cssi/SciSciGPT-SciSciNet huggingface dataset:
Tracking the burial and tectonic history of Devonian shale of the Appalachian Basin by analysis of joint intersection style

The most pervasive systematic joints hosted by Devonian black shale of the Appalachian Plateau include east-northeast joints and younger northwest-striking cross-fold joints. Both sets were driven exclusively by fluid pressure generated as a consequence of hydrocarbon-related maturation supplemented by subsequent tectonic compaction during the Alleghanian tectonic cycle. In the more deeply buried, proximal region of the Catskill Delta, joints of both sets cross-cut. However, in stratigraphically equivalent black shale of the distal, shallower region of the delta to the west, ~25% of the joint intersections are crosscutting whereas ~75% of the intersections are defined by east-northeast joints curving into and abutting cross-fold joints. East-northeast joints in the distal shale propagated early but were neither as long nor as pervasive as similarly oriented joints in the more deeply buried proximal delta deposits. However, these same joints are much better developed (more closely spaced) stratigraphically lower in the distal shale succession, where essentially all intersections are crosscutting. It is likely that relatively high contact stress, an effective stress on east-northeast joints, in the more deeply buried parts of the delta enabled the unimpeded transmission of elastic stress concentration at the tip of cross-fold joints across the older joints. In the distal delta, exhumation of the Devonian shale sequence following establishment of the contemporary stress field in middle Tertiary time to within ~1 km of the Earth's surface resulted in renewed propagation of east-northeast joints. The propagation path of the reactivated joints curved into and terminated against cross-fold joints at angles of 60°–90°. The curving-to-termination intersection style is a manifestation of crack-tip stress-field blunting as a consequence of slippage along the interface of cross-fold joints enabled by exhumation-induced relaxation of contact stress on these latter joints. It is noteworthy that the orientation of the densely formed east-northeast joints parallel to the maximum horizontal stress direction of the contemporary lithospheric stress field likely imparts a meaningful permeability anisotropy to these hydrocarbon source rocks.
AT(2), judgment day: which angiotensin receptor is the culprit in cardiac hypertrophy?

As reviewed recently in these pages,1 the vasoconstrictor angiotensin II (Ang II) is one of the circulating peptide growth factors, and clinically the most relevant, that fulfill many of Koch’s postulates for having additional effects locally in the myocardium. These criteria include local production of Ang II within the heart, its upregulation there by hypertrophic signals, its release from cardiac cells after mechanical load, the presence of its receptors on the surface of cardiac cells, and the responsiveness of both cardiac myocytes and cardiac fibroblasts to provocation by this peptide.1,2 This local circuit of Ang II production, release, binding, and transduction within the myocardium itself is the most cogent explanation for the effectiveness of ACE inhibitors in heart failure, even at doses that do not alter loading conditions.1,2 See p 346 Three related receptors exist for Ang II: AT1a, AT1b, and AT2, which communicate with a complex cell-wide web of signaling cascades through GTP-binding (G) proteins as the proximal transducer. The operation of a local circuit for Ang II within the myocardium poses two questions, which have attracted much recent experimental effort, and an even larger share of controversy. First, given that multiple receptors exist for Ang II, which type or types are responsible for pathobiology provoked by the local circuit? Second, given that cardiac muscle and nonmuscle cells are both potential targets for Ang II, what is the respective role of each? Genetic models that altogether lack the receptors individually provide an invaluable experimental tool beyond what is achievable by use of pharmacological inhibitors alone. Surprisingly, the Ang II receptor …
GaN Quantum Dots Grown at High Temperatures by Molecular Beam Epitaxy

In this paper we report the growth by MBE of GaN quantum dot superlattices (QDSLs) with AlN barriers on (0001) sapphire substrates at relatively high temperatures (770 oC) by the modified Stranski-Krastanov method. TEM studies indicate that the GaN QDs are truncated pyramids. We find that the height distribution of the dots depends strongly on the number of GaN monolayer coverage on the top of AlN. Specifically, we find that the height distribution consists of two Gaussian distributions (bimodal) for coverage of 3 and 4 MLs, and becomes single Gaussian distribution for 5 and 6 MLs of coverage. Furthermore, we find that the density of quantum dots increases with the degree of coverage and saturates at 2×1011 dots/cm2. The number of stacks in the superlattice structure was also found to lead to bimodal height distribution of the QDs. Ordering of the quantum dots was accomplished by thermal annealing of the sapphire substrates at 1400 oC prior to the growth of GaN QDs. The annealing process reveals the vicinal steps due to the miscut of the substrates and the GaN QDs were found to line up along those steps. Photoluminescence studies show a broad luminescence spectrum centered at 3 eV which is red shifted with respect to that of bulk GaN and is consistent with internal fields due to polarization (Quantum Confined Stark Effect). Furthermore, we find that the luminescence intensity increases with the number of stacks in the superlattice structure due to higher spatial density of QDs.
Understanding protein aggregation from the view of monomer dynamics

Much work in recent years has been devoted to understanding the complex process of protein aggregation. This review looks at the earliest stages of aggregation, long before the formation of fibrils that are the hallmark of many aggregation-based diseases, and proposes that the first steps are controlled by the reconfiguration dynamics of the monomer. When reconfiguration is much faster or much slower than bimolecular diffusion, then aggregation is slow, but when they are similar, aggregation is fast. The experimental evidence for this model is reviewed and the prospects for small molecule aggregation inhibitors to prevent disease are discussed.
Intra-articular gene delivery and expression of interleukin-1Ra mediated by self-complementary adeno-associated virus.

Background The adeno-associated virus (AAV) has many safety features that favor its use in the treatment of arthritic conditions; however, the conventional, single-stranded vector is inefficient for gene delivery to fibroblastic cells that primarily populate articular tissues. This has been attributed to the inability of these cells to convert the vector to a double-stranded form. To overcome this, we evaluated double-stranded self-complementary (sc) AAV as a vehicle for intra-articular gene delivery. Methods Conventional and scAAV vectors were used to infect lapine articular fibroblasts in culture to determine transduction efficiency, transgene expression levels, and nuclear trafficking. scAAV containing the cDNA for interleukin (IL)-1 receptor antagonist (Ra) was delivered to the joints of naive rabbits and those with IL-1β-induced arthritis. From lavage of the joint space, levels of transgenic expression and persistence were measured by enzyme-linked immunosorbent assay. Infiltrating leukocytes were quantified using a hemocytometer. Results Transgene expression from scAAV had an earlier onset and was approximately 25-fold greater than conventional AAV despite the presence of similar numbers of viral genomes in the nuclei of infected cells. Fibroblasts transduced with scAAV produced amounts of IL1-Ra comparable to those transduced with adenoviral and lentiviral vectors. IL1-Ra was present in lavage fluid of most animals for 2 weeks in sufficient quantities to inhibit inflammation of the IL-1β-driven model. Once lost, neither subsequent inflammatory events, nor re-administration of the virus could re-establish transgene expression. Conclusions scAAV-mediated intra-articular gene transfer is robust and similarly efficient in both normal and inflamed joints; the resulting transgenic expression is sufficient to achieve biological relevance in joints of human proportion. Copyright © 2009 John Wiley & Sons, Ltd.
Empirical Analysis of the Business Value of Recommender Systems

Online retailers are increasingly using information technologies to provide value added services to customers. Prominent examples of these services are online recommender systems and consumer feedback mechanisms that serve to reduce consumer search costs and uncertainty associated with the purchase of unfamiliar products. The central question we address is the business value of online recommender systems to online retailers. We develop a robust empirical method that incorporates indirect impact of recommendations on sales through retailer pricing, potential simultaneity between sales and recommendations, and a comprehensive measure of the strength of recommendations. Applying the model to a panel data set collected from two online retailers, we found that the strength of recommendations has a positive impact on sales. We also found empirical evidence for the reinforcing effect of sales on recommendations and for the positive impact of recommendations on prices. These results suggest that recommendations not only improve sales but also provide added flexibility to retailers to adjust their prices. A comparative analysis reveals that recommendations have a higher impact on sales than consumer feedback. Our study demonstrates the value provided by information technology to an online retailer and provides guidelines for integrating recommender systems into their overall marketing strategy.
Extensively drug-resistant Mycobacterium tuberculosis: Charles Darwin would understand.

In this issue of Clinical Infectious Diseases Pillay and Sturm document the evolution over a decade of an extensively drug-resistant strain of Mycobacterium tuberculosis (XDR-TB) in the KwaZulu-Natal region of South Africa. This is the latest iteration in the on-going struggle between the tubercle bacillus and Homo sapiens. In the most profound single insight in the history of biology Darwins The Origin of Species laid out the simple tenets of evolution: diversity among progeny and factors in the environment that favored the survival and replication of certain of those progeny. This is the modern story of tuberculosis (TB). Consumption was rampant in Europe and North America in the past 400 years estimated to take the life of 1 in 5 adults in Europe at the turn of the 19th century. However with the discovery of para-aminosalicylic acid (PAS; in 1944) streptomycin (in 1944) and isoniazid (in 1951) the long-sought cure seemed at hand. An early study by the British Medical Research Council found that the combination treatment with PAS and streptomycin was more effective than treatment with either agent alone. By use of the novel technology of in vitro drug susceptibility testing it was observed that 2-drug therapy delayed or inhibited the appearance of drugresistant strains of M. tuberculosis. (excerpt)
Brain phospholipases and their role in signal transduction.

In response to stimuli, neural membranes release arachidonate which is then metabolized to biologically active eicosanoids (Chang et al., 1987). In neural membranes arachidonate is located exclusively in the sn-2position of membrane phospholipids and is released through various direct and indirect enzymic pathways. The direct pathway involves the stimulation of phospholipase A2. One indirect pathway requires the activation of phospholipase C followed by diacylglycerol and monoacylglycerol lipases. A second indirect pathway releases arachidonate by utilizing a lysophospholipase preceded by phospholipase A?. The hydrolysis of phospholipids by phospholipase D produces phosphatidic acid, which can then be hydrolyzed by a phosphatidic acid-specific phospholipase A2. The action of a phosphatase on phosphatidic acid generates diacylglycerol, which can be hydrolyzed by diacylglycerol and monoacylglycerol lipases.
Sustained Effects of the Communities That Care System on Prevention Service System Transformation

Objectives. We examined whether the Communities That Care (CTC) system sustained effects 1.5 years after study funding ended on prevention system constructs expected to be important for community-level reductions in drug use and antisocial behaviors among youths.Methods. Data were from a community trial of 24 towns in the United States randomized to either the CTC intervention or control conditions. Participants were 928 community key leaders interviewed at 1 to 4 waves from 2001 to 2009. Intervention activities, including training and technical assistance, were conducted between 2003 and 2008 in the CTC communities.Results. Leaders from CTC communities reported higher levels of adoption of a science-based approach to prevention and a higher percentage of funding desired for prevention activities in 2009 than did leaders in control communities. CTC communities showed a higher increase over time in community norms against adolescent drug use as well as adoption of a science-based approach compared with con...
Eligibility for Lipid-Lowering Drug Therapy in Primary Prevention How Do the Adult Treatment Panel II and Adult Treatment Panel III Guidelines Compare?

In May 2001, the Adult Treatment Panel III (ATP III) of the National Cholesterol Education Program issued revised guidelines for diagnosing and treating high blood cholesterol.1 These guidelines represent a major advance in risk assessment. They were preceded by the ATP I guidelines (1988), which focused on primary prevention of coronary heart disease (CHD), and by the ATP II guidelines (1993),2 which discussed primary and secondary prevention. In the ATP II and ATP III guidelines, low-density lipoprotein cholesterol (LDL-C) is the primary target of risk-reduction therapy. See p 152 The ATP II recommendations were based on epidemiological, preclinical, and incomplete clinical trial evidence. Within a few years after their publication, the results of 5 large-scale trials of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (ie, “statins”) were reported. Two of these (West of Scotland Coronary Prevention Study [WOSCOPS] and Air Force/Texas Coronary Atherosclerosis Prevention Study [AFCAPS/TexCAPS]) were primary-prevention trials.3,4 The remaining 3 focused on secondary prevention.5-7 Based on these epic trials and other laboratory, epidemiological, and clinical evidence, the ATP III guidelines were developed (Tables 1 and 2⇓). View this table: Table 1103484. ATP III Guidelines: New Features View this table: Table 2103484. ATP III Guidelines: Global Risk Assessment The major statin trials and resulting meta-analyses provided a firm foundation for a truly evidence-based approach to guideline revision. Involving 5 different populations with widely varying absolute risk levels and using 3 different statins (simvastatin, pravastatin, lovastatin), they produced remarkably consistent reductions of 24% to 37% in relative risk for major CHD events. In WOSCOPS, 6595 men with moderate hypercholesterolemia (LDL-C=192 mg/dL±SD) received pravastatin 40 mg/day for up to 4.9 years. Results indicated a 31% relative decrease in major CHD events, with a 26% reduction in LDL-C levels. AFCAPS/TexCAPS evaluated lovastatin 20 to 40 mg/day for up to 5.2 years in 6605 generally healthy men and women with …
Global methods for simulating contacting flexible bodies

A model for the dynamic simulation of flexible bodies subject to nonpenetration constraints is presented. Flexible bodies are described in terms of global deformations of a rest shape. The dynamical behavior of these bodies that most closely matches the behavior of ideal continuum bodies is derived, and subsumes the results of earlier Lagrangian dynamics-based models. The dynamics derived for the flexible-body model allows the unification of previous work on flexible body simulation and previous work on nonpenetrating rigid body simulation. The nonpenetration constraints for a system of bodies that contact at multiple points are maintained by analytically calculated contact forces. Frictional effects are also included. An implementation for first- and second-order polynomially deformable bodies is described. The simulation of second-order or higher deformations currently involves a polyhedral boundary approximation for collision detection purposes. >
The System SiO2–P2O5

Phase relations in the binary system between SiO2-P2O5 and SiO2 were investigated by the quenching method using sealed platinum tubes to prevent the loss of P2O5. The compound Si02-P2O5 exists in two forms, the low-temperature β form inverting sluggishly but reversibly to the high-temperature β form at 1030°C. The β form melts congruently at 1290°C. The compound 2SiO2-P2O5 melts incongruently at 1120°C to a silica-rich liquid and SiOa-P2O5. In the region between 5 and 25 mole % PO2, reactions were so sluggish that no data could be obtained by quenching.
Physiology and Diversity of Ammonia-Oxidizing Archaea

The discovery of ammonia-oxidizing archaea (AOA), now generally recognized to exert primary control over ammonia oxidation in terrestrial, marine, and geothermal habitats, necessitates a reassessment of the nitrogen cycle. In particular, the unusually high affinity of marine and terrestrial AOA for ammonia indicates that this group may determine the oxidation state of nitrogen available to associated micro- and macrobiota, altering our current understanding of trophic interactions. Initial comparative genomics and physiological studies have revealed a novel, and as yet unresolved, primarily copper-based pathway for ammonia oxidation and respiration distinct from that of known ammonia-oxidizing bacteria and possibly relevant to the production of atmospherically active nitrogen oxides. Comparative studies also provide compelling evidence that the lineage of Archaea with which the AOA affiliate is sufficiently divergent to justify the creation of a novel phylum, the Thaumarchaeota.
Adaptive recursive order statistic filters

The ideas embodied by the recursive median filter are merged into a more general class of recursive LI-filters which includes both the infinite impulse response (IIR) filters and all the order statistic filters. The recursive LI-filter is a special case of a state-dependent system, and it can be seen as a more general IIR filter whose coefficients are picked up at every time step from a fixed set according to the order relationships existing among the elements of the observed window. An algorithm for adaptive computation of the coefficients of the recursive order statistic filters is derived. The algorithm is a steepest-descent search which follows an approach similar to that of the output-error formulation used in adaptive IIR filters. As a verification of convergence an example is shown in which the adaptive algorithm identifies successfully a recursive median filter and a recursive LI-filter. An example that shows how the recursive generalized filter has improved characteristics with respect to transient instabilities is also shown. >
Stellar Multiplicity and the Initial Mass Function: Most Stars Are Single

In this Letter I compare recent findings suggesting a low binary star fraction for late-type stars with knowledge concerning the forms of the stellar initial and present-day mass functions for masses down to the hydrogen-burning limit. This comparison indicates that most stellar systems formed in the Galaxy are likely single and not binary, as has been often asserted. Indeed, in the current epoch two-thirds of all main-sequence stellar systems in the Galactic disk are composed of single stars. Some implications of this realization for understanding the star and planet formation process are briefly mentioned.
Comparison of risk prediction scoring systems for ward patients: a retrospective nested case-control study

The rising prevalence of rapid response teams has led to a demand for risk-stratification tools that can estimate a ward patient’s risk of clinical deterioration and subsequent need for intensive care unit (ICU) admission. Finding such a risk-stratification tool is crucial for maximizing the utility of rapid response teams. This study compares the ability of nine risk prediction scores in detecting clinical deterioration among non-ICU ward patients. We also measured each score serially to characterize how these scores changed with time. In a retrospective nested case-control study, we calculated nine well-validated prediction scores for 328 cases and 328 matched controls. Our cohort included non-ICU ward patients admitted to the hospital with a diagnosis of infection, and cases were patients in this cohort who experienced clinical deterioration, defined as requiring a critical care consult, ICU admission, or death. We then compared each prediction score’s ability, over the course of 72 hours, to discriminate between cases and controls. At 0 to 12 hours before clinical deterioration, seven of the nine scores performed with acceptable discrimination: Sequential Organ Failure Assessment (SOFA) score area under the curve of 0.78, Predisposition/Infection/Response/Organ Dysfunction Score of 0.76, VitalPac Early Warning Score of 0.75, Simple Clinical Score of 0.74, Mortality in Emergency Department Sepsis of 0.74, Modified Early Warning Score of 0.73, Simplified Acute Physiology Score II of 0.73, Acute Physiology and Chronic Health Evaluation II of 0.72, and Rapid Emergency Medicine Score of 0.67. By measuring scores over time, it was found that average SOFA scores of cases increased as early as 24 to 48 hours prior to deterioration (P = 0.01). Finally, a clinical prediction rule which also accounted for the change in SOFA score was constructed and found to perform with a sensitivity of 75% and a specificity of 72%, and this performance is better than that of any SOFA scoring model based on a single set of physiologic variables. ICU- and emergency room-based prediction scores can also be used to prognosticate risk of clinical deterioration for non-ICU ward patients. In addition, scoring models that take advantage of a score’s change over time may have increased prognostic value over models that use only a single set of physiologic measurements.
GPR1 encodes a putative G protein‐coupled receptor that associates with the Gpa2p Gα subunit and functions in a Ras‐independent pathway

The yeast RAS1 and RAS2 genes appear to be involved in control of cell growth in response to nutrients. Here we show that this growth control also involves a signal mediated by the heterotrimeric G protein alpha subunit homolog encoded by GPA2. A GPA2 null allele conferred a severe growth defect on cells containing a null allele of RAS2, although either mutation alone had little effect on growth rate. A constitutive allele of GPA2 could stimulate growth of a strain lacking both RAS genes. Constitutive GPA2 conferred heat shock sensitivity on both wild-type cells and cells lacking RAS function, but had no effect in a strain containing a null allele of SCH9, which encodes a kinase related to protein kinase A. The GPR1 gene was isolated and was found to encode a protein with the characteristics of a G protein-coupled receptor. Double Deltagpr1 Deltaras2 mutants displayed a severe growth defect that was suppressed by expression of the constitutive allele of GPA2, confirming that GPR1 acts upstream of GPA2. Gpr1p is expressed on the cell surface and requires sequences in the membrane-proximal region of its third cytoplasmic loop for function, as expected for a G protein-coupled receptor. GPR1 RNA was induced when cells were starved for nitrogen and amino acids. These results are consistent with a model in which the GPR1/GPA2 pathway activates the Sch9p kinase to generate a response that acts in parallel with that generated by the Ras/cAMP pathway, resulting in the integration of nutrient signals.
Protist Communities from Four Castes and Three Species of Reticulitermes (Isoptera: Rhinotermitidae)

Abstract Previous studies indicate subterranean termite protist communities are qualitatively similar within termite species but differ in relative species abundance between castes. We investigated protist communities from four castes of Reticulitermes flavipes (Kollar), Reticulitermes virginicus (Banks), and Reticulitermes hageni Banks. We used a standardized counting technique and found termite workers and early stage nymphs had the largest population of protists, followed by soldiers and alates. R. flavipes workers averaged 59,000 flagellates compared with 21,000 in R. hageni and 14,000 in R. virginicus. We recorded two new genera, Microjoenia Grassi and Monocercomonas Grassi, from R. virginicus. We identified eight protist species from R. hageni, whereas only four have been previously noted. This is the first report of Dinenympha fimbriata Kirby, Holomastigotes elongatum Grassi, Monocercomonas Grassi, Pyrsonympha minor Powell, Spirotrichonympha flagellata (Grassi), and Trichonympha agilis Leidy from R...
Behavior compilation for AI in games

In order to cooperate effectively with human players, characters need to infer the tasks players are pursuing and select contextually appropriate responses. This process of parsing a serial input stream of observations to infer a hierarchical task structure is much like the process of compiling source code. We draw an analogy between compiling source code and compiling behavior, and propose modeling the cognitive system of a character as a compiler, which tokenizes observations and infers a hierarchical task structure. An evaluation comparing automatically compiled behavior to human annotation demonstrates the potential for this approach to enable AI characters to understand the behavior and infer the tasks of human partners.
Determining Structures of Protein/DNA Complexes by NMR

It is axiomatic that a detailed understanding of the function of macromolecules necessitates knowledge of their three-dimensional structures. At the present time, the two main techniques that can provide a compete description of the structures of macromolecules at the atomic level are X-ray crystallography in the solid state (single crystals) and nuclear magnetic resonance spectroscopy in solution. Both techniques have different advantages and drawbacks and taken together yield highly complementary results.
Immunological relationships between rabbit acrosin and pancreatic trypsin.

Specific anti-rabbit acrosin antibodies were prepared by immunizing female guinea pigs with rabbit acrosin. Acrosin was purified by molecular sieve and proflavin-Sepharose affinity chromatography. Inhibition studies to characterize unique antigenic determinants of acrosin compared to pancreatic trypsin indicate that anti-rabbit acrosin yglobuli-115 specifically reduced the catalytic effects of acrosin but not trypsin on Azocoll. Anti-acrosin antibodies had no effect on altering the catalytic activities of either acrosin or trypsin on the substrate N-α-benzoyl-L-arginine ethyl ester.
Ultrasound Guidance for Venous Therapy: VNUS, Endovenous Laser Treatments, and Foam

Duplex ultrasound sonography (US) represents the best choice in the evaluation of venous reflux in lower limbs.1 This test is noninvasive, generally acceptable to the patient, and inexpensive.2 It provides direct imaging, localization, and extent of venous reflux with a surprisingly high sensitivity (95%) and specificity (100%).3 Duplex US findings have also been confirmed with angioscopic observations of incompetent vein valves in advanced chronic venous insufficiency (CVI).4 As demonstrated by Yamaki, high peak reflux velocities (>30 cm/s), reflux duration greater than 3 s, and an enlarged valve annulus measured by duplex US at the saphenofemoral junction (SFJ) are closely related to angioscopically deformed and incompetent terminal valves (Type III and Type IV valves of Hoshino).4
Aln-TMP: A Subcutaneously Administered RNAi Therapeutic Targeting Tmprss6 For The Treatment Of β-Thalassemia

Abstract The b-Thalassemias are a group of hereditary blood disorders resulting from insufficient beta globin production, ultimately giving rise to the signature clinical sequelae associated with β-Thalassemia which includes anemia, ineffective erythropoiesis, and secondary iron overload. Previously, we demonstrated that intravenous administration of an siRNA targeting hepatic Tmprss6 expression significantly ameliorated the disease phenotype in the Hbbth3/+ mouse model of Thalassemia Intermedia (Blood. 2013; 14;121(7):1200-8). The Tmprss6 gene encodes for the protein Matriptase-2 which negatively regulates Hepcidin gene expression by cleaving the Hepcidin regulatory protein Hemojuvelin; RNAi-mediated suppression of Tmprss6 removes this negative regulator, ultimately leading to an increase in Hepcidin expression. Increased Hepcidin expression leads to a significant decrease in serum iron concentration and Transferrin Saturation (TfSat), which in the β-Thalassemia disease setting, corrects ineffective erythropoiesis, ameliorates anemia, and mitigates secondary iron overload. The role of Tmprss6 in iron metabolism has been extensively characterized in animal and human studies and, together with the observation in the Hbbth3/+ mouse, represents an attractive therapeutic target for the treatment of β-Thalassemia. To this end, we developed ALN-TMP, a subcutaneous RNAi therapeutic targeting hepatic Tmprss6 for the treatment of β-Thalassemia. ALN-TMP employs the GalNAc conjugate siRNA delivery platform that safely and effectively delivers siRNA to the liver for hepatic gene silencing. Preclinical animal data demonstrate ALN-TMP exhibits robust and durable dose-dependent gene suppression as single dose administration of ALN-TMP leads to > 80% Tmprss6 gene suppression for up to 3 weeks post-dose. This leads to concomitant increases in Hepcidin gene expression (>2x baseline levels) and subsequent decreases in total serum iron and TfSat (>50% decrease from baseline). The degree to which ALN-TMP modulates Hepcidin and serum iron mobilization is nearly identical to that observed in the previous Hbbth3/+ mouse studies and suggests ALN-TMP is a potent RNAi therapeutic with the potential of producing disease modifying effects in β-Thalassemia. Disclosures: Butler: Alnylam: Employment. Fishman: Alnylam: Employment. Racie: Alnylam Pharmaceutical, Inc: Employment. Hettinger: Alnylam Pharmaceuticals: Employment. Bettencourt: Alnylam Pharmaceuticals: Employment. Charisse: Alnylam Pharmaceuticals: Employment. Fitzgerald: Alnylam: Employment.
Electron Localization, Tunneling and Energy Spectrum for Systems of Double Quantum Dots

Semiconductor heterostructures as quantum dots demonstrate discrete atom-like energy level structure based on several hundred of electron confinement states. In the case of double QD (DQD) or double QR (DQR), there is a single electron spectrum composed of a set of quasi-doublets. We study these specific spectrum properties with their relation to the electron tunneling in DQD (DCQR) when the wave function of electron localized initially in one of the double quantum object is spread into whole system. The double InAs/GaAs quantum dots are considered within the effective approach. Tunneling in DQD is studied in connection with change of inter-dot distance and QD geometry. There are two types of such tunneling in DQD. The first is related to tunneling in the system of two identical QDs; the second one occurs in the system of non-identical QDs. The tunneling in the DQR is a tunneling in the system with non-identical quantum objects. The quasi-doublets of the DQD spectrum play an important role in the tunneling. We study effect of violation of symmetry of DQD geometry on the tunneling and show that the violation of symmetry makes difficulties for such tunneling.
Effect of the ratio of follicle-stimulating hormone to luteinizing hormone on rat granulosa cell proliferation and oestradiol-17β secretion

The present study examined the effects of the ratio of follicle-stimulating hormone (FSH) to luteinizing hormone (LH) on granulosa cell proliferation and oestradiol-17 beta secretion. For these studies, ovarian segments from either immature rats or those primed with pregnant mares serum gonadotrophin (PMSG) were incubated for 5 h with [3H]thymidine and FSH (0-100 mIU/ml) with or without equivalent doses of LH. After incubation, granulosa cells were isolated and their mitotic activity estimated by determining the amount of [3H]thymidine incorporated into the DNA. The amount of oestradiol secreted into the media was measured by radioimmunoassay. Compared to granulosa cells from immature ovaries, granulosa cells from PMSG-primed ovaries required significantly less FSH to stimulate incorporation of [3H]thymidine, had a 9-fold higher basal level of oestradiol production and increased oestradiol secretion in response to gonadotrophins. At pharmacological serum levels (10-20 mIU of total gonadotrophin), FSH:LH ratios of less than or equal to 2 increased oestradiol secretion from PMSG-primed ovaries but did not increase the rate of [3H]thymidine incorporation. Conversely, FSH:LH ratios of greater than or equal to 3 stimulated [3H]thymidine incorporation without altering oestradiol secretion. These data demonstrate that granulosa cells of immature follicles not secreting oestradiol are relatively unresponsive to gonadotrophins at any dose tested. Once the capacity for oestradiol secretion develops, then both the dose and ratio of FSH and LH play major roles in determining whether the follicle will grow or secrete oestradiol.
Dynamic Social Judgment Scheme (DSJS) with Information Lag: An Agent Based Model

Davis’s (1996) Social Judgment Scheme (SJS) is a conceptually well established and empirically well tested group decision model. This study uses an agent based model to simulate the dynamic interaction in Social Judgment Scheme (SJS) and expand it as Dynamic Social Judgment Scheme (DSJS) by including group members’ real-time interaction. One of the main different of dynamic SJS and SJS is information time lag. Therefore, this study examined how information time lag would affect a group decision. The result shows that dynamic group decision process is highly sensitive to information time lag. The real-time simulation shows that a virtual sales group will make similar group decision as SJS model at the beginning, but information time lag cause by communication may significantly change the decision path soon after. However, the overall pattern of DSJS is still similar with SJS. The information time lag is important, but not determinant.
Computer Technology-Integrated Projects Should not Supplant Craft Projects in Science Education

The current emphasis on computer technology integration and narrowing of the curriculum has displaced arts and crafts. However, the hands-on, concrete nature of craft work in science modeling enables students to understand difficult concepts and to be engaged and motivated while learning spatial, logical, and sequential thinking skills. Analogy use is also helpful in understanding unfamiliar, complex science concepts. This study of 28 academically advanced elementary to middle-school students examined student work and perceptions during a science unit focused on four fossil organisms: crinoid, brachiopod, horn coral and trilobite. The study compared: (1) analogy-focused instruction to independent Internet research and (2) computer technology-rich products to crafts-based products. Findings indicate student products were more creative after analogy-based instruction and when made using technology. However, students expressed a strong desire to engage in additional craft work after making craft products and...
Detection and significance of circulating tumor cells (CTC) in patients with metastatic pancreatic cancer (PC) receiving systemic therapy

4596 Background: Detection of CTC in the peripheral circulation of pts with solid tumors may provide useful prognostic and predictive information. In a previously reported pilot study, we detected ...
Study on characteristics of panicle and grain structure matched with high-yield for new hybrid rice combination "Teyou 649"

The experiment utilized the split-plot design with fertilizers as main plots and plant density as subplots,to study the characteristics of panicle and grain structure matched with a yield of more than 9t/ hm~2 for the new hybrid rice combination "Teyou 649".The results showed that there was obvious difference between productive panicles derived from different nodes in terms of contribution to the yield.The contribution rate of the panicles from different nodes derived tillers was like this: the panicles from lower node tillers the panicles from secondary tillers the main panicle.The percentage of the panicles from lower node tillers was the most with 62%～73%,that of secondary tillers was 20% and the main panicle was 15%.Moreover,with fertilizer and planting density increasing,the contribution of the main panicle to the yield was increasing.
The New Wagner Mayoralty and the Shaping of Modern New York

After the 1961 election, Mayor Wagner possessed new charter power and was a Democratic Party mayor free from the influence or control of Tammany or other party organizations because of his decisive victory. Running on his liberal, New Deal policy record, Wagner entered his third term at the height of his powers. While he exercised significant administrative powers with the revised charter, his efforts to organize and discipline the Democratic Party in the city as the new chief were frustrated and less successful. By the end of his third and last term in 1965, most of the characteristics of the modern political system in New York were in place: a strong administrative mayor, a weak party/strong interest group system, and strong programmatic linkages between the mayoralty and the public.
Broad Inhibition and Local Disinhibition Characterize Local Cortical Circuits.

The term “blanket of inhibition” has been proposed to explain the dense and indiscriminate inhibitory connectivity of several classes of GABAergic interneurons with nearby pyramidal neurons ([Karnani et al., 2014][1]). This inhibition is extensive in both space and time. The inhibition extends
A nonlinear observer for friction estimation and compensation in harmonic drives

A nonlinear observer is designed for the estimation of the nonlinear dynamic friction in harmonic drive systems with hysteresis. The hysteresis phenomenon in a harmonic drive system is modeled by a nonlinear differential equation. A nonlinear observer-based controller for friction compensation is next developed and its stability analysis is performed using the Lyapunov theory. The performance and asymptotic stability of the proposed system is validated using numerical simulation.
Actigraphy measured sleep disruption as a predictor of survival in advanced breast cancer.

9532 Background: Sleep disruption, prevalent in cancer patients and survivors, is associated with disrupted hormonal circadian rhythms and poor quality of life. Previous studies in cancer patients ...
Self-Consistent Determination of the Ice-Air Interfacial Tension and Ice-Water-Air Line Tension from Experiments on the Freezing of Water Droplets

We propose an indirect experimental method to self-consistently determine the line tension of a solid–liquid–vapor contact region and the interfacial tension of the solid–vapor interface via experiments on the homogeneous crystallization of droplets. The crucial idea of our method is that, even in the surface-stimulated mode, when a crystal nucleus forms with one of its facets at the droplet surface it initially emerges (as a subcritical cluster) homogeneously in the subsurface layer, not “pseudo-heterogeneously” at the surface. This mode is negligible for large droplets but becomes increasingly important with decreasing droplet size and is dominant in small droplets. The proposed method requires experimental data on the rate of homogeneous crystal nucleation as a function of droplet size. Using this method to examine experimental data on homogeneous crystal nucleation in droplets of 1.0, 1.7, and 2.9 μm radii in the temperature range from 234.8 to 236.2 K, we evaluated the line tension τ of ice–water–air...
Multi-user FSO communication link

Free Space Optical (FSO) communication technology has a data rate higher than other wireless communication techniques. Although FSO has enjoyed widespread notoriety for its point-to-point communication, the increasing demand of mobile platforms and multi-user communications requires considerable improvement over current FSO systems. Developing multi-point mobile FSO systems is highly desirable. To aid in this effort, the work presented in this paper details a solution for overcoming the Blind Source Separation (BSS) problem in a multi-user communication link. A multi-user FSO link with various atmospheric conditions that leverages the FastICA algorithm is detailed below. Experimental results have been obtained with a system composed of two transmitters operating at different wavelengths and two receivers. Results demonstrate that using this method, the original optically transmitted signals can be separated from their received mixtures, even during high turbulence conditions.
Beyond 250: A Comprehensive Strategy to Maximize the Operative Experience for Junior Residents.

Objectives Among surgical educators, duty-hour restrictions led to concern regarding the adequacy of operative experience during residency, especially for junior residents. The American Board of Surgery recently instituted guidelines mandating “a minimum of 250 operations by the end of the PGY-2 year”. A series of programmatic and institutional changes were implemented at our institution to augment the junior resident operative experience and to exceed compliance with this mandate. Methods Operative data from Accreditation Council for Graduate Medical Education case logs for categorical and nondesignated preliminary interns from our large academic surgical residency were identified for 5 consecutive academic years, 2011 until 2016. American Board of Surgery In-Training Examination (ABSITE) scores were collected anonymously. The program systematically instituted the following changes: night float minimization, identification of new surgical opportunities, augmenting use of midlevel care providers, identification of rotations with suboptimal operative experiences, maximizing rotations with involvement of junior residents in the operating room, and systematic review of junior case logs. Results After implementation, average total cases for residents completing postgraduate year (PGY)-2 increased from 176 to 330 (p Conclusions Before implementation of these interventions, our program would have had 0% compliance with the 250 junior resident case rule. Within 12 months of implementation, total case volumes for residents completing PGY-2 increased by 88%—exceeding minimum standards. Overall, 100% programmatic compliance was achieved. Our program’s experience exemplifies how mandates from the American Board of Surgery can lead to programmatic changes that improve the experience of surgical house officers.
STEM Deserves an F: The Role of Foundations of Education in the UTEACH Model of Teacher Preparation

The relative position of the social foundational studies of education (SFE) within the overall curriculum of teacher preparation has been tenuous for decades. Within the last several years, the confluence of three streams of pressure have undermined the inclusion of SFE courses within such curricula. These include, the perceived lack of direct applicability to the tasks of teaching, the rapidly rising costs of higher education, and political disillusionment. This paper explores each of the streams of resistance to SFE courses within teacher preparation. This exploration culminates in an examination of the latest incarnation of SFE-free teacher preparation programs, the UTeach model for preparing in the areas of science, technology, engineering and mathematics (STEM). Only two of the 39 reviewed UTeach replication programs required the inclusion of SFE courses for prospective STEM teachers. The paper concludes with a discussion of importance of including SFE coursework in the preparation of STEM teachers.
On the ergodic strong interference channel under lattice coding and decoding

The capacity region of the ergodic fading interference channel remains unknown. Moreover, most achievable rate regions known to date for fading interference channels are based on Gaussian codes, whose encoding and decoding complexity is too high. In this paper, we study the two-user ergodic interference channel with channel knowledge only at the receiver side. First, we establish the capacity region for the case where interference (cross) link gains are statistically stronger than forward link gains, denoted the ergodic strong interference channel. Additionally, we establish the rate region for this channel under lattice coding and decoding, whose complexity is significantly less than Gaussian codes. We show that the sum rate achieved using lattice codes is very close to sum capacity.
Changing oviposition times of the crab spider Misumena vatia (Thomisidae) correlate with climate change

The crab spider Misumena vatia (Clerck, 1757) (Thomisidae) is an important sit-and-wait predator at flowers visited by nectar or pollen-seeking insects. Typically, female M. vatia molt into their adult stage when many insect-attracting flowers come into bloom, and the spiders quickly gain weight leading up to oviposition. Between 1979 and 2010, the first spider ovipositions shifted one month earlier, from late July to late June, at my study site in coastal Maine, USA, in accordance with a concurrent temperature increase of ca. 0.44°C and a lengthening growing season. Flowering times of the spiders' most important hunting site, common milkweed Asclepias syriaca, as well as recruitment dates of their most important prey, bumblebees Bombus spp., to flowering milkweed, advanced as well. The shift in spider oviposition times increased the feasibility of second broods, though I found no successful second broods in the field, and the success of such broods would be problematic because of heavy overwintering losses. Differing rates of change of spider, milkweed and bumblebee activity indicated decreasing synchrony among these species; in particular, lessening future hunting opportunities for the spiders.