cssi/SciSciGPT-SciSciNet huggingface dataset:
Development of a Novel Assay for Pink1-Parkin-Miro1 Pathway

Mutations in the parkin and PINK1 genes are a major cause of autosomal recessive early-onset Parkinson disease (PD). Several studies have shown that PINK1 phosphorylates Parkin, Parkin substrates, and ubiquitin, thereby stimulating ubiquitination of proteins on the mitochondrial surface (i.e. Miro1) by the Parkin E3 ligase. The ubiquitinated proteins then are degraded, which signals for mitochondrial clearance. Although it is imperative to understand these events at the molecular level, current biochemical methods are cumbersome and lack the resolution to answer these questions thoroughly. Most importantly, physiological E2 partners for Parkin ligase are contested in the field. Here, we report a novel assay to study the PINK1-Parkin-Miro1 pathway that fundamentally addresses the aforementioned problems. In our assay, the ubiquitin c-terminus is chemically activated as a thioester that can undergo transthiolation with the catalytic cysteine of the Parkin E3 ligase, thereby directly charging ubiquitin to Parkin E3s without the need for E1, E2 and ATP. We demonstrate that this simplified two-component system recapitulates two native functions of Parkin, Miro1 ubiquitination and autoubiquitination. This simplified E2-bypassing assay will be generally useful to study the Parkin mechanism and to screen small molecular Parkin activators to treat PD.
PEG-farnesyl thiosalicylic acid telodendrimer micelles as an improved formulation for targeted delivery of paclitaxel.

We have recently designed and developed a dual-functional drug carrier that is based on poly(ethylene glycol) (PEG)-derivatized farnesylthiosalicylate (FTS, a nontoxic Ras antagonist). PEG5K-FTS2 readily form micelles (20–30 nm) and hydrophobic drugs such as paclitaxel (PTX) could be effectively loaded into these micelles. PTX formulated in PEG5K-FTS2 micelles showed an antitumor activity that was more efficacious than Taxol in a syngeneic mouse model of breast cancer (4T1.2). In order to further improve our PEG-FTS micellar system, four PEG-FTS conjugates were developed that vary in the molecular weight of PEG (PEG2K vs PEG5K) and the molar ratio of PEG/FTS (1/2 vs 1/4) in the conjugates. These conjugates were characterized including CMC, drug loading capacity, stability, and their efficacy in delivery of anticancer drug PTX to tumor cells in vitro and in vivo. Our data showed that the conjugates with four FTS molecules were more effective than the conjugates with two molecules of FTS and that FTS conjug...
Scaling of fracture in quasibrittle materials and the question of possible influence of fractal morphology

The paper presents a review of recent results on the problem of size effect (or the scaling problem) in nonlinear fracture mechanics of quasibrittle materials and on the validity or recent claims that the observed size effect may be caused by the fractal nature of crack surfaces. The problem of scaling is approached through dimensional analysis and asymptotic matching. Large-size and small-size asymptotic expansions of the size effect on the nominal strength of structures are presented, considering not only specimens with large notches (or traction-free cracks) but also structures with no notches. Simple size effect formulas matching the required asymptotic properties are given. Regarding the fractal nature of crack surfaces, it is concluded that it cannot be the cause of the observed size effect.
Histamine Methyltransferase: Inhibition and Potentiation by Antihistamines

The activities of histamine methyltransferase preparations partially purified from several mammalian sources are activated by low concentrations of histamine ( K m = 6-9 µM) and are markedly inhibited by histamine concentrations in excess of 10 µM. A variety of antihistaminic drugs are potent competitive inhibitors of histamine methyltransferase in the presence of histamine concentrations below 10 µM, but enhance enzyme activity at higher histamine concentrations. These effects of antihistamines correlate partially with their antihistaminic activity. ACKNOWLEDGMENTS We wish to thank the following companies for donations of drugs: d -chlorpheniramine maleate. d -brompheniramine maleate, l -chlorpheniramine maleate, l -brompheniramine maleate, and chlorpheniramine maleate, Schering Corporation; brompheniramine maleate, A. H. Robins Company; chlorcyclizine hydrochloride and triprolidine hydrochloride, Burroughs Wellcome and Company; bromdiphenhydramine hydrochloride and diphenhydramine hydrochloride, Parke, Davis and Company; diphenylpyramine hydrochloride and chlorpromazine hydrochloride. Smith Kline & French Laboratories, carbinoxamine maleate and haloperidol, McNeil Laboratories; dimethindene, antazoline phosphate, and tripelennamine hydrochloride, Ciba Pharmaceutical Company; fenazoxine hydrochloride and orphenadrine hydrochloride, Riker Laboratories; promethazine hydrochloride, Wyeth Laboratories; pyrathiazine hydrochloride, Upjohn Company; thioridazine, Sandoz Pharmaceutical Company; cyclizine, Sterling-Winthrop Research Institute; chlordiazepoxide and diazepam, Hoffmann-La Roche, Inc.; pentobarbital sodium, Abbott Laboratories; and α-hydrazinohistidine, Merck Institute for Therapeutic Research. We would like to thank Drs. Donald Coffey, Allen Fenselau, and David Chou for their advice on some of the theoretical aspects of this work, and Mrs. Birgitta Brown for her technical assistance.
Investigation and Estimation of the Population Size of Men having Sex with Men in Main Urban Area of Kunming

Objective To estimate the population size of men who have sex with men(MSM),so as to provide reference for taking AIDS intervention measures of MSM population and planning health resources input in Kunming.Methods Multiplier method was used to estimate the population size of MSM.Related parameters were collected by Website questionnaire survey and questionnaire surveys among places for MSM's activities.Results The average number of MSM in main urban area of Kunming was 14164(95%CI: 12968-16078).The average number of MSM frequently being on line was 5722(95%CI: 5239~6496) and the average number being seen frequently in public place was 11084(95%CI: 10148 ~12581).Conclusion It is feasible to estimate the population size of MSM by multiplier method,which basiclly reveals the population size of MSM in main urban area of Kunming.
Development of Values Questionnaire for Middle School Students and Confirmatory Study on Its Structure

Based On summarization related theories and findings of open survey with adolescents,A Questionnaire of Values for Middle School Students(QVMSS)was developed,and 971 middle school students were administered with the questionnaire.The findings showed that(1)The Values of middle school students' includes the terminal and the instrumental values.The terminal Values consists of 11 dimensions such as health and safety,enjoyment,substance,self-fulfillment,cognition,respect,adscription,emotion,nonobjective feeling,society and justice;the instrumental Values consists of 4 dimensions such as capacity,character,attitude to others,acting fashion.(2)Excellent reliability,and construct validity of QVMSS are confirmed in this study.The dimension and structure are found to be stable across gender and grades after comparisons among multiple samples.
Abstract 119: Assessing Modifications to Increase Power in a Stepped Wedge Designed Trial Targeting Improved Medication Adherence for Ischemic Heart Disease Patients

Background: Stepped wedge trial designs are often used to avoid simultaneous roll out of an intervention to all sites, yet time and monetary constrains may prevent all sites from receiving the intervention. In a multi-faceted trial using proactive real-time monitoring of patients to improve medication adherence for ischemic heart disease (IHD) patients, control data are passively collected through the standard electronic health record. Thus, study power may be augmented in a cost-efficient manner by modifying the traditional stepped wedge design to include sites acting strictly as controls, rather than by including more intervention sites. Methods: Based on previously collected data, we simulated models using a continuous adherence outcome and a traditional stepped wedge design rolling out an intervention to 4 sites over 4 waves (plus 1 baseline period). We varied the proportion of total variation attributed to site level variation in baseline outcomes (intraclass correlation or ICC). Power was estimated using theory and simulation with linear mixed models accounting for site level variation and time trend. Control sites were then added and the additional power generated was compared to a strategy in which the number of intervention sites was increased. Results: The addition of 3 or fewer control sites provides more power compared to the addition of a similar number of intervention sites. The effect of additional control sites plateaus and eventually is surpassed by additional intervention sites (see figure). Increasing the ICC decreases both power and the asymptote for the additional control sites; however, power with additional intervention sites continues to increase towards 100%. Conclusions: The use of sites acting strictly as controls in a trial targeting medication adherence for IHD patients provides more power at lower cost, especially with initial additional sites. Simulation provides results needed to achieve a balance between required power for the study, hypothesized site level variation, and resources required for additional control versus intervention sites to determine the number and type of sites to include. ![][1] [1]: /embed/graphic-1.gif
Algebraic Theory of the Three-Body Problem

The three-body problem appears in many branches of physics (Fig.1). Many techniques have been developed to solve the non-relativistic quantum mechanical problem for 3 particles interacting through a two-body or three-body force. These techniques are designed to solve the differential or integro-differential Schrodinger equation. In this article, an alternative formulation of the three-body is given, in terms of Lie algebras. This formulation provides a framework for detailed calculations and, most importantly, allows one to classify all solutions that can be obtained in closed form (exactly solvable problems).
Diagnosis and treatment of incontinence in the institutionalized elderly.

A selective, stepped strategy will diagnose the cause of incontinence in most institutionalized elderly patients. It consists of rectifying the transient causes of incontinence, searching for serious and treatable underlying conditions, and then formulating a differential diagnosis. If the benefit of empiric therapy exceeds the risk it can be initiated, recalling that incontinence in these patients is multifaceted, and that small improvements in many areas unrelated to the urinary tract will often be sufficient to restore continence. If the risk of empiric therapy exceeds the benefit, further urodynamic testing is warranted since it is safe, feasible, and reproducible. Such an approach will minimize the use of invasive testing, indwelling catheters, and toxic medications. Coupled with optimism, creativity, and persistence, it can lead to substantial improvements in the lives of many incontinent institutionalized patients. Ultimately, the optimal care of incontinence in the nursing home will require an increased number of motivated and well-paid nursing assistants, less invasive diagnostic testing, and improved, better targeted therapy. Still, even in 1989, much can be done to "cure sometimes, relieve often, and comfort always."
Modeling and Design Space Exploration for Bit-Cells Based on Voltage-Assisted Switching of Magnetic Tunnel Junctions

The effect of voltage on the anisotropy of a magnetic tunnel junction (MTJ) is of substantial interest for low-power nonvolatile memory applications. In this paper, we develop a device-to-bit-cell level simulation framework for voltage-assisted switching of the MTJs, which can satisfactorily reproduce the published experimental data. Our simulation framework is based on a coupled Landau–Lifshitz–Gilbert–Slonczewski equation and nonequilibrium greens function formalism. Using this simulation framework, we investigate the effect of scaling the oxide thickness of an MTJ to enhance the electric field effect. Although it seems attractive for an isolated device, yet, in a bit-cell configuration, reducing the oxide thickness leads to an increase in the supply voltage. In addition, we demonstrate that the unipolar characteristic of the voltage-assisted switching leads to write failures depending on the initial state stored in the MTJ. We, therefore, suggest a read before write scheme exhibiting approximately $2\times $ improvement in the write energy consumption at a bit-cell level compared with a standard STT-MRAM for iso-oxide thickness. However, the latency overhead associated with voltage-assisted MTJs results in a $1.55\times $ degradation of the write speed. Moreover, our layout analysis indicates that the bit-cell area reduction is constrained by the metal pitch, in spite of smaller access transistors.
Obscure Groin Pain in Women

The concept of hidden hernias was first introduced in the 1970s by two separately interested surgeons from the United States: William Webb from Alabama and Jack Herrington from Wisconsin. They each noticed that women were presenting with symptoms suggestive of inguinal hernia; however, the surgeons had a hard time diagnosing hernia on physical examination. Their patients reported intermittent pain along the inguinal canal that was related to physical activity. However, the physical examination was essentially normal and “without detectable impulse.”
Translating STAT Inhibitors from the Lab to the Clinic

Oncogenic transcription factors represent unique and potentially high value targets for cancer therapy. Proteins like STAT3 and STAT5 are generally not mutated themselves. However, oncogenic signals arising from a wide array of upstream mutations and signaling events converge on a small number of these transcription factors to regulate expression of key genes involved in critical processes including proliferation, survival and invasion. While cancer cells frequently show a high dependency on continued activation of these proteins, normal cells are largely tolerant to interruption of these pathways due to redundancies in transcriptional regulators. Consequently, inhibition of STATs holds the potential to have a very high therapeutic index. The challenge has been to develop strategies to inhibit these proteins that lack domains that are easily amenable to antagonism by small molecules. In recent years, a number of promising strategies have emerged, and now clinical trials of approaches to directly inhibit activated STATs have been developed. The success of these studies, both in terms of clinical efficacy and understanding the molecular effects of STAT inhibitors in humans, may open a new front in the rational, targeted eradication of cancer.
Lost in Desirada: Who is Her Daughter’s Keeper?

To uplift, empower and save our daughter(s) is ultimately a conscious choice and conscientious practice. —K. Simeon-JonesThe age-old focus on the father-daughter relationship, with the damaging imp...
Chapter 4 - Magnetic Structures

Neutron scattering is the most powerful tool for the detailed study of magnetic structures and is an essential step in understanding underlying physical phenomena occurring in complex magnetic materials. The main goal of this chapter is to expose the reader to the current state of how magnetic structures are determined using neutron diffraction and how they are described. The chapter includes a short history of the beginnings of magnetic structure determination, theoretical and practical aspects in determining magnetic structures, and offers important examples of magnetic structures hierarchized on the basis of the dimensionality of magnetic correlations determined by the underlying crystal structure. The selected examples range from simple ferro- and antiferromagnetic orders to the more complex helical and conical spiral orders, commensurate and incommensurate.
Nonalcoholic fatty liver disease and gastric bypass surgery regulate serum and hepatic levels of pyruvate kinase isoenzyme M2

Treatment of nonalcoholic fatty liver disease (NAFLD) focuses on the underlying metabolic syndrome, and Roux-en-Y gastric bypass surgery (RYGB) remains one of the most effective options. In rodents...
Athlete Scandals and Endorsement Marketing: Research Trends and Introduction to Topics

ABSTRACTEndorsement marketing has been widely used to generate consumer attention, interest, and purchase behaviors among targeted consumers. However, relatively little systematic research has been...
The Value of Real-Time Thoracic Radiology Consulting in an Integrated Lung Center Clinic: Bringing the Radiologist to the Center of Multidisciplinary Health Care.

Purpose:We have established an integrated thoracic radiology reading room within a multidisciplinary lung center clinic (LC). While our subjective experience has been positive, we sought to quantify how this model affects radiology workflow and whether the referring practitioners perceive value in h
Marital Satisfaction and an Information-Processing Measure of Partner-Schemas

In comparison with most research on relationship cognitions that has focused on cognitive contents as assessed by self-report measures, this study introduces an information-processing measure of partner-schemas, based on the incidental recall task. Indices from this task include judgments as to whether negative and positive personal adjectives describe the partner (i.e., a measure of schema content) and incidental recall of adjectives initially endorsed as describing the partner (i.e., a measure of facilitated recall of schema-relevant information). Results from a sample of married couples indicated that the newly introduced measure of partner—schemas was correlated with marital satisfaction, and that these correlations remained significant when controlling for symptoms of depression. These findings suggest that the incidental recall task may be a useful measure of partner-schemas.
Sustainable Water Management Defies Long-term Solutions

The popular and academic media are rife with calls to sustainably manage our water resources and to ‘solve our water problems.’ Yet, evidence suggests that throughout history, our efforts to ‘solve’ water problems have simply generated new problems. Humans have drained swamps to solve problems of disease and land shortage. This subsequently reduced water supply and increased flooding in many areas. Humans dammed rivers to solve problems related to energy and irrigation, thereby reducing ecosystem resiliency. Humans established a water-based sewerage system to solve problems of aesthetics and health and as a result increased water consumption and created a dependency on massive infrastructure. The insistence on solutions may exacerbate rather than alleviate negative conditions, in part, because it discourages decision-makers and citizens from accepting long-term responsibility for managing water to sustain ourselves. The authors argue that addressing water problems requires a cognitive shift to recognize the concept of ‘wicked problems’ and to subsequently change discourse about water to resist the idea of solutions.
The Case for Total Androgen Blockade in the Management of Metastatic Prostate Cancer

Claims have been made by Labrie et al for a dramatically improved survival and time to progression in patients with Stage D2 prostate cancer treated with total androgen blockade. (1) They used daily injections of an LHRH agonist to suppress pituitary LH and testosterone along with an antiandrogen, flutamide, to block residual prostatic DHT derived from adrenal androgens. With this therapeutic program, Labrie has claimed 90 percent survival in 52 patients followed for 2 years compared to an average survival at 2 years of 40 to 60 percent in a variety of historical controls. (1) In addition, this group has reported that progression of disease at 17 months averaged 26 percent in 88 patients, compared to 70 percent progression in a recent historical control group treated with either leuprolide (LHRH) or DES, 3 mg. per day. Recent reports of attempts to reproduce the results of Labrie et al have been unsuccessful and both Brisset et al (2) from France and Beland et al from Canada have reported no difference in time to progression or survival in relatively small numbers of patients followed for 18 months and treated with either orchiectomy alone or total androgen blockade. In view of these conflicting findings it was felt important to review the role of adrenal androgens in prostate cancer, since total androgen blockade differs from traditional therapy only in regard to the addition of adrenal blockade to blockade of gonadal androgen.
The Presentation of Ethics in Undergraduate Psychology Syllabi: A Review

To identify where ethics is presented to undergraduate psychology students, this study reviewed a national sample of 706 syllabi for required mandatory psychology courses. The results indicated tha...
"The Expanding First Amendment" in an Age of Free Speech Paradox

In terms of felt experience, many Americans perceive that their capacity to speak freely is increasingly being imperiled in ways for which they have no legal recourse. Yet it has never been easier for individuals to find platforms from which to communicate pretty much anything at all to an audience of potentially global reach. This is largely because of the influence of the new digital platforms on which so much speech occurs. On one hand, the Supreme Court in recent years has broadened the domain of communicative activity covered by the First Amendment’s “speech” protection and has limited in other ways the capacity of government to regulate communication based on content. Yet private web hosts have no legal obligation to deny a forum for communications that others may find offensive or intimidating. Thus, at the same time that digital technologies (along with print, broadcast, and cable) provide unprecedented opportunities for people to share provocative views, many people may find that they enter public debate only at risk of unleashing a torrent of personal attack that may be a source of embarrassment or worse. In short, Americans find their lived experience of “free speech” conditioned not only by the First Amendment’s restrictions on government censorship, but also by social norms, the exercise of private authority, the ways in which speaking rights interact with other rights, and the opportunities and risks associated with expanding information technologies.
Sour gas transport in poly(ether-b-amide) membranes for natural gas separations

Abstract Innovations in membranes for natural gas processing frequently consider ideal separation performance as the defining success metric for removing carbon dioxide (CO2) from methane (CH4). However, realistic natural gas feeds are complex mixtures containing additional constituents of varying concentrations, including hydrocarbons, inert gases, and hydrogen sulfide (H2S). As natural gas demand spurs production from sub-quality sour natural gas wells, simultaneous CO2 and H2S removal becomes an increasingly relevant separation challenge. Although CO2 separations are well studied, health and environmental hazards of H2S often impede mixed gas permeation testing of membranes with H2S-containing feeds. This work aims to further sour gas membrane research by studying the impact of feed compositions on gas transport properties of membranes formed from five different grades of commercial polyether-b-amide (Pebax®). High pressure mixed gas permeation testing confirmed the importance of membrane stability: CO2/CH4 selectivity values for each membrane dropped by 24–42% under mixed sour gas feeds compared to ideal selectivities. Membrane stability correlates well with extents of hydrogen bonding, but overall performance depends largely on block type and relative block content. When exposed to a 20% H2S-containing feed, Pebax® 1074 and 1657 retained the highest selectivities of 12.0–12.8 for CO2/CH4 and 79.9–80.6 for H2S/CH4 at 800 psi. The changes in membrane performance with variations in gas content and pressure highlight the importance of screening membranes with realistic gas feeds.
Remote Sensing for Maritime Monitoring and Vessel Characterization

The main objective of the work described here concerns the development of automatic ICT procedures in charge of processing imagery data captured by satellite-borne sensors to assess the status of a given maritime area. The mentioned assessment may refer to the detection and identification of peculiar objects, such as oil leaks or, in case of maritime traffic control, the recognition of navigating vessels. This paper specifically focuses on the development of methods for estimating the kinematics of a navigating vessel through the detection and analysis, in the 2D satellite imagery, of the corresponding wake pattern. The proposed method differentiates from those retrieved in previous literature for the introduction of a novel preprocessing stage, which allows for an enhancement in the overall performance of the wake detector. The resulting procedure represents a key functionality to be included in platforms dedicated to sea surveillance.
Veering off track in U.S. high schools? Redirecting student trajectories by disrupting punishment and math course-taking tracks

Abstract Students in punishment “tracks” are rarely in advanced course-taking “tracks” in high school. Yet, there is little research that demonstrates the relationships between punishment and advanced course-taking, nor research that demonstrates how punishment and advanced course-taking together can impact long-term student trajectories. Using multi-level modeling with a national longitudinal study of high school students, we observed reciprocal disruptions. Advanced math courses significantly impacted future suspensions when accounting for prior suspensions, while suspensions significantly impacted future advanced math course-taking when accounting for prior math courses. We also observed that both suspensions and advanced math courses significantly influenced dropout status and college attendance. As baseline measures often maintained a strong relationship with their respective outcomes, disadvantages appeared to accumulate when students were excluded both from advanced math courses and through suspensions. Nevertheless, while we cannot undo the harms of previous disadvantages in punishment, our findings suggest that we can facilitate potential turning points in students’ lives by opening up new opportunities in math. By doing so, we can redirect students towards college. We conclude with a discussion of implications for policy and practice.
CosR Is a Global Regulator of the Osmotic Stress Response with Widespread Distribution among Bacteria

ABSTRACT Bacteria accumulate small, organic compounds called compatible solutes via uptake from the environment or biosynthesis from available precursors to maintain the turgor pressure of the cell in response to osmotic stress. The halophile Vibrio parahaemolyticus has biosynthesis pathways for the compatible solutes ectoine (encoded by ectABC-asp_ect) and glycine betaine (encoded by betIBA-proXWV), four betaine-carnitine-choline transporters (encoded by bccT1 to bccT4), and a second ProU transporter (encoded by proVWX). All of these systems are osmotically inducible with the exception of bccT2. Previously, it was shown that CosR, a MarR-type regulator, was a direct repressor of ectABC-asp_ect in Vibrio species. In this study, we investigated whether CosR has a broader role in the osmotic stress response. Expression analyses demonstrated that betIBA-proXWV, bccT1, bccT3, bccT4, and proVWX are repressed in low salinity. Examination of an in-frame cosR deletion mutant showed that expression of these systems is derepressed in the mutant at low salinity compared with the wild type. DNA binding assays demonstrated that purified CosR binds directly to the regulatory region of both biosynthesis systems and four transporters. In Escherichia coli green fluorescent protein (GFP) reporter assays, we demonstrated that CosR directly represses transcription of betIBA-proXWV, bccT3, and proVWX. Similar to Vibrio harveyi, we showed betIBA-proXWV was directly activated by the quorum-sensing LuxR homolog OpaR, suggesting a conserved mechanism of regulation among Vibrio species. Phylogenetic analysis demonstrated that CosR is ancestral to the Vibrionaceae family, and bioinformatics analysis showed widespread distribution among Gammaproteobacteria in general. Incidentally, in Aliivibrio fischeri, Aliivibrio finisterrensis, Aliivibrio sifiae, and Aliivibrio wodanis, an unrelated MarR-type regulator gene named ectR was clustered with ectABC-asp, which suggests the presence of another novel ectoine biosynthesis regulator. Overall, these data show that CosR is a global regulator of osmotic stress response that is widespread among bacteria. IMPORTANCEVibrio parahaemolyticus can accumulate compatible solutes via biosynthesis and transport, which allow the cell to survive in high salinity conditions. There is little need for compatible solutes under low salinity conditions, and biosynthesis and transporter systems need to be repressed. However, the mechanism(s) of this repression is not known. In this study, we showed that CosR played a major role in the regulation of multiple compatible solute systems. Phylogenetic analysis showed that CosR is present in all members of the Vibrionaceae family as well as numerous Gammaproteobacteria. Collectively, these data establish CosR as a global regulator of the osmotic stress response that is widespread in bacteria, controlling many more systems than previously demonstrated.
Grading systems of oral cavity pre-malignancy: a systematic review and meta-analysis.

Oral potentially malignant disorders (OPMDs) may have varying degrees of oral epithelial dysplasia (OED). Traditional grading schemes separate OED into three-tiers (mild, moderate, and severe). Alternatively, a binary grading system has been previously proposed that stratifies OED into low-risk and high-risk categories based on a quantitative threshold of dysplastic pathologic characteristics. This systematic review evaluates the predictive value of a binary OED grading system and examines agreement between pathologists. This meta-analysis queried 4 databases (PubMed, Ovid-MEDLINE, Cochrane, and SCOPUS) and includes 4 studies evaluating binary OED grading systems. Meta-analysis of proportions and correlations was performed to pool malignant transformation rates (MTR), risk of malignant transformation between OED categories, and measures of interobserver agreement. Pooled analysis of 629 lesions from 4 different studies found a six-time increased odds of malignant transformation in high-risk lesions over low-risk lesions [odds ratio (OR) 6.14, 95% 1.18–15.38]. Reported ORs ranged from 2.8 to 22.4. The overall MTR was 26.8%, with the high-risk and low-risk lesions having MTRs of 57.9% (95% CI 0.386–0.723) and 12.7% (95% CI − 0.210 to 0.438), respectively. Pooled unweighted interobserver kappa values for the binary grading system and three-tiered system were 0.693 (95% CI 0.640–0.740) and 0.388 (95% CI 0.195–0.552), respectively. Binary grading of OED into low-risk and high-risk categories may effectively determine malignant potential, with improved interobserver agreement over three-tiered grading. Improved grading schemes of OED may help guide management (watchful waiting vs. excision) of these OPMDs.
Food and place: a critical exploration

It is well established now that food as a matter of both popular and academic interest is having its time in the sun. Chefs have become celebrities. Nutritional, socio-political, and environmental ...
Exoskeleton Assistance Improves Crouch during Overground Walking with Forearm Crutches: A Case Study

Research, development and testing of wearable robotic exoskeletons for gait training and improved mobility in children with cerebral palsy (CP) and other movement disorders has become increasingly prevalent in recent years. Broadly, these devices are split into two categories: fully wearable devices that are affixed to the lower limbs and/or pelvis and systems that include a mobile frame that moves with the user. The former systems have generally targeted more functional individuals who are independent walkers while the latter target more affected individuals who do not ambulate on their own. The best strategy for children in the middle of this mobility spectrum (GMFCS III), who can walk short distances using assistive instruments like crutches or walkers, is not clear. Yet, these children may benefit most from gait training because they are at the highest risk to lose their independent mobility. Here, we present a case study of a wearable robotic exoskeleton for overground walking in a child with CP at GMFCS III. Our results demonstrate that the exoskeleton was able to synchronize assistance to five discrete phases of the gait cycle during overground walking with forearm crutches. Peak knee extension improved on average by 10 degrees in the right leg and 7 degrees in the left leg when walking with exoskeleton assistance during early stance, mid-stance and late swing without reduction in muscle activity. Therefore, state-based control for providing robotic extension assistance to individuals with crouch from CP who walk with assistive instruments should be further investigated as a potential rehabilitation strategy.
Lipid metabolism dysregulation in diabetic retinopathy.

Abstract Lipid metabolic abnormalities have emerged as potential risk factors for the development and progression of diabetic complications, including diabetic retinopathy (DR). This review article provides an overview of the results of clinical trials evaluating the potential benefits of lipid-lowering drugs, such as fibrates, omega-3 fatty acids, and statins, for the prevention and treatment of DR. Although several clinical trials demonstrated that treatment with fibrates leads to improvement of DR, there is a dissociation between the protective effects of fibrates in the retina, and the intended blood lipid classes, including plasma triglycerides, total cholesterol, or HDL:LDL cholesterol ratio. Guided by these findings, plasma lipid and lipoprotein-independent mechanisms are addressed based on clinical, cell culture, and animal model studies. Potential retinal-specific effects of fatty acid oxidation products, cholesterol, and ceramide, as well as lipid-independent effects of PPAR alpha activation, are summarized based on the current literature. Overall, this review highlights promising potential of lipid-based treatment strategies further enhanced by the new knowledge of intraretinal lipids and lipoproteins in DR.
Looking at induced pluripotent stem cell (iPSC) differentiation through the lens of the noncoding genome

Abstract Clinical application of induced pluripotent stem cell–based (iPSC-based) therapies has recently experienced some success for the treatment of degenerative diseases; however, the long-term effects remain unknown. Comprehensive and cell type–specific validation of iPSC-derived cells is a crucial component of their clinical application. Incomplete analyses could obscure potentially dangerous downstream effects when used in a clinical setting. Recently, more comprehensive analyses of iPSC-derived cell types have revealed the retention of an epigenetic memory derived from the somatic cell type source used for pluripotential reprogramming. An epigenetic memory has the potential to be propagated throughout the differentiation process, leading to target cells harboring epigenetic vestiges of their parent somatic cell source. Retention of an epigenetic memory is characterized by aberrant gene expression in iPSCs relative to their native undifferentiated counterparts. Likely contributors to maintenance of epigenetic memory are long noncoding RNAs (lncRNAs) via their role in the regulation of epigenetic and epitranscriptomic modifications, in addition to being epigenetically and epitranscriptomically modified themselves. As epigenetic regulators, lncRNAs have recently been implicated in the regulation of stem cell differentiation and pluripotency programs. Considering the role of the noncoding genome in iPSC reprogramming and differentiation offers the potential to improve clinical outcomes of iPSC-derived tissues. This review will examine iPSC reprogramming, differentiation, target cell type validation, and maintenance of an epigenetic memory. The role of lncRNAs in regulating tissue-specific expression in the context of stem cell differentiation and pluripotency programs will also be reviewed. Exploration of the noncoding genome toward improving current validation standards and iPSC-associated clinical outcomes will be addressed in the future trends and directions.
Special Report from the CDC: Readiness to surge: State health departments’ workforce infrastructure during the opioid crisis

Abstract Introduction: As part of scaling up the response to the opioid overdose epidemic, there is an opportunity to examine how state public health departments addressed workforce and other infrastructure needs to implement a large-scale opioid overdose prevention program. Understanding how this was done—and any lessons learned from the process—can inform future workforce development and capital improvement efforts. Methods: Administrative data from the Centers for Disease Control and Prevention (CDC) Prescription Drug Overdose Prevention for States (PfS) program were analyzed to understand how states adapted to this emerging public health priority. Results: Six months into the first year of funding, 6 of the 16 state health departments had filled all anticipated staffing positions. States faced challenges obtaining timely expenditure authority and hiring staff. However, states were able to overcome these challenges by strategically reassigning staff, hiring from within, and utilizing existing contract mechanisms. Conclusion: Our analysis revealed how planning, using existing infrastructure, and maintaining a prepared workforce are critical to ensure that public health agencies have the ability to surge to meet emerging challenges and effectively utilize resources to achieve program goals. practical applications: Greater attention should be directed toward strategically addressing known barriers and timelines in work plans and budgets during the application and selection process to ensure implementation readiness.
Associations between electronic nicotine delivery systems and birth outcomes.

Nicotine crosses the placenta and is a known teratogen. The use of electronic nicotine delivery systems (ENDS) has increased among pregnant women in the US, but there is limited knowledge about the...
Multi-layer CRISPRa/i circuits for dynamic genetic programs in cell-free and bacterial systems.

Summary CRISPR-Cas transcriptional circuits hold great promise as platforms for engineering metabolic networks and information processing circuits. Historically, prokaryotic CRISPR control systems have been limited to CRISPRi. Creating approaches to integrate CRISPRa for transcriptional activation with existing CRISPRi-based systems would greatly expand CRISPR circuit design space. Here, we develop design principles for engineering prokaryotic CRISPRa/i genetic circuits with network topologies specified by guide RNAs. We demonstrate that multi-layer CRISPRa/i cascades and feedforward loops can operate through the regulated expression of guide RNAs in cell-free expression systems and E. coli. We show that CRISPRa/i circuits can program complex functions by designing type 1 incoherent feedforward loops acting as fold-change detectors and tunable pulse-generators. By investigating how component characteristics relate to network properties such as depth, width, and speed, this work establishes a framework for building scalable CRISPRa/i circuits as regulatory programs in cell-free expression systems and bacterial hosts. A record of this paper’s transparent peer review process is included in the supplemental information .
Practicing Social Skills Training for Young Children with Low Peer Acceptance: A Cognitive-Social Learning Model

Peer acceptance during early childhood is related to children's academic achievement, adjustment in school, and even psychological well-being in adulthood. Children who experience low peer acceptance exhibit socially inappropriate behavior patterns, which are associated with irrelevant patterns of information processing. Therefore, as a way of helping children with low peer acceptance, a cognitive-social learning model of social skills training has been used because the model focuses on cognitive changes as well as behavioral changes. Three parts of the social skills training—enhancing skill concepts, promoting skill performance, and fostering skill maintenance/generalization—are discussed. In order to be successful, a trainer should understand the training model as well as behavioral patterns of children with low peer acceptance to provide theory-based and individualized feedback to each participant.
Radiation control with selectively reflective overcoats

Selectively reflective overcoats can be used to significantly reduce the temperature of a heated surface under conditions where short-wavelength radiation is the predominant mode of heat transfer to the surface and the total heating is below the melting or ablation limit. In addition, these overcoats can be used to detect and characterize radiation. Theoretical models are used to predict the optical properties of selectively reflective overcoats on an opaque substrate, such as metal or reaction-cured glass. The computed surface reflectance is compared with experimental data. The predicted optical properties of selectively reflective overcoats are used to compute the reduction in surface temperature attainable with this strategy. Design curves are presented for investigating selectively reflective overcoats of different materials. Nomenclature A = absorption coefficient a = absorption, m"1, series coefficient B = backscatter fraction b = series coefficient c - separation between particles, m d = particle diam, m e = blackbody function, W/m2 • /xm fv = solid-volume fraction
Comparing outdated and updated textbook figures helps introduce undergraduates to primary literature.

Many of the didactic tools used in the undergraduate classroom, including textbooks, often highlight science as a body of knowledge, presenting learners with a field’s current “up-to-date” understanding of a subject. It is important that students grasp the idea that this body of knowledge is not static, but evolving through a process by which scientists continually test, revise, and build upon that knowledge. Science as a process is best highlighted in the primary scientific literature. In the context of the undergraduate classroom, we have used side-by-side comparison of old and updated textbook figures to introduce 200- and 300-level Genetics students to the field as a dynamic area of scientific inquiry. We also use this exercise as an opportunity to introduce students to relevant primary literature. We find that this is an effective way to transition students from their textbook to primary literature as a source of information.
Lithium-doped β-tricalcium phosphate: Effects on physical, mechanical and in vitro osteoblast cell-material interactions.

In this work, we have investigated the effects of lithium (Li) dopant at different concentrations and sintering temperatures on the physical and mechanical properties of β-tricalcium phosphate (β-TCP). Our results showed that Li addition at concentrations of 0.65 and 1.0 wt % inhibits the β-TCP to α-TCP phase transformation. 0.15 wt % Li addition resulted in grain growth and extensive liquid phase was formed at higher concentrations. At 1150°C, compressive strength of β-TCP increased from 138.7 ± 19.9 MPa to 170.9 ± 29.8 MPa with the addition of 0.15 wt % Li. Addition of higher amounts of Li decreased the compressive strength and the lowest compressive strength of 99.8 ± 13.7 MPa was found in samples containing 1.0 wt % Li. After 3 days of culture, osteoblast cells grew to confluence on samples containing 0.65 and 1.0 wt % Li. Cells grew to confluence on all doped samples after 11 days of culture and optical cell density was 4-5 folds higher on 0.15 and 1.0 wt % Li-doped TCP samples. Our results show that both Li content and sintering temperature have significant influence toward physicochemical and mechanical properties of β-TCP which affects the osteoblast cell-materials interaction in Li-doped TCP scaffolds. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 391-399, 2017.
CMOS hot carrier lifetime improvement from deuterium anneal

It has been demonstrated that post-metallization anneal in a deuterium ambient increases the hot carrier lifetime of NMOS devices biased at the peak substrate current (Lyding et al, 1996; Kizilyalli et al., 1997). In this work, for the first time, we report on the lifetime improvement factor for both NMOS and PMOS devices stressed at a variety of DC and AC bias conditions. The devices studied were fabricated using an advanced 0.25 μm dual-poly gate CMOS technology with 4 nm gate oxide thickness.
Dietary inulin suppresses azoxymethane-induced preneoplastic aberrant crypt foci in mature Fisher 344 rats.

Preneoplastic aberrant crypt foci (ACF) are generally accepted as reliable markers for colon carcinogenesis in animal models. Rat model ACF studies, however, use younger rats, and there are no published reports on the suitability of adult rats for ACF studies. In this study, inulin, a known suppressor of azoxymethane (AOM)-induced ACF, was tested for its ability to suppress ACF formation in mature rats. After a 2-wk acclimation period, 12-mo-old Fisher 344 retired male breeders received two subcutaneous injections of AOM dissolved in saline at weekly intervals. In experiment 1, six groups received 0, 4, 8, 10, 12 and 16 mg AOM/kg body at each injection and were fed AIN-93M diet. In experiment 2, four groups of rats were fed 10 mg AOM/kg body at each injection based on the results of experiment 1, and were fed 0, 2.5, 5 and 10 g long-chain inulin diets/100 g. All the rats were killed after 11 -wk feeding periods. In experiment 1, there was a significant (P 10 mg of AOM had greater (P < 0.05) mortality. In experiment 2, there was a significant increase in cecal weight and a decrease in cecal pH from 7.17 in the control group to 6.87, 6.61 and 5.76 in the groups fed inulin at 2.5, 5.0 and 10 g/100 g, respectively. Long-chain inulin dose-dependently reduced ACF incidence in the colon (P < 0.01). Compared with rats fed the control diet, the percentage reductions of ACF in rats fed 2.5, 5.0 and 10 g inulin diets/100 g were 25, 51, and 65, respectively. The results of this study indicate that mature rats can be used as models in ACF studies, and dietary long-chain inulin dose-dependently suppresses AOM-induced ACF formation in Fisher 344 mature male rats.
Implementing Vehicle–Infrastructure Integration: Real-World Challenges

In recent years, much attention in the field of intelligent transportation systems has been devoted to conceptualizing and starting development of vehicle-infrastructure integration (VII), which would provide new vehicles with the capability to communicate data with each other and with roadside transceivers located throughout the roadway network. The bulk of the federal VII activities have focused on defining an overall architecture and the wireless vehicle-infrastructure communication link, while exploring the institutional challenges to deployment. A somewhat different perspective to VII focuses on the real-world challenges that have been encountered and overcome in implementing the first VII test bed environment in California. It is important to understand these practical aspects of installing, operating, and maintaining the VII communications infrastructure when developing plans and cost estimates for large-scale national VII deployment. Lessons learned from the initial VII California test bed develop...