cssi/SciSciGPT-SciSciNet huggingface dataset:
The Effect of Earnings Forecasts on Earnings Management

We develop a theory of the association between earnings management and voluntary management forecasts in an agency setting. Earnings management is modeled as a “window dressing” action that can increase the firm’s reported accounting earnings but has no impact on the firm’s real cash flows. Earnings forecasts are modeled as the manager’s communication of the firm’s future cash flows. We show that it is easier to prevent the manager from managing earnings if he is asked to forecast earnings. We also show that earnings management is more likely to follow high earnings forecasts than low earnings forecasts. Finally, our analysis shows that shareholders may not find it optimal to prohibit earnings management. Earlier results rationalize earnings management by violating some assumption underlying the Revelation Principle. By contrast, in our model the principal can make full commitments and communication is unrestricted. Nonetheless, earnings management can be beneficial as it reduces the cost of eliciting truthful forecasts.
Mycobacterium bovis BCG-Mediated Protection against W-Beijing Strains of Mycobacterium tuberculosis Is Diminished Concomitant with the Emergence of Regulatory T Cells

Despite issues relating to variable efficacy in the past, the Mycobacterium bovis BCG vaccine remains the basis for new-generation recombinant vaccines currently in clinical trials. To date, vaccines have been tested mostly against laboratory strains and not against the newly emerging clinical strains. In this study, we evaluated the ability of BCG Pasteur to protect mice from aerosol infections with two highly virulent W-Beijing clinical strains, HN878 and SA161. In a conventional 30-day protection assay, BCG was highly protective against both strains, but by day 60 of the assay, this protection was diminished. Histological examination of the lungs of vaccinated animals showed reduced lung consolidation and smaller and more-organized granulomas in the vaccinated mice after 30 days, but in both cases, these tissues demonstrated worsening pathology over time. Effector T cell responses were increased in the vaccinated mice infected with HN878, but these diminished in number after day 30 of the infections concomitant with increased CD4(+) Foxp3(+) T cells in the lungs, draining lymph nodes, and the spleen. Given the concomitant decrease in effector immunity and continued expansion of regulatory Foxp3(+) cells observed here, it is reasonable to hypothesize that downregulation of effector immunity by these cells may be a serious impediment to the efficacy of BCG-based vaccines.
Genetic deletion of p21WAF1 enhances papilloma formation but not malignant conversion in experimental mouse skin carcinogenesis.

Tumor suppression by p53 is believed to reside in its ability to regulate gene transcription, including up-regulation of p21WAF1. In p53(−/−) mice, chemical- or oncogene-induced skin tumors undergo accelerated malignant conversion. To determine the contribution of the p21WAF1 gene product to epidermal carcinogenesis, animals +/+, + /−, and −/− for a null mutation in the p21WAF1 gene were treated once with 25 nmol 7,12-dimethylbenz[a]anthracene, followed by 5 μg of TPA two times/week for 20 weeks. Papilloma frequency was higher in the p21WAF1-deficient mice. However, the frequency of malignant conversion was similar among all three genotypes. After TPA treatment, all genotypes developed epidermal hyperplasia, although the labeling index was lower in p21WAF1 (−/−) epidermis compared with p21WAF1 (+/+). Furthermore, the expression of differentiation markers was the same across genotypes in untreated or TPA-treated epidermis. Similar frequencies of malignant conversion were also observed in an in vitro assay. Thus, p21WAF1 suppresses early stages of papilloma formation but not malignant progression in mouse skin carcinogenesis, and decreased levels of p21WAF1 do not account for the enhanced malignant conversion of p53 null epidermal tumors.
Testing scalar-tensor gravity with gravitational-wave observations of inspiralling compact binaries.

Observations of gravitational waves from inspiralling compact binaries using laser-interferometric detectors can provide accurate measures of parameters of the source. They can also constrain alternative gravitation theories. We analyze inspiralling compact binaries in the context of the scalar-tensor theory of Jordan, Fierz, Brans, and Dicke, focusing on the effect on the inspiral of energy lost to dipole gravitational radiation, whose source is the gravitational self-binding energy of the inspiralling bodies. Using a matched-filter analysis we obtain a bound on the coupling constant ${\mathrm{\ensuremath{\omega}}}_{\mathrm{BD}}$ of Brans-Dicke theory. For a neutron-star--black-hole binary, we find that the bound could exceed the current bound of ${\mathrm{\ensuremath{\omega}}}_{\mathrm{BD}}$g500 from solar-system experiments, for sufficiently low-mass systems. For a 0.7${\mathit{M}}_{\mathrm{\ensuremath{\bigodot}}}$ neutron star and a 3${\mathit{M}}_{\mathrm{\ensuremath{\bigodot}}}$ black hole we find that a bound ${\mathrm{\ensuremath{\omega}}}_{\mathrm{BD}}$\ensuremath{\approxeq}2000 is achievable. The bound decreases with increasing black-hole mass. For binaries consisting of two neutron stars, the bound is less than 500 unless the stars' masses differ by more than about 0.5${\mathit{M}}_{\mathrm{\ensuremath{\bigodot}}}$. For two black holes, the behavior of the inspiralling binary is observationally indistinguishable from its behavior in general relativity. These bounds assume reasonable neutron-star equations of state and a detector signal-to-noise ratio of 10.
Immunoglobulin and Histamine-Sensitivity Response of Mice to Live Bordetella pertussis

Abstract Mice injected intranasally (it.n.) and intraperitoneally (i.p.) with a nonlethal dose (2.5 × 105 colony-forming units) of live Bordetella pertussis were examined for 50 days for infection, respiratory tract immunoglobulins (Ig), changes in serum Ig, and histamine sensitivity. With mice infected it.n., respiratory infection markedly declined between day 20 and day 30. Ig classes (A, G1, G2a, G2b, but no M), which had specificity for B. pertussis, were present in tracheobronchial wash (TBW) by day 15; by day 50, TBW immunodiffusion and immunoelectrophoretic precipitin bands were more intense. A sharp rise in serum IgA after day 30 was the only significant change relative to controls among the five serum Ig examined. A high degree of histamine sensitivity developed by day 15 to 20 and persisted for the 50 days. With mice inoculated i.p., no bacteria were recovered, no Ig or only traces were found in TBW and IgA only was specific, and no significant changes in the serum Ig relative to controls occurred. Histamine sensitivity developed somewhat more slowly and to a lesser degree than in it.n.-injected mice but persisted for the 50 days. A similar small number of killed bacteria (pertussis vaccine) injected it.n. or i.p. likewise induced slowly developing histamine sensitivity in contrast to published reports of 4 to 5 day peak sensitivity and decline following i.p. injection of 109 or more killed bacteria.
Decomposition and Multilevel Optimization

The resources required for the solution of an optimization problem typically increase with the dimensionality of the problem at a rate which is more than linear. That is, if we double the number of design variables in a problem, the cost of solution will typically more than double. Large problems may also require excessive computer memory allocations. For these reasons we often seek ways of breaking a large optimization problem into a series of smaller problems.
An Introduction to Pidgins and Creoles

An Introduction to Pidgins and Creoles. John Holm. Cambridge: Cambridge University Press, 2000. 282 pp.
Increased Neointima Formation in Cysteine-Rich Protein 2–Deficient Mice in Response to Vascular Injury

In response to arterial injury, medial vascular smooth muscle cells (VSMCs) proliferate and migrate into the intima, contributing to the development of occlusive vascular disease. The LIM protein cysteine-rich protein (CRP) 2 associates with the actin cytoskeleton and may maintain the cytoarchitecture. CRP2 also interacts with transcription factors in the nucleus to mediate SMC gene expression. To test the hypothesis that CRP2 may be an important regulator of vascular development or function we generated Csrp2 (gene symbol of the mouse CRP2 gene)-deficient ( Csrp2 −/− ) mice by targeted mutation. Csrp2 −/− mice did not have any gross vascular defects or altered expression levels of SM α-actin, SM22α, or calponin. Following femoral artery injury, CRP2 expression persisted in the vessel wall at 4 days and then decreased by 14 days. Intimal thickening was enhanced 3.4-fold in Csrp2 −/− compared with wild-type (WT) mice 14 days following injury. Cellular proliferation was similar between WT and Csrp2 −/− VSMC both in vivo and in vitro. Interestingly, Csrp2 −/− VSMC migrated more rapidly in response to PDGF-BB and had increased Rac1 activation. Our data demonstrate that CRP2 is not required for vascular development. However, an absence of CRP2 enhanced VSMC migration and increased neointima formation following arterial injury.
Nicotinic Acid Receptor Abnormalities in Human Skin Cancer: Implications for a Role in Epidermal Differentiation

Background: Chronic UV skin exposure leads to epidermal differentiation defects in humans that can be largely restored by pharmacological doses of nicotinic acid. Nicotinic acid has been identified as a ligand for the human G-protein-coupled receptors GPR109A and GPR109B that signal through Gi-mediated inhibition of adenylyl cyclase. We have examined the expression, cellular distribution, and functionality of GPR109A/B in human skin and skin derived epidermal cells. Results: Nicotinic acid increases epidermal differentiation in photodamaged human skin as judged by the terminal differentiation markers caspase 14 and filaggrin. Both GPR109A and GPR109B genes are transcribed in human skin and in epidermal keratinocytes, but expression in dermal fibroblasts is below limits of detection. Receptor transcripts are greatly over-expressed in squamous cell cancers. Receptor protein in normal skin is prominent from the basal through granular layers of the epidermis, with cellular localization more dispersive in the basal layer but predominantly localized at the plasma membrane in more differentiated epidermal layers. In normal human primary and immortalized keratinocytes, nicotinic acid receptors show plasma membrane localization and functional Gi-mediated signaling. In contrast, in a squamous cell carcinoma derived cell line, receptor protein shows a more diffuse cellular localization and the receptors are nearly non-functional. Conclusions: The results of these studies justify future genetic and pharmacological intervention studies to define possible specific role(s) of nicotinic acid receptors in human skin homeostasis.
Residues Required for Bacillus subtilis PhoP DNA Binding or RNA Polymerase Interaction: Alanine Scanning of PhoP Effector Domain Transactivation Loop and α Helix 3

Bacillus subtilis PhoP is a member of the OmpR family of response regulators that activates or represses genes of the Pho regulon upon phosphorylation by PhoR in response to phosphate deficiency. Because PhoP binds DNA and is a dimer in solution independent of its phosphorylation state, phosphorylation of PhoP may optimize DNA binding or the interaction with RNA polymerase. We describe alanine scanning mutagenesis of the PhoP α loop and α helix 3 region of PhoPC (Val190 to E214) and functional analysis of the mutated proteins. Eight residues important for DNA binding were clustered between Val202 and Arg210. Using in vivo and in vitro functional analyses, we identified three classes of mutated proteins. Class I proteins (PhoPI206A, PhoPR210A, PhoPL209A, and PhoPH208A) were phosphorylation proficient and could dimerize but could not bind DNA or activate transcription in vivo or in vitro. Class II proteins (PhoPH205A and PhoPV204A) were phosphorylation proficient and could dimerize but could not bind DNA prior to phosphorylation. Members of this class had higher transcription activation in vitro than in vivo. The class III mutants, PhoPV202A and PhoPD203A, had a reduced rate of phosphotransfer and could dimerize but could not bind DNA or activate transcription in vivo or in vitro. Seven alanine substitutions in PhoP (PhoPV190A, PhoPW191A, PhoPY193A, PhoPF195A, PhoPG197A, PhoPT199A, and PhoPR200A) that specifically affected transcription activation were broadly distributed throughout the transactivation loop extending from Val190 to as far toward the C terminus as Arg200. PhoPW191A and PhoPR200A could not activate transcription, while the other five mutant proteins showed decreased transcription activation in vivo or in vitro or both. The mutagenesis studies may indicate that PhoP has a long transactivation loop and a short α helix 3, more similar to OmpR than to PhoB of Escherichia coli.
Space weathering processes on airless bodies: Fe isotope fractionation in the lunar regolith

Nanophase Fe metal grains (np-Fe°) are a product of space weathering, formed by processes related to meteorite impacts, and solar-wind sputtering on airless planetary bodies, such as the Moon. Iron isotopes of lunar soils are fractionated during these processes, and the np-Fe° in the finest (<10 μm), mature, size fractions of the soil become enriched in heavier isotopes by ∼0.3‰ in 56Fe/54Fe in comparison to the bulk rocks (0.03±0.05‰), from which the soil was formed. A positive correlation of δ56Fe values with the soil maturity index, IS/FeO, suggests that the high δ56Fe values reflect production of nanophase Fe metal that is produced by space weathering that occurs on airless planetary bodies. Furthermore, the enrichment of δ56Fe in the smallest size fraction of lunar soils supports a model for creation of np-Fe° through vapor deposition induced by micrometeorites, as well as that by solar-wind sputtering.
Relationship of Vancomycin Minimum Inhibitory Concentration to Mortality in Patients With Methicillin-Resistant Staphylococcus aureus Hospital-Acquired, Ventilator-Associated, or Health-care-Associated Pneumonia

Background Methicillin-resistant Staphylococcus aureus (MRSA) is a leading cause of hospital-acquired pneumonia (HAP), ventilator-associated pneumonia (VAP), and health-care-associated pneumonia (HCAP). These infections are associated with significant morbidity, mortality, and cost. The impact of vancomycin minimum inhibitory concentration (MIC) on mortality for patients with MRSA pneumonia has not been determined. Methods Adult patients in ICUs with a diagnosis of MRSA HAP, VAP, or HCAP were entered in the study. Clinical and laboratory information were prospectively collected. Vancomycin MIC and heteroresistance were determined for each MRSA isolate. Data were collected from February 2006 through August 2007. The primary outcome variable was all-cause mortality at day 28. A propensity score approach was used to adjust for confounding variables. Results The study sample consisted of 158 patients. All-cause mortality at day 28 was 32.3%. The majority of MRSA isolates had a vancomycin MIC ≥ 1.5 mg/mL (115/158, 72.8%). Propensity score analysis demonstrated an increase in 28-day mortality as vancomycin MIC increased from 0.75 to 3 mg/mL (P ≤ .001). Heteroresistance to vancomycin, demonstrated in 21.5% isolates, was not associated with mortality. Conclusions Mortality in patients with MRSA HAP, VAP, and HCAP increases as a function of the vancomycin MIC, even for strains with MIC values within the susceptible range. Evaluation of vancomycin MICs should be contemplated at the institutional level and for individual cases of MRSA pneumonia. The use of vancomycin therapy in patients with MRSA pneumonia caused by isolates with MICs between 1 and 2 mg/mL should be undertaken with caution, and alternative therapies should be considered.
A Unitary MUSIC-Like Algorithm for Coherent Sources

This paper proposes a method for direction of arrival (DOA) estimation which can be applied in case of both non-coherent and coherent sources. In comparison to the well-known subspace algorithms such as MUSIC, the proposed method has several advantages. First, in contrast to MUSIC, no forward/backward spatial smoothing for the covariance matrix is needed in the case of coherent sources. Second, the proposed method is more suitable for realtime implementation since it only requires one or a few snapshots in order to provide an accurate DOA estimation, whereas MUSIC requires a large number of snapshots. Third, the proposed method exploits the eigenvalue decomposition (EVD) of a real-valued covariance matrix thereby reducing the computational cost by at least a factor of four. Simulation results show that the proposed method can estimate the DO As of the incident sources with high accuracy even when the sources are coherent.
Creating a sense of "Presence" in a web-based PSI course: the search for Mark Hopkins' log in a digital world

The technical term presence concerns the feeling that a student is in a real classroom, in real time, with a real person managing the learning. This paper considers the two major factors affecting presence: 1) the choice of pedagogical strategy and 2) its implementation using a freshman computer course taught over the Web by the Personalized System of Instruction (PSI) method. Special attention is paid to the location of professor, proctor, and students in this study as well as other strategies to heighten a sense of presence in Web-based courses.
Dopaminergic regulation of a transfected preproenkephalin promoter in primary rat astrocytes in vitro and in vivo.

Abstract The clinical benefit of transplantation therapies utilizing genetically modified cells could be enhanced if expression of engineered genes was regulated by clinically useful pharmacological agents. Toward this end, we examined pharmacologic effects on the expression of hybrid gene constructs transfected into primary rat striatal astrocytes. These astrocytes are known to express receptors for the neurotransmitter dopamine (DA). In vitro, we found that expression of a transiently transfected human ppEnk promoter-driven chloramphenicol acetyltransferase (CAT) reporter construct was induced by DAergic agonists, as much as 20-fold. This induction was blocked by a DA receptor antagonist. The same concentration of DA also increased the endogenous rat ppEnk mRNA, by >2-fold. In vivo, regulation of CAT expression by DA was tested by implanting the genetically modified astrocytes into the normal striatum and the contralateral striatum which had >95% DA depletion induced by a previous 6-hydroxy-DA lesion of the substantia nigra. As hypothesized on the basis of the in vitro data, CAT activity on the lesioned side, where the stimulating effect of endogenous DA was lacking, was 30% lower than on the control side where the normal DA content was present. The data suggest that control of the enkephalin gene in astrocytes may involve second messenger pathways activated by DA receptors. Moreover, the evidence that clinically applicable drugs can regulate inducible genes introduced into the brain by astrocyte implantation is of potential importance in development of therapeutic strategies.
Magmatic-tectonic interaction during early Rio Grande rift extension at Questa, New Mexico

Pre-caldera and caldera-related igneous rocks near Questa, New Mexico, provide a well-constrained example of upper-crustal extension over a magma chamber. Extensional strain exceeding 200% occurred over many square kilometers in a region now underlain by a batholith. The most intense deformation followed emplacement of intrusions related to formation of Questa caldera at 25.7 Ma and preceded the cooling of 24.6 Ma plutons. Detailed mapping of the southern part of Questa caldera indicates the sequence (1) extension concurrent with plutonism, resulting in an overlying carapace of highly tilted blocks bounded by low-angle faults; (2) renewed intrusion into overlying units, with the orientation of pluton tops, dikes, and molybdenum-bearing alteration zones controlled by previously formed low-angle faults; (3) reactivation or continued motion of low-angle normal faults, possibly aided by hydrothermal fluids; and (4) high-angle normal faults that formed after the magmatic system waned. Early high-angle faults remained active, again possibly aided by fluids, during their rotation to low angles. At upper-crustal levels, the magma chamber is believed to have provided a zone of ductility into which overlying brittle normal structures were rooted. At mid-levels in the crust, regional magmatism thermally softened the crust and allowed it to deform in a ductile manner. Regional extension appears to have been focused in a thermally and mechanically weakened area during the period of maximum plutonic activity. The features at Questa provide insights into processes that may have occurred in similar systems in the Basin and Range province and elsewhere.
Temporal Requirements for B Cells in the Establishment of CD4 T Cell Memory

CD4 T cell memory generation is shaped by a number of factors, including the strength and duration of TCR signaling, as well as the priming environment, all of which can be modified by B cells. Studies using B cell-deficient mice indicate B cells play a critical role in generating effector and memory CD4 T cells; however, when and how B cells are acting to promote these responses has not yet been ascertained. In this study, we use anti-CD20 Ab depletion of B cells at different times following Listeria monocytogenes infection to show that B cells are necessary for the induction of optimal CD4 T cell memory, but not for the transition and maintenance of this population. Importantly, the prerequisite of B cells early postinfection is partially dependent on their expression of MHC class II. B cells are not only required during the priming phase, but also necessary for the initiation of robust secondary responses by memory CD4 T cells. Interestingly, the requirement during the recall response is independent of B cell Ag presentation. Overall, these studies demonstrate the temporally and functionally distinct roles for B cells in regulating CD4 T cell responses.
In vitro characterization of macrophage interaction with mesenchymal stromal cell-hyaluronan hydrogel constructs

Macrophages play a critical role in mediating not only normal tissue healing, but also the host reaction against biomaterial scaffolds. There is increasing interest in regenerative medicine to combine mesenchymal stromal/stem cells (MSCs) with biomaterial scaffolds to modulate inflammatory response while restoring tissue architecture. The objective of the current study was to investigate the interaction between MSCs (derived from bone marrow, adipose or vocal fold tissue) encapsulated in hyaluronan-based hydrogel and differentiating macrophages as measured by extracellular matrix (ECM) gene expression and cytokine, chemokine, and growth factor concentrations. Gene expression was analyzed using real-time polymerase chain reaction from MSCs embedded in Carbylan-GSX after 7 days of coculture with or without CD14+ cells. Protein concentrations were measured using a Bio-plex assay from cell culture supernatants on days 3 and 7 for all conditions. Following 7 days, we identified upregulation of collagen-I, collagen-III, procollagen, and matrix metalloproteinase-9 genes compared to control conditions. We demonstrate increased concentrations of immunoregulatory cytokines [interleukin (IL)-1β, tumor necrosis factor-α, macrophage inflammatory protein-1α, IFN-γ, IL-12, and IL-10] and remodeling growth factors (vascular endothelial growth factor, hepatocyte growth factor) in MSC-3D constructs cocultured with macrophages compared to control conditions, with some temporal variation. Our results indicate an alteration of expression of ECM proteins important to tissue regeneration and cytokines critical to the inflammatory cascade when 3D constructs were cultured with differentiating macrophages.
Examining the efficacy of a persuasive technology package in reducing texting and driving behavior

Over the past decade, texting and driving has become a prevalent form of distracted driving and resulted in an alarming rate of deaths and injuries. Research has documented the debilitating cognitive effects of engaging in texting and driving, comparing it to the dangers of driving drunk. Several states have implemented legislation banning texting and driving, however it remains a national epidemic. There is a paucity of empirical research examining the effectiveness of strategies in decreasing texting and driving behavior. Research employing technology as a potential solution has focused on using strategies such as hands-free technology or monitoring devices and applications. The current study takes on a different approach, by examining the efficacy of a persuasive technology package in motivating and facilitating behavior change. Findings provide preliminary evidence for the efficacy of pairing a video documentary and text message reminders in decreasing texting and driving behavior.
Simon on Realism, Fallibilism, and the Power of Reason

One of Bob Simon’s greatest contributions to the philosophy of sport literature lies in his epistemology, his careful methodology. As is well known, he faithfully relied on and defended the power o...
Surgical Management of Fibrocystic Liver Disease

Fibrocystic liver diseases comprise a large spectrum of mostly congenital disorders, all of which have varying degrees of cystic transformation of the liver and disease severity. This chapter will briefly discuss diagnostic strategies as well as current surgical treatment options for both non-infective (congenital cystic diseases, choledochal cysts, etc.) and infective (echinococcal cysts, amoebic or pyogenic abscesses) processes. We will discuss therapies for the most commonly seen forms of disease in greater detail. Many of the non-infective conditions present as a disease spectrum involving multiple organs (such as renal and hepatic involvement in polycystic syndromes) – we shall limit the discussion to management of hepatic conditions insofar as possible. It is, of course, clearly recognized by the author that management of these syndromes is often predicated by degree of involvement of other associated organs. There are a variety of cystic neoplasms of the liver, whose surgical treatment will also be discussed.
Aspirin for the Primary Prevention of Cardiovascular Disease and Colorectal Cancer: A Decision Analysis for the U.S. Preventive Services Task Force

This modeling study, conducted to inform new recommendations from the U.S. Preventive Services Task Force, evaluates the balance of benefits and harms of routine aspirin use for men and women in di...
A study of the probing response of Aedes aegypti. 4. Effect of dry and moist heat on probing.

The effect of dry and moist heat was quantitated on the probing of Aedes aegypti (L.). The temperatures used ranged from 28 to 12 with 2° increments. Fully satiated, slightly dehydrated, and 18-hr-water-starved mosquitoes were used. The dry heat activated the mosquitoes, but did not induce probing. Moist heat induced probing and 34°C was found to be most effective. Water-satiated mosquitoes turned away from temperatures higher than 34° and so did mosquitoes that were denied access to water for a short period. Water starved mosquitoes continued to probe avidly to moist heat up to 42°C. An attempt is made to explain this difference in behavior.
Eminent Structural Engineer: Michel Virlogeux – Structural Artist of Modern French Bridges

(2013). Eminent Structural Engineer: Michel Virlogeux – Structural Artist of Modern French Bridges. Structural Engineering International: Vol. 23, No. 3, pp. 350-353.
Unconventional Nanoparticle Technology of Superconductor Ceramic Articles

Applied wet colloidal nano-processing and thermal, physical, and chemical treatments of superconductor ceramic particles result in sintered 3D-textured crystal conglomerates to produce functionally effective macro-products, such as advanced electrical and electronic articles including superconductive adhesion coated continuous and flexible round wire. AFM images show texture evolution and confirm effectiveness of the developed combination of original ceramic-silicone material formulation and invented crystal organization methods.
Hepatitis C virus incidence among HIV+ men who have sex with men: The role of non-injection drug use

s / Drug and Alcohol Dependence 146 (2015) e118–e201 e133 Hepatitis C virus incidence among HIV+ men who have sex with men: The role of non-injection drug use H. Hagan1, Joshua Neurer1, Ashly E. Jordan1, Don C. Des Jarlais2, Jennifer Wu3, Kirk Dombrowski4, Bilal Khan5, Scott Braithwaite1, Jason Kessler1 1 New York University, New York, NY, United States 2 Beth Israel Medical Center, New York, NY, United States 3 New York University School of Medicine, New York, NY, United States 4 University of Nebraska, Lincoln, NE, United States 5 John Jay College of Criminal Justice, New York, NY,
Role of oxide seed layer in plastic response of epitaxially grown textured metal films

Abstract The elastic/plastic mechanical behavior of freestanding polycrystalline {111}-textured Pt films with thicknesses 50–1000 nm and different combinations of grain size and film thickness, grown epitaxially on a 35–50 nm thick polycrystalline (100)-TiO 2 (rutile) seed layer, was studied at uniaxial tension strain rates 10 −6 - 10 s −1 . The mismatch strain between the {111}-Pt films and the underlying (100)-TiO 2 seed layer gives rise to an interfacial dislocation network, which, in turn, determines the initiation of plastic deformation in Pt. Experiments showed that the flow stress increases, while the plastic strain accumulation at failure decreases with decreasing Pt film thickness. A modified Thompson model that accounted for the combined effect of film thickness and grain size provided good predictions for the elastic limit of Pt films. However, the yield stress was underestimated by the same model; a Taylor strain hardening model was superimposed to the modified Thompson model to account for additional hardening as a result of dislocation interactions during plastic deformation, which provided good predictions for the evolution of flow stress with plastic strain.
ADAR1-Mediated RNA Editing, A Novel Mechanism Controlling Phenotypic Modulation of Vascular Smooth Muscle Cells

Rationale: Vascular smooth muscle cell (SMC) phenotypic modulation is characterized by the downregulation of SMC contractile genes. Platelet-derived growth factor-BB, a well-known stimulator of SMC phenotypic modulation, downregulates SMC genes via posttranscriptional regulation. The underlying mechanisms, however, remain largely unknown. Objective: To establish RNA editing as a novel mechanism controlling SMC phenotypic modulation. Methods and Results: Precursor mRNAs (pre-mRNA) of SMC myosin heavy chain and smooth muscle α-actin were accumulated while their mature mRNAs were downregulated during SMC phenotypic modulation, suggesting an abnormal splicing of the pre-mRNAs. The abnormal splicing resulted from SMC marker pre-mRNA editing that was facilitated by adenosine deaminase acting on RNA 1 (ADAR1), an enzyme converting adenosines to inosines (A→I editing) in RNA sequences. ADAR1 expression inversely correlated with SMC myosin heavy chain and smooth muscle α-actin levels; knockdown of ADAR1 restored SMC myosin heavy chain and smooth muscle α-actin expression in phenotypically modulated SMC, and editase domain mutation diminished the ADAR1-mediated abnormal splicing of SMC marker pre-mRNAs. Moreover, the abnormal splicing/editing of SMC myosin heavy chain and smooth muscle α-actin pre-mRNAs occurred during injury-induced vascular remodeling. Importantly, heterozygous knockout of ADAR1 dramatically inhibited injury-induced neointima formation and restored SMC marker expression, demonstrating a critical role of ADAR1 in SMC phenotypic modulation and vascular remodeling in vivo. Conclusions: Our results unraveled a novel molecular mechanism, that is, pre-mRNA editing, governing SMC phenotypic modulation.
Long-CPI multi-channel SAR based ground moving target indication

The detection of ground moving targets with arbitrary linear motion from an airborne multi-channel radar via a long coherent processing interval is considered. A reparameterization of the target's linear motion is developed which allows for maximizing the target signal energy in synthetic aperture radar images, and decouples the array processing from the image formation process. The algorithm genrates estimates of the target's along-track and cross-track velocity components, making a unique determination of the target's motion parameters possible.
Implications of Recent Drug Approvals for Older Adults

More than 100 medications were approved by the US Food and Drug Administration as new drugs or for new indications in 2014 and 2015. Several of the new drugs may benefit older adults, but adverse events and pharmacokinetic changes due to aging must be considered. This article will focus on three recently approved drugs that are marketed for chronic conditions that can affect older adults: suvorexant, for treatment of insomnia; edoxaban, for prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation and for treatment of venous thromboembolism; and droxidopa, for treatment of symptomatic neurogenic orthostatic hypotension. Information about indications, mechanisms of action, dosing, efficacy, and safety are reviewed. The place of each agent in therapy for older adults is also discussed.
Introduction to Channel Coding

Channel coding, also known as forward error control coding (FECC), is a process of detecting and correcting bit errors in digital communication systems. Channel coding is performed both at the transmitter and at the receiver. At the transmit side, channel coding is referred to as encoder, where extra bits (parity bits) are added with the raw data before modulation. At the receive side, channel coding is referred to as the decoder. Channel coding enables the receiver to detect and correct errors, if they occur during transmission due to noise, interference and fading. This book presents the salient concepts, underlying principles and practical realization of channel coding schemes, as listed below: Automatic repeat request (ARQ) Block coding Convolutional coding Concatenated coding Orthogonal coding
Fatty Infiltration of Rotator Muscles: A Comparison of Cuff Tear Arthropathy and Glenohumeral Osteoarthritis

Aim: Rotator cuff tear arthropathy (CTA) and glenohumeral osteoarthritis (OA) are age-related chronic diseases of the shoulder representing debilitating, painful conditions with functional loss. Surgical intervention provides the most reliable treatment, but studies have shown that prognosis is contingent upon a variety of factors, one of the most reliable of which is fatty infiltration of the rotator cuff muscles. This study tests the hypothesis that fatty infiltration (FI) is increased in CTA subjects compared with OA subjects. Materials and methods: CTA subjects (n=22, age 71.9 ± 7.8 years) and OA (n=22, age 62.9 ± 9.6 years) subjects were evaluated for extent of fatty infiltration by Magnetic Resonance Imaging (MRI) and Computed Tomography (CT) imaging using Goutallier’s classification system and a novel scoring system of % FI. Results: Goutallier classification showed that FI of the supraspinatus and infraspinatus rotator cuff muscles in CTA subjects was greater than those in OA subjects (p= 0.0001, p = 0.003, respectively). The % FI method revealed similar results (p= 0.003, p = 0.0008, respectively). Neither classification system revealed significant differences in FI for the subscapularis or teres minor cuff muscles (Goutallier: p= 0.123, p=0.890; % FI: p= 0.142, p = 0.666, respectively). Analysis using age-matched controls revealed similar results. There was a strong correlation in scores for the two classification systems (Spearman r = 0.96, p < 0.0001). Conclusion: Extent of fatty infiltration of the rotator cuff muscles in subjects suffering from rotator cuff tear arthropathy is significantly greater than in subjects with osteoarthritis.
Dynamics of BCR-ABL Kinase Domain Mutations in Patients with Chronic Myeloid Leukemia (CML) after Treatment with One, Two or Three Tyrosine Kinase Inhibitors (TKI).

Dasatinib (D) and nilotinib (N) are potent tyrosine kinase inhibitors (TKIs) with activity against many imatinib (IM) resistant BCR-ABL kinase domain mutants, except T315I. In vitro mutant models have selected specific mutations occurring after incubation with IM, D and N. Therapy with these new TKI may select for patients with T315I or other mutations relatively insensitive to them. We assessed the change in mutation status of the bcr-abl kinase domain (codons 220 to 500) in 113 patients (pts) with CML who received therapy with D and/or N after imatinib failure. Median age was 60 years (range, 21 to 82 years). Seventy-one (63%) pts received prior interferon (IFN). Median time on imatinib was 28 months (range, 2 to 78 months). At the time of imatinib failure, mutations were detected in 46 of 85 (54%) pts who had DNA sequencing. The evolution of mutations after a second TKI was as follows (Table 1). Twenty pts received a third TKI after failing IM and a second TKI. The evolution of mutations in this cohort was as follows (Table 2). Overall, 19 of 101 evaluable pts (19%), cases had new mutations emerge following TKI switch 17 after a 2nd TKI (12 nilotinib, 5 dasatinib), and 2 after a 3rd TKI (2 dasatinib). We analyzed whether these N- and D-associated new mutations were at sites that have been detected following D and N treatment in vitro (Burgess et al, PNAS 2005; Bradeen et al, Blood 2006; Von Bubnoff et al, Blood 2006). Only 14/46 (30%) kinase domain mutations that developed after D (7) or N (7) corresponded with an in vitro-identified site. Only 5 of 134 (4%) mutations identified were T315I (3 after dasatinib, 2 after nilotinib), but the mutation status of these patients was unknown after IM. We conclude that the spectrum of mutations that develops in vivo after TKI switch is broader and includes common imatinib-resistance sites as well. There appears to no marked increase in the incidence of T315I mutation after TKI switch. | Post IM mutation | No. | Post-2nd TKI Mutation (New + Same + Lost) | |:------------------------------------------------------------------------------------------------------------------------------------ | --- | ----------------------------------------- | ---------- | | *1 pt acquired new mutation with persistence of pre-existing mutation, 1 lost 3 mutations and acquired 1, and 1 pt lost 2 mutations. | | | | Nilotinib | Dasatinib | | Absent | 39 | 8+NA+NA/21 | 3+NA+NA/18 | | Present | 46 | 3+20+3/26 | 2+16+2*/20 | | Unknown | 28 | 8/9 | 13/19 | Table 1. Dynamics of mutations after 2nd TKI | Post IM mutation | No. | Post-3nd TKI Mutation (compared to status after 2nd TKI) (New + Same + Lost) | |:---------------- | --- | ---------------------------------------------------------------------------- | --------- | | | | Nilotinib | Dasatinib | | Absent | 5 | 0/1 | 1+NA+NA/4 | | Present | 12 | 0+1+0/1 | 2+6+3/11 | | Unknown | 3 | 1/3 | NA | Table 2. Dynamics of mutations after 3rd TKI
Postoperative atrial tachycardias after mitral valve surgery: Mechanisms and outcomes of catheter ablation

Background Atrial tachycardias (ATs) including atrial fibrillation are common arrhythmias occurring late after mitral valve (MV) surgery, and their management is challenging. Objective The purpose of this study was to determine the electrophysiological mechanisms of ATs in patients with prior MV surgery and the long-term outcomes of catheter ablation. Methods We studied 67 consecutive patients (mean age 59.4 ± 10.6 years; 41 men [61%]) with prior MV surgery who presented with ATs postoperatively between 2007 and 2015. Results AT was clinically documented before the electrophysiology study in 55 patients, whereas in the remaining 12 patients AT was inducible at the study. A total of 99 ATs (35 spontaneous and 64 inducible) were characterized. Overall, the right atrium (RA) was the chamber of origin in 56%. The underlying mechanism was macroreentry in 91 cases and included typical RA flutter (n = 37), mitral annular flutter (n = 21), incisional right AT (n = 16), roof-dependent reentry (n = 12), and local left atrial reentry (n = 5). Eight focal ATs were also documented: 6 from the left atrium and 2 from the RA. Left-sided ATs were more common in patients with prior Maze procedure (53%), and mitral annular flutter was twice as prevalent in this group (42% vs 21%; P = .05). The ablation was acutely successful in 98.5%. Freedom from atrial arrhythmias was 62% at 12 months, with 42% requiring more than 1 procedure. Conclusion Macroreentry is the predominant AT mechanism in patients with prior MV surgery. Circuits are most often localized to the RA, with left-sided ATs more common in patients with prior Maze procedure. Repeat procedures are common and outcomes with 1 year complete AT control good.
Superporous Intelligent Hydrogels for Environmentally Adaptive Building Skins

This work explores responsive hydrophilic polymers for convergent functions of climate control with architectural material systems. In buildings, the transition across exterior and interior space occurs through the envelope, which is an enclosure system that mediates heat, light, air and moisture transfer functions. Conventional building envelopes are typically constructed to form a barrier that insulates and hermetically separates outdoor and indoor conditions. The dynamic environmental responses of superporous intelligent hydrogels are shown to be beneficial at the interior layer of a double-skin glazing system for building envelope applications. If the hydrogels are integral to the building envelope system, then various environmental functions (such as natural daylighting, heat transfer, airflow and moisture control) can be achieved through integrated actuators to result in improved building energy performance. The composite embodiments emulate bio-analytical functions when embedded microbore-tube water channels serve as actuators for swelling and deswelling kinetics respectively. Each prototype is conceived in response to hot-arid climate contexts. The prototype presented here is a lightweight ventilation cooling and daylighting system. Initial prototypes are inserted into an environmental test-bed that is consequently divided into two chambers to represent an outdoor and indoor condition. The input chamber includes controllable heat and light elements that affect the dynamics of the hydrogel system. The output chamber on the opposite side of the prototype division includes temperature, humidity and photo sensors that are connected to an Arduino board for data collection. Dependent upon the environmental conditions of chamber two, a control program actuates small hydro-pump to saturate the gels with water. The initial results provide correlations between mechanical (elasticity) and thermal (conductivity) properties. Current work in progress includes documentation of average rates for sorption-desorption kinetics and correlations between saturation loading and visible transmittance. The physical test data will also be integrated into building-scale energy performance simulations and hygrothermal transfer numerical analysis for building envelope compositions. The embedded material logic of the hydrogel is exploited in an architectural configuration for a convergence of prior building mechanical system and building envelope functions. The current work demonstrates a highly promising application of soft-skin membranes for much needed reductions in energy consumption within the building sector.
A Direct Comparison System for Measuring Radio Frequency Power (100 kHz to 18 GHz)

A direct comparison power measurement system has been developed to measure power sensor effective efficiency in the 100 kHz to 18 GHz frequency range. This system is capable of measuring thermistor...
The semantics of many, much, few, and little

The words many, much, few, and little (and their cross-linguistic counterparts) are quite unusual semantically. They have traditionally been characterized as quantifiers (like every) or adjectives (like tall); however, these analyses can only account for instances of these terms in which they encode information about an individual or a set of individuals, as they do when they occur prenominally (in e.g., much traffic). Recent degree-semantic analyses instead characterize the meaning of these words in terms of intervals or sets of degrees; this accounts for their canonical uses and uses in which they don't appear to be ranging over individuals (as in their differential use, e.g., much taller).
Connections Between Manganese Neurotoxicity and Neurological Disease

Abstract Manganese (Mn) is an essential nutrient for the human body but is associated with neurotoxicity in excess. Here we discuss evidence support hypotheses that deviations in brain Mn homeostasis are associated with the etiology of neurodegenerative and neurodevelopmental diseases like manganism, Huntington's disease, restless legs syndrome (RLS), attention deficit hyperactive disorder (ADHD) and Tourette syndrome (TS). Most of these neurological disorders have overarching motor symptoms—indicating a role of the basal ganglia and by extension the dopaminergic system. Brain Mn levels are normally enriched in the basal ganglia, and excessive levels are associated with dopaminergic dysfunction. Although the etiology and cellular pathophysiology of RLS, ADHD and TS are not defined, all three have a strong genetic component, a role for dopaminergic dysfunction, and show comorbidities with each other. Genetic studies have indicated overlapping single nucleotide polymorphisms and genes between RLS and ADHD and Tourette's. Recent evidence has linked changes in brain Mn to the associated genotypes or phenotypes of these disorders and support hypotheses that Mn dyshomeostasis may contribute to their pathophysiology. It is important to consider how changes in other divalent metals within the brain affect Mn distribution, since Mn shares transporters with iron, zinc and other metals. This review will collate the current knowledge about the potential function of Mn and dopamine in RLS, ADHD and TS, and the interplay between these three disorders.
History and Epidemiology of Tattoos and Piercings. Legislation in the United States

Tattooing and body piercing date back to early civilizations. In the past, they were used during initiation rites or as an indication of social status. Tattooing has been used to identify criminals, prisoners, and slaves, and for punishment. Body modification has become more common and more sophisticated over the last 30 years. Body art may be associated with risky behavior. Body piercing may be associated with depression. Regulation in the United States of America is variable from state to state.
Do Hsp40s Act as Chaperones or Co-Chaperones?

The Hsp70 family plays an essential role in cellular protein metabolism by acting as a polypeptide binding and release factor that interacts with nonnative regions of proteins at different stages of their life cycles.1 Hsp40 proteins not only act as co-chaperones to facilitate complex formation between Hsp70 and client proteins, but it has also been proposed that Hsp40s use an intrinsic chaperone activity to bind and deliver the nonnative substrates to Hsp70. Herein, we review genetic, biochemical and structural data that describes the mechanisms by which Type I and Type II Hsp40 proteins act to bind substrates. The manner by which the functions of the Type I and Type II proteins are specified is also discussed.