging capabilities developed for 1 organ or disease can be adapted for other diseases and organs, whereas some have promise for clinical utility within the next 5-10 yr. Several speakers demonstrated that multimodal imaging measurements integrated with serum-based measures could improve in robustness for clinical utility. All speakers agreed that multiple inflammatory measures should be acquired longitudinally to comprehend the dynamics of unresolved inflammation that leads to disease development. They also agreed that the best strategies for accelerating clinical translation of imaging inflammation capabilities are through integration between new imaging techniques and biofluid-based biomarkers of inflammation as well as already established imaging measurements.-Liu, C. H., Abrams, N. D., Carrick, D. M., Chander, P., Dwyer, J., Hamlet, M. R. J., Kindzelski, A. L., PrabhuDas, M., Tsai, S.-Y. A., Vedamony, M. M., Wang, C., Tandon, P. Imaging inflammation and its resolution in health and disease: current status, clinical needs, challenges, and opportunities.

Electronic medical records (EMRs) offer a potential opportunity to identify patients at high risk for cardiometabolic disease, which encompasses type 2 diabetes and cardiovascular disease (CVD). The objective of this retrospective cohort study is to use information gathered from EMR to investigate the association between triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C) and cardiometabolic outcomes in a general population of subjects over 50 years of age during a follow-up period of 8-9 years. TG/HDL-C was recorded for each of 1428 subjects in 2008, and diagnoses of type 2 diabetes and CVD were recorded through chart review until 2017. Cox proportional hazards models controlling for demographic characteristics and other risk factors demonstrated that high TG/HDL-C (>2.5 in women or >3.5 in men) was significantly associated with increased incidence of type 2 diabetes (HR 1.66; 95% CI 1.07 to 2.57; p=0.0230). There was also a suggested association between high TG/HDL-C and incidence of CVD (HR 1.51; 95% CI 0.98 to 2.35; p=0.0628). These findings suggest that using TG/HDL-C, which can be easily calculated from data in an EMR, should be another tool used in identifying patients at high cardiometabolic risk., Competing Interests: Competing interests: None declared., (© American Federation for Medical Research 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Prenatal substance exposure is a growing public health concern worldwide. Although the opioid crisis remains one of the most prevalent addiction problems in our society, abuse of cocaine, methamphetamines, and other illicit drugs, particularly amongst pregnant women, are nonetheless significant and widespread. Evidence demonstrates prenatal drug exposure can affect fetal brain development and thus can have long-lasting impact on neurobehavioral and cognitive performance later in life. In this review, we highlight research examining the most prevalent drugs of abuse and their effects on brain development with a focus on endoplasmic reticulum stress and oxidative stress signaling pathways. A thorough exploration of drug-induced cellular stress mechanisms during prenatal brain development may provide insight into therapeutic interventions to combat effects of prenatal drug exposure.

In this study, an automatic glycated hemoglobin (HbA1c) impedance measurement system (AHMS) is developed for the detection of HbA 1c . The proposed device removes some of the drawbacks of common instruments for HbA 1c detection (i.e., large, expensive, difficult to operate) by detecting the ratio of HbA 1c to Hb. The method is label-free and requires only a small sample volume; no additional reagents are required. The manpower consumption and bulk of the instrument are also reduced. The method provides a simple way to analyze impedance deviation and effectively reduces the effort required by the operator. The ratios of HbA 1c to Hb (4%-7%) are well distinguished, and the experiment is used to build a database for AHMS. To check the reliability of the proposed system, a sample test using three different ratios of HbA 1c is applied in this study. The sample test uses HbA 1c to Hb ratios of 4.7%, 5.6%, and 6.8%, and the determined experimental values are 4.93%, 5.8%, and 6.83%, respectively. The sample test has an accuracy of approximately 96.99%. Based on these results, the proposed system for detecting HbA 1c through protein coverage is both effective and feasible.

The sigma-1 receptor (Sig-1R) is a chaperone that resides mainly at the mitochondrion-associated endoplasmic reticulum (ER) membrane (called the MAMs) and acts as a dynamic pluripotent modulator in living systems. At the MAM, the Sig-1R is known to play a role in regulating the Ca 2+ signaling between ER and mitochondria and in maintaining the structural integrity of the MAM. The MAM serves as bridges between ER and mitochondria regulating multiple functions such as Ca 2+ transfer, energy exchange, lipid synthesis and transports, and protein folding that are pivotal to cell survival and defense. Recently, emerging evidences indicate that the MAM is critical in maintaining neuronal homeostasis. Thus, given the specific localization of the Sig-1R at the MAM, we highlight and propose that the direct or indirect regulations of the Sig-1R on mitochondrial functions may relate to neurodegenerative diseases including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD) and amyotrophic lateral sclerosis (ALS). In addition, the promising use of Sig-1R ligands to rescue mitochondrial dysfunction-induced neurodegeneration is addressed.

Objective: The aim of this study was to examine the relationships of Cardiometabolic Disease Staging (CMDS), a validated five-stage system for assessing risk for diabetes, cardiovascular mortality, and all-cause mortality, with measures of individual engagement and health-related quality of life (HRQOL) in the US adult population., Methods: Data from the 2011-2014 National Health and Nutrition Examination Survey were used to derive the CMDS stages, five participant engagement measures, and four HRQOL measures among adult participants ≥ 40 years of age. Analyses accounted for the complex sampling design and sample weights., Results: Higher CMDS was associated with greater participant awareness of cardiometabolic risk, but after adjusting for covariates, only Stage 4 remained significant (odds ratio: 5.08; 95% CI: 3.25, 7.94). Higher CMDS was associated with receiving recommendations to engage in a healthy lifestyle, not meeting 2008 physical activity guidelines, and fewer leisure time moderate activities after controlling for covariates. For HRQOL measures, Stage 4 was associated with a higher likelihood of perceiving health as fair or poor (odds ratio: 4.85; 95% CI: 2.42, 9.73)., Conclusions: Higher CMDS was associated with greater individual awareness of risk, less leisure time physical activity, and worse self-rated health. CMDS is a clinically practical method for identifying individuals for targeted preventive strategies., (© 2017 The Obesity Society.)

Purpose of Review: Although pregnancy-related deaths are rare in the USA, they are on the rise and have more than doubled in the last 20 years. A substantial portion of these deaths are related to cardiovascular disease, specifically hypertensive disorders of pregnancy (HDP). In this review, we will discuss the definitions and proposed pathophysiology of HDP as well as its potential role in cardiovascular morbidity and mortality., Recent Findings: Placental hypoperfusion may lead to an imbalance in proangiogenic and antiangiogenic factors, notably an increase in soluble fms-like tyrosine kinsase-1 (sFlt-1), thereby leading to endothelial dysfunction. Progress has been made in terms of determining the factors which lead to preeclampsia. Potential novel biomarkers for predicting preeclampsia risk have been identified through this research. Preeclampsia not only has important implications for the health during pregnancy but also for future cardiovascular risk. However, the exact mechanism by which it increases cardiovascular risk and the degree of risk it portends are yet to be elucidated.

Skeletal muscle insulin resistance is considered to be the primary defect involved in type 2 diabetes mellitus (T2DM). Despite transcriptome studies in limited T2DM human subjects suggesting an association of T2DM with impaired oxidative phosphorylation in muscle, its molecular pathogenesis remains largely unknown. To identify dysregulated genes and gene networks that are associated with T2DM in human skeletal muscle, we examined expression patterns of 56,318 transcribed genes on 92 T2DM cases and 184 gender-, age- and race-matched non-diabetic controls from the Genotype-Tissue Expression (GTEx) database. RNA-Sequencing data suggest that diabetic skeletal muscle is characterized by decreased expression of genes that are related to insulin resistance (IRS2, MTOR, SLC2A4, and PPARA), carbohydrate, energy, and amino acid metabolism pathways (NDUFS1, NDUFA10, NDUFB4, NDUFB5, NDUFA5, NDUFB10, SDHB, SDHC, ATP5H, ATP5A, and ATP5J). Up-regulated genes in T2DM are mainly enriched in apoptosis pathways (TP53, GADD45A, TNFRSF10B, TP53AIP1, and PMAIP1), and notably include immune-related pathways suggestive of a response to various infectious diseases (C2, CFB, C4A, C4B, C1S, C1R, C3, HLA-DRA, HLA-DMA, HLA-DOA, and HLA-DPB1). These results confirm the essential regulation of impaired insulin signaling and oxidative phosphorylation in the muscle of T2DM patients, and provide novel molecular insights into the pathophysiological mechanisms of T2DM., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Sigma-1 receptor (Sig-1R) functions as a chaperon that interacts with multiple proteins and lipids and is implicated in neurodegenerative and psychiatric diseases. Here, we used Sig-1R KO mice to examine brain expression profiles of astrocytes and ubiquitinated proteins, which are both hallmarks of central nervous system (CNS) pathologies. Our results showed that Sig-1R KO induces increased glial fibrillary acidic protein (GFAP) expression in primary neuron-glia cultures and in the whole brain of fetus mice with concomitantly increased accumulations of ubiquitinated proteins. Astrogliosis was also observed in the neuron-glia culture. Upon proteasome or autophagy inhibitor treatments, the pronounced ubiquitinated proteins were further increased in Sig-1R KO neurons, indicating that the Sig-1R regulates both protein degradation and quality control systems. We found that Nrf2 (nuclear factor erythroid 2-related factor 2), which functions to overcome the stress condition, was enhanced in the Sig-1R KO systems especially when cells were under stressful conditions. Mutation or deficiency of Sig-1Rs has been observed in neurodegenerative models. Our study identifies the critical roles of Sig-1R in CNS homeostasis and supports the idea that functional complementation pathways are triggered in the Sig-1R KO pathology.

The endoplasmic reticular (ER) protein sigma-1 receptor (Sig-1R) has been implicated in CNS disorders including but not limited to neurodegenerative diseases, depression , amnesia, and substance abuse. Sig-1Rs are particularly enriched in the specific domain where ER membranes make contacts with the mitochondria (MAM). Within that specific domain, Sig-1Rs play significant roles governing calcium signaling and reactive oxygen species homeostasis to maintain proper neuronal functions. Studies showed that the Sig-1R is pivotal to regulate neuroplasticity and neural survival via multiple aspects of mechanism. Numerous reports have been focusing on Sig-1R's regulatory effects in ER stress, mitochondrial function, oxidative stress and protein chaperoning. In this book chapter, we will discuss the emerging role of Sig-1R in balancing the populations of neuron and glia and their implications in CNS diseases.

Few studies have used nationally representative data to focus specifically on gender differences in weight-related outcomes. This article examines gender differences in weight-related outcomes across the body mass index (BMI) spectrum in overweight and obese adults. Data from the National Health and Nutrition Examination Survey 2009-2010 was analyzed. Weight-related outcomes were accurate weight perception, weight dissatisfaction, attempted weight loss, successful weight loss, and weight loss strategies. Compared with women, overweight and obese men were less likely to have accurate weight perception (odds ratio [OR] = 0.36; 95% confidence interval [CI] = 0.30-0.44), weight dissatisfaction (OR = 0.39; 95% CI = 0.32-0.47), and attempted weight loss (OR = 0.55; 95% CI = 0.48-0.63). The modifying effect of gender on these associations decreased as BMI increased. By BMI 35, the mean probability of women and men to have accurate weight perception and weight dissatisfaction was 90%; attempted weight loss was 60% (women) and 50% (men). At lower BMIs, men had up to 40% less probability than women for these weight loss outcomes. Men who attempted weight loss were more likely than women to lose and maintain ≥10 lb over 1 year (OR = 1.41; 95% CI = 1.20-1.65) and increase exercise and eat less fat as weight loss strategies; women were more likely to join weight loss programs, take prescription diet pills, and follow special diets. A need exists for male-specific interventions to improve overweight and obese men's likelihood for accurate weight perception, attempted weight loss, and ultimately, successful weight loss., (© The Author(s) 2015.)

An ionic polymer metallic composite (IPMC) can perform a bending deformation under an electric field by a small bias voltage. A roughening process is necessary and typically included in the IPMC fabrication. Roughening processes bring several advantages, including better metal adhesion and actuation performance. However, the resulting large surface roughness is an obstacle for optical applications. In this paper, we coated polydimethylsiloxane to improve the surface roughness of IPMC. The improved surface roughness is around 28 nm versus tens of micrometers with an uncoated IPMC. The surface-improved IPMC achieved focusing power of 77 diopters under a 7 V bias voltage. We also found that the lifetime in atmosphere is 30 times longer than that of the nonimproved IPMC. Compared with other popular focusing techniques, such as liquid lenses or micromachined deformable mirrors, the driving voltage is at least one order of magnitude lower and the tunable range is two to three times larger. The effects of the surface-improved fabrication on reflectance, surface scattering, and actuation performance are also discussed. We demonstrate the surface-improved method to construct a patterned IPMC deformable membrane for optical applications.

This study investigated the activities of prepared and commercial V(2)O(5)-WO(3) catalysts for simultaneous removals of NO and polycyclic aromatic hydrocarbons (PAHs) and the influences of particulates, heavy metals, SO(2), and HCl on the performances of catalysts. The experiments were carried out in a laboratory-scale waste incineration system equipped with a catalyst reactor. The DREs of PAHs by prepared and commercial V(2)O(5)-WO(3) catalysts were 64% and 72%, respectively. Increasing the particulate concentrations in flue gas suppressed the DRE of PAHs, but increasing the carbon content on surface of catalysts promotes the NO conversions. The DRE of PAHs by the catalysts was significantly decreased by the increased concentrations of heavy metal Cd, but was promoted by high concentration of Pb. The influence level of SO(2) was higher than HCl on the performances of V(2)O(5)-WO(3) catalysts for PAHs removal, but was lower than HCl for NO removal. Prepared and commercial V(2)O(5)-WO(3) catalysts have similar trends on the effects of particulates, heavy metals, SO(2), and HCl. The results of ESCA analysis reveal that the presence of these pollutants on the surface of catalysts did not change the chemical state of V and W.

A novel structure, namely a laterally tapered undercut active-waveguide (LTUAWG) for an optical spot-size converter (SSC) is proposed and demonstrated in this paper. Using a selectively undercut-etching-active-region (UEAR) on a laterally tapered ridge to define a LTUAWG, a vertical waveguide directional coupler (VWGDC) can be fabricated simply by a wet etching-based technique. The VWGDC comprises a top LTUAWG and a bottom passive waveguide (PWG). An electroabsorption modulator (EAM) is monolithically integrated with a LTUAWG-VWGDC serving as the connecting active waveguide (AWG) and the optical transmission testing device. Through a loss budget analysis on an EAM-integrated VWGDC, an optical mode transfer loss of -1.6 dB is observed between the PWG and the AWG. By comparing the reverse directions of optical excitation, the identical optical transmission relations with bias are observed, further verifying the high efficiency properties in a SSC. Optical misalignment tolerance is employed to test the two transferred optical modes. 1dB misalignment tolerance of +/-2.9 microm (horizontal) and +/-2.2 microm (vertical) is obtained from the PWG, which is better than the value of +/-1.9 microm (horizontal) and +/-1.6 microm (vertical) from the AWG. Far-field angle measurement shows 6.0 degrees (horizontal) 9.3 degrees (vertical) and 11 degrees (horizontal) x 20 degrees (vertical) for the PWG and the AWG, respectively, exhibiting the capability of a mode transformer. All of these measurements are also examined by a 3D beam propagation method (BPM) showing quite consistent results. In this wet etching technique, no regrowth is needed during processing. Furthermore, UEAR processing controlled by in situ monitoring can lead to a simple way for submicron-size processing, showing that a highly reliable processing technique can thus be expected. A low cost of fabrication can also be realized, indicating that this method can be potentially used in optoelectronic integration.