cssi/SciSciGPT-SciSciNet huggingface dataset:
Insights into the Conformation of the Membrane Proximal Regions Critical to the Trimerization of the HIV-1 gp41 Ectodomain Bound to Dodecyl Phosphocholine Micelles

The transitioning of the ectodomain of gp41 from a pre-hairpin to a six-helix bundle conformation is a crucial aspect of virus-cell fusion. To gain insight into the intermediary steps of the fusion process we have studied the pH and dodecyl phosphocholine (DPC) micelle dependent trimer association of gp41 by systematic deletion analysis of an optimized construct termed 17–172 (residues 528 to 683 of Env) that spans the fusion peptide proximal region (FPPR) to the membrane proximal external region (MPER) of gp41, by sedimentation velocity and double electron-electron resonance (DEER) EPR spectroscopy. Trimerization at pH 7 requires the presence of both the FPPR and MPER regions. However, at pH 4, the protein completely dissociates to monomers. DEER measurements reveal a partial fraying of the C-terminal MPER residues in the 17–172 trimer while the other regions, including the FPPR, remain compact. In accordance, truncating nine C-terminal MPER residues (675–683) in the 17–172 construct does not shift the trimer-monomer equilibrium significantly. Thus, in the context of the gp41 ectodomain spanning residues 17–172, trimerization is clearly dependent on FPPR and MPER regions even when the terminal residues of MPER unravel. The antibody Z13e1, which spans both the 2F5 and 4E10 epitopes in MPER, binds to 17–172 with a Kd of 1 ± 0.12 μM. Accordingly, individual antibodies 2F5 and 4E10 also recognize the 17–172 trimer/DPC complex. We propose that binding of the C-terminal residues of MPER to the surface of the DPC micelles models a correct positioning of the trimeric transmembrane domain anchored in the viral membrane.
Jane Austen’s Names: Riddles, Persons, Places

In Val McDermid’s 2015 updating of Jane Austen’s Northanger Abbey, would-be romantic heroine Catherine Morland laments the unsuitableness of her neighborhood as a potential locale for her story, so...
The Adventitious Angles Problem: The Lonely Fractional Derived Angle

AbstractIn the “classical” adventitious angle problem, for a given set of three angles a, b, and c measured in integral degrees in an isosceles triangle, a fourth angle θ (the derived angle), also measured in integral degrees, is sought. We generalize the problem to find θ in fractional degrees. We show that the triplet (a, b, c) = (45°, 45°, 15°) is the only combination that leads to θ = 7½° as the fractional derived angle.
A Protocol for Using Förster Resonance Energy Transfer (FRET)-force Biosensors to Measure Mechanical Forces across the Nuclear LINC Complex

The LINC complex has been hypothesized to be the critical structure that mediates the transfer of mechanical forces from the cytoskeleton to the nucleus. Nesprin-2G is a key component of the LINC complex that connects the actin cytoskeleton to membrane proteins (SUN domain proteins) in the perinuclear space. These membrane proteins connect to lamins inside the nucleus. Recently, a Forster Resonance Energy Transfer (FRET)-force probe was cloned into mini-Nesprin-2G (Nesprin-TS (tension sensor)) and used to measure tension across Nesprin-2G in live NIH3T3 fibroblasts. This paper describes the process of using Nesprin-TS to measure LINC complex forces in NIH3T3 fibroblasts. To extract FRET information from Nesprin-TS, an outline of how to spectrally unmix raw spectral images into acceptor and donor fluorescent channels is also presented. Using open-source software (ImageJ), images are pre-processed and transformed into ratiometric images. Finally, FRET data of Nesprin-TS is presented, along with strategies for how to compare data across different experimental groups.
Long-wave dynamics of an elastic sheet lubricated by a thin liquid film on a wetting substrate

A model is presented to investigate the hydrodynamics of an elastic sheet lubricated by a thin film on a wetting substrate, with focus on elastic effects that lead to different film profiles, contact angles, and spreading dynamics.
Robust MIMO H 2 , H ∞ And l 1 Controller Design for an Advanced Aircraft

Abstract This paper presents a comparison of the several methods, namely, H2, H∞, μ-synthesis and l1, for robust MIMO control synthesis. The Delay Augmentation (DA) method presented in [DaBD1] allows for the solution of the discrete mulitblock l1 optimization problem. A nonlinear flight dynamic model of an advanced aircraft is developed and, using the three methods, MIMO control systems are synthesized based on the linearized model of the aircraft. Results of simulation experiments are presented for comparison of the individual controllers
Structural Differentiation of the Reactivity of Alcohols with Active Oxygen on Au(110)

A wide range of oxidative coupling reactions occur under mild conditions on gold, all of which are activated by atomically adsorbed oxygen (Oads). We have examined the reactivity of methanol and ethanol for self-coupling with well-ordered O-covered Au(110) surface structures, characterized by scanning tunneling microscopy (STM). Zig-zag O chains along the reconstructed (1 × 2) surface are observed up to a coverage of 0.25 Ml O that evolve into double row structures filling all threefold hollow sites along the topmost rows of gold atoms up to 0.5 Ml. Surface roughening occurs above 0.5 Ml O. Below 0.08 Ml O, both alcohols exhibit 100% selectivity for self-coupling to their corresponding ester. This adsorbed O consumed by abstraction of the alcoholic hydrogen, to form the adsorbed alkoxide. Under these conditions further C–H bond of both the adsorbed alkoxy and hemiacetal alcoholate intermediates necessary to form the ester predominates over reactions assisted by Oads. Above ~0.08 Ml the alcohols react very differently. Methanol is not activated by additional adsorbed O, whereas ethanol reacts readily up to a coverage of 0.35 Ml O. We attribute this differentiation to both a change in the energetics of the O bonding to the surface and differences in the energetics of reaction of the two alcohols to form adsorbed alkoxides.
Assesment of distress among breast cancer survivors following primary treatment completion

PURPOSETo evaluate the presence of distress among breast cancer survivors and to investigate demographic, psychosocial, tumor and treatment related variables that may be associated with distress in this patient population. Although elevated levels of distress have been well documented among cancer patients receiving active treatment, the magnitude of and contributors to distress in cancer survivors have not been well established. METHODSThis investigation is based on a retrospective chart review that includes 81 female breast cancer survivors, 21 years of age or older, who received care at the Stony Brook Cancer Center Survivorship Clinic and completed the National Comprehensive Cancer Network (NCCN) Distress Thermometer (DT) form between October 2012 and June 2014. RESULTSApproximately one-half of the breast cancer survivors reported a clinically significant distress level (4 or higher). Physical and emotional concerns were the most commonly reported problems among the sample of breast cancer survivors. Those who were on an anxiolytic or anti-depressant medication tended to have higher levels of distress (OR: 3.10; 95% CI: 0.90-10.74; P=0.07) and age greater than 60 years at the time of diagnosis was negatively correlated with distress (OR: 0.24; 95% CI: 0.07-0.84; P=0.03). CONCLUSIONSFindings from this study indicate that more than half of breast cancer survivors experienced distress during the early survivorship phase. This distress was attributable to emotional and physical problems. Although preliminary, these data suggest the need to develop targeted screening strategies for early recognition and interventions to alleviate distress in this population.
Rab27-Dependent Exosome Production Inhibits Chronic Inflammation and Enables Acute Responses to Inflammatory Stimuli.

Extracellular vesicles, including exosomes, have recently been implicated as novel mediators of immune cell communication in mammals. However, roles for endogenously produced exosomes in regulating immune cell functions in vivo are just beginning to be identified. In this article, we demonstrate that Rab27a and Rab27b double-knockout (Rab27DKO) mice that are deficient in exosome secretion have a chronic, low-grade inflammatory phenotype characterized by elevated inflammatory cytokines and myeloproliferation. Upon further investigation, we found that some of these phenotypes could be complemented by wild-type (WT) hematopoietic cells or administration of exosomes produced by GM-CSF–expanded bone marrow cells. In addition, chronically inflamed Rab27DKO mice had a blunted response to bacterial LPS, resembling endotoxin tolerance. This defect was rescued by bone marrow exosomes from WT, but not miR-155 −/− , cells, suggesting that uptake of miR-155–containing exosomes is important for a proper LPS response. Further, we found that SHIP1 and IRAK-M, direct targets of miR-155 that are known negative regulators of the LPS response, were elevated in Rab27DKO mice and decreased after treatment with WT, but not miR-155 −/− , exosomes. Together, our study finds that Rab27-dependent exosome production contributes to homeostasis within the hematopoietic system and appropriate responsiveness to inflammatory stimuli.
Identification of alpha-gal sensitivity in patients with a diagnosis of idiopathic anaphylaxis.

IgE antibodies (Ab) specific to galactose-α-1,3-galactose (alpha-gal) are responsible for a delayed form of anaphylaxis that occurs 3-6 hours after red meat ingestion. In a unique prospective study of seventy participants referred with a diagnosis of idiopathic anaphylaxis (IA), six (9%) were found to have IgE to alpha-gal. Upon institution of a diet free of red meat, all patients had no further episodes of anaphylaxis. Two of these individuals had indolent systemic mastocytosis (ISM). Those with ISM had more severe clinical reactions but lower specific IgE to alpha-gal and higher serum tryptase levels, reflective of the mast cell burden. The identification of alpha-gal syndrome in patients with IA supports the need for routine screening for this sensitivity as a cause of anaphylaxis, where reactions to alpha-gal are delayed and thus may be overlooked.
Post-intensive care syndrome symptoms and health-related quality of life in family decision-makers of critically ill patients.

ObjectiveFamily members of critically ill patients can suffer symptoms of post-intensive care syndrome-family (PICS-F), including anxiety, depression, and posttraumatic stress disorder (PTSD) with a diminished quality of life. Our aim was to examine the relationship between coping strategies used by family decision-makers (FDMs) of critically ill patients and the severity of PICS-F symptoms and to examine the relationship between FDM PICS-F symptoms and health-related quality of life (HRQOL).MethodA single-center, prospective, longitudinal descriptive study was undertaken of FDMs of intensive care unit (ICU) patients admitted to a large tertiary care hospital. PICS-F symptoms and coping strategy use were measured upon ICU admission (T1), 30 days (T2) after ICU admission, and 60 days (T3) after ICU admission. HRQOL was measured by the Short Form-36 version 2 at T1 and T3.ResultsWe found a significant prevalence of anxiety (45.8%), depression (25%), and PTSD (11.1%) symptoms among FDMs over the course of the study. The patient mortality rate in our sample was 50%. The HRQOL mental summary score in FDMs was low at T1 and decreased to M = 41.72 (standard deviation = 12.47) by T3. Avoidant coping demonstrated moderate relationships with PTSD symptoms and anxiety at T3. A previous history of anxiety, depression, or PTSD was a significant predictor of PICS-F symptom severity and prevalence. PICS symptom severity at T3 explained 75% of the variance in HRQOL mental summary score.Significance of resultsThis study describes a significant prevalence of PICS-F symptoms in FDMs with a diminished mental HRQOL.
A Worrisome Interventricular Septum: More Than Meets the Eye

![Figure][1] [![Graphic][3] ][3][![Graphic][4] ][4][![Graphic][5] ][5][![Graphic][6] ][6] A 59-year-old woman with known enteropathy-associated T-cell lymphoma (EATL) presented with weakness and malaise. An electrocardiogram demonstrated sinus tachycardia, right bundle
Inhibition of cholesterol biogenesis by arsenite: preparation of labeled lanosterol

SUMMARY When mevalonic a~id-2-C'~ was incubated with rat liver homogenate with the usual cofactors plus 10-3 M arsenite, the formation of labeled cholesterol wm inhibited and labeled lanosterol accumulated. This inhibitory effect of arsenite provides a convenient method of preparing labeled lanosterol in high yield (>lo%) from commercially available C14-labeled mevalonic acid.
Parsing the public domain: Research Articles

This article explores the use of the term public domain in the American context and finds that the symbol is subject to multiple meanings. Using historical and content analysis, the analysis explores the various uses of the term and provides a preliminary taxonomy for subsequent analysis and theory building. In conclusion, it suggests that more coherent information policies regarding national and international information access, creativity, governance, and private property rights will require a better understanding and delineation of the use of public domain in legislative and common practice. © 2005 Wiley Periodicals, Inc.
Highly Improved Cytocompatibility of Halloysite Nanotubes through Polymeric Surface Modification

Halloysite Clay nanotubes (HNTs) are naturally occurring nanomaterials composed of double layered aluminosilicate minerals with a hollow tubular structure. Due to their interesting structural characteristics, chemically active external and internal surfaces, cheap and abundant availability, HNTs have recently become the subject of research attention as a new type of material for various biological applications, including drug and gene delivery vehicles, cancer cells isolation, bone implants, ultrasound contrast agents, cancer and stem cells isolation and cosmetics. Therefore, assessment of HNT biocompatibility has gained importance to demonstrate its suitability for clinical purposes. In this study, HNTs were densely coated with poly(ethylene glycol) (PEG) and MTT measurements were carried out on two different human cancer cell lines, namely HeLa (cervical cancer) cells and HepG2 (hepatocarcinoma) cells, to quantify the biocompatibility of PEG-coated HNTs as a function of nanotube dosage and incubation time. While non-coated nanotubes exhibited significant concentration- and time-dependent toxicity, PEG-coated HNTs resulted fully biocompatible for concentrations up to 0.5 mg/mL and for incubation time up to 72 h, making them suitable candidates for nanomedicine applications.
A simplified energetics based planetary boundary layer (ePBL) approach for ocean climate simulations.

Abstract This paper presents a method to parameterize vertical turbulent mixing coefficients within the ocean surface boundary layer (OSBL) for climate applications. The new method is specifically constructed to satisfy two requirements. The first aspect is to explicitly consider the mechanical energy budget of the turbulence that drives mixing. This constraint ensures a realistic and robust simulation of the OSBL, which is critical for coupled climate simulations. The second aspect is that the model should be formulated so that it is not sensitive to the numerical limitations common to climate simulations, such as long time-steps and coarse vertical grids. This goal is achieved by combining an existing resolved shear-driven mixing parameterization (here Jackson et al., 2008) with a new method to avoid time step sensitivity. The new method is motivated by the Kraus-Turner-Niiler type bulk boundary layer parameterization, but relaxes the requirement for vertical homogeneity. The non-dimensional coefficients m* and n* from the Kraus-Turner-Niiler approach are parameterized for the new method based on results of simulations using a previously tested parameterization at high resolution. The resulting parameterization is evaluated by comparing simulations with the new parameterization to simulations with the k − ϵ parameterization over a wide range of combinations of surface wind stress, surface buoyancy flux, and latitudes. The new method for vertical turbulent OSBL mixing is therefore proposed as a computationally efficient, implicitly energetically constrained option appropriate for ocean climate modeling applications.
Defining Memory CD8 T Cell

CD8 T cells comprising the memory pool display considerable heterogeneity, with individual cells differing in phenotype and function. This review will focus on our current understanding of heterogeneity within the antigen-specific memory CD8 T cell compartment and classifications of memory CD8 T cell subsets with defined and discrete functionalities. While numbers of circulatory memory CD8 T cells can be stably maintained in secondary lymphoid organs following contraction, recent data suggest that phenotype and/or function are defined by the age of memory CD8 T cell (or time after initial antigen-encounter). In addition, history of antigen stimulations has a profound effect on memory CD8 T cell populations, suggesting that repeated infections (or vaccination) have the capacity to further shape the memory CD8 T cell pool. Finally, genetic background of hosts and history of exposure to diverse microorganisms likely contribute to the observed heterogeneity in the memory CD8 T cell compartment. Extending our tool box and exploring alternative mouse models (i.e. ‘dirty’ and/or outbred mice) to encompass and better model diversity observed in humans will remain an important goal for the near future that will likely shed new light into the mechanisms that govern biology of memory CD8 T cells.
The Effect of Locations on the 3-D Printing Bed Surface for Designing PC-ABS Based RF Circuits

In additive manufacturing, Poly Carbonate-Acrylonitrile Butadiene Styrene (PC-ABS)composite has better mechanical durability and heat-resistance compared to PolyLactic Acid (PLA)thermoplastics. 3-D printed radio frequency (RF)circuits often require being deployed in extreme conditions and hence PC-ABS RF circuits are preferable over PLA RF circuits. In this paper, variations of measured dielectric constant at 1 GHz and 10 GHz were reported for PC-ABS sample cubes based on the printing region on the printing bed surface of a 3-D printer. Also, an error analysis was presented using the measured permittivity at 1 GHz and 10 GHz and the reported average permittivity of PC- ABS from a literature.
Frequently debrided and misdiagnosed: Post-surgical pyoderma gangrenosum

Post-surgical pyoderma gangrenosum is rare. On average it develops 10 days after a surgical procedure. This timeframe is similar to post-operative wound infections, including post-operative necrotizing fasciitis. Consequently, post-surgical pyoderma gangrenosum is frequently misdiagnosed as an infection, leading to detrimental surgical debridement, unnecessary antibiotic use, and delay of proper treatment. We review a case of pyoderma gangrenosum of the right inguinal crease following percutaneous coronary catheterization and review of the literature.
Catalytic, Enantioselective 1,2-Difluorination of Cinnamamides

The enantio- and diastereoselective synthesis of 1,2-difluorides via chiral aryl iodide-catalyzed difluorination of cinnamamides is reported. The method uses HF-pyridine as a fluoride source and mCPBA as a stoichiometric oxidant to turn over catalyst, and affords compounds containing vicinal, fluoride-bearing stereocenters. Selectivity for 1,2-difluorination versus a rearrangement pathway resulting in 1,1-difluorination is enforced through anchimeric assistance from a N-tert-butyl amide substituent.
The algorithm at work? Explanation and repair in the enactment of similarity in art data

This paper examines the work practices involved in making data legible to machines and machine output legible to humans. The study is based on ethnographic research of a team of art experts at DNAr...
Greater soil carbon and nitrogen in a Mojave Desert ecosystem after 10 years exposure to elevated CO2

Abstract We investigated patterns and possible mechanisms in the greater soil organic carbon (SOC) and total nitrogen (N) after 10 years exposure to elevated atmospheric CO2 concentration ([CO2]) at the Nevada Desert FACE Facility, USA, reported by Evans et al. (2014) . Differences in SOC under elevated and ambient [CO2] depended on cover types, and most evident in soils under deciduous shrubs. Greater SOC was observed in soils close to the surface as well as 0.4 to 0.8 m suggesting elevated [CO2] stimulated production of aboveground litter, root litter, and rhizodeposition. Greater total N under elevated [CO2] was most evident under deciduous shrubs as well as plant interspace that had extensive coverage of biological soil crusts. Greater total N in the top soil profile under elevated [CO2] was accompanied with reduced δ15N by 0.4‰, suggesting elevated [CO2] stimulated N2-fixation and/or reduced N loss. We conclude that, in arid ecosystems under elevated [CO2], shrubs play a major role in determining C sink capacity in desert soils, and N limitation for vascular plants is unlikely to occur due to sustained net N supply.
Analytic model for the Orowan dislocation-precipitate bypass mechanism

Abstract The interaction between glissile dislocations and precipitates within a continuum is responsible for marked increases in material strength. Due to their desirable engineering features, dislocation-precipitate interactions have been the subject of study for decades. Towards enhancing our mechanistic understanding of the Orowan dislocation-precipitate bypass process, we present an analytic model of the Orowan bypass stress (τOrowan) required for a dislocation to bypass a planar array of precipitates. We initially consider spherical precipitates described by a diameter (D) and inner precipitate spacing (L). Our model suggests a τOrowan scaling logarithmically with the precipitate diameter, τ O r o w a n ∼ ln D e − D / L , which we validate against a well established, yet empirical model. We also examine the influence of precipitate aspect ratio on τOrowan. We find that the precipitate width along the dislocation line is the dominant length scale governing τOrowan. Finally, we demonstrate the application of our model towards predicting the scaling of τOrowan for an array of plate-shaped θ″ precipitates within an Al-Cu molecular statics materials system. Our analyses provide insight into relationships between precipitate size, shape, density, orientation and metallic strengthening mechanisms.
Senecan Tragedy: Twelve Propositions

I begin by stating what Senecan tragedy is not. Senecan tragedy is not a series of declamations cast into dramatic form, as Leo claimed. It is not purely verbal drama divorced from the inner psychological realities of character, as Eliot claimed. It is not character-static drama, incohesive, structureless, lifeless and monotonously versified, as Mackail and others have claimed. It is not Stoic propaganda, as Marti claimed. It is not recitation drama, if by recitation drama is meant drama to be recited by a single speaker and essentially unstageable, as Zwierlein claims. It is not a tissue of hackneyed commonplaces, as Ogilvie claimed, nor an artificial imitation of Greek tragedy, as Beare claimed; nor is it contemptible as literature, as Summers and most nineteenth and early twentieth century critics have claimed.What is Senecan tragedy? This essay presents twelve propositions, each of which isolates a characterising property of Senecan tragedy important for the understanding of it as literary and cultural artefact. These twelve propositions constitute neither an exhaustive list of such properties nor an analysis of genre. The latter question, however, I leave not to contemporary theory, but to the Codex Etruscus and the Elizabethans.
A New Perspective on R&D Accounting

U.S. GAAP generally requires firms to expense R&D outlays as incurred, a requirement that many prominent stakeholders view as deficient in reflecting the value of a firm’s R&D program. Prior academic research supports this view by applying a theory for tangible capital to the issue of R&D accounting. However, tangible capital is modeled in this theory as an item that can be used immediately to generate revenues with no uncertainty. Different from tangible capital, many R&D investments can be described as uncertain multi-period ventures in which measurable progress can be made each period, but revenues can only be generated in future periods after the venture is successfully completed. I apply and extend an alternative theory that models this well documented and uncertain time lag between R&D cash outflows and inflows. Theoretical analyses predict that R&D expensing results in more value relevant accounting numbers than R&D capitalization and amortization. Empirical tests confirm these predictions in a sample of R&D intensive firms, suggesting that current accounting reflects the value of a firm’s R&D program better than R&D capitalization and amortization. This research is timely because many prominent stakeholders believe the opposite, and such beliefs have motivated the FASB to consider changing U.S. GAAP in recent years.
Recycling as a planned behavior: the moderating role of perceived behavioral control

This study examines the effectiveness of a public service announcement (PSA) video designed based on the theory of planned behavior (TPB) in motivating people to engage in proper recycling. Based on a representative sample of New York State residents (N = 707), survey results show that all three TPB variables are significant predictors of recycling intention. The PSA video increases recycling intention through attitude, but this mediated relationship is only significant among individuals with low perceived behavioral control. In terms of practical implication, these results suggest that environmental campaigns using a video format may be particularly effective among audiences who perceive low self-efficacy in recycling. Theoretically, this moderated mediation effect suggests that future research based on the theory of planned behavior should not only examine the main effect of each predicting variable, but also assess the role of perceived behavior control as a moderating factor.
Treatment Planning Validation

In this chapter, we will discuss the use of machine learning to detect errors in radiotherapy plans and charts. We will cover some general principles and established techniques for detecting errors in radiotherapy. We will discuss the rationale for using machine learning to detect large errors or outliers in radiotherapy treatment plans. As a concrete example, an automated error detection system for radiation treatment plans will be described. The technique was based on unsupervised machine learning, i.e., data clustering, and achieved over 90 % success rates in detecting outliers in over 1,000 treatment plans. Finally, future research directions in the clinical applications of machine learning for treatment planning validation will be briefly discussed.
Fast parallel algorithms and the complexity of parallelism (Basic issues and recent advances)

The paper classifies the problems solvable very fast in parallel with a feasible number of processors and contrasts them with problems hard to parallelize. The notions of NC1-reducibilities, RNC1-reducibilities, log-space reducibilities are presented and problems complete (or randomly complete) for P are defined and discussed. The notion of optimal parallel time-number of processors tradeoff is highlighted and several techniques to achieve optimal tradeoff are presented. Several results about fast parallel approximations to P-complete problems are described. Finally, certain milestones in the design of efficient parallel algorithms are noted and their impact is discussed.
Regret-based Bayesian sequential decision-making for human-agent collaborative search tasks

We consider domain search tasks using autonomous multi-agent teams collaborating with a human operator. A Bayesian sequential decision-making strategy is first proposed for the optimal allocation of manual and autonomous sensing mode in the presence of sensing uncertainty. However, this type of optimal strategy is not always the style of human decision-making. In particular, regret has been shown to play a critical role in rational decision-making. Humans experience regret when they perceive that they are better off with another option and tend to make choices to avoid such experience. Furthermore, it has been shown that team members share a same mental model perform better than teams with a more accurate but less similar mental model. Therefore, to enable more effective human-agent collaboration (HAC) and better overall task performance, we embed regret analysis into the proposed decision-making framework to provide suboptimal but more human-like decisions. We compare simulation results of decision-making strategies with and without regret analysis and show that regret-based decision-making can integrate human tendency in risk-averse and risk-seeking for better HAC.
A Link between Mitophagy and Apoptosis in Endothelial Cells: Exosomal Delivery of Mfn-2 siRNA

Exosomes are lipid-bilayer vesicles (50-100 nm) derived from many cell types including endothelial cells that are a promising delivery vehicle for small interfering ribonucleic acid (siRNA). Exosom...
Population-based trends in urinary diversion among patients undergoing radical cystectomy for bladder cancer.

What's known on the subject? and What does the study add? Variations in the type of urinary diversion exist for patients undergoing radical cystectomy. Although its use has been increasing from 2001 to 2008, patients who are older, female, and primary insured by Medicaid are less likely to receive continent diversions. Furthermore, patients treated surgically at high-volume and teaching hospitals are more likely to receive continent diversions. Objective To describe the contemporary trends in urinary diversion among patients undergoing radical cystectomy (RC) for bladder cancer; and elucidate whether socioeconomic disparities persist in the type of diversion performed in the USA from a population-based cohort. Patients and Methods Using the Nationwide Inpatient Sample, we identified patients who underwent RC for bladder cancer between 2001 and 2008. Multivariable regression models were used to identify patient and hospital covariates associated with continent urinary diversion and enumerate predicted probabilities for statistically significant variables over time. Results Overall, 55 635 (92%) patients undergoing RC for bladder cancer received incontinent urinary diversion, while 4552 (8%) patients received continent diversion from 2001 to 2008. Receipt of continent urinary diversion increased from 6.6% in 2001–2002 to 9.4% in 2007–2008 (P < 0.001 for trend). Patients who were older (odds ratio [OR] 0.93; P < 0.001), female (OR 0.52; P < 0.001) and insured by Medicaid (OR 0.54; P = 0.002) were less likely to receive continent urinary diversion. However, patients treated at teaching (OR 2.14; P < 0.001) and high-volume hospitals (OR 2.39; P = 0.04) had higher odds of continent urinary diversion. Predicted probabilities of continent diversion remained lower for female patients, Medicaid insurance status, and non-teaching and medium/low-volume hospitals over time. Conclusions In this nationally representative sample of hospitals from 2001 to 2008, the use of continent diversion in RC gradually increased. Although variations in urinary diversion exist by hospital teaching status, case volume, patient gender and primary health insurance, increased attention in expanding the use of continent diversions may help reduce these disparities for patients undergoing RC for bladder cancer.
Resistance Genes of Oryza sativa for Protection Against Xanthomonas oryzae pv. oryzae, the Causative Agent of Bacterial Leaf Blight

Rice ( Oryza sativa ) is a major staple crop around the world, particularly in developing regions such as Africa and Asia. Attack of the rice crop by pathogens has the capacity to greatly diminish crop yield with major agricultural, economical and human consequences. Xanthomonas orzyza pv. oryzae ( Xoo ), the causative agent of bacterial leaf blight, has the ability to cause substantial crop loss, up to 80% worldwide. Genetic sources of resistance have long been considered the most sustainable method of disease control, both from an environmental and agricultural perspective. This review considers the discovery, evolution, characterization and utilization of resistance genes (R genes) in rice against Xoo. R genes for Xoo are plentiful and exist at multiple loci throughout the rice genome due to multiple gene duplication and transposition events. The presence of multiple gene loci makes gene pyramiding and resistance stacking accessible and fruitful applications in breeding for resistance. Biotechnological approaches to take advantage of R gene function have also begun to take root. However, a more global and concerted effort to study the multiple varieties and climates in which rice is grown is required in order to truly attain food security and find sustainable resistance.
Magnetic field dependence of 600 MHz SAW velocity changes for thin Ni films

The authors derive an expression for the change in SAW (surface acoustic wave) velocity as a function of in-plane magnetic field for thin magnetostrictive films, which compares well with the data for thin Ni films. The proposed dynamic model is based on describing the films' in-plane magnetization as being perturbed by the periodic magnetostrictive induced change in the anisotropy field. The dissipation is phenomenologically accounted for by the Gilbert equation. It is shown that the attenuation and velocity changes have the same qualitative field dependence. >
The Social Stratification of English in New York City: Other linguistic variables

In the survey of the Lower East Side, a great many other linguistic variables were studied in addition to the five main phonological variables. The stylistic and social differentiation of morphological variants, of syntactic forms, and many consonantal variants, were analyzed in the speech of the ALS informants. The distribution of many of these variables confirmed the linear array of the set of stylistic contexts, and the ten-point scale of socioeconomic classes. The distribution patterns of non-standard grammatical forms, such as double negatives, and person–number disagreements, showed a regular structure of stratification by socio-economic class which could not be duplicated by any single social parameter. The morphological variants of the suffix- ing showed a regular and fine structure of stylistic and social stratification. In addition, the distribution of the - ing variable in apparent time provided a case of stigmatization without linguistic change which confirmed in detail the analysis of Case I-A in Chapter 9. The mid-central vowel in her Chapter 9 has presented data on one variable which is closely associated with (r): the vowel of bird and work . This variable occurs in all contexts where historical (r) followed a mid-central vowel and was followed by a consonant. We will now consider the parallel case of historical final (r) preceded by a mid-central vowel: that is, words of the type her, were, occur, stir .
THE UNFAITHFUL LOVER Heterosexuals' Perceptions of Bisexuals and Their Relationships

To examine heterosexuals' perceptions of bisexuals, 353 young adults read a description of a dating couple and rated each partner and the couple on several dimensions. The gender and sexual orientation (bisexual, heterosexual, homosexual) of each partner was varied among research participants. Compared to heterosexuals, bisexuals were seen as less likely to be monogamous, more likely to give a sexually transmitted disease (STD) to a partner, and more able to satisfy a partner sexually. Compared to gay men and lesbians, bisexuals were seen as more likely to give an STD to a partner and less able to satisfy a partner sexually. Despite their seeming behavioral compliance to heterosexual relationship norms, bisexuals in male-female relationships were not viewed more positively than bisexuals in same-gender relationships. Participants perceived male and female bisexuals similarly. Explanations for these and other findings are considered.
Differential Kinetic Behavior and Distribution for Pteroylglutamic Acid and Reduced Folates: a Revised Hypothesis of the Primary Site of PteGlu Metabolism in Humans

Single (13)C(6)-labeled doses of pteroylmonoglutamic acid (PteGlu: 634 nmol; n = 14), (6S-)5-formyltetrahydrofolic acid (431-569 nmol; n = 16), or [(15)N(1-7)]-intrinsically labeled spinach (mainly 5-methyltetrahydrofolate) (588 nmol; n = 14) were fed to fasting adult volunteers. Plasma-labeled 5-methyltetrahydrofolic acid responses were monitored for 8 h. There was a slower rate of increase in plasma-labeled 5-methyltetrahydrofolic acid and longer time to peak (171 +/- 9 min; mean +/- SEM) following an oral dose of [(13)C(6)]PteGlu than either [(13)C(6)]5-formyltetrahydrofolic acid (54 +/- 10 min) or [(15)N(1-7)]spinach folate (60 +/- 13 min) suggesting saturated metabolic capacity for the biotransformation of PteGlu. Mathematical modeling generated a significantly higher mean "apparent absorption" for 5-formyltetrahydrofolic acid (38%) and spinach folate (44%) than for PteGlu (24%). The high "relative absorption" of reduced folates to PteGlu was unexpected given that PteGlu itself, from (14)C-tracer mass balance experiments, is almost completely absorbed. Although it is ubiquitously accepted that a physiological dose of PteGlu is reduced and methylated in the epithelial cells of the small intestine, and that essentially only 5-methyltetrahydrofolic acid is exported into the hepatic portal vein (HPV), as is the case for absorbed reduced 1-carbon-substituted folates, modeling indicated greater liver sequestration when PteGlu was used as the test dose, suggesting that PteGlu enters the HPV unaltered and that the liver is the primary site of initial metabolism. Because of the observed differential plasma response and the hypothesized difference in the site of initial metabolism, the historical use of PteGlu as a "reference folate" in studies of folate bioavailability is seriously questioned.
Direct observation of an enamine intermediate in amine catalysis

An enamine intermediate is believed to be the central feature of biological catalysts, such as aldolases and small molecule amine organocatalysts. Despite decades of investigation of naturally occurring aldolase enzymes and recent studies on designed aldolase antibodies and organocatalysts, direct structural observation of an enamine intermediate has proven to be rare. Herein, we report the observation of a stable enamine intermediate in the crystal structure of an aldolase antibody 33F12 in complex with a 1,3-diketone derivative. This enamine complex structure provides strong evidence that fewer residues are essential for amine catalysis within the hydrophobic environments of this catalytic antibody than speculated for natural aldolase enzymes and should serve to guide future studies aimed at the rational design of these types of catalysts, as well as organocatalysts. Indeed, enamine catalysis in proteins might be more simplistic than previously imagined.
Geometric invariants for nilpotent metric Lie algebras with applications to moduli spaces of nilsoliton metrics

We present new tools for determining whether two nilpotent metric Lie algebras are in the same isometry class. We exhibit new examples of continuous families of nilsoliton metric Lie algebras, including deformations of uniform metric Lie algebras. We show that all algebras of generalized Heisenberg type except for Heisenberg algebras and two others admit deformations by nilsoliton metric Lie algebras.
Use of a Nursing Checklist to Facilitate Implementation of Therapeutic Hypothermia After Cardiac Arrest

Therapeutic hypothermia has become a widely accepted intervention that is improving neurological outcomes following return of spontaneous circulation after cardiac arrest. This intervention is highly complex but infrequently used, and prompt implementation of the many steps involved, especially achieving the target body temperature, can be difficult. A checklist was introduced to guide nurses in implementing the therapeutic hypothermia protocol during the different phases of the intervention (initiation, maintenance, rewarming, and normothermia) in an intensive care unit. An interprofessional committee began by developing the protocol, a template for an order set, and a shivering algorithm. At first, implementation of the protocol was inconsistent, and a lack of clarity and urgency in managing patients during the different phases of the protocol was apparent. The nursing checklist has provided all of the intensive care nurses with an easy-to-follow reference to facilitate compliance with the required steps in the protocol for therapeutic hypothermia. Observations of practice and feedback from nursing staff in all units confirm the utility of the checklist. Use of the checklist has helped reduce the time from admission to the unit to reaching the target temperature and the time from admission to continuous electroencephalographic monitoring in the cardiac intensive care unit. Evaluation of patients' outcomes as related to compliance with the protocol interventions is ongoing.
Assessing Goodness of Fit of Item Response Theory Models: A Comparison of Traditional and Alternative Procedures

Testing the goodness of fit of item response theory (IRT) models is relevant to validating IRT models, and new procedures have been proposed. These alternatives compare observed and expected response frequencies conditional on observed total scores, and use posterior probabilities for responses across 0 levels rather than cross-classifying examinees using point estimates of 0 and score responses. This research compared these alternatives with regard to their methods, properties (Type I error rates and empirical power), available research, and practical issues (computational demands, treatment of missing data, effects of sample size and sparse data, and available computer programs). Different advantages and disadvantages related to these characteristics are discussed. A simulation study provided additional information about empirical power and Type I error rates. Item response theory (IRT) involves a class of mathematical models that are used to predict examinee performance using item and person characteristics. The properties of these models offer many well-known advantages in testing applications. However, the extent to which these properties are attained is dependent on the degree to which the IRT model itself is appropriate. To validate the use of an IRT model, goodness of fit for a model, or correspondence between model predictions and observed data, is often examined (see Hambleton & Swaminathan, 1985, for a discussion of other useful validation studies). When a model is not appropriate or does not fit the data, use of estimated parameters may be compromised. Several alternative approaches to assessing IRT model-data-fit have emerged in response to using traditional methods in different testing applications. Orlando and Thissen (2000) described a fit statistic that does not use ability estimates but provides a comparison of observed and expected frequencies for score responses across total score levels. Stone, Mislevy, and Mazzeo (1994) argued that uncertainty in ability estimation was responsible for deviations in the approximation of the goodness-of-fit statistics to the null distribution, and discussed a fit statistic based on posterior expectations that addressed the issue. A scaling correction for the chi-squared fit statistic based on resampling methods was subsequently described (Stone, 2000a). Donoghue and Hombo (1999, 2001a) also used the fit statistic based on posterior probabilities to evaluate goodness of fit for National Assessment of Educational Progress (NAEP) items, but derived a distribution for the fit statistic (labeled QDH) that could be used for hypothesis testing.
No praise without effort: experimental evidence on how rewards affect Wikipedia's contributor community

The successful provision of public goods through mass volunteering over the Internet poses a puzzle to classic social science theories of human cooperation. A solution suggested by recent studies proposes that informal rewards (e.g. a thumbs-up, a badge, an editing award, etc.) can motivate participants by raising their status in the community, which acts as a select incentive to continue contributing. Indeed, a recent study of Wikipedia found that receiving a reward had a large positive effect on the subsequent contribution levels of highly-active contributors. While these findings are suggestive, they only pertained to already highly-active contributors. Can informal rewards also serve as a mechanism to increase participation among less-active contributors by initiating a virtuous cycle of work and reward? We conduct a field experiment on the online encyclopedia Wikipedia in which we bestowed rewards to randomly selected editors of varying productivity levels. Analysis of post-treatment activity shows t...
Application of serum nicotine and plasma cotinine concentrations to assessment of nicotine replacement in light, moderate, and heavy smokers undergoing transdermal therapy.

As part of a clinical trial investigating the level of nicotine replacement with different doses of transdermal therapy for smoking cessation, peak and trough serum nicotine and plasma cotinine concentrations were measured in 70 subjects while they were actively smoking (baseline) and daily for 6 consecutive inpatient days while they were receiving transdermal nicotine. Subjects were randomly assigned to a daily 24-hour patch delivering a transdermal nicotine dose of 0, 11, 22, or 44 mg and stratified by self-reported smoking rate as either light (10-15 cigarettes per day), moderate (16-30 cigarettes per day), or heavy (>30 cigarettes per day). Steady-state concentrations of nicotine and cotinine were attained in 1 and 3 days, respectively, at all doses and were independent of baseline smoking rate. Mean percentage replacement of nicotine was calculated by dividing steady-state peak nicotine or cotinine concentrations by their respective baseline concentrations. Significant underreplacement occurred in subjects receiving the 11 mg/day patch regardless of baseline smoking rate. Underreplacement also occurred in moderate and heavy smokers receiving 22 mg/day and in light smokers at this same dose. Complete replacement occurred only in subjects receiving the 44 mg/day patch. These results have several implications for transdermal nicotine therapy. First, with the higher nicotine and cotinine levels observed with heavier smoking, it is inherent that one size does not fit all, and there is a need to consider more individualization of dosage for nicotine patch therapy. Second, there is substantial underreplacement with the 22 mg/day dose in moderate to heavy smokers and in some light smokers. Third, even with twice the usual dose (i.e., 44 mg/day), there was no accumulation of either nicotine or cotinine. Plasma cotinine levels after achievement of steady state (i.e., after 3 days of patch therapy) can be collected at any time and used to calculate percent replacement using baseline levels.