cssi/SciSciGPT-SciSciNet huggingface dataset:
Evidence from knockout mice against physiologically significant aquaporin 8-facilitated ammonia transport

Aquaporin (AQP)8-facilitated transport of NH3 has been suggested recently by increased NH3 permeability in Xenopus oocytes and yeast expressing human or rat AQP8. We tested the proposed roles of AQ...
Effect of Ras Inhibition in Hematopoiesis and BCR/ABL Leukemogenesis

Ras small GTPases are activated in many hematopoietic growth factor signaling and in hematological malignancies, but their role in hematopoiesis and leukemogenesis is not completely known. Here we examined the effect of Ras inhibition by a dominant negative mutant of Ras, N17 H-Ras, in adult hematopoiesis and in BCR/ABL leukemogenesis using the mouse bone marrow transduction and transplantation approach. We found that N17 H-Ras expression suppressed B- and T-lymphopoiesis and erythropoiesis. Interestingly, N17 H-Ras did not suppress myelopoiesis in the bone marrow, yet it greatly attenuated BCR/ABL-induced chronic myelogenous leukemia (CML)-like myeloproliferative disease. Most BCR/ABL + N17 H-Ras mice eventually developed pro-B lymphoblastic leukemia/lymphoma (B-ALL). These results suggest that Ras activation is essential for the development of lymphoid and erythroid cells but not myeloid cells and that Ras is a critical target of BCR/ABL in the pathogenesis of CML, but not B-ALL.
Placenta Accreta in a Separate Uterine Horn

We report the case of a 30-year-old woman who presented with intrauterine fetal demise of a 17-2/7-week male fetus. The patient failed misoprostol induction and was taken for surgical evaluation. At the time of surgery an ectopic pregnancy in a noncommunicating rudimentary uterine horn was found. Histologic examination of the excised remnant uterine horn showed there was a placenta accreta.
Ultrasound mediated drug delivery: The effect of microbubbles on a gel boundary

When microbubble contrast agents are driven by ultrasound, the transport of drugs and particles across cell membranes and blood vessel walls is enhanced. While a wide range of acoustic parameters enhance delivery, the acoustic parameters that maximize delivery while simultaneously minimizing biological effects have not been fully characterized. Here, we use a gel phantom with a Young's modulus similar to that of tissue to directly observe bubble interaction with the gel surface during insonation. Using parameters relevant to diagnostic imaging and drug delivery, we observe fluid jets that impinge on the surface and tunnels that follow the sound beam axis.
A Meta-Analysis of Aortic Root Size in Elite Athletes

Background—The aorta is exposed to hemodynamic stress during exercise, but whether or not the aorta is larger in athletes is not clear. We performed a systematic literature review and meta-analysis to examine whethere athletes demonstrate increased aortic root dimensions compared with nonathlete controls. Methods and Results—We searched MEDLINE and Scopus from inception through August 12, 2012, for English-language studies reporting the aortic root size in elite athletes. Two investigators independently extracted athlete and study characteristics. A multivariate linear mixed model was used to conduct meta-regression analyses. We identified 71 studies reporting aortic root dimensions in 8564 unique athletes, but only 23 of these studies met our criteria by reporting aortic root dimensions at the aortic valve annulus or sinus of Valsalva in elite athletes (n=5580). Athletes were compared directly with controls (n=727) in 13 studies. On meta-regression, the weighted mean aortic root diameter measured at the ...
Study of the effect of hyperbranched polyols on cationic UV curable coating properties

Cycloaliphatic epoxide-based cationic UV curable coatings containing three different hyperbranched polyols (HBPs) were systematically formulated and characterized. Polyether polyols were found to deter epoxide conversion under low UV intensity. For high UV intensity, the cycloaliphatic epoxide conversion increased with polyol content. Coatings with HBPs had better flexibility and solvent resistance than those containing a reference triol. Compared to the triol and polyester HBPs, polyether HBPs imparted lower Tg and hardness but a better flexibilizing effect to the coatings. At higher R values, the coating solvent resistance decreased except for those with one polyether HBP. A two-peak phenomenon was discovered in the residual thermal reaction heat curve after photoDSC experiments. These two peaks were found to be related to the thermal relaxation behavior of the photocured inhomogeneous film, and the reactivation and reaction of the ‘trapped living cationic species’. The capability of the polyol to lower the high-temperature-peak temperature corresponded well with the flexibilizing ability. Copyright © 2006 Society of Chemical Industry
Blood Pressure Genomics

Blood pressure genetics has been instrumental in understanding the pathways that regulate blood pressure and induce hypertension. Two types of approaches have been used with great success: First, studies of hypertensive families in which monogenic blood pressure elevation can be explained by mutations in one of a dozen genes identified so far. Unfortunately, the relevance of these rare familial variants is limited when predicting primary hypertension in the general population. Second, association meta-analyses based on genome-wide genotyping using large sample sizes that have so far yielded about around 60 common genetic variants predicting blood pressure with a small, but reproducible, impact on blood pressure in the general population. This chapter summarizes the current findings based on genome-wide association studies and outlines the conclusions that can be drawn when considering the variants identified in aggregate and gives an outlook of the challenges ahead.
Development and Analysis of a Long-Term, Global, Terrestrial Land Surface Temperature Dataset Based on HIRS Satellite Retrievals

AbstractLand surface temperature (LST) is a critical state variable for surface energy exchanges as it is one of the controls on emitted radiation at Earth’s surface. LST also exerts an important control on turbulent fluxes through the temperature gradient between LST and air temperature. Although observations of surface energy balance components are widely accessible from in situ stations in most developed regions, these ground-based observations are not available in many underdeveloped regions. Satellite remote sensing measurements provide wider spatial coverage to derive LST over land and are used in this study to form a high-resolution, long-term LST data product. As selected by the Global Energy and Water Exchanges project (GEWEX) Data and Assessments Panel (GDAP) for development of internally consistent datasets, the High Resolution Infrared Radiation Sounder (HIRS) data are used for the primary satellite observations because of the data record length. The final HIRS-consistent, hourly, global, 0.5°...
Experimental validation of the interfacial form of the Wiedemann-Franz law.

The thermal conductivity of four $\mathrm{Pd}/\mathrm{Ir}$ metal multilayers of total thickness 390 nm with 40, 80, 120, and 200 $\mathrm{Pd}/\mathrm{Ir}$ interfaces are measured at temperatures between 78 and 295 K using time-domain thermoreflectance. The thermal interface conductance $G$ of the $\mathrm{Pd}/\mathrm{Ir}$ interface is derived from the differences in thermal conductivity between the multilayers. A comparison of $G$ to previously reported data for the electronic specific resistance of the $\mathrm{Pd}/\mathrm{Ir}$ interface at 4 K supports the validity of the interfacial form of the Wiedemann-Franz law. The Lorenz number deduced from this comparison is within 10% of the Sommerfeld value at all temperatures, well within the experimental uncertainties of $\ensuremath{\approx}20%$.
Organic-Inorganic Hybrid Dental Restorative Material

A method for the preparation of dental restorative composites based on an organicinorganic hybrid material is presented. A sol-gel process was used to produce composites comprised of submicron silica in a polymer matrix. Using alcohols such as, 3-allyloxy-1, 2-propanediol and 2, 3-dihydroxypropyl methacrylate in combination with polysilicic acid or cyclic siloxane precursors, modified siloxanes are produced which can be polymerized photochemically with concurrent hydrolysis and condensation to generate a silica-reinforced polymer with superior mechanical properties and abrasion resistance.
Toward building highly available and scalable OpenStack clouds

OpenStack® (the leading open source platform for public and private infrastructure-as-a-service clouds) is composed of a set of loosely coupled and rapidly evolving projects that support a wide set of technologies and configuration options. Deciding how to combine and configure such projects is the determining factor on the overall quality of the cloud, in terms of performance, scalability, and availability. In this paper, we present a methodical framework and empirical analysis to help both cloud providers and users optimize their design and deployment decisions. Cloud providers can rely on this framework to select an appropriate configuration of their cloud for a given service-level agreement. Users developing and running applications on a cloud can better fit virtual resources to their workloads. We demonstrate the power of this framework using several scenarios collected by our CloudBench® tool using application benchmarks running on actual clouds.
Double Outlet Right Ventricle: Where are we Now?

During a nearly 20-year time period 36 patients were treated for DORV with a noncommitted VSD. Two-thirds of the patients had a biventricular repair and one-third had a univentricular repair. The early mortality was high in the patients having biventricular repair (20%) and the need for reoperation was also quite high (100% at 10 years). In the univentricular repair group the early mortality was nil but the known complications of long-term Fontan physiology are inherently present. The Fontan group had a similar ultimate long-term survival but fewer reoperations (30% at 10 years). The primary take-away message from this review for me was that for the particular patient with the combination of DORV, noncommitted VSD, and associated atrioventricular septal defect biventricular repair has a very high early mortality. In that
Happy Land Amusement Park

The story of Happy Land Amusement Park in this chapter revolves around the organization’s learning and the changes put in place after each of two fatalities, which made it clear that the Park was not “safe,” as presumed. Safety had been managed by a set of rules that guests and employees were expected to follow, norms that worked as long as everyone followed the rules. When the rules were broken, so was the illusion of safety. Leaders put systems and practices in place during several phases after these fatalities that were based on learning they gained through new talent, outside networks, industry best practices, and experience in other organizations. Each phase built on gains from prior changes. The outcome was a changed climate, increased commitment, and an aligned organization with a strong pervasive safety culture.
Study of Simulation for Non-linear Phenomena in PFC Boost Converter

The operation theory of PFC Boost Converter based on average current control was analyzed. The switch model of PFC Converter was built by Simulink and S-Function, and the simulation of converter was carried out. The result of simulation shows that there is two different time scale instability in PFC Boost Converter based on average current control. The bifurcation map was derived from system model by S-Function in Simulink. The result also verifies the correction of the model of system in PFC. A reliable tools was proposed for studying dynamics of the power electronics system accurately under variation of some parameters in circuit based on this converter model.
Standardization of 1588v2 for Application in Telecommunication Networks

This article introduces the requirements of 1588v2 for application in telecommunication networks and discusses 1588v2 standardization in the ITU-T with reference to frequency and time/phase synchronization.Issues affecting the application of 1588v2 include network Packet Delay Variation(PDV) limits(which impact 1588v2 frequency recovery),and application scenarios and specifications for 1588v2 end to end frequency transmission.This paper also discusses the characteristics and basic thought of 1588v2 in telecommunications deployment.Problems arising during standardization are discussed in conclusion.
Recent Japanese Research on Republican Period Political and Economic History

(1979). Recent Japanese Research on Republican Period Political and Economic History. Chinese Republican Studies Newsletter: Vol. 4, No. 2, pp. 7-13.
Functional Residues Essential for the Activation of the CB1 Cannabinoid Receptor

Abstract Recently developed X-ray crystal structures of active state G-protein-coupled receptors have opened the way for detailed examination of the movement of the transmembrane (TM) helices and the specific residues involved in the receptor activation upon ligand binding. Previous modeling studies have indicated that the brain cannabinoid (CB1) receptor binds with a ligand at least in part through a hydrophobic tail on the ligand. This interaction is believed to be similar to the rotameric toggle switch proposed for the β2 adrenergic receptor (β2AR). In the present study, an active state model for the CB1 receptor, guided by the X-ray structure of the active state for β2AR, was constructed with HU210 bound as a ligand. Molecular dynamics (MD) simulations were employed to provide a smooth progression between inactive and active states of the receptor. This model was compared with our previously published CB1 receptor model to identify the functional residues that play key roles in triggering receptor conformational changes upon agonist binding. Movements in TM helices and functional residues are discussed. W279 5.43 , contributing to an inward movement of the fifth TM helix (TM5) to the helical core, could serve as another rotameric switch for receptor activation. V282 5.46 , interacting with the ligand's hydrophobic C3 alkyl chain, appears to play a key role in TM5 inward movement centered at L286 5.50 and subsequent coupling to V204 3.40 . V204 3.40 , closely interacting with the TM5 and TM6 hydrophobic patch residues in the middle of the receptor, particularly I290 5.54 and L352 6.44 , appears to facilitate helical rearrangements, leading to the breakage of the ionic lock and the rotameric change of Y397 7.53 , which are key features of the active state.
Management of Chronic Lymphocytic Leukemia in the Elderly

BackgroundBecause chronic lymphocytic leukemia (CLL) typically follows an indolent course, many patients do not need to initiate therapy until they reach a relatively advanced age, when frailty and...
Metal-catalyzed Reductive Carbocyclization (C C, C C, C O Bonds)

Beginning with the Fischer–Tropsch reaction (1922) and alkene hydroformylation (1938), catalytic methods for the reductive coupling of π-unsaturated reactants began to appear in the chemical literature nearly a century ago. While these processes have long been applied to the industrial manufacture of commodity chemicals, catalytic reductive C–C bond formation has only begun to achieve critical mass in the context of fine chemical synthesis. In this review, the rapidly growing subset of metal-catalyzed reductive C–C bond formations comprising the hydrometallative and hydrogenative carbocyclization of π-unsaturated substrates is cataloged, along with the application of these methods in target-oriented synthesis. Content is organized on the basis of reaction type, and is categorized further on the basis of catalyst type (e.g., early transition metals, group III metals and lanthanides, and late transition metals). Reductive cyclization involving σ-bond activation is not covered.
School Transitions and African American Youth

School transitions have long been associated with drops in academic motivation. Literature is reviewed on both the transition from elementary school to middle school and the transition from middle school to high school, showing how changes in school context, combined with developmental changes in the child, may lead to either positive or negative changes in academic motivation. We summarize literature on school transitions for American youth in general as well as the limited literature on these transitions and their motivational consequences among African American youth. Contextual changes that occur with school transitions (e.g., race composition of schools and classrooms) co-occur with youths’ growing awareness of race, influencing the identity development and academic motivation of African American youth through several mechanisms. Three such mechanisms are discussed in detail. Race and gender academic stereotypes have the potential to shape youths’ self-perceptions, values, and goals. Racial discrimination occurs both at an institutional level (e.g., differences in school quality that place African American youth at a disadvantage) and at a personal level (e.g., a teacher’s failure to recommend a high-achieving Black child for an honors class). Racial identity can serve both as a protective factor and as a risk factor. Suggestions for future research include a closer study of specific aspects of school contexts that shape motivation, the role of families, ways in which school policies and pedagogical practices affect transition experiences, and the examination of ways in which school transitions are opportunities for fresh starts and positive change in African American youth.
Data detection of amplify-and-forward user cooperation in MIMO broadcasting systems without channel state information feedback

In this paper, we consider the broadcasting of data streams from a multiantenna source to several single-antenna or multiantenna users in a data broadcasting network. To improve the received data quality for all single-antenna users simultaneously while not compromising the data rates of multiantenna users, we propose a new cooperation scheme among single-antenna users. Users cooperate in the amplify-and-forward (AF) mode to jointly detect the spatially multiplexed data streams from the source with estimated channel state information. Simulation results verify the effectiveness of the proposed channel estimation scheme based on very few pilots in conjunction with the maximum likelihood (ML) detection scheme.
State Definitions of Social Work Practice: Implications for our Professional Identity

Purpose For over a century, the social work profession has been concerned with describing the unique and specific characteristics that define its core functions in society; however, the profession has yet to agree to a single definition of social work. In the absence of a unifying definition, 51 different statutory definitions of social work have been created by each state and the District of Columbia. Methods Using qualitative methods, each statutory definition of social work was analyzed to gain an understanding of how social work is defined and understood across the United States. Results Findings indicate that 57% of the statutory language blend the full range of micro to macro social work practice skills into their definition. However, even within these and those remaining, there are vast differences in definitions. Discussion Implications for state licensing laws, are considered, along with how this impacts education, the work force, and professional identity.
Using Kronecker products to construct mimetic gradients

This paper describes how discrete versions of the derivative on the real line induce discrete version of the gradient and divergence in higher dimensions. This is geometrically motivated by results in algebraic graph theory since the grid in n dimensions is the graph Kronecker product of the path on n vertices. The resulting technique relies heavily on the matrix Kronecker product, and is an analogue of a derivation in multilinear algebra.
Distributed adaptive switching consensus control of heterogeneous multi-agent systems with switched leader dynamics

Abstract In this paper, the leader-following distributed consensus control problem is addressed for general linear multi-agent systems with heterogeneous uncertain agent dynamics and switched leader dynamics. Different from most existing results with a single linear time-invariant (LTI) leader dynamics, the leader dynamics under consideration is composed by a family of LTI models and a switching logic governing the switches among them, which is capable of generating more diverse and sophisticated reference signals to accommodate more complicated consensus control design tasks. A novel distributed adaptive switching consensus protocol is developed by incorporating the model reference adaptive control mechanism and arbitrary switching control technique, which can be synthesized by following a two-layer hierarchical design scheme. A numerical example has been used to demonstrate the effectiveness of the proposed approach.
A systematic review and meta-analysis of the direct anterior approach for hemiarthroplasty for femoral neck fracture

We performed a systematic review and meta-analysis to assess whether the direct anterior approach (DAA) is associated with improved functional and clinical outcomes compared to other surgical approaches for hemiarthroplasty for displaced femoral neck fractures. Randomized trials and cohort studies of hemiarthroplasty performed via DAA versus another surgical approach (anterolateral, lateral, posterolateral, posterior) were included. Our primary outcome was postoperative functional mobility. Secondary outcomes included overall complication rate, dislocation rate, perioperative fracture, infection rate, re-operation rate, overall mortality, operative time, pain, intra-operative blood loss, and length of stay. Nine studies met inclusion criteria, comprising a total of 698 hips (330 direct anterior, 57 anterolateral, 89 lateral, 114 posterolateral, 108 posterior approach). With regard to functional mobility, DAA was favored in 4 studies, and no study favored another approach over DAA. DAA had a significantly lower dislocation rate compared to posterior capsular approaches. Analysis of other secondary outcomes did not identify statistically significant differences. This is the first systematic review and meta-analysis of the DAA for hemiarthroplasty. Available evidence suggests superior early functional mobility with the DAA. The DAA is associated with a significantly lower dislocation rate compared to posterior capsular approaches for hemiarthroplasty.
Masculinity-Femininity Applied to Cooperative and Competitive Facework

This chapter discusses the cultural dimension of masculinity versus femininity. In particular, the association between masculinity and competitive facework and cultural femininity and cooperative facework and leveling facework is presented. Schwartz’ theory is explained and an explanation is provided for not using it over Hofstede’s theory. The issue of sexual harassment is discussed along with how it is more rampant in masculine cultures than feminine cultures. Issues of work-life balance are also described as related to masculinity in Chap. 6. Issues relating to saving face are interspersed throughout the chapter.
Structural and functional analysis of BRCA1 isoforms

4532 BRCA1 is a tumor suppressor gene that is either lost or mutated in families with breast and ovarian cancer. Among sporadic cases of breast cancer, expression of BRCA1 is reduced, suggesting the involvement of this gene in the etiology of breast cancer. Several BRCA1 splice variants are found in different tissues, but their regulation and possible functions are poorly understood at the moment. We have previously isolated and characterized two splice variants of BRCA1 named BRCA1a/1b, which are evolutionary conserved of all the BRCA1 isoforms. BRCA1a/1b differ from BRCA1 due to an in frame deletion of a major portion of the exon 11 sequences (amino acids 263-1365). Further, BRCA1b has an additional deletion of exons 9 and 10. They code for smaller p110/p100 kD proteins, respectively. We have found BRCA1a/1b to be multifunctional proteins that interact with several proteins involved in transcriptional activation/repression, cell cycle regulation, growth suppression, apoptosis, etc. In this study, we have analyzed the structure/function relationships of these isoforms and compared them to the wild type BRCA1 protein using several criteria such as in vivo expression in normal and tumor cell lines by RNase protection assays, subcellular localization using FLAG or GFP tagged vectors by immunofluorescence, transcriptional activation/repression using several biologically relevant promoters and growth suppression in breast cancer cells. Our results suggest that even though both wild type BRCA1 and its isoforms exhibit overlapping as well as distinct transcriptional activation functions they still possess antiproliferative activity in breast cancer cells. These results suggest that the exon 11 sequences (amino acids 263-1365) which contain two nuclear localization signals, p53, Rb, c-myc, γ-tubulin, Stat, Rad 51 and Rad 50 binding domains and an angiopoietin-1 repression domain are not absolutely required for the growth suppressor function of these proteins. It is tempting to speculate that mutations that are present in the patients within these regions may not be functionally significant for the tumor suppressor activity of BRCA1 protein. This work is supported by the Georgia Cancer Coalition Distinguished Cancer Scholar Award, NIH Ovarian Cancer SPORE award, and P60 grant to V. N. Rao. *Contributed equally.
Sharpness of Falconer’s Estimate and the Single Distance Problem in \(\mathbb{Z}_{q}^{d}\)

In the paper introducing the celebrated Falconer distance problem, Falconer proved that the Lebesgue measure of the distance set is positive, provided that the Hausdorff dimension of the underlying set is greater than \(\frac{d+1} {2}\). His result is based on the estimate $$\displaystyle{ \mu \times \mu \{(x,y): 1 \leq \vert x - y\vert \leq 1+\varepsilon \} \lesssim \varepsilon, }$$ (1) where μ is a Borel measure satisfying the energy estimate \(I_{s}(\mu ) =\int \int \vert x - y\vert ^{-s}\) d μ(x)d μ(y) \frac{d+1} {2}\). An example due to Mattila ([15], Remark 4.5; [14]) shows in two dimensions that for no \(s < \frac{3} {2}\) does I s (μ) < ∞ imply (1). His construction can be extended to three dimensions, but not to dimensions four and higher. Mattila’s example, as well as Falconer’s result, readily applies to the case when the Euclidean norm in (1) is replaced by a norm generated by a convex body with a smooth boundary and nonvanishing Gaussian curvature.
Placental development during early pregnancy in sheep: Progesterone and estrogen receptor protein expression.

Abstract The aim of this study was to evaluate the pattern of protein expression of the steroid receptor isoforms of nuclear progesterone receptors (PGR) A and B, and estrogen receptors (ESR1 and 2) in utero-placental compartments during early pregnancy. Utero-placental tissues were collected from days 14–30 (n = 4 ewes/day), and uterine tissues were collected from non-pregnant ewes on day 10 after estrus (n = 4). Cross sections of formalin-fixed and paraffin embedded tissues were immunofluorescently stained to detect PGRAB, PGRB, ESR1 and ESR2, followed by image generation of entire cross-sections of uterine and utero-placental tissues, confocal imaging of individual uterine and utero-placental compartments, and image and statistical analyses. PGRAB, PGRB, ESR1 and ESR2 were detected in several compartments of uterine and utero-placental tissues. Quantitative image analysis of staining intensity demonstrated that compared to non-pregnant controls 1) expression of PGRAB and PGRB was less in luminal epithelium and endometrial glands from day 14–16 till 30; 2) PGRAB expression tended to be greater in endometrial and myometrial blood vessels on days 28 and/or 30; 3) PGRB expression in myometrum was lower on days 16 and 28; 4) ESR1 in endometrial stroma was lower in all days of pregnancy; 5) ESR2 expression was similar in all compartments and not affected by pregnancy stage; and 6) in FM, expression of steroid receptors was similar. Thus, we have demonstrated spatial and temporal expression of nuclear PGR and ESR isoforms in utero-placental compartments during early pregnancy.
Hypomethylation of CYP2E1 and DUSP22 Promoters Associated With Disease Activity and Erosive Disease Among Rheumatoid Arthritis Patients.

Author(s): Mok, Amanda; Rhead, Brooke; Holingue, Calliope; Shao, Xiaorong; Quach, Hong L; Quach, Diana; Sinclair, Elizabeth; Graf, Jonathan; Imboden, John; Link, Thomas; Harrison, Ruby; Chernitskiy, Vladimir; Barcellos, Lisa F; Criswell, Lindsey A | Abstract: OBJECTIVE:Epigenetic modifications have previously been associated with rheumatoid arthritis (RA). In this study, we aimed to determine whether differential DNA methylation in peripheral blood cell subpopulations is associated with any of 4 clinical outcomes among RA patients. METHODS:Peripheral blood samples were obtained from 63 patients in the University of California, San Francisco RA cohort (all satisfied the American College of Rheumatology classification criteria; 57 were seropositive for rheumatoid factor and/or anti-cyclic citrullinated protein). Fluorescence-activated cell sorting was used to separate the cells into 4 immune cell subpopulations (CD14+ monocytes, CD19+ B cells, CD4+ naive T cells, and CD4+ memory T cells) per individual, and 229 epigenome-wide DNA methylation profiles were generated using Illumina HumanMethylation450 BeadChips. Differentially methylated positions and regions associated with the Clinical Disease Activity Index score, erosive disease, RA Articular Damage score, Sharp score, medication at time of blood draw, smoking status, and disease duration were identified using robust regression models and empirical Bayes variance estimators. RESULTS:Differential methylation of CpG sites associated with clinical outcomes was observed in all 4 cell types. Hypomethylated regions in the CYP2E1 and DUSP22 gene promoters were associated with active and erosive disease, respectively. Pathway analyses suggested that the biologic mechanisms underlying each clinical outcome are cell type-specific. Evidence of independent effects on DNA methylation from smoking, medication use, and disease duration were also identified. CONCLUSION:Methylation signatures specific to RA clinical outcomes may have utility as biomarkers or predictors of exposure, disease progression, and disease severity.
Some new angles on the magic angle: what MSK radiologists know and don’t know about this phenomenon

Magic angle effects (MAE) are well-recognized in musculoskeletal (MSK) MRI. With short TE acquisitions, the signal intensity of tendons, ligaments, and menisci depend on their orientation relative to the main magnetic field (B0). An interactive resident physics teaching module simulating MR imaging of a tendon forced us to identify and correct several misconceptions we had about MAE. We suspected these misconceptions were shared by other MSK radiologists. We surveyed members of the Society of Academic Bone Radiologists (SABR) regarding which pulse sequences, acquisition parameters, tissues and angles relative to B0 were most likely to produce MAE. Survey respondents knew that MAE strongly depend on TE and commonly appear on T1W, FSE and PD sequences, but were less aware that MAE may also appear on T2W, STIR and DWI sequences. They knew of MAE effects in tendons, ligaments and cartilage, but were less aware of those in entheses, peripheral nerves and intervertebral discs. Respondents underestimated the wide angular range (full-width at half-maximum ≈ 40∘) over which significant MAE can be seen with short TE. Collagen-containing tissues with parallel molecular alignment exhibit increased signal intensity when oriented at 55∘ relative to B0. Experienced MSK radiologists were found to underestimate the combinations of image parameters, pulse sequences, tissues and collagen orientations in which significant MAE may be seen. Our survey results highlight the need for ongoing MR physics education for practicing radiologists.
Translating insights from optogenetics into therapies for Parkinson's disease

Abstract Movement disorders including Parkinson’s disease and dystonia are caused by neurological dysfunction, typically resulting from the loss of a neuronal input within a circuit. Neuromodulation, specifically deep brain stimulation (DBS), has proven to be a critical development in the treatment of movement disorders. Continuing efforts aim to improve DBS techniques, both in how they exert their effects and in the efficacy of the mechanism involved in eliciting those effects. While optogenetic stimulation is currently infeasible in human patients, opto-DBS research provides an indispensible avenue to understand the mechanisms of DBS therapeutic and adverse effects. We review the benefits of cell-type specific manipulations in understanding the root cause of movement disorders and how DBS might optimally combat those causes. We also explore new circuit-inspired applications of DBS suggested by thorough, high-throughput optogenetic techniques. Maximizing the efficacy and outcome of DBS requires a multi-tiered approach; research employing optogenetics provides the specificity and feasibility to uncover the mechanisms that will help realize these gains in patient care.
Unnatural Chemical Biology: Research-Based Laboratory Course Utilizing Genetic Code Expansion

The content and design scheme for a readily adaptable, research-based laboratory course in chemical biology are presented. In this course, students interrogate protein structure and function using ...
Comparison of Two Commercially Available Liquid Human Milk Fortifiers for Feeding Tolerance in Premature Infants

Background: Human milk is the ideal food for most babies, particularly for infants born prematurely. However, premature infants require fortification of human milk to meet the higher nutritional needs of their developmentally expected intra-uterine growth rates. Studies have shown that premature infants who are fed fortified breast milk have increased weight gain, length and head circumference, as well as improved bone mineralization. Premature infants who receive breast milk without fortification are at risk for extra-uterine growth retardation with lower growth rates and compromised neurodevelopmental outcomes. The two most commonly used commercially …
A nanophotonic-based assay for point-of-care medical diagnostics of malaria in low and middle income countries

Direct detection of genetic biomarkers in tissue and body fluids without complex target extraction and amplification processes can revolutionize nucleic acid-based diagnostics by enabling the use of this technology at the point-of-care. The development of point-of-care diagnostics is important to increase access to early treatment in underserved populations in low to middle income countries, which are disproportionally affected by infectious diseases and increasingly affected by certain types of cancer. The main obstacle to the development of such technologies is the low concentration of target sequences that makes this goal challenging. We report a method for direct detection of pathogen RNA in blood lysate using a bioassay using surface-enhanced Raman spectroscopy (SERS)-based detection assay that can be integrated in a “lab-in-a-stick” portable device. We could directly detect synthetic target with a limit of detection of 200 fM and, more importantly, we detected P. falciparum malaria parasite RNA directly in infected red blood cells lysate. Additionally, this paper will discuss the use of the developed assay for the identification of head and neck squamous cell carcinoma (HNSCC), which is an increasingly prevalent malignancy in low to middle income countries.
Some Principles of Interdisciplinary Investigation for Recreating the Historical Topography of Urban Spaces

Studying the historical urban topography requires addressing the maps and city plans from a particular time period. Due to the fact that the city plans of the locations, in what is present-day western Ukraine, only begun being developed in the 17th and 18th century, a need to formulate a method of creating reconstruction maps for the previous periods of time has emerged. Such a method is based on retrospective comparisons of the written sources with the cartographic, iconographic, toponimic (urbanonimic), and archaeological ones. The following article tackles the problem of reconstructing historical topography using the retrospective method in the case of Lviv and other, smaller towns in the region. The historical topography and its methods are closely connected with historical geography and methodology implemented therein. Both fields aim to illustrate historical events on the map, which allows for depictions of the cultural landscape. The most important sources, fundamental for the research presented, are the Josephine topographical maps of Galicia and Josephine Land’s cadastration comprising the registers of all the 18th century properties. Their comparison with the earlier sources enables, to some extent, the identification of settlements, built-up areas, and elements of the landscape dating back to the Modern Period, or even the late Middle Ages, while contrasting them with both the Franciscan Cadastre and the 19th and 20th century indexes allows for the location of the current addresses. It is worth mentioning that, in such studies, the cartographical sources are indispensable, the iconographic ones are of a secondary, ancillary role, and the urbanonimic sources are of the greatest value. The method presented can be applied to the historical-topographical analyses of the cities of the whole former Austrian and Austro-Hungarian Empire.
Fountains for Environmental Justice: Public Water, Homelessness, and Migration in the Face of Global Environmental Change

Abstract Environmental justice has been defined as equitable distribution of environmental burdens and benefits, including access to sufficient and clean water. While many major cities are represen...
Triamterene Solubility and Metabolism are not Causative Factors of Triamterene Nephrolithiasis

Although the risk of passing a kidney stone during triamterene therapy is not yet fully understood1,2 there is enough evidence to suggest that deposition of triamterene and other drugs in kidney stones is a frequent occurrence3. Since our initial report on the presence of triamterene in kidney stones, only a few studies have appeared on this topic and it still remains unclear as to why triamterene is found in stones. We now report the true composition of kidney stones passed during triamterene therapy, which may help to explain why it is incorporated. Also, we will report the first data on triamterene metabolism in patients passing these stones, as well as in patients chronically using triamterene. Previously published data will also be discussed in the light of our data.
Radiotracers in Studies of Trace Metal Behavior in Mesocosms: Advantages and Limitations

Radioisotopes have been used to study the movement and transformation of chemicals in natural systems for at least three decades, and from an oceanic scale to that of laboratory animals or the human body. For obvious reasons, radioisotopes cannot be added at will to open, natural ecosystems. Enclosed ecosystems are therefore ideal for this technique. Radioisotopes have been used extensively in laboratory-scale bioaccumulation studies (e.g., International Atomic Energy Agency 1975, and references therein). Few, however, have used isotopes other than 14 C in mesocosms which simulate or isolate part of a natural aquatic ecosystem (e.g., Brungs 1967, Hesslein et al. 1980, Adler et al. 1980, Santschi et al. 1980c). The methodology we use at the Marine Ecosystems Research Laboratory (MERL), at the University of Rhode Island, Narragansett, R.I., U.S.A., will serve to illustrate the advantages and drawbacks of radiotracer experiments in enclosed ecosystems.
Erythrocyte Pyruvate Kinase Deficiency in Non-spherocytic Hemolytic Anemia: A System of Multiple Genetic Markers?

Extreme intrafamilial differences between PK-deficient phenotypes regarding hemolysis, ATP stability, and glucose consumption were observed in two pedigrees in which the index cases had severe nonspherocytic hemolytic anemia. Genetic analysis was consistent with heterozygosity for two distinct interacting mutants in minimally affected relatives of severely anemic homozygotes. Neither the mature erythrocytes of the former nor the reticulocyte-rich cell populations of the latter showed accumulation of glycolytic intermediates, but 2,3-DPG was elevated in both. Despite severe PK deficiency, red cell survival in the minimal type was near normal, glucose consumption was unaffected in three of four subjects tested, and ATP maintenance in vitro was adequate, in contrast to the severe type in which these parameters were grossly depressed. The genetic and pathophysiologic implications of these findings are discussed. The possibility is considered that defective glycolysis may play a subordinate role in the hemolytic process associated with PK deficiency and that the enzyme defect may be a genetic marker for as yet unknown erythrocytic abnormalities involving an increase of 2,3-DPG and possibly primary membrane lesions creating excessive demands on the energy metabolism of the erythrocytes. Regardless of the mode of gene action, it is concluded that the nonspherocytic hemolytic anemias associated with PK deficiency are genetically and phenotypically heterogeneous, and that the genetic diagnosis cannot rest on PK assay alone.
AAV diffuses across zona pellucida for effortless gene delivery to fertilized eggs.

Gene delivery to fertilized eggs is often the first step in creation of transgenic animals, CRISPR knock-out, or early developmental studies. The zona pellucida, a hardened glycoprotein matrix surrounding the mammalian fertilized eggs, often complicates gene delivery by forming a barrier against transfection reagents and viruses. High efficiency techniques to perforate or penetrate the zona allow for access and gene delivery to fertilized eggs. However, these techniques often rely on highly skilled technologists, are costly, and require specialized equipment for micromanipulation, laser perforation, or electroporation. Here, we report that adenoassociated viruses (AAVs) with serotypes 1 or DJ can efficiently diffuse across the zona to deliver genes without any manipulations to fertilized eggs. We observe lowered rates of embryo development after treatment of embryos with all AAV serotypes. However, we were able to reduce adverse effects on embryo development by exposing embryos to AAVs at later stages of in vitro development. AAVs have low immune response and do not incorporate into their host chromosomes to cause insertional mutations. Hence, AAVs can serve as a highly effective tool for transient delivery of genes to fertilized mammalian eggs.
Smoke and Scan: A Content Analysis of QR Code-Directed Websites Found on Cigarette Packs in China.

Introduction Quick Response codes, or "QR" codes, are used widely in China-for mobile payment, marketing, public transportation, and various other applications. In this study, we examined the content of websites linked from QR codes on cigarette packs collected in China. Aims and methods In February 2017, 738 unique cigarette packs were collected from five Chinese cities (Beijing, Guangzhou, Shanghai, Kunming, and Chengdu) using a systematic protocol. Cigarette packs were coded for presence of QR codes on packaging. Packs containing QR codes were then scanned using the WeChat app. Websites sourced from QR codes were coded for required verification, website type, age- and health-related statements, engagement strategies, and marketing appeals. Results From the sample of 738 unique packs, 109 packs (14.8%) had a QR code on the packaging. The QR codes were linked to 24 unique websites of which 23 could be analyzed. All 23 unique websites were either brand-specific or social media websites; none focused on health or quit information. Of the 23 websites, only three (13.0%) websites had age-restricted site access and just six (26.1%) had any mention of health-related risks associated with product usage. Engagement strategies and/or marketing appeals were found on 20 (87.0%) websites. Conclusions The Chinese tobacco industry uses QR codes on cigarette packaging to link to web-based marketing content including social media recruitment, contests and giveaways, and product advertisement. It is important to understand where packs send consumers online and what messages they receive, and to consider QR codes on packaging when drafting policy. Implications Scanning QR codes in China is a commonplace activity. The authors are aware of no published studies on the role QR codes play on the marketing of cigarette packs, in China or elsewhere. This study demonstrates QR codes on cigarette packs can expose users and nonusers to cigarette marketing on interactive websites and protobacco social media pages, mostly without restrictive access or health warnings. This is an area that health authorities can consider regulating, given that this is a channel through which the tobacco industry can communicate with current and potential consumers.
Characteristics of Lightning Faults of 220 kV and Above Overhead Transmission Lines in Zhejiang Province in last 15 Years

Lightning is the most frequent reason for high voltage overhead transmission lines faults. Due to the stochastic nature of lightning, the theoretic approaches for evaluation of the performance of overhead transmission lines are far from complete. The field experiences from the practitioners are of great value in lightning performance researches. This work collected a large dataset of lightning faults happened during 2004-2018 in the 220 kV and above overhead transmission lines in Zhejiang province. The characteristics, like temporal, spatial and double circuits faults, of the lightning faults are analyzed in this work. The mechanisms behind these characteristics are also explained in this work, which hope will be helpful in the future researches in lightning performance of overhead transmission lines.
An Attack Vector Taxonomy for Mobile Telephony Security Vulnerabilities

A simplified cybersecurity threat matrix may provide a unifying way to define the security risk posed by current and future generations of mobile telephony.