cssi/SciSciGPT-SciSciNet huggingface dataset:
An alternating sheared AA pair and elements of stability for a single sheared purine-purine pair flanked by sheared GA pairs in RNA.

A previous NMR structure of the duplex revealed an unusually stable RNA internal loop with three consecutive sheared GA pairs. Here, we report NMR studies of two duplexes, (replacing the UG pair with a UA closing pair) and (replacing the middle GA pair with an AA pair). An unusually stable loop with three consecutive sheared GA pairs forms in the duplex . The structure contrasts with that reported for this loop in the crystal structure of the large ribosomal subunit of Deinococcus radiodurans [Harms, J., Schluenzen, F., Zarivach, R., Bashan, A., Gat, S., Agmon, I., Bartels, H., Franceschi, F., and Yonath, A. (2001) Cell 107, 679−688]. The middle AA pair in the duplex rapidly exchanges orientations, resulting in alternative base stacking and pseudosymmetry with exclusively sheared pairs. The internal loop is 2.1 kcal/mol less stable than the internal loop at 37 °C. Structural, energetic, and dynamic consequences upon functional group substitutions within related 3 × 3 and 3 × 6 internal loops are also repo...
Levels of circulating myeloid subpopulations and of heme oxygenase-1 do not predict CD4+ T cell recovery after the initiation of antiretroviral therapy for HIV disease

The level (or frequency) of circulating monocyte subpopulations such as classical (CD14hiCD16-) and non-classical (CD14dimCD16+) monocytes varies during the course of HIV disease progression and antiretroviral therapy (ART). We hypothesized that such variation and/or differences in the degree to which these cells expressed the immunoregulatory enzyme, heme oxygenase-1 (HO-1), would be associated with CD4+ T cell recovery after the initiation of ART. This hypothesis was tested in a cross-sectional study of four groups of HIV-infected subjects, including those who were seronegative, untreated virologic controllers [detectable viral load (VL) of 10,000 copies/mL], and ART-mediated virologic controllers [VL < 75 copies/mL]. A longitudinal analysis of ART-treated subjects was also performed along with regression analysis to determine which biomarkers were associated with and/or predictive of CD4+ T cell recovery. Suppressive ART was associated with increased levels of classical monocyte subpopulations (CD14hiCD16-) and decreased levels of non-classical monocyte populations (CD14dimCD16+). Among peripheral blood mononuclear cells (PBMCs), HO-1 was found to be most highly up-regulated in CD14+ monocytes after ex vivo stimulation. Neither the levels of monocyte subpopulations nor of HO-1 expression in CD14+ monocytes were significantly associated with the degree of CD4+ T cell recovery. Monocyte subpopulations and HO-1 gene expression were, however, restored to normal levels by suppressive ART. These results suggest that the level of circulating monocyte subpopulations and their expression of HO-1 have no evident relationship to CD4+ T cell recovery after the initiation of ART.
Uniform total internal reflection fluorescence illumination enables live cell fluorescence resonance energy transfer microscopy.

Fluorescence resonance energy transfer (FRET) microscopy is a powerful technique to quantify dynamic protein-protein interactions in live cells. Total internal reflection fluorescence (TIRF) microscopy can selectively excite molecules within about 150 nm of the glass-cell interface. Recently, these two approaches were combined to enable high-resolution FRET imaging on the adherent surface of living cells. Here, we show that interference fringing of the coherent laser excitation used in TIRF creates lateral heterogeneities that impair quantitative TIRF-FRET measurements. We overcome this limitation by using a two-dimensional scan head to rotate laser beams for donor and acceptor excitation around the back focal plane of a high numerical aperture objective. By setting different radii for the circles traced out by each laser in the back focal plane, the penetration depth was corrected for different wavelengths. These modifications quell spatial variations in illumination and permit calibration for quantitative TIRF-FRET microscopy. The capability of TIRF-FRET was demonstrated by imaging assembled cyan and yellow fluorescent protein–tagged HIV-Gag molecules in single virions on the surfaces of living cells. These interactions are shown to be distinct from crowding of HIV-Gag in lipid rafts.
A comparison of production technology using primal and dual approaches: The case of Dutch dairy farms

Two models of profit-maximizing farms are developed using the duality that exists between the normalized profit function and the production function. Some production factors are fixed in the short term. The specification used is the translog form with variable intercepts. The equations are estimated with an incomplete panel using a SUR and 3SLS estimation method. The theoretical framework fits the data well. Assumptions often made about the production technology are tested. Linear homogeneity and Hicks' neutrality are rejected by both models. The production and substitution elasticities calculated by both models do not differ significantly. Therefore, using data from dairy farms in the Netherlands the dual models perform similarly. Copyright 1992 by Oxford University Press.
Cytotherapy with naive rat umbilical cord matrix stem cells significantly attenuates growth of murine pancreatic cancer cells and increases survival in syngeneic mice

AbstractBackground aims. Pancreatic cancer, sometimes called a ‘silent killer’, is one of the most aggressive human malignancies, with a very poor prognosis. It is the fourth leading cause of cancer-related morbidity and mortality in the USA. Methods. A mouse peritoneal model was used to test the ability of unengineered rat umbilical cord matrix-derived stem cells (UCMSC) to control growth of pancreatic cancer. In vivo results were supported by various in vitro assays, such as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), direct cell count, [3H]thymidine uptake and soft agar colony assays. Results. Co-culture of rat UCMSC with PAN02 murine pancreatic carcinoma cells (UCMSC:PAN02, 1:6 and 1:3) caused G0/G1 arrest and significantly attenuated the proliferation of PAN02 tumor cells, as monitored by MTT assay, direct cell counts and [3H]thymidine uptake assay. Rat UCMSC also significantly reduced PAN02 colony size and number, as measured by soft agar colony assay. The in vivo mouse studi...
Clinical Reasoning: A 12-year-old boy with ascending weakness

A 12-year-old boy presented with 3 weeks of calf pain, tripping, and progressive inability to walk. The onset was preceded by a sore throat 4 weeks prior, but no recent immunizations and no sick contacts. He began having problems "catching his toes" for 2 weeks. He had no visual complaints and no bowel or bladder incontinence. He had no recent travel and there were no heavy metal or solvent exposures. He had no prior medical history and he was on no prescription medications. Developmentally, he was on track and had just successfully completed fifth grade. However, he was reported to be behaviorally oppositional, especially regarding his diet which was restricted to beef jerky, yogurt from a squeeze tube, and fruit drinks. Family history included diabetic peripheral neuropathy in his mother, idiopathic peripheral neuropathy in his maternal grandfather, and left lower extremity neuropathy from trauma in his father. There was no known family history of recurrent pressure palsies or cardiac problems.
Anesthetic considerations for laparoscopy in children.

As experience, equipment, and techniques have improved, minimally invasive surgery is being applied to increasingly younger children. With the advent of this new surgical approach, there are also specific modifications necessary in anesthetic technique. When considering the anesthetic implications in these patients, one must consider both the patient's underlying health status as well as physiological derangements induced by the surgery. This article describes the specific anesthetic implications for laparoscopic procedures in neonates, infants, and children. This information includes the preoperative evaluation, intraoperative anesthetic care, and monitoring with a special emphasis on the physiological alterations induced by the endoscopic procedures.
Irigaray’s Alternative Buddhist Practices of the Self

In lieu of an abstract, here is the opening paragraph of the essay: Luce Irigaray’s critics charge that her attempt to carve out a space for nature and the feminine self through an engagement with Buddhism smacks of Orientalism. Associating Buddhism with a philosophy of nature can lead to feminizing and exoticizing the non-Western other. Because she relies more on lessons learned from yogic teachers than Buddhist texts or scholarship, her work seems to be an appropriation of Buddhist ideas and a critique of Western ideology 3 rather than a reflection of Buddhist philosophy. I trace Orientalist readings of Buddhism, including those of Irigaray, back to Hegel’s influence on comparative philosophy. Indeed, her analysis of the feminine self and nature often seem more like a response to Hegel than an examination of Buddhist principles. Some scholars resist Hegel’s reading by arguing that the Buddhist Absolute manifests in the indeterminately disjunctive and alternative versions of reality and self. Others suggest that the meaning of Buddhism can be found in examining its practices rather than its logic.
Weapons for Oil: An Analysis of Contemporary Chinese Weapons Sales to Africa in Exchange for Oil

Since 1949, China has gradually increased the scope of its weapons sales overseas to include 40 countries, 23 of which are located in Africa. With Chinese weapons sales in 2009 reaching 946 million U.S. dollars, the global community cannot help but pay attention to China‘s overseas weapons sales model. Over the past few years, resource-rich African nations have become the center of China‘s new geopolitical strategies and the starting point for oil development and extraction programs. With decades of cooperative experience in the energy sector, Africa has become an important area through which China is able to further diversify its energy resources. While China helped Africa develop an oil market, many other forms of aid and investment were also necessary. The most important form of aid can be best seen through "goods for goods" bartering transactions, especially in the form of Chinese weapons for African oil. This article will examine the realities of weapons-for-oil transactions as well as other Chinese involvement in Africa‘s natural resources and domestic economies, paying particular attention to how China is defining its interactions with African nations as those of a socialist leader. Through research and analysis of both historical and contemporary Sino-African relations, this article will illustrate the implications continued weapons-for-oil exchanges have for the future of Sino-Africa relations as well as for the international community.
A new theoretic framework for cross-layer optimization with message exchanges

Existing cross-layer optimization solutions are often based on the assumption that each layer's parameters are fully accessible to other layers or a centralized optimizer, thereby violating the layered network architecture of the protocol stack. This paper presents a new systematic framework named layered Markov decision process (MDP) for cross-layer optimization, which allows each layer to make autonomous decisions individually and determine the optimal message to be exchanged among layers in order to cooperatively maximize the utility of the wireless station. Hence, this layered cross-layer framework does not change the current layered architecture and is suitable for the delay-sensitive applications over wireless networks.
Studies on the pathogenesis of avascular retina and neovascularization into the vitreous in peripheral severe retinopathy of prematurity (an american ophthalmological society thesis)

Results: On p14, when retinas were only 70% vascularized in the model but fully vascularized in RA, VEGF164 expression was threefold greater in the model compared to RA. On p18, intravitreous neovascularization was associated with a 5-fold increase in VEGF164 mRNA in the model compared to RA. By analysis of variance, VEGF164 and VEGFR2 mRNAs were up-regulated in association with increasing developmental age (P<.0001 for both comparisons) or exposure to the model compared to RA (P<.0001 and P=.0247, respectively), whereas increasing developmental age was associated only with up-regulated VEGF120 (P=.0006), VEGF188 (P=.0256), and VEGFR1 (P<.0001) mRNAs. VEGF protein increased significantly in the model and on p14 and p18 compared to RA (P<.0001). Conclusions: The model mimics contemporary severe ROP in the United States unlike other models of oxygen-induced retinopathy. Compared to RA retinas, VEGF significantly increased in association with avascular retina and intravitreous neovascularization. A hypothesis is proposed that VEGF up-regulation plays a role in the development of both important features.
Evaluating inter-continental transport of fine aerosols:(2) Global health impact

In this second of two companion papers, we quantify for the first time the global impact on premature mortality of the inter-continental transport of fine aerosols (including sulfate, black carbon, organic carbon, and mineral dust) using the global modeling results of (Liu et al., 2009). Our objective is to estimate the number of premature mortalities in each of ten selected continental regions resulting from fine aerosols transported from foreign regions in approximately year 2000. Our simulated annual mean population-weighted (P-W) concentrations of total PM2.5 (aerosols with diameter less than 2.5 mm) are highest in East Asia (EA, 30 m gm �3 ) and lowest in Australia (3.6 m gm �3 ). Dust is the dominant component of PM2.5 transported between continents. We estimate global annual premature mortalities (for adults age 30 and up) due to inter-continental transport of PM2.5 to be nearly 380 thousand (K) in 2000. Approximately half of these deaths occur in the Indian subcontinent (IN), mostly due to aerosols transported from Africa and the Middle East (ME). Approximately 90K deaths globally are associated with exposure to foreign (i.e., originating outside a receptor region) non-dust PM2.5. More than half of the premature mortalities associated with foreign non-dust aerosols are due to aerosols originating from Europe (20K), ME (18K) and EA (15K); and nearly 60% of the 90K deaths occur in EA (21K), IN (19K) and Southeast Asia (16K). The lower and higher bounds of our estimated 95% confidence interval (considering uncertainties from the concentration–response relationship and simulated aerosol concentrations) are 18% and 240% of the estimated deaths, respectively, and could be larger if additional uncertainties were quantified. We find that in 2000 nearly 6.6K premature deaths in North America (NA) were associated with foreign PM2.5 exposure (5.5K from dust PM2.5). NA is least impacted by foreign PM2.5 compared to receptors on the Eurasian continent. However, the number of premature mortalities associated with foreign aerosols in NA (mostly occurring in the U.S.) is comparable to the reduction in premature mortalities expected to result from tightening the U.S. 8-h O 3 standard from 0.08 ppmv to 0.075 ppmv. International efforts to reduce inter-continental transport of fine aerosol pollution would substantially benefit public health on the Eurasian continent and would also benefit public health in the United States.
A novel approach for increasing security and data embedding capacity in images for data hiding applications

Data hiding in multimedia is the process of secretly embedding information into data sources such as image, video, or audio signals without changing the perceptual quality of the data source. We present a novel blind data hiding technique for hiding information in still images. This technique is based on embedding the information in the transform domain, after decorrelating the samples in the spatial domain. This results in a significant increase in the number of transform coefficients that can be used to transmit the hidden information. The technique is suitable for a variety of data hiding applications such as steganography, data authentication and captioning. The technique achieves a higher and more secure data embedding rate than existing data embedding transform domain techniques developed for these particular applications.
Evolutionary diversification of clades of squamate reptiles.

We analysed the diversification of squamate reptiles (7488 species) based on a new molecular phylogeny, and compared the results to similar estimates for passerine birds (5712 species). The number of species in each of 36 squamate lineages showed no evidence of phylogenetic conservatism. Compared with a random speciation‐extinction process with parameters estimated from the size distribution of clades, the alethinophidian snakes (2600 species) were larger than expected and 13 clades, each having fewer than 20 species, were smaller than expected, indicating rate heterogeneity. From a lineage-through-time plot, we estimated that a provisional rate of lineage extinction (0.66 per Myr) was 94% of the rate of lineage splitting (0.70 per Myr). Diversification in squamate lineages was independent of their stem age, but strongly related to the area of the region within which they occur. Tropical vs. temperate latitude exerted a marginally significant influence on species richness. In comparison with passerine birds, squamates share several clade features, including: (1) independence of species richness and age; (2) lack of phylogenetic signal with respect to clade size; (3) general absence of exceptionally large clades; (4) over-representation of small clades; (5) influence of region size on clade size; and (6) similar rates of speciation and extinction. The evidence for both groups suggests that clade size has achieved long-term equilibrium, suggesting negative feedback of species richness on the rate of diversification.
Optimization of E-service solutions with the Systems of Servers library

The paper describes a modeling library for analysis and optimization of distributed service systems: enterprise computing infrastructures, E-commerce, and E-service systems. The library uses a small number of basic notions, such as service, server, cluster (of servers), clients and message, which allow describing, analyzing and optimizing various system configurations and distributions of services among servers. The service requests and responses are modeled by messages traveling in the system and using its common resources. Clients send their requests to servers, which either return responses or may issue secondary requests for other services. To find the optimal deployment of services among servers, different partition policies can be deployed including partitions based on genetic algorithms. The library is built on top of Communicating Structures Library (CSL), a modeling environment for large-scale distributed systems (V.E. Kotov, 1998). In its turn, Systems of Servers is a base for specialized libraries that target specific classes of service systems.
G Protein Coupled Receptor Kinases as Therapeutic Targets in Cardiovascular Disease

G protein-coupled receptors (GPCRs) represent the largest family of membrane receptors and are responsible for regulating a wide variety of physiological processes. This is accomplished via ligand binding to GPCRs, activating associated heterotrimeric G proteins and intracellular signaling pathways. G protein-coupled receptor kinases (GRKs), in concert with β-arrestins, classically desensitize receptor signal transduction, thus preventing hyperactivation of GPCR second-messenger cascades. As changes in GRK expression have featured prominently in many cardiovascular pathologies, including heart failure, myocardial infarction, hypertension, and cardiac hypertrophy, GRKs have been intensively studied as potential diagnostic or therapeutic targets. Herein, we review our evolving understanding of the role of GRKs in cardiovascular pathophysiology.
Compact routing on power law graphs with additive stretch

We present a universal routing scheme for unweighted, undirected networks that always routes a packet along a path whose length is at most an additive factor of d more than OPT (where OPT is the length of an optimal path), using O(e log2 n)-bit local routing tables and packet addresses, with d and e parameters of the network topology. For power-law random graphs, we demonstrate experimentally that d and e take on small values. The Thorup-Zwick universal multiplicative stretch 3 scheme has recently been suggested for routing on the Internet inter-AS graph; we argue, based on the results in this paper, that it is possible to improve worst-case performance on this graph by directly exploiting its power-law topology.
Zonation in the deep benthic megafauna : Application of a general test.

A test based on Maxwell-Boltzman statistics, instead of the formerly suggested but inappropriate Bose-Einstein statistics (Pielou and Routledge, 1976), examines the distribution of the boundaries of species' ranges distributed along a gradient, and indicates whether they are random or clustered (zoned). The test is most useful as a preliminary to the application of more instructive but less statistically rigorous methods such as cluster analysis. The test indicates zonation is marked in the deep benthic megafauna living between 200 and 3000 m, but below 3000 m little zonation may be found.
Isolation of the Ferulates from Rice Germ Oil

Some ferulates as phenolic substances have been confirmed in rice germ oil. These ferulic acid esters are resemble to that from rice bran oil. The unsaponifiable fractions from these ferulates were confirmed to consist mainly of two triterpenoid alcohols (C30H50O and C31H52O) and sterol.
Building up the Population III initial mass function from cosmological initial conditions

We simulate the growth of a Population III stellar system, starting from cosmological initial conditions at z=100. We follow the formation of a minihalo and the subsequent collapse of its central gas to high densities, resolving scales as small as ~ 1 AU. Using sink particles to represent the growing protostars, we model the growth of the photodissociating and ionizing region around the first sink, continuing the simulation for ~ 5000 yr after initial protostar formation. Along with the first-forming sink, several tens of secondary sinks form before an ionization front develops around the most massive star. The resulting cluster has high rates of sink formation, ejections from the stellar disc, and sink mergers during the first ~ 2000 yr, before the onset of radiative feedback. By this time a warm ~ 5000 K phase of neutral gas has expanded to roughly the disc radius of 2000 AU, slowing mass flow onto the disc and sinks. By 5000 yr the most massive star grows to 20 M_sol, while the total stellar mass approaches 75 M_sol. Out of the ~ 40 sinks, approximately 30 are low-mass (M_* < 1 M_sol), and if the simulation had resolved smaller scales an even greater number of sinks might have formed. Thus, protostellar radiative feedback is insufficient to prevent rapid disc fragmentation and the formation of a high-member Pop III cluster before an ionization front emerges. Throughout the simulation, the majority of stellar mass is contained within the most massive stars, further implying that the Pop III initial mass function is top-heavy.
Aspectos Teóricos e Aplicados da Integração da Fenomenologia à Prática da Conservação do Patrimônio / Theorethical and applied aspects of integrating phenomenology into built heritage conservation practice

Qual e o papel do patrimonio? Como estabelecemos criterios para o tombamento? Qual e a relacao das pessoas com este processo e com os bens tombados? Essas sao apenas algumas das questoes motrizes desta conferencia em que o arquiteto Jeremy Wells reflete sobre as atuais normas de patrimonializacao a luz da ciencia positiva, propondo uma radicalizacao das abordagens por meio do pensamento (e do agir) fenomenologico. O foco passa a ser a nocao de lugar, a experiencia e as sensacoes que locais de importância historica e de aparencia antiga provocam nas pessoas que se relacionam cotidianamente com eles.
Bacterial computing

Undergraduate students find that a genetically engineered machine can solve Hamiltonian Path Problems.
Composting of Aged Reed Bed Biosolids for Beneficial Reuse: A Case Study in New Jersey, USA

ABSTRACTReed beds with Phragmites australis (common reed) have been utilized to decrease the water, nutrient, and volatile solids content of sewage sludge. An efficient disposal/reuse option was sought for reed bed biosolids accumulated over a 15-year period at a wastewater treatment facility in New Jersey, USA. The study facility had 14 reed beds, each with 1000 wet tons capacity, which were full, and so the solids needed to be removed. Because P. australis is considered an invasive species in New Jersey and several other states in the United States, disposal or reuse of solids containing this plant is regulated. Composting was examined as a potential treatment for destroying the plant's reproductive rhizomes. The high temperatures achieved during composting were also tested to determine if regulatory criteria for pathogen reduction could be met, making the composted product suitable for unrestricted land application. Preliminary studies indicated the sludge had stabilized to the point where self-heating...
Polypropylene mesh for hernia repair following transplantation.

Introduction: Infected incisional hernias are common in kidney transplant patients. Treating them in immunosuppressed patients can take months, increasing costs and implying loss of working productivity. Abdominal wall prostheses have not been used in infected immunosuppressed patients because of poor infection control. We evaluated the outcome of the surgical treatment of these patients with polypropylene mesh to shorten the hospitalization time and patient recovery. The records of 462 consecutive kidney transplant patients (March 2000 to February 2004) were reviewed. Of these 462 patients, 13 (2.8%) had infected or contaminated herniations at the transplant incision. They developed between 2 and 60 days (mean 14) after transplantation. The racial distribution was not significant, but herniations were more common in patients from cadaveric donors (4.5% versus 0%, P = 0.005). Predisposing factors were found in 6 patients (46.2%) and included complications from transplant surgery in 2, obesity in 1, leukopenia in 3, sepsis in 1, diabetes mellitus in 1, and wall weakness in 1 patient (3 had more than one risk factor). Technical Considerations: A prospective protocol of surgical correction with polypropylene mesh was established. After wound cleansing with normal saline, repair was done by primary fascial approximation and polypropylene mesh reinforcement. Broad-spectrum antibiotics and large-bore drains were used. Follow-up ranged from 1 to 40 months (mean 14.5). All patients did well except for one recurrence, 14 months after correction. Conclusions: Surgical repair with polypropylene mesh is safe and effective in treating infected or contaminated herniations in kidney transplant patients, with an acceptable (9.1%) incidence of recurrence.
Newton-Like Methods on Generalized Banach Spaces and Fractional Calculus

We present a semilocal convergence study of Newton-like methods on a generalized Banach space setting to approximate a locally unique zero of an operator.
Sponsors of Policy: A Network Analysis of Wealthy Elites, Their Affiliated Philanthropies, and Charter School Reform in Washington State.

Background/ContextCharter school policy has evolved into a major component of the current education reform movement in the United States. As of 2012, all but nine U.S. states allowed charter school...
Delay discounting in opioid use disorder: Differences between heroin and prescription opioid users

Abstract Background Among those with opioid use disorder, heroin use is associated with poorer prognosis relative to use of prescription opioids alone. However, relatively little is known about distinguishing features between those who use heroin relative to those who use prescription opioids. In the present study we evaluated differences in delay discounting in those with opioid use disorder based on primary opioid of use. Delay discounting is associated with a range of negative outcomes and is an important therapeutic target in this population. Methods Treatment-seeking adults with opioid dependence completed self-report measures including past-month opioid use and the Monetary Choice Questionnaire (Kirby and Marakovic, 1996; Kirby et al., 1999), a measure of delay discounting. Participants were divided into two groups based on whether they used any heroin in the past 30 days or only prescription opioids, and delay discounting scores were compared between the groups. Group differences in sociodemographic or clinical variables were included in the analysis as covariates. Results Results from a forward stepwise linear regression indicated that heroin use was associated with significantly higher delay discounting (B = −0.99, SEB = 0.34, t = −2.88, p = 0.005), even when considering covariates. Conclusions Adults with opioid dependence who exclusively used prescription opioids had lower delay discounting relative to those who used heroin. This finding contributes further to the literature suggesting that heroin use is associated with greater clinical severity among those with opioid use disorder.
Inhibition of the GAS6/AXL pathway augments the efficacy of chemotherapies

The AXL receptor and its activating ligand, growth arrest-specific 6 (GAS6), are important drivers of metastasis and therapeutic resistance in human cancers. Given the critical roles that GAS6 and AXL play in refractory disease, this signaling axis represents an attractive target for therapeutic intervention. However, the strong picomolar binding affinity between GAS6 and AXL and the promiscuity of small molecule inhibitors represent important challenges faced by current anti-AXL therapeutics. Here, we have addressed these obstacles by engineering a second-generation, high-affinity AXL decoy receptor with an apparent affinity of 93 femtomolar to GAS6. Our decoy receptor, MYD1-72, profoundly inhibited disease progression in aggressive preclinical models of human cancers and induced cell killing in leukemia cells. When directly compared with the most advanced anti-AXL small molecules in the clinic, MYD1-72 achieved superior antitumor efficacy while displaying no toxicity. Moreover, we uncovered a relationship between AXL and the cellular response to DNA damage whereby abrogation of AXL signaling leads to accumulation of the DNA-damage markers γH2AX, 53BP1, and RAD51. MYD1-72 exploited this relationship, leading to improvements upon the therapeutic index of current standard-of-care chemotherapies in preclinical models of advanced pancreatic and ovarian cancer.
University student perceptions about the motives for and consequences of nonmedical use of prescription drugs (NMUPD).

ABSTRACTObjective: The purpose of the current study was to increase qualitative understanding of student motives for and consequences associated with nonmedical use of prescription drugs. Participants: Sixty-one students participated in eight focus groups between April and November 2013. Methods: Students described prescription drugs commonly used for nonmedical reasons, as well as the motives for and consequences associated with their use. Data were analyzed using thematic content analysis. Results: Students reported stimulants as the most commonly used prescription drug for nonmedical reasons, least expensive, and easiest to obtain on campus, followed by benzodiazepines. Opioids were less commonly used, more expensive, and difficult to acquire. Motives and consequences varied by prescription drug class. Conclusions: Our qualitative findings extend previous research by suggesting differences in students' perceived motives for using and consequences associated with the different classes of prescription dr...
Plasma microbiome-modulated indole- and phenyl-derived metabolites associate with advanced atherosclerosis and postoperative outcomes.

Abstract Objective Multiple studies have shown that gut microbes contribute to atherosclerosis, and there is mounting evidence that microbial metabolism of dietary nutrients influences pathophysiology. We hypothesized that indole- and phenyl-derived metabolites that originate solely or in part from bacterial sources would differ between patients with advanced atherosclerosis and age- and sex-matched controls without clinically apparent atherosclerosis. Methods Plasma from the advanced atherosclerosis cohort (n = 100) was from patients who underwent carotid endarterectomy, open infrainguinal leg revascularization, or major leg amputation for critical limb ischemia. The controls (n = 22) were age- and sex-matched participants who had no peripheral arterial disease or history of stroke or myocardial infarction. Patients with chronic kidney disease were excluded. Metabolites and internal standards were measured using high-performance liquid chromatography and tandem mass spectrometry. Results Plasma metabolite concentrations differed significantly between the advanced atherosclerosis and control cohorts. After adjustment for traditional atherosclerosis risk factors, indole (odds ratio [OR], 0.84; 95% confidence interval [CI], 0.75-0.95; P = .004), tryptophan (OR, P P = .02), and indole-3-aldehyde (OR, 0.12; 95% CI, 0.014-0.92; P = .04) concentrations negatively associated with advanced atherosclerosis, whereas the kynurenine/tryptophan ratio (OR, 61.7; 95% CI, 1.9->999; P = .02) was positively associated. Furthermore, tryptophan and indole-3-propionic acid concentrations (Spearman coefficients of 0.63 and 0.56, respectively; P P = .001) and hippuric acid ( P = .03). In a multivariate analysis, only the kynurenine/tryptophan ratio remained significantly associated with a postoperative cardiac complication (OR, 44.1; 95% CI, 3.3-587.1; P = .004). Twenty patients in the advanced atherosclerosis cohort experienced a major adverse cardiac event during the follow-up period, which was associated with hippuric acid ( P = .002) and the kynurenine/tryptophan ratio ( P Conclusions Specific microbe-derived metabolite signatures associate with advanced human atherosclerosis and postoperative cardiac complications. We suggest that these metabolites are potential novel biomarkers for atherosclerotic disease burden and that further investigation into mechanistic links between defined microbial metabolic pathways and cardiovascular disease is warranted.
Diseases of Dairy Animals | Infectious Diseases: Listeriosis

Listeria monocytogenes is a Gram-positive bacterial pathogen that can cause disease in humans and a variety of animal species. Although listeriosis is increasingly recognized as a severe disease in dairy animals, including sheep, goats and cattle, it is still regarded by some as a relatively uncommon disease, probably due to the fact that it may be underreported and underdiagnosed. Listeria monocytogenes is of particular concern not only because it may cause significant disease and financial tolls for the dairy livestock industry, but also due to the human health significance of this organism. Human listeriosis is primarily a foodborne disease, which is estimated to be responsible for about 2500 cases annually in the United States. Although the number of human listeriosis cases is low as compared to many other foodborne disease, listeriosis has a high case mortality rate of about 20%. Thus in the United States alone, there are an estimated 500 human deaths attributable to listeriosis annually. Stringent control of L. monocytogenes in farm and food-processing environments and control and prevention of listeriosis in food-producing animals are important measures to assure human and animal health.
MEASUREMENT OF ROOTING PATTERNS FOR DETERMINATE AND INDETERMINATE SOYBEAN GENOTYPES WITH A FIBER-OPTIC SCOPE

Summary A fiber-optic scope technique was utilized to investigate the rooting habits of indeterminate and determinate soybean genotypes. Although these genotypes were not isolines, they were similar lines. There were no significant differences in the total root densities produced by either genotype throughout the growing season, but there were differences in root distribution. Indeterminate soybeans tended to produce larger root densities under the row than determinate ones. However, during the reproductive stages of soybean development, determinate soybeans produced significantly larger root densities in the interrow spaces. Both genotypes maintained at least 50 per cent of their root system in the Ap horizon throughout the growing season. From the seasonal data, four stages of root development were deduced and correlated with stages of soybean development (shoot portion). The data indicate that the root distribution may be more important than root density in influencing soybean yields. The performance of the fiber-optic scope technique proved to be a valuable tool for determining soybean root densities and distributions. Particular care should be taken in the installation of the observation tube to insure uniform contact between the soil and the surface of the tube. In soils where swelling or shrinkage occur, preliminary tests should be made to ascertain the effect on the uniformity of the soil-tube interface contact.
Community-Level Exposure to the Rural Mining Industry: The Potential Influence on Early Adolescent Alcohol and Tobacco Use.

PURPOSE Rural youth have higher rates of alcohol and tobacco use compared to their urban counterparts. However, the economic dependence of rural communities may differentially influence risk behaviors. While research has shown that adults working in mining have elevated rates of alcohol and tobacco use, the influence of living in a mining community on early adolescent substance use is unknown. METHODS Using data from a representative sample of 4,535 middle school students in a state with heavy reliance on mining, we conducted weighted logistic regression to investigate whether community-level mining economic dependence influences rural-urban differences in adolescent alcohol and tobacco use. All models adjusted for sociodemographics, military family involvement, parental monitoring, and length of residence. FINDINGS Over one quarter of the sampled students lived in rural counties and approximately half of these counties met the USDA mining economic typology. After stratifying rural counties by mining and nonmining economic dependence, students in rural mining counties had significantly higher odds of all measures of alcohol use (AORs ranged from 1.83 to 3.99) and tobacco use (AORs ranged from 1.61 to 5.05) compared to students in urban counties. Only use of smokeless tobacco was higher among students in rural nonmining counties. CONCLUSIONS Our findings demonstrate rural-urban disparities in adolescent substance use that are particularly pronounced among youth living in counties with economic dependence on mining. Future research on this subject should include a wider range of community-level factors that may have specific relevance in rural settings to inform the development of population-level interventions.
P54: Nitroglycerin-induced loss of caveolin-1 results in eNOS dysfunction, peroxynitrite production and nitrate tolerance

Prolonged treatment with nitroglycerin (GTN) has been shown to induce nitrate tolerance and cross-tolerance. However, much of the mechanism of how GTN leads to tolerance remains unknown. Recent evidence indicated that pharmacological doses ( Disclosure Supported by American Heart Association Grant to M.G.B (09SDG2250933).
General Considerations for Studying Bacterial Adhesion to Biomaterials

Bacterial adherence to biomaterial and tissue surfaces is an important step in the pathogenesis of prosthetic37,94 and tissue13 infection and the exact mechanism of prosthetic infection remains unclear. Before effective preventive or therapeutic methods can be achieved, the process, characteristics, or the mechanism of bacterial adhesion to biomaterials have to be studied. In this review, the experimental methods for bacterial adhesion to biomaterial surfaces are discussed.
Transthyretin and the Transthyretin Amyloidoses

Transthyretin is a normal serum protein that carries the secondary thyroid hormone thyroxine and retinol binding protein when it is loaded with retinol. It is synthesized primarily in the liver but there is also significant production in the choroid plexus and the retina. Both message and protein are found in the kidney but that site does not appear to contribute to the serum level in any meaningful way. The protein is a homotetramer composed of the 14-kDa monomer with the thyroxine binding sites in the central groove. The structure is highly conserved particularly in the regions responsible for ligand binding, suggesting that its carrier function has been retained over the millennia. More than 80 mutations at 55 different positions in the gene encoding the protein are the primary cause of a set of human disorders collectively known as the familial amyloidotic polyneuropathies and cardiomyopathies. In these diseases, the soluble protein becomes insoluble under physiologic conditions resulting in functional compromise in the organs in which the protein is deposited. Peripheral nerves, heart, kidneys, gastrointestinal tract, and the leptomeninges have all been described as sites of deposition. It is possible that particular syndromes are associated with particular sets of mutations but, because of the rarity of some of the mutations, it is uncertain if the relationship between any mutation and any clinical syndrome is absolute. Further, it is also clear that the wild-type protein can deposit in tissues with subsequent dysfunction, particularly in the heart and carpal tunnel. Biophysical studies in vitro indicate that the process leading from soluble tetramer to insoluble aggregates involves monomer release, misfolding, oligomerization, and extension and lateral aggregation apparently as a downhill polymerization to a more stable lower energy state. How this is modulated in vivo is not known, although accessory molecules appear to be involved in the process. The early, albeit incomplete, understanding of the processes have led to potential therapies directed at stabilizing the tetramer or interfering with the interaction with other molecules as well as replacing the offending gene by liver transplantation.
The Solid—Vapor Equilibrium of Carbon Dioxide—Nitrogen

The effects of nitrogen on the solid-vapor equilibrium of carbon dioxide have been measured In the range 140°–190°K and 5–100 atm absolute pressure. No attempt was made to analyze the solid phase, due to the difficulty of such measurements and the expectation that the nitrogen concentration would be negligible, at least at moderate pressures. The gas-phase composition was of primary concern, due to the highly nonideal behavior of the system in this region of temperature and pressure.
Human Rights and the Shadow of Chile’s Dictatorship: Patricio Guzmán and the Poetics of a Cinematic Landscape

In the later documentaries by Patricio Guzman, Nostalgia for the Light (2010) and The Pearl Button (2015), the filmmaker develops an aesthetic rooted in specific landscapes, a term that Winterbottom unpacks in a comparative analysis as a protagonizing and vital presence in the sublime narrative power of the films. Guzman’s immersive style centred on landscape creates a subtle yet profound activism that allows for an intense reflection on the human rights abuses of the dictatorship. Yet, while Guzman’s work is deeply rooted in Chile and the atrocities under Pinochet’s military rule (1973–1990), these documentaries are particularly and transcendentally powerful in how they engage with the landscapes to explore fundamental questions about the fragile nature of existence.
Other Pain Management Techniques for Older Adults

Effectively managing pain in older adults often requires an interdisciplinary approach that utilizes less traditional methods such as massage therapy, myofascial release therapy, yoga, electrical muscle stimulation, acupuncture, chiropractic adjustment, hypnosis, holistic approaches, surgical interventions, plasma injections, and prolotherapy. These methods are often used in complement to one another and may also coincide with traditional physical and pharmacological interventions. In addition to developing a customized management program, older adults face unique challenges that must be considered by healthcare providers exceeding the physical experience of pain and incorporating the social and psychological aspects of the pain experience. Older adults often face additional complications with traditional physical and pharmacological therapeutic approaches as stand-alone treatments due to comorbid conditions, the number of medications taken daily, lack of social support, and financial concerns. This chapter will focus on these therapeutic options for pain management in older adults as well as emphasizing the importance and effectiveness of customizable, interdisciplinary strategies.
Intractable stokes adams attack with myriad of ventricular arrythmias masquerading acute myocarditis

Convulsive syncope can be difficult to distinguish from seizures at times. Misdiagnosis can result in unnecessary, and usually unsuccessful, treatment with antiepileptic drugs. A detailed history taking and physical examination along with continuous cardiac monitoring can help in making the correct diagnosis. Our patient was eventually found to have viral myocarditis. More detailed studies for the role of noninvasive cardiac testing such as Cardiac MRI (CMR) and newer treatment modalities such as anti-thymocyte immunoglobulin are required for the management of Viral Myocarditis.