cssi/SciSciGPT-SciSciNet huggingface dataset:
Update on the clinical utility of once-daily tacrolimus in the management of transplantation.

Dear editor The review by Posadas Salas and Srinivas of the clinical utility of once-daily tacrolimus formulations in the management of transplant patients1 was timely and relevant. It is worth noting, however, the data were presented in a way that overlooked several key differences between two distinct once-daily tacrolimus formulations. These formulations differ in bioavailability, Cmax, Tmax, dose required to achieve target trough levels, and time to reach target trough. The specific formulation and dosing information of one product was detailed in this review (described as modified release 4 [MR-4]; Astagraf®, Astellas Pharma Inc., Tokyo, Japan), but no formulation or dosing details were provided for a very different once-daily tacrolimus formulation (LCP-Tacro™; Veloxis Pharmaceuticals A/S, Horsholm, Denmark) for which a thorough review was recently published.2 The latter product is currently approved in Europe and under review by the US Food and Drug Administration in the US. In presenting data in this review, the authors did not identify which product was investigated in each of the studies discussed. This could easily lead to misinterpretation of results or erroneous conclusions, ie, that both once-daily formulations are the same. In fact, a careful parsing of the data clearly demonstrates that they are not equivalent. Misunderstanding of this point could have a potentially serious impact on appropriate dosing, safety, and patient management in the post-transplant setting. Differentiation between the two products is needed to clarify what appear to be conflicting results of the studies presented in this review.
Asthma in schoolchildren in Monroe county, Florida: school-based needs assessment

AbstractObjectives: Asthma is the most common chronic pediatric condition (14%) and the leading cause of school absenteeism in the USA. However, little is known about asthma prevalence and distribution in schoolchildren in the Florida Keys region (Monroe County). Thus, the objectives of this study were to assess asthma prevalence, symptoms, cost and distribution in schoolchildren in the Florida Keys region and to pinpoint where asthma management services are most needed. Methods: Cross-sectional survey data on asthma prevalence, symptoms and socio-demographics was collected and analyzed by race, sex, grade and zip code. A total of 2313 parents of schoolchildren in the Florida Keys completed the adapted Harlem Empowerment Zone Asthma Initiative Questionnaire. The questionnaire was distributed to school principals, who sent them home with students to be filled out by parents or caregivers. We also analyzed data from the online Monroe County 2012 Florida Youth Tobacco Survey, the 2011 Florida CHARTS, the Med...
NSAIDS for the chemoprevention of Alzheimer’s disease

Epidemiologic and laboratory studies suggest that non-steroidal anti-inflammatory drug (NSAID) use reduces the risk of Alzheimer’s disease (AD). Initial reports in the early 1990’s indicated that a history of arthritis, a presumed surrogate of NSAID use, was associated with a lower risk of AD. [1] These reports were followed by epidemiologic studies in which NSAID use was assessed directly and the majority of these reports confirmed the inverse association with risk for AD. [2,3] Postmortem studies in humans [4], studies in animal models of AD [5,6], and in vitro studies [7,8] generally support the notion that NSAIDs can reduce the deleterious inflammation which surrounds amyloid beta (Aβ) plaques in the AD brain. In addition, some studies conducted in vitro and in rodents point to a subgroup of NSAIDs that may work by inhibiting amyloidogenic APP metabolism rather than through traditional anti-inflammatory mechanisms. [9-11] This novel property of NSAIDs is currently being explored in epidemiologic studies. Results from randomized clinical trials of NSAIDs and established AD and one trial on secondary prevention have not been promising and there have been no prevention trials completed. The feasibility of using NSAIDs as a chemopreventive agent in AD is discussed
Noninvasive pulsed focused ultrasound allows spatiotemporal control of targeted homing for multiple stem cell types in murine skeletal muscle and the magnitude of cell homing can be increased through repeated applications

Stem cells are promising therapeutics for cardiovascular diseases, and i.v. injection is the most desirable route of administration clinically. Subsequent homing of exogenous stem cells to pathological loci is frequently required for therapeutic efficacy and is mediated by chemoattractants (cell adhesion molecules, cytokines, and growth factors). Homing processes are inefficient and depend on short-lived pathological inflammation that limits the window of opportunity for cell injections. Noninvasive pulsed focused ultrasound (pFUS), which emphasizes mechanical ultrasound–tissue interactions, can be precisely targeted in the body and is a promising approach to target and maximize stem cell delivery by stimulating chemoattractant expression in pFUS-treated tissue prior to cell infusions. We demonstrate that pFUS is nondestructive to murine skeletal muscle tissue (no necrosis, hemorrhage, or muscle stem cell activation) and initiates a largely M2-type macrophage response. We also demonstrate that local upregulation of chemoattractants in pFUS-treated skeletal muscle leads to enhance homing, permeability, and retention of human mesenchymal stem cells (MSC) and human endothelial precursor cells (EPC). Furthermore, the magnitude of MSC or EPC homing was increased when pFUS treatments and cell infusions were repeated daily. This study demonstrates that pFUS defines transient “molecular zip codes” of elevated chemoattractants in targeted muscle tissue, which effectively provides spatiotemporal control and tunability of the homing process for multiple stem cell types. pFUS is a clinically translatable modality that may ultimately improve homing efficiency and flexibility of cell therapies for cardiovascular diseases. Stem Cells 2013;31:2551–2560
Effects of open and closed system oxidation on texture and magnetic response of remelted basaltic glass

As part of an experimental and observational study of the magnetic response of submarine basaltic glass (SBG), we have examined, using ion backscattering spectrometry (RBS), transmission and scanning electron microscopy, energy dispersive X-ray spectrometry, and surface X-ray diffraction, the textures wrought by the controlled, open and closed system oxidation of glasses prepared by the controlled environment remelting and quenching of natural SBG. Initial compositions with ∼9 wt % FeO* were melted at 1430°C with the oxygen fugacity buffered at fayalite-magnetite-quartz; melts were cooled at a rate of 200°C min−1 near the glass transition (Tg = 680°C). In open system experiments, where chemical exchange is allowed to occur with the surrounding atmosphere, polished pieces of glass were reheated to temperatures both below and above Tg for times 1–5000 h; undercooled melts were oxidized at 900°C and 1200°C for 18 and 20 h, respectively. RBS demonstrates unequivocally that the dynamics of open system oxidation involves the outward motion of network-modifying cations. Oxidation results in formation of a Fe-, Ca-, and Mg-enriched surface layer that consists in part of Ti-free nanometer-scale ferrites; a divalent-cation-depleted layer is observed at depths >1 μm. Specimens annealed/oxidized above Tg have magnetizations elevated by 1–2 orders of magnitude relative to the as-quenched material; this does not appear to be related to the surface oxidation. Quenched glass (closed system, i.e., no chemical exchange between sample and atmosphere) exhibits very fine scale chemical heterogeneities that coarsen with time under an electron beam; this metastable amorphous immiscibility is the potential source for the nucleation of ferrites with a wide range of Ti contents, ferrites not anticipated from an equilibrium analysis of the bulk basalt composition.
New Deoxyribonuclease Activity After Bacteriophage P22 Infection

Extracts from P22-infected and uninfected cultures of Salmonella typhimurium were subjected to deoxyribonucleic acid (DNA)-cellulose and diethylaminoethyl-cellulose chromatography. Comparison of the elution patterns revealed that in infected cells there is a decrease in the amount of nuclease activity specific for denatured DNA and an increase in the amount of nuclease activity specific for native DNA. The latter activity was shown to differ from a similar host enzyme in Mg(2+), Mn(2+), and pH optima. This new activity is not found after infection of a lysogen with a nonvirulent phage or after infection under nonpermissive conditions with P22ts25.1 (a mutant in gene 25 that carries out no known functions other than adsorption and injection) and thus appears to be specified by the phage genome.
Generalized pharmacokinetic modeling for drugs with nonlinear binding: I. Theoretical framework

The following integrodifferential equation is proposed as the basis for a generalized treatment of pharmacokinetic systems in which nonlinear binding occurs $$\phi '(c_u )c'_u = - q(c_u ) + g*c_u + f$$ where cu≡unbound plasma drug concentration, f≡drug input rate,'indicates the derivative of a function, and * indicates the convolution operation: (g* cu)(t)=∫0tg(t−u)cudu.Possible physical interpretations of the functions q, g and f are: q (cu)≡ rate at which drug leaves the sampling compartment, g * cu≡ rate at which drug returns to the sampling compartment from the peripheral system (tissues that are kinetically distinct from the sampling compartment), and φ(cu) ≡ amount of drug in the sampling compartment. The approach assumes that drug binding is sufficiently rapid that it may be treated as an equilibrium process. It may be applied to systems in which nonlinear binding occurs within the sampling compartment, i.e., in the systemic circulation or in tissues to which drug is rapidly distributed. The proposed relationship is a generalization of most existing models for drugs with nonlinear binding. It can serve as a general theoretical framework for such models or as the basis for “model-independent” methods for analyzing the pharmacokinetics of drugs with nonlinear binding. Computer programs for the numerical solution of the integrodifferential equation are presented. Methods for pharmacokinetic system characterization, prediction and bioavailability are presented and demonstrated.
L-systems and mutually recursive function systems

In this paper, we investigate the relationship between two different approaches to generate fractal images--L-systems and mutually recursive function systems. We consider two different ways in which L-systems have been used to generate images. The first is the well-known turtle geometry method, and the other is the vector interpretation method as used by Dekking. We show that a uniformly growing D0L-system can be simulated by an MRFS, and any D0L-system can be simulated by a control set produced by an iterative GSM.
Gene Expression Profiling of Neonatal Mouse Uterine Development

Postnatal uterine development involves differentiation and development of the endometrial glandular epithelium from the luminal epithelium as well as development of the mesenchyme into the endometrial stroma and myometrium. This period of development is critical because exposure of neonates to endocrine disruptors compromises reproductive cycles and pregnancy in the adult. However, the hormonal, cellular, and molecular mechanisms regulating postnatal uterine development remain largely unknown. In order to identify candidate genes and gene networks that regulate postnatal uterine development, uteri were collected from CD-1 outbred mice on postnatal days (PND) 3, 6, 9, 12, and 15, and gene expression profiling was conducted using Affymetrix mouse genome U74Av2 GeneChips in study 1. Of the approximately 12,000 genes analyzed, 9002 genes were expressed in the uterus and expression of 3012 genes increased or decreased 2-fold during uterine development. In study 2, the uterine epithelium was enzymatically separated from the stroma/myometrium on PNDs 3, 6, and 9, and gene expression profiling was conducted using CodeLink UniSet Mouse I Expression Bioarrays. Results from these two studies support the hypothesis that postnatal uterine development is a complex process involving overlapping positive and negative changes in uterine epithelial and stromal/myometrial gene expression. Candidate genes regulating uterine development encode secreted factors (Wnt5a, Wnt7a), transcription factors (Hoxa10, Hoxa11, Hoxd10, MSX-1), enzymes (matrix metalloproteinases, cathepsin, carbonic anhydrase), growth factors (IGF-II, IGF binding proteins), and components of the extracellular matrix (osteopontin) to name a few. The candidate genes and gene networks identified by transcriptional profiling provide an important foundation to discern and understand mechanisms regulating postnatal uterine morphogenesis.
Development of a three-dimensional valence-band structure in Ag overlayers on Cu(001)

Using monochromatic synchrotron radiation over the energy range of 6--32 eV, the development of the valence-band electronic structure of Ag overlayers on Cu(001) was followed with angle-resolved photoelectron spectroscopy. The d-band electronic structure was observed to be two dimensional for a single adlayer of c(10 x 2)Ag/Cu(001). With five layers of coverage, the silver valence-band structure was bulklike, three-dimensional, and very similar to that of Ag(111).
Hydrologic characteristics of lake- and stream-side riparian wetted margins in the McMurdo Dry Valleys, Antarctica.

Water is a limiting factor for life in the McMurdo Dry Valleys (MDV), Antarctica. The active layer (seasonally thawed soil overlying permafrost) accommodates dynamic hydrological and biological processes for 10–16 weeks per year. Wetted margins (visually wetted areas with high moisture content) adjacent to lakes and streams are potential locations of great importance in the MDV because of the regular presence of liquid water, compared with the rest of the landscape where liquid water is rare. At 11 plots (four adjacent to lakes, seven adjacent to streams), soil particle size distribution, soil electrical conductivity, soil water content and isotopic signature, width of the wetted margin, and active layer thaw depth were characterised to determine how these gradients influence physicochemical properties that determine microbial habitat and biogeochemical cycling. Sediments were generally coarse-grained in wetted margins adjacent to both lakes and streams. Wetted margins ranged from 1·04 to 11·01 m in average length and were found to be longer at lakeside sites than streamside. Average thaw depths ranged from 0·12 to 0·85 m, and were found to be deepest under lake margins. Lake margins also had much higher soil electrical conductivity, steeper topographic gradients, but more gradual soil moisture gradients than stream margins. Patterns of soil water δ18O and δD distribution indicate capillary action and evaporation from wetted margins; margin pore waters generally demonstrated isotopic enrichment with distance from the shore, indicating evaporation of soil water. Lake margin pore waters were significantly more negative in DXS (DXS = δD-8δ18O) than streamside pore waters, indicating a longer history of evaporation there. Differences between lake and stream margins can be explained by the more consistent availability of water to lake margins than stream margins. Differences in margin characteristics between lakes and streams have important consequences for the microbial habitat of these margins and their functional role in biogeochemical cycling at these terrestrial–aquatic interfaces. Copyright © 2009 John Wiley & Sons, Ltd.
A developmental psychopathology model of overgeneral autobiographical memory

Abstract Overgeneral memory (OGM) is a phenomenon that refers to difficulty retrieving specific autobiographical memories. The tendency to be overgeneral in autobiographical memory recall has been commonly observed among individuals with emotional disorders compared to those without emotional disorders. Despite significant advances in identifying mechanisms that underlie OGM, etiological models are not particularly developmental in nature and, instead, are focused on identifying isolated cognitive presentations of individuals with high OGM. The aim of the current paper is to utilize a developmental psychopathology framework, which emphasizes the interface between typical and atypical development, and risk and protective factors at multiple ecological levels, to propose a comprehensive model of OGM development. Specifically, (1) the progression of current etiological models of OGM is reviewed; (2) developmental theory and research on autobiographical memory that have relevance for OGM are discussed; and (3) an integrative model of OGM that includes processes at psychological, biological, social, and cultural levels is proposed. Directions for future research are formulated and treatment implications derived from this perspective are addressed.
Changes in Life Satisfaction as a Function of Stay in a Residential Setting

ABSTRACT Various authors have argued for the inclusion of well-being measures in order to assess children's quality of life in residential settings. In the present study, twenty-two children admitted to a residential treatment program were administered a multidimensional life satisfaction scale. The children were re-administered the instrument again approximately four months later. Results revealed that the present sample reported positive satisfaction ratings across all life satisfaction domains. Further, significant positive increases on their Global, Friends, Self, and Total satisfaction scores were noted upon re-administration. Implications of the findings, as well as suggestions for future research, are discussed.
Susceptibility of Adult Alfalfa Leafcutting Bees1 and Honey Bees2 to a Microbial Control Agent, Beauveria bassiana

Abstract. Pollination by bees is required for production of seed alfalfa, Medicago sativa L. The alfalfa leafcutting bee, Megachile rotundata (F.) Hymenoptera: Megachilidae, and the honey bee, Apis mellifera L. Hymenoptera: Apidae, are the most commonly used pollinators. The fungus Beauveria bassiana (Balsamo) Vuillemin has been proposed as a microbial control for Lygus spp. (Hemiptera: Miridae), a common pest of this crop. In laboratory bioassays, we found that adult alfalfa leafcutting and honey bees were susceptible to three strains of B. bassiana. A commercial strain, GHA, was the most pathogenic and virulent, causing approximately 45–80% mortality at a dose of 1 × 105 conidia per bee, and >80% mortality at 1 × 106 conidia per bee. A new strain that is very pathogenic to lygus, 17–41, caused less than 20% mortality in honey bees at 1 × 105 conidia per bee. The alfalfa leafcutting bee was more susceptible than honey bees to all three strains of the fungus. B. bassiana killed almost twice as many alfalf...
Regulation of intrauterine prostaglandin biosynthesis: Interactions between protein kinase C and interleukin 1β

Abstract Activation of protein kinase C with phorbol esters stimulates prostaglandin (PG) biosynthesis in many cell types whereas down-regulation of protein kinase C can suppress stimulatory responses. Interleukin-1β (IL-1β) can stimulate PG production by intrauterine tissues and may play a significant part in the mechanisms of preterm labor associated with intrauterine infection. Hence we have evaluated the effects of staurosporine and H7 (inhibitors of protein kinase C) on IL-1β stimulation of amnion, chorion and decidual prostaglandin E2 (PGE2) production. Staurosporine and H7 alone were without effect on PGE2 production by any cell type. However with minor exceptions both protein kinase C inhibitors enhanced the stimulatory actions of IL-1β on PGE2 production by all three cell types. Hence we believe that protein kinase C is closely linked to the regulation of intrauterine PG biosynthesis and that these links may have multiple layers of complexity.
An Extension to a Theorem of Jörgens, Calabi, and Pogorelov

(1.1) det(D2u) = 1 in Rn must be a quadratic polynomial. For n = 2, a classical solution is either convex or concave; the result holds without the convexity hypothesis. A simpler and more analytical proof, along the lines of affine geometry, of the theorem was later given by Cheng and Yau [9]. The first author extended the result for classical solutions to viscosity solutions [4]. It was proven by Trudinger and Wang in [19] that the only open convex subset of Rn which admits a convex C2 solution of det(D2u) = 1 in with limx→∂ u(x) = ∞ is = Rn . In this paper we give the following extension to the theorem of Jorgens, Calabi, and Pogorelov: Let u be a convex viscosity solution of det(D2u) = 1 outside a bounded subset of
Update on National Science Foundation funding of the “Collaboratory”

NSF-funded collaboratories are experimental and empirical research environments in which domain scientist work with computer, communications, behavioral and social scientists to design systems, participate in collaborative science, and conduct experiments to evaluate and improve the systems. These research projects are concerned with distributed and collaborative research that requires intense reliance on wide-area networks and the Internet, to bring together instruments, laboratories and researchers.
Thermoresponsive composite hydrogels with aligned macroporous structure by ice-templated assembly.

Natural tissues, such as bone, tendon, and muscle, have well-defined hierarchical structures, which are crucial for their biological and mechanical functions. However, mimicking these structural features still remains a great challenge. In this study, we use ice-templated assembly and UV-initiated cryopolymerization to fabricate a novel kind of composite hydrogel which has both aligned macroporous structure at micrometer scale and a nacre-like layered structure at nanoscale. Such hydrogels are macroporous, are thermoresponsive, and exhibit excellent mechanical performance (they are tough and highly stretchable), attractive properties that have a significant impact on the wide applications of composite hydrogels, especially as tissue-engineering scaffolds. The fabrication method in this study including freeze-casting and cryopolymerization can also be applied to other materials, which makes it promising for designing and developing smart and multifunctional composite hydrogels with hierarchical structures.
The dynamics of translating cables

Abstract The dynamics of a translating catenary are studied. The static and linearized dynamic governing equations are derived along the local tangential and normal directions and it is shown that in this form two simpler equations can be derived and solved asymptotically for both small and large sag cables, horizontal or inclined. For small sag cables the solutions of one of the asymptotic equations undergo fundamental changes for specific values of the elastic stiffness, inclination angle, sag-to-span ratio and speed of translation resulting in strong mode interactions. For horizontal cables this explains the phenomena of frequency coalescence and mode reversion [1], as well as the frequency crossover and modal changes of non-translating cables [2]. For inclined cables frequency coalescence never occurs, while mode reversion is partial and strongly dependent on the inclination angle. However, in all cases of mode interaction the dynamic tension is greatly amplified. For large sag cables the solution accounts for the significant tension and curvature variation. The solution reduces to previous results for non-translating cables horizontal [3, 4] or inclined [5].
Contextualizing Impressions of Neighborhood Change: Linking Business Directories to Ethnography

This article suggests a research tool, the temporal map, for ethnographers to employ in supplementing the accounts of urban change provided by local informants. Such a map, created using city business directories, can provide an external validity check to ethnographic research. The authors' tool allows urban ethnographers to extend contemporary ethnographic accounts backward to a period prior to the beginning of fieldwork. It provides a geo-temporal contextualization by fitting fragmented, geographically and historically specific ethnographic accounts into a broader area and across a broader period of time. The authors show how two ethnographic case studies were enhanced by such temporal maps. Their cases involve a redeveloped central business district in North Carolina and a gentrified neighborhood in New York City.
INCREASING SHELF LIFE BY CARBON DIOXIDE TREATMENT AND LOW TEMPERATURE STORAGE OF BULK PACK FRESH CHICKENS PACKAGED IN NYLON/SURLYN FILM

Simulated commercial bulk pack, whole chickens were subjected to conventional ice pack and three modified atmospheric, vacuum and two levels of CO2 within a Nylon/Surlyn film, storage environments. Pathogenic and nonpathogenic microbial growth, void space gas composition (except ice pack) and off-odor development were monitored on samples stored at 1.1°C. Polynomial regression analysis of aerobic growth curves revealed that the lag phase was extended to 8-10 days by using a CO2 addition rate of 3.61 × 10-4 and 7.22 × 10-4 m3/kg, respectively. The transition from lag to log phase appeared when the residual level of CO, in the void space reached 15-55%. Following initial replacement of the air in the pouch with 95% CO2, the growth of anaerobic microorganisms was limited by the presence of CO2. The growth of potential pathogens, salmonella, coliforms, Staphylococcus aureus and Clostridium perfringens in the presence or absence of CO2 was negligible at 1.1°C. Off-odor development can be detected when the colony forming units (CFU) numbers reach 106/g of body weight. Carbon dioxide restricts the growth of most objectionable putrefactive off-odor bacteria; lactic acid organisms are encouraged by its presence on the surface of the sample and in the pouch void space. A recommended usage rate of 7.22 × 10-4 m3 CO2/kg of body weight extends shelf life quality to 27 days at 1.1°C.
Creating shared leadership environments in institutional and international settings

Abstract The current leadership literature includes the concepts of visionary leadership, transformational leadership, situational leadership, breakthrough leadership, and shared leadership. This article relates the literature to specific distance education settings and presents cases in higher education that reflect relevant leadership issues and dimensions of leadership. The article includes theory‐ and practice‐based applications to assist leaders in higher education in the implementation of distance education initiatives. Case examples from outside the United States illustrate important leadership variables in exporting distance education to new settings. The significance of networking and collaboration as leadership strategies is explored as a major theme of the article.
Design for dynamic loads: lack of uniqueness

This paper explores some practical implications of the lack of uniqueness in the inverse problem of finding the stiffness of a system undergoing free vibrations given its frequency of vibration.
A course on the Relationship of Formal Language Theory to Automata

This paper describes the second course in a graduate sequence in Computer Science given at the University of Tennessee, Knoxville. The purpose of this sequence is to provide students with a theoretical base in formal language theory for understanding and interpretation of concepts and relationships in programming and automata theory. The explicit purpose of the second course, “The Relationship of Formal Language Theory to Automata”, is to use the structure of grammars, primarily context-free grammars, to examine various aspects of automata theory. These aspects include deterministic and non-deterministic acceptors, processors with pushdown stores, and finite state machines. The first course in the series employs formal language theory as the vehicle for presenting concepts related to the theory of programming languages; this second course employs the same vehicle for presenting aspects of automata theory. The two courses combined achieve a unity whereby important relationships between programming and automata theory as well as applications stemming from these theories can be derived.This course meets for one and a half hours twice a week for ten weeks. Prerequisites for this course include the first course in this sequence, as well as, an intermediate sequence of courses in machine organization and programming languages plus basic courses in numerical analysis, probability and statistics, and at least two years of calculus.
Independent regulation of atrial coronary blood flow by atrial contraction rate in conscious dogs

The effects of separate increases in atrial and ventricular contraction rates on the distribution of coronary flow within the heart were determined in conscious dogs with chronic heart block. Atrial tachycardia increased atrial blood flow and did not change ventricular blood flow. Ventricular tachycardia increased ventricular blood flow but not atrial blood flow. The results are consistent with the concept of local regulation of coronary perfusion by local myocardial energy turnover. The results also call attention to a potential adverse impact of atrial tachyarrhythmia in patients with underlying coronary ischemia.
Generalized insulin allergy.

INSULIN allergy is the term used to denote the specifically altered, acquired antigenic response to insulin protein in contradistinction to insulin sensitivity, which denotes an altered physiologic response to the hormone. To illustrate this differentiation, Lowell (1), in extensive immunologic studies, presents evidence indicating the presence of two antibodies for crystalline insulin in one patient who was both allergic and resistant to crystalline insulin. He demonstrated the presence of a heat-labile allergic antibody which was capable of passively transferring skin sensitivity and an insulin-neutralizing antibody which was heat-stabile and capable of destroying the physiologic effect of crystalline insulin. Various workers (2 a, b, c, d) have definitely established that crystalline insulin is a complete and soluble protein and, upon examining the insulins derived from the pancreases of various mammals (ox, sheep, hog) and fish, have found them to be similar in microscopic appearance, isoelectric poin...
Heterogeneity of Mitral Leaflet Matrix Composition and Turnover Correlates with Regional Leaflet Strain

To determine how extracellular matrix and contractile valvular cells contribute to the heterogeneous motion and strain across the mitral valve (MV) during the cardiac cycle, regional MV material properties, matrix composition, matrix turnover, and cell phenotype were related to regional leaflet strain. Radiopaque markers were implanted into 14 sheep to delineate the septal (SEPT), lateral (LAT), and anterior and posterior commissural leaflets (ANT-C, POST-C). Videofluoroscopy imaging was used to calculate radial and circumferential strains. Mechanical properties were assessed using uniaxial tensile testing and micropipette aspiration. Matrix composition and cell phenotypes were immunohistochemically evaluated within each leaflet region [basal leaflet (BL), mid-leaflet (ML), and free edge]. SEPT-BL segments were stiffer and stronger than other valve tissues, while LAT segments demonstrated more extensibility and strain. Collagens I and III in SEPT were greater than in LAT, although LAT showed greater collagen turnover [matrix metalloprotease (MMP)-13, lysyl oxidase] and cell activation [smooth muscle alpha-actin (SMaA), and non-muscle myosin (NMM)]. MMP13, NMM, and SMaA were strongly correlated with each other, as well as with radial and circumferential strains in both SEPT and LAT. SMaA and MMP13 in POST-C ML was greater than ANT-C, corresponding to greater radial strains in POST-C. This work directly relates leaflet strain, material properties, and matrix turnover, and suggests a role for myofibroblasts in the heterogeneity of leaflet composition and strain. New approaches to MV repair techniques and ring design should preserve this normal coupling between leaflet composition and motion.
Transverse phase locking for vortex motion in square and triangular pinning arrays

We analyze transverse phase locking for vortex motion in a superconductor with a longitudinal dc drive and a transverse ac drive. For both square and triangular arrays we observe a variety of fractional phase-locking steps in the velocity versus dc drive which correspond to stable vortex orbits. The locking steps are more pronounced for the triangular arrays which is due to the fact that the vortex motion has a periodic transverse velocity component even for zero transverse ac drive. All the steps increase monotonically in width with ac amplitude. We confirm that the width of some fractional steps in the square arrays scales as the square of the ac driving amplitude. In addition we demonstrate scaling in the velocity versus applied dc driving curves at depinning and on the main step, similar to that seen for phase locking in charge-density-wave systems. The phase-locking steps are most prominent for commensurate vortex fillings where the interstitial vortices form symmetrical ground states. For increasing temperature, the fractional steps are washed out very quickly, while the main step gains a linear component and disappears at melting. For triangular pinning arrays we again observe transverse phase locking, with the main and several of the fractional step widths scaling linearly with ac amplitude.
Suspected malingering and the Digit Memory Test: a replication and extension.

Abstract This study replicated a previous finding that suspected malingerers often perform at a level worse than patients with unequivocal brain dysfunction on the Digit Memory Test (DMT). In addition, it was demonstrated that patients suffering from aphasia as well as temporal and “frontal lobe” damage perform at a level higher than suspected malingerers. DMT performance of patients with true dementia, however, may be difficult to distinguish from suspected malingerers. If an individual is not demented (as judged by such tests as the BNI Screen for Higher Cerebral Functions) and performs at a level less than 95% across three trials of the DMT, the question of noncooperation with testing procedures or “malingering” should be considered. © 1997 National Academy of Neuropsychology. Published by Elsevier Science Ltd
LSD and creativity.

The effects of lysergic acid diethylamide (LSD) on creativity were examined in a unique experiment in the late 1950's. In this project, artists were asked to draw and paint a Kachina doll both prior to and one hour after the ingestion of LSD. Evaluations of these artistic productions were analyzed by a professor of art history in order to investigate the impact of LSD on artistic creativity. Certain representative changes were found in the artists' predominant style. The most significant change was noted in those artists whose styles were intrinsically representational or abstract to more expressionistic or nonobjective. Other changes noted included the following: relative size expansion; involution; movement; alteration of figure/ground and boundaries; greater intensity of color and light; oversimplification; symbolic and abstract depiction of objects; and fragmentation, disorganization, and distortion. Many artists judged their LSD productions to be more interesting and aesthetically superior to their u...
Double resonance 1-D glass-on-silicon photonic crystal cavities for single-molecule mid-infrared photothermal spectroscopy: Theory and design

We propose a mid-infrared spectroscopic technique capable of detecting a single small molecule without using cryogenically cooled detectors. Such record sensitivity is attained by leveraging dramatically amplified photothermal effects in a pump-probe doubly resonant cavity.
RELATIVE AVAILABILITY COEFFICIENTS OF ORGANIC AND INORGANIC Zn FERTILIZERS

Zinc sulfate (ZnSO4) has traditionally been the “reliable” source of Zn fertilizer but other sources of Zn are also available. Some are derived from industrial by-products, varying from flue dust reacted with sulfuric acid to organic compounds derived from the paper industry. The degree of Zn availability in Zn sources derived from these various by-products is related to the manufacturing process, the source of complexing or chelating agents (organic sources), and the original product used as the Zn source. Many claims are made regarding the relative efficiency of traditional inorganic Zn fertilizers and complexed Zn sources. The objective of this greenhouse study was to determine the availability coefficients of several commercial Zn fertilizer materials (organic and inorganic) that are commonly used to correct Zn deficiencies in soils. We evaluated the dry matter production, total Zn uptake, and Zn concentration in corn (Zea mays L. cv. P3752) plants fertilized with six different commercial Zn fertilize...
The Fundamental Role of Flexibility on the Strength of Molecular Binding

Non-covalent molecular association underlies a diverse set of biologically and technologically relevant phenomena, including the action of drugs on their biomolecular targets and self- and supra-molecular assembly processes. Computer models employed to model binding frequently use interaction potentials with atomistic detail while neglecting the thermal molecular motions of the binding species. However, errors introduced by this simplification and, more broadly, the thermodynamic consequences of molecular flexibility on binding, are little understood. Here, we isolate the fundamental relationship of molecular flexibility to binding thermodynamics via simulations of simplified molecules with a wide range of flexibilities, but the same interaction potential. Disregarding molecular motion is found to generate large errors in binding entropy, enthalpy and free energy, even for molecules that are nearly rigid. Indeed, small decreases in rigidity markedly reduce affinity for highly rigid molecules. Remarkably, precisely the opposite trend occurs for more flexible molecules, for which increasing flexibility leads to stronger binding affinity. We also find that differences in flexibility suffice to generate binding specificity: for example, a planar surface selectively binds rigid over flexible molecules. Intriguingly, varying molecular flexibility while keeping interaction potentials constant leads to near-linear enthalpy–entropy compensation over a wide range of flexibilities, with the unexpected twist that increasing flexibility produces opposite changes in entropy and enthalpy for molecules in the flexible versus the rigid regime. Molecular flexibility is thus a crucial determinant of binding affinity and specificity and variations in flexibility can lead to strong yet non-intuitive consequences.
Physician performance measures in dermatology

Performance measures serve as a method of assessing and reporting on the quality of care that physicians are delivering to their patients. Although measures have been developed and integrated into other fields of medicine, a comprehensive set of measures specific to the specialty of dermatology is lacking. It is likely that quality measures will become an increasingly significant component of health care, thus it is important for dermatologists to actively participate in their development. There are multiple topics relevant to the various components of dermatology practice (medical, surgical, and cosmetic dermatology and dermatopathology) upon which measures can be based.
A convenient method for determining chlorides in urine; modification of Northrop's potentiometric titration.

Summary and conclusions1. Modifications of Northrop's method of potentiometric titration of chloride are presented which retain its great convenience while eliminating interference from urates. 2. Analyses can be completed at the rate of 20 to 30 per hour, using aliquots of 0.1 to 1.0 ml, with a precision of better than 1%. 3. Accuracy of at least 1% for urine chloride determinations is evidenced by analysis of known solutions of NaCl, recovery of both KCl and NaCl added to urine specimens, and comparison of the values with those obtained by standard methods. 4. The method appears satisfactory for the analysis of evaporated milk preparations without modification: giving accurate recovery of added chloride, better consistency than reference methods, and as good agreement with them as their own variation (up to 5%) will allow. 5. The apparent unsuitability of the method for unmodified serum is discussed briefly.
2012 Introduction to the Curt Stern Award: Jay Shendure1

One of the greatest perks of being in the field of science is being able to recognize one’s colleagues as a result of scientific excellence and innovation. It is a special pleasure for me today to introduce to you the 2012 American Society of Human Genetics Curt Stern Awardee, Jay Shendure.
The relationship between depressive symptoms and medication nonadherence in type 2 diabetes: the role of social support

Abstract Objective Medication adherence promotion interventions are needed that target modifiable behavioral factors contributing to the link between depressive symptoms and poor adherence to diabetes self-care behaviors. In an effort to identify what factors contribute to this link, we examined the role of social support as a mediator of the relationship between depressive symptoms and medication nonadherence. Method We recruited 139 subjects with type 2 diabetes. Using an indirect effect test with bias-corrected (BC) bootstrapping, we tested whether depressive symptoms had an indirect effect on medication nonadherence through a lack of social support. Results More depressive symptoms were associated with medication nonadherence (total effect=.06, P P =.02), and less social support was associated with medication nonadherence (direct effect of the mediator on the outcome=−.01, P Conclusion Providing social support to patients with diabetes who have symptoms of depression may ameliorate some of the deleterious effects of depressive symptoms on medication nonadherence, but social support alone is not enough.
Electron transport in the conduction channel of the HEMT

Abstract The electron transport in the conduction channel of the HEMT is investigated using an Ensemble Monte Carlo method, which includes the first two subbands in the quantum well. The interaction between the channel and the rest of the device is accounted for, including intravalley and intervalley transitions between confined and 3-D states. The model allows an evaluation of the real-space transfer effects.
Directed assembly of nanoparticles in block copolymer thin films: Role of defects

The structure of A-b-B diblock copolymer (BCP) thin films is often exploited for “tailoring” the self-assembly of nanoparticles into various geometries, characterized by long-range order. Mechanistically, the nanoparticles are sequestered within the A or B domains of the copolymer, and the domains act as scaffolds to direct the assembly of the nanoparticles. We show that in BCP thin films, which order at suboptimal thicknesses, dislocations play a dominant role in determining the spatial organization of sufficiently large nanoparticles. The nanoparticles preferentially segregate to the core of edge dislocations, which are ubiquitous in these materials. To this end, the two-dimensional planar shape of the islands and holes determine the self-assembled geometry of the nanoparticles. We also show that the so-called “healing length”, λ, increases with film thickness, h, in a manner consistent with λ ∝ h1/2, in accordance with theory. In films of thickness between L < h < 3L, where L is the domain spacing, λ l...
Efficacy of Glycine and Arginine in Alleviating the Stress Induced by Dietary Excesses of Single Amino Acids

Abstract MOST amino acids, when given in excess, produce toxic effects as measured by growth inhibition in the case of orally administered amino acids (reviewed by Harper et al., 1955), or by death and/ or gross variations in certain blood constituents in the case of intravenously or intraperitoneally injected amino acids (Gullino et al., 1956; Winitz et al., 1956; du Ruisseau et al., 1956; and Harper et al., 1956). Except for a few cases the majority of the investigations of this type in avian nutrition have studied the relationships of amino acids with a concurrent deficiency of one or more of the B complex vitamins (Naber et al., 1952; Anderson et al., 1951; Hsu and Combs, 1952; Machlin et al., 1952, among others). Madden et al. (1945) demonstrated that glycine administered intravenously increases the tolerance of the dog for certain toxic mixtures of amino acids. Gullino et al. (1956) and Najarian…
Salvage stereotactic radiosurgery effectively treats recurrences from whole‐brain radiation therapy

BACKGROUND. The purpose of the current study was to examine overall survival (OS) and time to local failure (LF) in patients who received salvage stereotactic radiosurgery (SRS) for recurrent brain metastases (BM) after initial management that included whole-brain radiation therapy (WBRT). METHODS. The records of 1789 BM patients from August 1989 to November 2004 were reviewed. Of these, 111 underwent WBRT as part of their initial management and SRS as salvage. Patients were stratified by Radiation Therapy Oncology Group (RTOG) recursive partitioning analysis class, primary disease, dimension of the largest metastases and number of BM at initial diagnosis, and time to first brain recurrence after WBRT. Overall survival, survival after SRS, and time to local and distant failure were analyzed. RESULTS. The median OS from the initial diagnosis of BM was 17.7 months. Median survival after salvage SRS for the entire cohort was 9.9 months. Median survival after salvage SRS was 12.3 months in patients who had their first recurrence >6 months after WBRT versus 6.8 months for those who developed disease recurrence ≤6 months after (P = .0061). Primary tumor site did not appear to affect survival after SRS. Twenty-eight patients (25%) developed local recurrence after their first SRS with a median time of 5.2 months. A dose 2 cm were found to be predictive of local failure. CONCLUSIONS. In this study, patients who recurred after WBRT and were treated with salvage SRS were found to have good local control and survival after SRS. WBRT provided good initial control, as 45% of these patients failed >6 months after WBRT. Those with a longer time to failure after WBRT had significantly longer survival after SRS. Cancer 2008. © 2008 American Cancer Society.
Building local legitimacy into corporate social responsibility: Gold mining firms in developing nations

Abstract A transnational model of global strategy suggests that multi-national enterprises generally rely on proven global capabilities to adapt existing business models. Alternatively, this paper argues that the transnational model needs to be amended to allow for a hybrid approach that balances local and global strategies for multi-national gold (MNGs) firms working in developing nations. This is illustrated by Newmont Mining's efforts to develop local legitimacy through contributions to community development around its gold mining operations in Peru. We then compare the Newmont case with corporate social responsibility (CSR) at other MNGs. We have found that there appears to be an industry-wide institutional environment developing which includes local CSR projects in an attempt to balance the effects of capitalism between global markets and developing nations.
Cracks in the Glass Slipper: Does It Really “Get Better” for LGBTQ Youth, or Is It Just Another Cinderella Story?

This study examines narratives of the 20 most popular video submissions to the It Gets Better Project campaign to explore how they create a shared story around lesbian, gay, bisexual, transgender, ...