cssi/SciSciGPT-SciSciNet huggingface dataset:
Synaptic inputs and morphology of sustained ON-ganglion cells in the mudpuppy retina

1. Sustained ON-ganglion cells from the mudpuppy retina were studied with a combined approach, including intracellular and extracellular recording from the superfused retina-eyecup preparation, pharmacology with bath-applied 2-amino-4-phosphonobutyrate (APB), and retrograde and intracellular staining using horse radish peroxidase (HRP). 2. Bath application of micromolar levels of APB selectively blocks the light response of ON-bipolar cells; APB was used to separate synaptic inputs into those which originate from ON- vs. OFF-bipolar cells. This approach clearly demonstrates that the light response of the vast majority of sustained ON-ganglion cells is primarily the result of sustained excitatory inputs that arise (directly or indirectly) from ON-bipolar cells. 3. APB revealed the presence of transient excitatory OFF-inputs in many sustained ON-ganglion cells that are normally not evident. 4. Five sustained ON-ganglion cells were intracellularly stained with HRP and their morphology was analyzed with the aid of a computer-assisted neuron reconstruction system. The stained cells are anatomically similar, based on quantitative analysis of a number of morphological parameters. The dendritic trees of all five cells are primarily confined to sublamina b of the inner plexiform layer, although some cells have a small number of processes that ramify in sublamina a. These latter processes may relate to the transient excitatory OFF-inputs revealed with APB application. 5. Ganglion cells which are morphologically similar to the stained, intracellularly sustained ON-ganglion cells were found in a collection of Golgi-like cells that were labeled by retrograde HRP transport. This raises the possibility that sustained ON-ganglion cells in the mudpuppy may constitute a morphologically identifiable class of retinal ganglion cells in this species. There is also some suggestion that a morphologically similar class of OFF-cells may be present.
Analysis of nutrition judgments using the Nutrition Facts Panel.

Abstract Consumers’ judgments and choices of the nutritional value of food products (cereals and snacks) were studied as a function of using information in the Nutrition Facts Panel (NFP, National Labeling and Education Act, 1990). Brunswik’s lens model (Brunswik, 1955; Cooksey, 1996; Hammond, 1955; Stewart, 1988) served as the theoretical and analytical tool for examining the judgment process. Lens model analysis was further enriched with the criticality of predictors’ technique developed by Azen, Budescu, & Reiser (2001). Judgment accuracy was defined as correspondence between consumers’ judgments and the nutritional quality index, NuVal®, obtained from an expert system. The study also examined several individual level variables (e.g., age, gender, BMI, educational level, health status, health beliefs, etc.) as predictors of lens model indices that measure judgment consistency, judgment accuracy, and knowledge of the environment. Results showed varying levels of consistency and accuracy depending on the food product, but generally the median values of the lens model statistics were moderate. Judgment consistency was higher for more educated individuals; judgment accuracy was predicted from a combination of person level characteristics, and individuals who reported having regular meals had models that were in greater agreement with the expert’s model. Conclusions: Lens model methodology is a useful tool for understanding how individuals perceive the nutrition in foods based on the NFP label. Lens model judgment indices were generally low, highlighting that the benefits of the complex NFP label may be more modest than what has been previously assumed.
The Real Homeland Security Gaps

This Article reveals the real security gaps in the Department of Homeland Security’s Federal Protective Service (“FPS”) and suggests that the excessive delegation of FPS’s vital security functions to private contractors should be treated as an unconstitutional delegation of an inherently governmental function. It presents the FPS mission of protecting critical federal infrastructure as a national priority that Congress recognized after 9/11 as vitally important to the nation’s homeland security. Despite this recognition, there has been widespread delegation of the FPS security function to private contractors. The Article considers the regulatory and constitutional law concerns raised by privatization, suggesting that excessive privatization of the FPS security function undermines core democratic precepts and therefore ought to be treated as an unconstitutional private delegation.
Carbonic Anhydrase Type II Deficiency Syndrome

Researchers at King Saud University, Saudi Arabia and other centers describe the neurological, neuro-ophthalmological and neuroradiological features of 23 patients (10 male, 13 female; age at final exam 2-29 years) from 10 unrelated consanguineous families with carbonic anhydrase type II deficiency syndrome due to homozygous mutation (the ‘Arabic mutation’).
Calling conventions on the carpet: Travis Brisini’s “The Conference Room Carpet” as poetic response

ABSTRACTIn this essay I examine representations and subversions of power in Travis Brisini’s “The Conference Room Carpet” and Charlotte Perkins Gilman’s short story “The Yellow Wallpaper.” I argue Brisini’s “The Conference Room Carpet” is a successful performative attempt to write his way out of the oppressive conventions of academic success.
Recruitment and retention challenges and successes

ABSTRACTObjective: Addressing health disparities requires well designed, culturally adapted research. However, recruiting/retaining minority participants has often been challenging. We present strategies used to successfully recruit and retain rural Hispanic women during a breastfeeding education intervention.Design: This study involved a two-group repeated measures quasi-experimental design with assessments at seven intervals between enrollment and 6 months postpartum. Participants (Hispanic women ≥ 15 years old) were recruited through a regional hospital.Results: We successfully met our recruitment goals, most women contacted were enrolled (46 of 58), and 100% completed the study.Discussion: Research staff with ties within the community helped establish trust. Using bilingual study materials, simple language, and an interpreter addressed language/literacy concerns. Phone assessments facilitated participation as transportation was an issue. Accommodating requests to deliver or mail study materials and pr...
How dose sparing of cardiac structures correlates with in-field heart volume and sternal displacement

Cardiac irradiation increases the risk of coronary artery disease in patients with left-sided breast cancer. Techniques exist to reduce cardiac irradiation, but the optimum technique depends on individual patient anatomy and physiology. We investigated the correlation of delta heart volume in field (dHVIF) and sternal excursion with dose sparing in heart and left anterior descending artery (LAD) to develop quantitative predictive models for expected dose to heart and LAD. A treatment planning study was performed on 97 left-breast cancer patients who underwent whole breast radiotherapy (prescription dose = 50 Gy) under deep inspiratory breath hold (DIBH). Two CT datasets, free breathing (FB) and DIBH, were utilized for treatment planning and for determination of the internal anatomy-based DIBH amplitude. The mean heart and LAD dose were compared between FB and DIBH plans and dose to the heart and LAD as a function of dHVIF and sternal excursion were determined. The [Average (STD); Range] mean heart doses from free breathing and DIBH are [120.5(65.2); 28.9 ~ 393.8] cGy and [67.5(25.1); 19.7 ~ 145.6] cGy, respectively. The mean LAD doses from free breathing and DIBH are [571.0(582.2); 42.2 ~ 2332.2] cGy and [185.9(127.0); 41.2 ~ 898.4] cGy, respectively. The mean dose reductions with DIBH are [53.1(50.6); -15.4 ~ 295.1] cGy for the heart and [385.1(513.4); -0.6 ~ 2105.8] cGy for LAD. Percent mean dose reductions to the heart and LAD with DIBH are 44% (p < 0.0001) and 67% (p < 0.0001), respectively, compared to FB. The dHVIF mean dose reduction correlation is 8.1 cGy/cc for the heart and 81.6 cGy/cc for LAD (with linear trend and y intercept: 26.0 cGy for the heart, 109.1 cGy for LAD). DIBH amplitude using sternal position was [1.3(.48); .38 ~ 2.5] cm. The DIBH amplitude mean dose reduction correlation is 14 cGy/cm for the heart and 212cGy/cm for LAD (with linear trend with y intercept: 35.6 cGy for the heart, 102.4 cGy for LAD). The strong correlation of dose sparing to the heart and LAD with dHVIF and sternal excursion suggests that mean dose sparing to heart and LAD can be predicted with either dHVIF or sternal excursion equally well. The metrics proposed could be utilized to allow providers to determine the relative dosimetric benefits of different heart-sparing techniques as early as time of consultation.
Multicatalytic, Light-Driven Upgrading of Butanol to 2-Ethylhexenal and Hydrogen under Mild Aqueous Conditions

Microbes produce low-molecular-weight alcohols from sugar, but these metabolites are difficult to separate from water and possess relatively low heating values. A combination of photo-, organo-, and enzyme catalysis is shown here to convert C4 butanol (BuOH) to C8 2-ethylhexenal (2-EH) using only solar energy to drive the process. First, alcohol dehydrogenase (ADH) catalyzed the oxidation of BuOH to butyraldehyde (BA), using NAD+ as a cofactor. To prevent back reaction, NAD+ was regenerated using a platinum-seeded cadmium sulfide (Pt@CdS) photocatalyst. An amine-based organocatalyst then upgraded BA to 2-EH under mild aqueous conditions rather than harsh basic conditions in order to preserve enzyme and photocatalyst stability. The process also simultaneously increased total BuOH conversion. Thus, three disparate types of catalysts synergistically generated C8 products from C4 alcohols under green chemistry conditions of neutral pH, low temperature, and pressure.
Bcl11a Causes Leukemia/Lymphoma in Cooperation with Nf1 Inactivation.

Loss of the NF1 (Neurofibromatosis Type 1) tumor suppressor gene is associated with chronic and acute forms of myeloid diseases including juvenile myelomonocytic leukemia (JMML). In the BXH-2 strain of mice, acute myeloid leukemia (AML) is caused by chronic infection by a murine leukemia virus (MuLV). We have reported the identification of 37 common proviral insertion sites (CIS), loci containing candidate genes whose mutation could cooperate with inactivation of Nf1 to result in BXH-2 AML. Among these candidate genes, Bcl11a , was shown to be expressed in JMML and CMML leukemia samples, and to confer a growth advantage when expressed in Nf1 -deficient myeloblast cells. In this report, we have first tried to determine whether dysregulation of Bcl11a affects cellular behavior other than promoting cell growth. Using a granulocyte-colony stimulating factor induced myeloid terminal differentiation of 32D cell culture model, we found no difference in the percentage of differentiated cells between Bcl11a -transduced cells and empty vector-transduced cells, indicating overexpression of Bcl11a may have no influence on myeloid differentiation. Moreover, no effect of Bcl11a on 32D survival after IL-3 withdrawal was detected. To investigate the potential role of Bcl11a in the development of leukemia with Nf1 loss, a bone marrow transplantation assay was then performed. Bone marrow cells were collected from the Nf1 (+/+) or Nf1 (Flox/Fcr) donor mice carrying pIpC-induced expression of Cre , and transduced with Bcl11a -expressing retroviral construct or empty vector, before transplantation via the tail vein into the lethally irradiated recipient BoyJ mice. Successful bone marrow engraftment, pIpC-induced deletion of Nf1 and delivery of Bcl11a were confirmed by PCR on peripheral blood cells. Interestingly, 5 months after pIpC induction, 10 out of 11 Nf1(Flox/Fcr);Cre+;Bcl11a -transduced bone marrow recipient mice became moribund, whereas no or only 1 out of 10 or 11 recipient mice in each control groups died for unknown reason. The Nf1(Flox/Fcr);Cre+;Bcl11a -transduced mice display myeloid blast-like cells in their peripheral blood, enlarged lymph node and liver, and splenomegaly. Spleen touchpreps also showed excessively infiltration of blast-like cells in their spleens. Unexpectedly, two out of ten moribund recipient mice also developed markedly enlarged thymi. These tumors were demonstrated to be derived from transplanted donor cells by immunophenotyping for the presence of the differential cell surface marker CD45.2, expressed on the donor cells. The nature and cell lineage origin of these tumors are under study. These data show that BXH-2 mouse is a powerful genetic system to dissect Nf1 -cooperating genetic events in leukemogenesis, and suggest that overexpression of Bcl11a can induce leukemia/lymphoma with Nf1 gene inactivation.
Traction curves for the decohesion of covalent crystals

We study, by first principles, the energy versus separation curves for the cleavage of a family of covalent crystals with the diamond and zincblende structure. We find that there is universality in the curves for different materials which is chemistry independent but specific to the geometry of the particular cleavage plane. Since these curves do not strictly follow the universal binding energy relationship (UBER), we present a derivation of an extension to this relationship that includes non-linear force terms. This extended form of UBER allows for a flexible and practical mathematical description of decohesion curves that can be applied to the quantification of cohesive zone models.
Phase Resetting of Respiratory Rhythm — Experiments in Animals and. Models

Resetting of respiratory rhythm was studied in cats and in two models (Van der Pol and Fitzhugh-Bonhoeffer) of a limit cycle oscillator. All three behave similarly when perturbed by brief stimuli, when respiratory drive is changed or when stochastic processes are added. The findings support the idea that a limit cycle oscillator underlies mammalian respiration and show that a number of features of in vivo respiration can be mimicked by limit cycle models.
Female-Headed Households Associated with Lower Childhood Stunting Across Culturally Diverse Regions of Pakistan: Results from a Cross-Sectional Household Survey

Objectives Early childhood stunting adversely influences long-term cognitive and health outcomes. There is limited evidence on whether female empowerment within households could reduce its prevalence. We investigated this relationship in Punjab, Pakistan, which has high stunting rates and a sizeable proportion of female-headed households, and whether this relationship differed across three provincial regions with diverse cultural attitudes towards the role of women in society. Methods Using cross-sectional data from the 2011 Multiple Indicator Cluster Survey, we identified 13,412 children aged 1-4 from 8985 two-parent households in three culturally distinct regions in Punjab, Pakistan. Logistic regression models assessed whether the likelihood of stunting was associated with female-headed households, a proxy for female empowerment, and whether this relationship differed by region. Regressions controlled for child- and household-level covariates. Results Children had 26% lower odds of stunting among female-headed households (OR 0.74, CI 0.60, 0.90). The interaction term for female-headed households and child stunting by provincial region was not statistically significant, suggesting that the relationship holds across the three culturally distinct regions. Conclusions for Practice Female empowerment was associated with lower rates of stunting among young children, and the results did not vary by provincial region. This suggests that women can play important roles as agents of change, even in areas where females have limited freedoms. Greater investments in public education and awareness campaigns to improve health literacy might have important spillover effects for child health and improve the success of existing public health interventions targeting childhood stunting.
The Mitochondrial-Derived Peptides, HumaninS14G and Small Humanin-like Peptide 2, Exhibit Chaperone-like Activity

Mitochondrial-derived peptides (MDPs) and their analogs have emerged as wide-spectrum, stress response factors protective in amyloid disease models. MDP cytoprotective functions are generally attributed to anti-apoptotic activity, however, little is known about their capacity to facilitate the cell’s unfolded protein response via direct interactions with amyloidogenic proteins. Here, we explored the effects of the MDP-analog, humaninS14G (HNG), and the MDP, small humanin-like peptide 2 (SHLP2), on the misfolding of islet amyloid polypeptide (IAPP), a critical pathogenic step in type 2 diabetes mellitus (T2DM). Our thioflavin T fluorescence studies show that HNG inhibits IAPP misfolding at highly substoichiometric concentrations. Seeded fluorescence and co-sedimentation studies demonstrate MDPs block amyloid seeding and directly bind misfolded, seeding-capable IAPP species. Furthermore, our electron paramagnetic resonance spectroscopy and circular dichroism data indicate MDPs do not act by binding IAPP monomers. Taken together our results reveal a novel chaperone-like activity wherein these MDPs specifically target misfolded amyloid seeds to inhibit IAPP misfolding which, along with direct anti-apoptotic activity and beneficial metabolic effects, make HNG and SHLP2 exciting prospects as T2DM therapeutics. These data also suggest that other mitochondrial stress response factors within the MDP family may be amenable to development into therapeutics for protein-misfolding diseases.
Examining the Impact of Parental Socialization on the Coping Styles of Black Graduate Students Faced with Microaggressions

This article explores case examples of two graduate students who endure microaggressions from their math professor at a predominantly White university. The role that parental socialization plays in how these students developed their racial identities and the coping strategies they employed, is analyzed through the lens of Triple Quandary theory (Boykin and Toms 1985). Findings from this investigation suggest that parental socialization is critical in preparing these students to cope with and respond to microaggressions in protective and adaptive ways. This paper illuminates coping styles, although divergent, that served these graduate students9 needs and protected their individual racial identities. Further, the support these students received from their faculty advisor who is also Black, exemplifies the importance of mentorship and advocacy from faculty of color to Black college students9 success. Direction for continuity in parental teachings for K-12 and university level educators are discussed.
Transition From Peer Review to Peer Learning: Experience in a Radiology Department

Abstract Purpose To describe the process by which a radiology department moved from peer review to peer collaborative improvement (PCI) and review data from the first 16 months of the PCI process. Materials and Methods Data from the first 16 months after PCI were reviewed: number of case reviews performed, number of learning opportunities identified, percentage yield of learning opportunities identified, type of learning opportunities identified, and comparison of the previous parameters between case randomly reviewed versus actively pushed (issues actively identified and entered). Changes in actively pushed cases were also assessed as volume per month over the 16 months (run chart). Faculty members were surveyed about their perception of the conversion to PCI. Results In all, 12,197 cases were peer reviewed, yielding 1,140 learning opportunities (9.34%). The most common types of learning opportunities for all reviewed cases included perception (5.1%) and reporting (1.9%). The yield of learning opportunities from actively pushed cases was 96.3% compared with 3.88% for randomly reviewed cases. The number of actively pushed cases per month increased over the course of the period and established two new confidence intervals. The faculty survey revealed that the faculty perceived the new PCI process as positive, nonpunitive, and focused on improvement. Conclusions The study demonstrates that a switch to PCI is perceived as nonpunitive and associated with increased radiologist submission of learning opportunities. Active entering of identified learning opportunities had a greater yield and perceived value, compared with random review of cases.
Incidence and survival of hematological cancers among adults ages ≥75 years.

Evaluating population-based data of hematologic malignancies (HMs) in older adults provides prognostic information for this growing demographic. Incidence rates and one- and five-year relative survival rates were examined for specific HMs among adults ages ≥75 years using data from the Surveillance, Epidemiology and End Results (SEER) Program. Hematologic malignancy cases (Hodgkin lymphoma (HL), non-Hodgkin lymphoma (NHL), multiple myeloma (MM), acute lymphocytic leukemia (ALL), chronic lymphocytic leukemia (CLL), acute myeloid leukemia (AML), and chronic myeloid leukemia (CML)) were reported to one of 18 SEER registries. Recent average annual (2010-2014) incidence rates and incidence trends from 1973 to 2014 were examined for cases ages ≥75 years. One- and five-year relative cancer survival rates were examined for adults ages ≥75 years diagnosed 2007-2013, with follow-up into 2014. From 1973 to 2014, incidence rates increased for NHL, MM, and AML, decreased for HL, and remained relatively stable for ALL, CLL, and CML among adults ages ≥75 years. The highest one- and five-year relative survival rates were observed among adults with CLL ages 75-84 years (1 year: 91.8% (95% CI = 91.8-90.8)) and 5 years: 76.5% (95% CI = 74.2-78.6)). The lowest one- and five-year survival rates were observed among adults with AML ages 75-84 (1 year: 18.2% (95% CI = 74.2-78.6) and 5 years: 2.7% (95% CI = 2.0-3.6)). Survival for older adults ages ≥75 years with HMs is poor, particularly for acute leukemia. Understanding the heterogeneity in HM outcomes among older patients may help clinicians better address the hematological cancer burden and mortality in the aging population.
Muddling through Lawlessness

The Fascist “police forces of order” engaged in nefarious conduct by striking out blindly against all and sundry. Roving vigilante gangs chased down and tortured partisans, Jews, wobbly Fascists, draft dodgers, and innocent victims. Interior Minister Guido Buffarini made haphazard efforts to re-establish order, but encountered stout defiance on the part of regional authorities and rogue militia leaders. To make matters worse in this splintered RSI world, the Germans aided and protected their favorite desperados and militias. At the penultimate hour, Paolo Zerbino, who had replaced Buffarini, undertook police reform to drain the swamp of corruption and wanton violence, but with highly mixed results.
Extended Implementation Method for Virtual Sensors: Web-Based Real-Time Transportation Data Collection and Analysis for Incident Management

Open data sources and social media data are gaining increasing attention as important information providers in transportation and incident management. In this paper, practical evidence for the emerging potential of online and open data sources is presented. The authors’ previous research on virtual sensors is combined and extended by integrating real-time incident information and social media network engagement. The fundamental contribution of this paper is the development of an extended virtual sensor framework to provide an automated travel time data collection method as incidents occur. In addition, social media data can be useful for more effective real-time incident response. The proposed framework can easily be modified and used to evaluate travel time effects of incidents on roadways and clearance times and to make use of social media data in obtaining time-critical incident-related information.
Finite Element Weak Statement CFD Algorithms for Fluid-Thermal System Analysis

The weak statement theory is developed for construction of approximate solutions to laminar and turbulent Navier-Stokes (NS) equations for incompressible fluidthermal flow applications. Introduction of a domain discretization assists in finite element compact-support trial space basis construction. Implementation steps are highlighted for several NS reconstructions to account for the incompressibility constraint. Theoretical issues of accuracy and convergence are highlighted, and numerical benchmark test results document the important performance comparisons.
Information-Processing Theories of Biologically Inspired Design

Starting from in situ studies, we develop an information-processing theory of biologically inspired design. We compare our theory with two popular theories of biologically inspired design: Biomimicry 3.8 Institute’s Design Spiral and Vincent et al.’s BioTRIZ. While Design Spiral and BioTRIZ are normative and prescriptive, our information-processing theory provides a descriptive and explanatory account of the design paradigm. We examine if and how the process of biologically inspired design is different from that of other design paradigms beyond the differences between biological and technological systems. We posit that biologically inspired design appears to be a distinct design paradigm in part because it entails solution-based analogies in addition to the problem-driven analogies typical of other design paradigms.
Self-synchronizing Series-connected Inverters

This paper describes a virtual oscillator based approach to synchronize series-connected single-phase inverters. Each inverter controller includes a digital implementation of a Van der Pol oscillator. When connected in series, such inverters synchronize automatically, without the need for a central controller, communication channels, phase locked loops, or additional hardware such as powerline communication. A linearization-based analysis is used to prove system stability of the synchronized state. The approach is experimentally verified on a 180 W system consisting of three 60 W inverters.
Design Philosophy of Large Interactive Systems

Publisher Summary This chapter describes design philosophy applicable to large-scale structural mechanics program systems. Engineering applications software suffers from a major shortcoming. In contrast to hardware, and, more recently, certain types of systems and utility software, applications software is seldom produced in an orderly manufacturing process of design, development, and fabrication. A conceptual structure that appears particularly attractive for engineering project-design applications is one of the hierarchies of tables, where a conceptual data item may be either a terminal datum (word, vector, or matrix) or a subtable containing additional data, including sub-subtables. Given a collection of data and program files residing in the database, it is necessary to develop a control mechanism that, on the basis of suitable commands, assembles the necessary components to produce an executable sequence of operations, including the implicit or explicit data access and storage operations. Both implementation and user language are highly environment-dependent, the first being heavily influenced by the organization and operating system of the computer on which the system is to be run, the latter depending on the operational procedures and preferences of the user organization.
Gene expression amplification by nuclear speckle association

Many active genes reproducibly position near nuclear speckles, but the functional significance of this positioning is unknown. Here we show that HSPA1B BAC transgenes and endogenous Hsp70 genes turn on 2-4 min after heat shock (HS), irrespective of their distance to speckles. However, both total HSPA1B mRNA counts and nascent transcript levels measured adjacent to the transgene are approximately twofold higher for speckle-associated alleles 15 min after HS. Nascent transcript level fold-increases for speckle-associated alleles are 12-56-fold and 3-7-fold higher 1-2 h after HS for HSPA1B transgenes and endogenous genes, respectively. Severalfold higher nascent transcript levels for several Hsp70 flanking genes also correlate with speckle association at 37°C. Live-cell imaging reveals that HSPA1B nascent transcript levels increase/decrease with speckle association/disassociation. Initial investigation reveals that increased nascent transcript levels accompanying speckle association correlate with reduced exosome RNA degradation and larger Ser2p CTD-modified RNA polymerase II foci. Our results demonstrate stochastic gene expression dependent on positioning relative to a liquid-droplet nuclear compartment through "gene expression amplification."
Effects of Semaglutide Versus Dulaglutide on Epicardial Fat Thickness in Subjects with Type 2 Diabetes and Obesity.

Background and Aims Epicardial adipose tissue (EAT), the visceral fat depot of the heart, is a modifiable cardio-metbolic risk factor and therapeutic target. Semaglutide and dulaglutide, glucagon-like peptide-1 (GLP-1) receptor agonists, are indicated for the treatment of type 2 diabetes mellitus (T2DM). GLP-1 receptor agonists have recently shown to reduce cardiovascular risk. Epicardial adipose tissue expresses GLP-1 receptors (GLP-1Rs). GLP-1 receptor agonist liraglutide is known to significantly decrease EAT thickness. However, the effects of GLP-1 receptor agonists semaglutide and dulaglutide on EAT thickness are unknown. Materials and Methods We performed a 12-week, controlled, parallel study in 80 subjects with T2DM and obesity. Patients received either semaglutide, up to 1 mg subcutaneous (sc) weekly, or dulaglutide, up to 1.5 mg sc weekly, as the standard of care in addition to their usual medication regimen. Twenty subjects with T2DM and obesity were started on metformin and a diet and served as the control group. Ultrasound-measured EAT thickness was measured at baseline and at the 12-week follow-up. Results Epicardial adipose tissue thickness significantly decreased in both semaglutide and dulaglutide groups (P < 0.001) after 12 weeks, accounting for a 20% reduction. There was no EAT reduction in the metformin group. Body mass index (BMI) and HbA1c improved in all groups without reaching statistical significance. Epicardial adipose tissue thickness reduction was significantly greater (P < 0.01) with the higher doses of semaglutide (1 mg) and dulaglutide (1.5 mg), respectively. Conclusion Weekly administration of either GLP-1 receptor agonists semaglutide or dulaglutide causes a rapid, substantial, and dose-dependent reduction in EAT thickness.
Rational design of small molecule fluorescent probes for biological applications

Fluorescent small molecules are powerful tools for visualizing biological events, embodying an essential facet of chemical biology. Since the discovery of the first organic fluorophore, quinine, in 1845, both synthetic and theoretical efforts have endeavored to "modulate" fluorescent compounds. An advantage of synthetic dyes is the ability to employ modern organic chemistry strategies to tailor chemical structures and thereby rationally tune photophysical properties and functionality of the fluorophore. This review explores general factors affecting fluorophore excitation and emission spectra, molar absorption, Stokes shift, and quantum efficiency; and provides guidelines for chemist to create novel probes. Structure-property relationships concerning the substituents are discussed in detail with examples for several dye families. We also present a survey of functional probes based on PeT, FRET, and environmental or photo-sensitivity, focusing on representative recent work in each category. We believe that a full understanding of dyes with diverse chemical moieties enables the rational design of probes for the precise interrogation of biochemical and biological phenomena.
Early-Life Nutrition Interventions and Associated Long-Term Cardiometabolic Outcomes: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Early-life nutrition interventions can have lifelong cardiometabolic benefits. Most evidence on this topic is derived from observational studies. We evaluated the association of randomized controlled nutritional trials in early life and long-term cardiometabolic outcomes. Through literature search of PubMed, CABI Global Health, Embase, and Cochrane, with manual reference check and weekly alert from PubMed, we identified 8312 records, and included 53 records from 40 cohorts in 21 countries. The total number of participants was 33,551. Interventions were initiated as early as conception, and the longest until 7 y (except 1 study from infancy to 20 y). The cohorts were followed up for between 3 and 73 y. We identified 7 types of interventions (protein-energy supplements, long-chain PUFAs, single micronutrient, multiple micronutrients, infant and young child feeding, dietary counseling, and other) and 4 categories of cardiometabolic outcomes (biomarkers, cardiovascular, body size and composition, and subclinical/clinical outcomes). Most findings were null. Fasting glucose concentration was 0.04 mmol/L lower (95% CI: -0.05, -0.02 mmol/L; I2 = 0%) in the intervention groups than in the control groups (15 studies). BMI (kg/m2) was 0.20 higher (95% CI: 0.12, 0.28; I2 = 54%) in the intervention groups than control groups (14 studies). No significant effect was observed for total cholesterol (12 studies) or blood pressure (17 studies). Ongoing and personalized dietary counseling was associated with lower glucose and cholesterol, better endothelial function, and reduced risk of metabolic syndrome. The timing of intervention mattered, with earlier initiation conferring greater benefit (improved lipid profile and marginally lower glucose concentration) based on 2 studies. In sum, glucose concentration was lower following early-life nutrition interventions, but there is a risk of unintended consequences, including higher BMI. Maternal and child nutrition interventions must be evidence-based and tailored to each population to promote long-term cardiometabolic health.
Cross-sectional study of sex differences in psychosocial quality of life of long-term melanoma survivors

A cancer diagnosis and subsequent treatment can have a significant impact on an individual’s quality of life. Differences in quality of life by sex among long-term melanoma survivors remain unclear. The objective of this study was to describe sex differences in cancer-specific psychosocial quality of life of long-term melanoma survivors. Melanoma survivors 7–10 years post-diagnosis from a previously conducted population-based case-control study were recruited for a cross-sectional survey. Validated measures of psychosocial quality of life related to melanoma diagnosis were assessed. Outcomes were compared by sex using linear regression models adjusting for age, education, income, and marital status. The survey response rate was 62% (433 females, 291 males; 86% stage I disease). Females were more likely to report changes in their appearance (p = 0.006) and being more fearful of recurrence (p = 0.001) or a second melanoma (p = 0.001) than males but were also more likely to report that melanoma had a positive impact on their lives (p < 0.0001). Males were more likely to agree with statements that emphasized that life’s duration is limited (p < 0.0001). Long-term melanoma survivors reported generally favorable measures of psychosocial quality of life related to their diagnosis. Females and males reported unique quality of life concerns and may require varied methods of support following a melanoma diagnosis.
Treatment planning and outcomes effects of reducing the preferred mean esophagus dose for conventionally fractionated non-small cell lung cancer radiotherapy.

Based on an analysis of published literature, our department recently lowered the preferred mean esophagus dose (MED) constraint for conventionally fractionated (2 Gy/fraction in approximately 30 fractions) treatment of locally advanced non-small cell lung cancer (LA-NSCLC) with the goal of reducing the incidence of symptomatic acute esophagitis (AE). The goal of the change was to encourage treatment planners to achieve a MED close to 21 Gy while still permitting MED to go up to the previous guideline of 34 Gy in difficult cases. We compared all our suitable LA-NSCLC patients treated with plans from one year before through one year after the constraint change. The primary endpoint for this study was achievability of the new constraint by the planners; the secondary endpoint was reduction in symptomatic AE. Planners were able to achieve the new constraint in statistically significantly more cases during the year following its explicit implementation than in the year before (P = 0.0025). Furthermore, 38% of patients treated after the new constraint developed symptomatic AE during their treatment as opposed to 48% of the patients treated before. This is a clinically desirable endpoint although the observed difference was not statistically significant. A subsequent power calculation suggests that this is due to the relatively small number of patients in the study.
Correlation of Change in Central Subfield Thickness and Change in Visual Acuity in Neovascular AMD: Post Hoc Analysis of VIEW 1 and 2.

PURPOSE Determine correlation between change in central subfield thickness (CST) and change in best-corrected visual acuity (BCVA) in neovascular age-related macular degeneration (nAMD) receiving anti-VEGF agents. DESIGN Post hoc analysis of VIEW 1 and 2 randomized clinical trials. METHODS This analysis included participants randomized to ranibizumab 0.5 mg q4 weeks (Rq4), intravitreal aflibercept injection (IAI) 2 mg q4 weeks (2q4), and IAI q8 weeks after 3 monthly doses (2q8) to Week 52, followed by capped pro re nata (at least q12 weeks) dosing to Week 96. Relationship between changes in CST and BCVA was determined using Pearson correlation coefficient. RESULTS Of 1815 eyes, 595 were assigned to Rq4, 613 to 2q4, and 607 to 2q8 arms. Correlations (95% confidence intervals [CI]) at Weeks 12, 52, and 96 were -0.08 (-0.17, 0.00), -0.05 (-0.14, 0.04), and -0.15 (-0.24, -0.06) for Rq4; -0.13 (-0.21, -0.04), -0.06 (-0.14, 0.03) and -0.04 (-0.13, 0.05) for 2q4, and -0.04 (-0.12, 0.05), -0.01 (-0.09, 0.08), and -0.01 (-0.10, 0.09) for 2q8. Linear regression analysis adjusted for relevant baseline factors showed CST changes accounted for 11% of BCVA changes. Every 100 µm decrease in CST was associated with 0.3 letter decrease (P = .25) at Week 52 and 0.14 letter decrease (P = .69) at Week 96. CONCLUSIONS Weak or no correlation was found between changes in CST and BCVA with either agent or regimen, suggesting changes in CST should not be used as a surrogate for visual acuity outcomes in nAMD.
Requirements and Usage of NVM in Advanced Onboard Data Processing Systems

This viewgraph presentation gives an overview of the requirements and uses of non-volatile memory (NVM) in advanced onboard data processing systems. Supercomputing in space presents the only viable approach to the bandwidth problem (can't get data down to Earth), controlling constellations of cooperating satellites, reducing mission operating costs, and real-time intelligent decision making and science data gathering. Details are given on the REE vision and impact on NASA and Department of Defense missions, objectives of REE, baseline architecture, and issues. NVM uses and requirements are listed.
Social Work with West Indian Families

SUMMARY This conceptual analysis explores the psychosocial and cultural experiences of English-speaking West Indians in the United States. Relevant factors include family role changes; parent/child conflicts; prolonged separation from and reunification with parents; finding suitable employment and education-related issues. The challenge for social work is to develop programs for these families that contribute to their social and economic integration. Given the extent to which social, economic and related policies impact on the needs of this population, the author suggests that a multilevel approach which utilizes the micro skills associated with individual intervention and the macro strategies of intervening at the societal and institutional levels is needed. This approach necessarily includes activities such as advocacy and empowerment.
Juvenile Subsistence Effort, Activity Levels, and Growth Patterns

Attention has been given to cross-cultural differences in adolescent growth, but far less is known about developmental variability during juvenility (ages 3-10). Previous research among the Pume, a group of South American foragers, found that girls achieve a greater proportion of their adult stature during juvenility compared with normative growth expectations. To explain rapid juvenile growth, in this paper we consider girls' activity levels and energy expended in subsistence effort. Results show that Pume girls spend far less time in subsistence tasks in proportion to their body size compared with adults, and they have lower physical activity levels compared with many juveniles cross-culturally. Low activity levels help to explain where the extra energy comes from to support rapid growth in a challenging environment. We suggest that activity levels are important to account for the variation of resource and labor transfers in mediating energy availability.
Abstract 3920: Understanding the molecular nature of cancer cell lines

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Large-scale cancer genome programs have generated rich data of genetic abnormalities observed in thousands of clinical patient tumors, which provides a major opportunity to develop a landscape of molecular aberrations across tumor types and propose new therapeutic targets. Although human tumor cell lines have been important tools for the cancer researcher for decades, there is a lack of bio-functional validation of genetic alterations and systematic molecular characterization across commonly used cell lines in this genomic age. To meet the need of applying cancer genome knowledge to facilitate basic and translational cancer research, an updated and accurate knowledge of the cell lines in use, particularly from a molecular viewpoint, is critical for in vitro studies. Here, we show systematic molecular characterization and clustering of 90 authenticated human tumor cell lines, which represent the most common human cancer types found in the clinic, such as lung, breast, colon, pancreatic, skin cancer and so on. By next generation sequencing and molecular profiling, those tumor cell lines were fully analyzed to capture the driver gene mutations, DNA copy number variations, gene expressions, protein expressions and relevant cell signaling pathway activations. In addition to driver mutations such as BRAF V600, KRAS G12, PI3K E545 and EGFR T790, the gene copy number amplifications of AKT, FGFR, MET, ERBB2 and deletion of PTEN are presented in this work. Moreover, correlating with the verified genetic alternations, the endogenous basal levels of protein expression and signaling pathway activations within the cells were analyzed by western blot and immunofluorescence staining. A set of 6 wild type control cell lines that were derived from either normal tissues or tumors were characterized in parallel. Furthermore, live cell growth kinetics was continually monitored by label-free cell based assay. Finally, the cell lines are clustered into 10 genetic alteration panels according to driver genes, critical protein kinases, or key components of signaling pathways. Cell lines are essential models for progressing our understanding of the cancer genome, as they allow for the functional and biological validation of the genetic alterations proposed by NGS data. The genetic alteration tumor cell panels and their molecular signature profiles provide powerful tools to accelerate the discoveries in basic cancer research, compound screening, biomarker selection, pathway analysis, and targeted therapeutic development. Citation Format: Lysa A. Volpe, Anupreet Bal, John Foulke, Michael Jackson, Luping Chen, Fang Tian. Understanding the molecular nature of cancer cell lines. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3920. doi:10.1158/1538-7445.AM2014-3920
Deep Roots Support New Branches: The Impact of Dynamic, Cross-Generational Rural Culture on Older Women’s Response to Formal Health Care

Rural, older adults experience marked disparity in access to quality health care when compared to their urban counterparts. One aspect of promoting health access to these individuals that has received little attention is rural cultural competence. Semi-structured interviews and review of cultural artifacts informed this case study of a rural, community-dwelling, 83 year old woman who is co-managing her chronic disease with the formal healthcare system. The purpose of the study was to situate the life story of one rural, elderly woman within the context of the rural culture that she has experienced, and, through the application of Bonder, Martin, and Miracle’s (2002) Culture Emergent Theory, illuminated the theoretical and practical aspects of how dynamic culture influences health care practices and nurse-client encounters. Recommendations discussed include individual and system level strategies for developing cultural awareness, cultural knowledge, cultural skill, methods for participating in cultural encounters, and considerations for growing cultural desire. These strategies are considered imperative for the promotion of culturally competent rural nursing, nursing education, and rural patient advocacy.
Functional model of water balance variability at the catchment scale: 2. Elasticity of fast and slow runoff components to precipitation change in the continental United States

Assessing the sensitivity of annual streamflow to precipitation is challenging due to the complexity of the processes that control the water balance. A low-dimensional model can be useful to interrogate data in regional assessments of a large number of catchments, and can provide insights into the broad similarities and differences between catchments' behaviors. This work assesses the sensitivity to precipitation of total annual streamflow, as well as its slow and fast flow components, within the framework of the Ponce and Shetty water balance model. This framework assumes that there are upper limits on the ability of a catchment to store and evaporate water, and there are minimum threshold amounts of precipitation and wetting (precipitation minus fast flow) needed to initiate fast and slow runoff. The flow elasticities (percent of change in flow per percent of change in annual precipitation) were estimated for 405 catchments in the Model?Parameter Estimation Experiment data set (including an assessment of parameter uncertainty). The elasticity of total discharge was 2.1 on average across the catchments, which is consistent with other studies. The fast component was higher (? 2.4) and slow flow was lower (? 2.0). Elasticities were highest and most variable in arid areas. The variations in elasticity between sites were shown to be primarily controlled by the two threshold parameters. The thresholds were a high proportion of mean annual precipitation in arid sites where only a small proportion of catchment wetting is released as slow flow. This provides some insight into previous observations that the sensitivity is correlated with climate.
A NEW TYPE OF IDIOPATHIC HYPERGLYCINEMIA WITH HYPO-OXALURIA

A 5½-year-old male is described, with severe mental retardation, failure to thrive, inability to make adequate muscular movements, seizures, and spasticity. Laboratory studies revealed hyperglycinuria and hyperglycinemia, but a much reduced excretion of oxalic acid in the urine. It seems likely that this represents an inborn enzymatic defect, probably of glycine oxidase.