cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 18929: Pacing in the Adult Fontan Patient: Risky Business?

Introduction: Chronic ventricular pacing can induce a cardiomyopathy in patients with a biventricular heart; however, the effect of chronic pacing in adult patients with a Fontan has not been well characterized. We hypothesized that paced adult Fontan patients would be at higher risk for death or heart transplant. Methods: We performed a retrospective, cohort of study of all adult Fontan patients at the Schneeweiss Adult Congenital Heart Center seen between 1/1997 and 5/2014. Two Cohorts were defined based on whether a patient did or did not have a permanent pacemaker. Demographic and clinical characteristics were collected via chart review. The primary endpoint was a composite of death or heart transplant. Results: Of the 98 adult Fontan patients followed (mean age at last follow-up 32± 8 years), 30 (31%) had a pacemaker. Pacemaker specific data was available on 25 of the 30 (83%) paced patients. Of those, 88% were paced >50% of the time. Patient diagnoses included double inlet left ventricle in 33 (34%), tricuspid atresia in 26 (27%), hypoplastic left heart in 9 (9%), heterotaxy in 8 (8%), and 22 (22%) with other diagnoses. Fifty-two patients (53%) had a classic RA-PA Fontan and 46 (47%) had a lateral tunnel or extracardiac Fontan. Over the study period, 16 patients met the primary endpoint and 12 (75%) were paced. Paced patients were significantly more likely to have worse functional status (p 4-fold increase in the rate of death or heart transplant (p=0.009) in a multivariate cox-proportional hazard model that included Fontan type, age at Fontan completion, age at follow-up, and pacing status. Discussion: In our cohort of 98 adult Fontan patients, paced patients were more likely to have worse functional status, require diuretics and had a >4-fold increased risk of death or heart transplant. These results suggest that chronic pacing may be detrimental in this population.
Sex differences in romantic attachment: A facet-level analysis

Abstract Evolutionary models predict systematic sex differences in romantic avoidance and anxiety; however, observed effect sizes are typically small. Here I explore the possibility that larger and more reliable differences may emerge at the level of narrower attachment facets. In two datasets from the US and Italy, five facets could be identified in the Experiences in Close Relationships questionnaire. As predicted, attachment facets showed larger sex differences (US: d = −.14 to .31, Italy: d = −.53 to .39) than avoidance and anxiety (US: d = .00 and −.03, Italy: d = .18 and −.40); moreover, different facets of the same dimension showed opposite-sign effects. These findings suggest that sex differences in attachment can be fruitfully investigated at the level of facets.
Critical appraisal of dabigatran in the treatment of deep vein thrombosis and pulmonary embolism.

To compare the safety and efficacy of dabigatran to warfarin for the treatment of deep vein thrombosis and pulmonary embolism.Venous thromboembolism (VTE) is a disease comprised of two conditions: deep vein thrombosis and pulmonary embolism. VTE is a major cause of morbidity and mortality worldwide with an annual incidence estimated at 1-3 cases per 1,000 individuals. This incidence increases with age from 0.1 per 1,000 in adolescence to eight per 1,000 in those 80 years of age and older. As the proportion of patients 65 years of age and older expands, the number of patients presenting with VTE will also increase. Anticoagulation remains the cornerstone of VTE treatment. Traditionally, vitamin K antagonists have been used to minimize the risk of thrombus extension and for secondary prevention. Unpredictable pharmacokinetics and pharmacodynamics, routine monitoring, drug-food and drug-drug interactions, and potentially severe adverse events have all been cited as barriers to optimal care. Dabigatran has been proposed as a suitable alternative to warfarin therapy in the treatment of VTE. Therefore, a critical appraisal of dabigatran's safety and efficacy is necessary to determine its role in therapy.Dabigatran remains an alternative to warfarin therapy for the treatment of VTE. However, dabigatran also has distinct disadvantages that warrant consideration. Clinicians must ensure that drug characteristics align with patient characteristics to optimize patient outcomes.
Does Estimation Uncertainty Affect Investors’ Preference for the Form of Financial Statement Presentation?

The uncertainty underlying transactions and estimates, and how it is communicated in financial statements, is of increasing concern to financial statement users, preparers, standard setters, and auditors. In this study we examine how the underlying uncertainty of financial statement information influences well-informed investors’ preference for point versus range presentation and for the width of the estimated range. Consistent with congruity theory (Budescu and Wallsten, 1995), which states that individuals prefer the form of communication that best correlates to the inherent precision or uncertainty of the information communicated, we find that as uncertainty increases, investors prefer that financial statement information be presented as a range rather than a point estimate. We find that preferences among point, narrow-range and wide-range estimate forms depend more on the level of underlying uncertainty for financial statement information than the previous literature reports for management forecasts. We also find that investors deem ranges to be more accurate, credible and informative than point estimates, especially in situations of high uncertainty. These findings provide regulators with a clearer idea of how investors view uncertainty and the form in which they prefer uncertain financial statement information to be communicated.
A COMPARATIVE STUDY OF COLLABORATIVE VS. TRADITIONAL MUSICAL MOOD ANNOTATION

Organizing music by emotional association is a natural process for humans, but the ambiguous nature of emotion makes it a difficult task for machines. Automatic systems for music emotion recognition rely on ground truth data collected from humans, and more effective methods for collecting such data are being continuously developed. In previous work, we developed MoodSwings, an online collaborative game for crowdsourcing dynamic (persecond) mood ratings from multiple players within the twodimensional arousal-valence (A-V) representation of emotion. MoodSwings has proven effective for data collection, but potential data effects caused by collaborative labeling have not yet been analyzed. In this work, we compare the effectiveness of MoodSwings to that of a more traditional data collection method, where annotation is performed by single, paid annotators. We implement a simplified labeling task to run on Amazon’s crowdsourcing engine, Mechanical Turk (MTurk), and analyze the labels collected with each method. A statistical comparison shows consistencies between MoodSwings and MTurk data, and we produce similar results using each as training data for automatic emotion production via supervised machine learning. Furthermore the new dataset collected via MTurk has been made available to the Music Information Retrieval community.
Bacteriophages isolated from Lake Michigan demonstrate broad host-range across several bacterial phyla

The study of bacteriophages continues to generate key information about microbial interactions in the environment. Many phenotypic characteristics of bacteriophages cannot be examined by sequencing alone, further highlighting the necessity for isolation and examination of phages from environmental samples. While much of our current knowledge base has been generated by the study of marine phages, freshwater viruses are understudied in comparison. Our group has previously conducted metagenomics-based studies samples collected from Lake Michigan - the data presented in this study relate to four phages that were extracted from the same samples. Four phages were extracted from Lake Michigan on the same bacterial host, exhibiting similar morphological characteristics as shown under transmission electron microscopy. Growth characteristics of the phages were unique to each isolate. Each phage demonstrated a host-range spanning several phyla of bacteria – to date, such a broad host-range is yet to be reported. Genomic data reveals genomes of a similar size, and close similarities between the Lake Michigan phages and the Pseudomonas phage PB1, however, the majority of annotated genes present were ORFans and little insight was offered into mechanisms for host-range. The phages isolated from Lake Michigan are capable of infecting several bacterial phyla, and demonstrate varied phenotypic characteristics despite similarities in host preference, and at the genomic level. We propose that such a broad host-range is likely related to the oligotrophic nature of Lake Michigan, and the competitive benefit that this characteristic may lend to phages in nature.
Regulation of Rat Basophilic Leukemia-2H3 Mast Cell Secretion by a Constitutive Lyn Kinase Interaction with the High Affinity IgE Receptor (FcεRI)

Signaling through the high affinity IgE receptor is initiated by noncovalently associated Lyn kinase, resulting in the secretion of inflammatory mediators from mast cells. A fraction of the total cellular Lyn is associated via its N-terminal unique domain with the cytoplasmic domain of the FceRI β subunit before receptor aggregation. In the current study, we stably transfected the unique domain of Lyn into rat basophilic leukemia-2H3 mast cells and examined the consequences on FceRI-induced signal transduction and mediator secretion to further define the role of the unique domain of Lyn in mast cell secretion. Tyrosine phosphorylation of FceRI β and γ subunits was partially inhibited in the Lyn unique domain transfectants after Ag stimulation. Ag stimulation of Lyn unique domain transfectants was accompanied by enhanced phosphorylation of MEK and ERK-2, which are required for leukotriene C4 (LTC4) release, and production of LTC4 was increased 3- to 5-fold, compared with cells transfected with vector alone. Conversely, tyrosine phosphorylation of the adaptor protein Gab2, which is essential for mast cell degranulation, was inhibited after Ag stimulation of Lyn unique domain transfectants, and Ag-induced release of histamine was inhibited up to 48%. In rat basophilic leukemia-2H3 cells, Lyn thus plays a dual role by positively regulating FceRI phosphorylation and degranulation while negatively regulating LTC4 production. This study provides further evidence that the constitutive interaction between the unique domain of Lyn and the FceRI β subunit is a crucial step in the initiation of FceRI signaling and that Lyn is limiting for FceRI-induced secretion of inflammatory mediators.
Candida Cell Wall Mannan: A Polysaccharide with Diverse Immunologic Properties

It is clear that mannan has the potential to influence multiple biologic functions in vivo and in vitro, including both mannan-specific and mannan-nonspecific activities. Based on in vitro studies, various mechanisms have been proposed for the regulatory activities observed, ranging from interference with normal PMNL and monocyte function to the induction of T suppressor cells. It may well be, in fact, that different mechanisms function at different levels depending upon the specific phenomenon being influenced. Approaches to determining the mechanisms involved in these regulatory phenomena, however, have been complicated by the fact that many studies were performed with mannan extracted in the laboratory by traditional methods and used as such without further purification. Most laboratory-acquired mannans appear to be heterogeneous mixtures containing polymers of differing size and charge. When such mixtures have been separated on the basis of size or charge, it has been shown that biologic function can be correlated with individual fractions, and that a single bulk preparation of mannan can contain components with opposing biologic activities. Resolution of the specific mechanisms involved in the regulatory phenomena described, therefore, will not be complete until homogeneous preparations of mannan are employed to investigate the mechanisms.
The role of the kinetic energy density in approximations to the exchange energy

Abstract Local and gradient corrected functionals for the non-interacting kinetic energy (Ts) are applied to the atomization process. These functionals and a newly developed generalized gradient approximation (GGA) for Ts are not accurate enough for thermochemistry. The limited accuracy of the gradient expansion approximation for Ts is shown to be related to the remaining errors in existing GGAs for the exchange energy Ex. Various new approximation schemes for Ex are developed which attempt to overcome the problems arising from approximations to Ts.
Sézary syndrome patients demonstrate a defect in dendritic cell populations: effects of CD40 ligand and treatment with GM-CSF on dendritic cell numbers and the production of cytokines

Sezary syndrome (SzS) is an advanced form of cutaneous T-cell lymphoma associated with involvement of the peripheral blood by malignant T cells. The disease is defined by impaired cell-mediated immunity and the production of interferon-gamma (IFN-gamma) and interleukin-2 (IL-2), possibly as a result of deficient IL-12 production. To understand the mechanism of this impairment, we examined the composition and function of dendritic cells and monocytes in the blood of SzS patients with different levels of peripheral blood tumor burden. Consistent with our previous observations, numbers of monocytes in SzS patients were comparable to numbers observed in healthy donors. In contrast, decreased IL-12 production correlated with a decrease in the numbers of CD11c(+) dendritic cells, which was particularly profound among patients with medium (20%-50% circulating malignant T cells) and high (more than 50% circulating malignant T cells) tumor burden. Furthermore, CD123(+) dendritic cells, major producers of IFN-alpha, were significantly diminished in SzS patients, regardless of the level of tumor burden. Granulocyte macrophage-colony-stimulating factor-treated patients experienced an increase in the number of dendritic cells but not in IFN-alpha or IL-12 production. However, in vitro stimulation of peripheral blood mononuclear cells from SzS patients with rCD40L and IFN-gamma significantly increased the production of IL-12. Thus, our results demonstrate a profound defect in circulating dendritic cells in SzS patients that may contribute to the pathogenesis of the cytokine disorders and to the depressed cellular immunity. Importantly, the ability of rCD40L to potently induce IL-12 production from monocytes and residual dendritic cells of SzS patients could potentially serve as an immune-restorative therapeutic agent.
Effects of muscle strength and activation profile on foot drag in a simulated SCI rat

Introduction Spinal cord injury (SCI) can lead to decreases in overall motoneuron output, changes in muscle activation patterns, and atrophy of the affected muscles. Depending upon the severity of SCI, foot drag can occur during the stance-to-swing transition during locomotion. Our preliminary experimental data suggests that muscles co-activate following SCI, which may cause foot drag. To assess the relative roles of neural and muscular changes, a 3D neuro-musculoskeletal model of the rat hindlimb is being developed. Initially, a 2D, one degree-of-freedom ankle model with gastrocnemius (GAS) and tibialis anterior (TA) muscles was developed. Given that GAS can produce more ankle torque than TA, this simulation study tested the hypothesis that GAS motoneuronal deactivation profile dominates the ability of the foot to transition from stance to swing. Our results suggest that even small changes in the ability to precisely de-activate muscles could lead to kinematic deficits commonly observed following SCI.
Listening Otherwise: The Voice of Ethics

The issues of response and responsibility are woven into the center of dialogic ethics (Levinas, 1996, 1998, 1999; Schrag, 1986; Hyde, 2001, 2006), yet quietly embedded persists a hidden but presupposed prior action-that of listening-about which the philosophy of dialogue falls, ironically, silent. The idea of the response as related to ideas of reply, answer, and reaction as well as its etymological derivation from the Latin spondere ‘to pledge’ (promise, offer, sacrifice) stresses only the speaking of an ethical actor. The act of listening is itself concealed and rendered invisible. This paper suggests that the answer to the ethical call of conscience is not a speaking, but a listening. It is, moreover, a listening otherwise that suspends the willfulness of self and fore-knowledge in order to receive the singularities of the alterity of the other. To say that ethics arises from listening is thus to subordinate speaking to a kind of listening that speaks—a listening that is awakened and attuned to the so...
The responsible victim: nurses' perceptions of victims of rape.

Are victims seen by nurses as being more responsible for the occurrence of a rape than for the occurrence of a violent nonsexual crime? If so, what are some of the determinants of victim blame? The present study considers how judgments made by hospital nurses (N = 312) regarding victim responsibility are influenced by the type of crime (i.e., rape or beating), the victim's marital status, her dress, her relationship with the assailant, evidence of her resistance, the extent of her injuries, and psychological attributes and sociodemographic characteristics of the nurse. Evaluations of victim responsibility were elicited through the use of vignettes. Findings suggest that although nurses make relatively similar assignments of blame to rape and beating victims, the assignment of blame differs significantly for those victims described as "respectable" (married, wore print dress, was not acquainted with assailant, struggled with assailant, suffered serious injuries) and those described as "disrespectable" (divorced, wearing halter top and shorts, casual acquaintance of assailant, no struggle, minor scratches as a result of the crime). Psychological attributes of the nurse emerged as the strongest predictors of victim blaming.
Analysis of cell populations of normal and injured mouse lens epithelium. II. Contribution of local and migrating cells to wound healing

The contribution of progenitor cells in the normal peripheral region of mouse lens epithelium to healing of a centrally located wound was studied using an autoradiographic technique designed to follow migrating 3H-thymidine labeled cells. It was found that few progenitor cells labeled before or at the time of injury migrate toward the wound and hence contribute little to the repair of the wound. Moreover, the central injury did not delay or reverse the normal migration of the labeled peripheral cells in the opposite direction into the bow. It is concluded from this and other studies that a central injury to the mouse lens is healed mainly by numerous local cells which are stimulated for the most part to traverse one replicative cycle of normal duration, and that the injury does not affect formation of new lens fibers. These findings are thought to be related to the observed low incidence of traumatic cataract in the mouse.
A mapping of the electron localization function for earth materials

The electron localization function, ELF, generated for a number of geometry-optimized earth materials, provides a graphical representation of the spatial localization of the probability electron density distribution as embodied in domains ascribed to localized bond and lone pair electrons. The lone pair domains, displayed by the silica polymorphs quartz, coesite and cristobalite, are typically banana-shaped and oriented perpendicular to the plane of the SiOSi angle at ~0.60 A from the O atom on the reflex side of the angle. With decreasing angle, the domains increase in magnitude, indicating an increase in the nucleophilic character of the O atom, rendering it more susceptible to potential electrophilic attack. The Laplacian isosurface maps of the experimental and theoretical electron density distribution for coesite substantiates the increase in the size of the domain with decreasing angle. Bond pair domains are displayed along each of the SiO bond vectors as discrete concave hemispherically-shaped domains at ~0.70 A from the O atom. For more closed-shell ionic bonded interactions, the bond and lone pair domains are often coalesced, resulting in concave hemispherical toroidal-shaped domains with local maxima centered along the bond vectors. As the shared covalent character of the bonded interactions increases, the bond and lone pair domains are better developed as discrete domains. ELF isosurface maps generated for the earth materials tremolite, diopside, talc and dickite display banana-shaped lone pair domains associated with the bridging O atoms of SiOSi angles and concave hemispherical toroidal bond pair domains associated with the nonbridging ones. The lone pair domains in dickite and talc provide a basis for understanding the bonded interactions between the adjacent neutral layers. Maps were also generated for beryl, cordierite, quartz, low albite, forsterite, wadeite, akermanite, pectolite, periclase, hurlbutite, thortveitite and vanthoffite. Strategies are reviewed for finding potential H docking sites in the silica polymorphs and related materials. As observed in an earlier study, the ELF is capable of generating bond and lone pair domains that are similar in number and arrangement to those provided by Laplacian and deformation electron density distributions. The formation of the bond and lone pair domains in the silica polymorphs and the progressive decrease in the SiO length as the value of the electron density at the bond critical point increases indicates that the SiO bonded interaction has a substantial component of covalent character.
Mathematical models for estimating mutation rates in cell populations

SUMMARY A number of mathematical models for cell populations in which mutations are occurring are studied and compared by viewing the models as filtered Poisson processes. Based upon these models, a statistical analysis is given of the mutant accumulation method of estimating mutation rates. Phenotypic delay, that is delay from the epoch at which a cell mutates until cells in resulting clone possess the property which distinguishes them from nonmutant cells, is incorporated into the models and its effect upon some estimation procedures is determined. A suggestion is also given for obtaining information about the duration of phenotypic delay.
Stress and Mental Illness Among the Young: A Comparison of the Sexes

The sociological and psychological literature almost uniformly suggests that young boys experience more stress than young girls, in part because of social expectations and in part because of different rates of biological development and other physiological factors. But it also suggests that with advancing age the sex difference in experienced stress tends to disappear and by late adolescence the situation of girls appears to be at least as stressful if not more so than that of boys. On the premise that the differences in experienced stress would be reflected in rates of treated mental illness, the national rates of males and females in psychiatric treatment between ages five and nineteen are compared. The data consistently show preadolescent males to have higher rates of mental illness, while by late adolescence females appear to have as high if not higher rates of mental illness than males.
The role of race and gender as determinants of local TV news coverage

This study compares the frequency and nature of appearances in the news for different racial or gender groups to test the theory that white women have been making progress at the expense of minorities. Findings based on local TV news coverage in a major market suggest that white women are not faring better than minorities. Rather, the interaction of race and gender reveals more about the frequency of appearance in the news than does either race or gender alone. Even so, despite changes wrought by minority and women's interest groups, being a white male remains the most significant advantage for representation in the news, just as it appears to be of an advantage in the world at large.
Mechanisms of coexistence and competition between ants and land hermit crabs in a Bahamian archipelago

Ants and land crabs are common inhabitants of many coastal and insular communities across the tropics and subtropics, and yet direct evidence of interspecific competition between ants and land crabs has only recently been documented. I conducted a series of observational and manipulative experiments to further elucidate the mechanisms of competition, as well as coexistence, in these two groups in an archipelago of small Bahamian islands. Diel baiting trials demonstrated a significant temporal difference in foraging activity between the land hermit crab, Coenobita clypeatus (Herbst), and ant Brachymyrmex obscurior Forel, suggesting this is one mechanism underlying their coexistence on small oceanic islands. Reciprocal manipulative baiting experiments, in which one of a pair of species was removed from baits, documented that aggressive interspecific interactions underlie patterns of complementary distribution and temporal turnover at rich food resources. This was true for competition between hermit crabs and B. obscurior, and between B. obscurior and a second ant species, Dorymyrmex pyramicus Roger. Negative species associations at baits were found to be common throughout an archipelago of 69 small islands. A trade-off in exploitative and interference abilities may be a second mechanism allowing species coexistence on these small islands. Interspecific interactions such as competition and predation may occur commonly between ants and land crabs and have important consequences for the structure and function of tropical and subtropical insular ecosystems.
Library OPACs with search forms on the World Wide Web

Searching many library online public access catalogues (OPACs) on the World Wide Web is now possible without starting a telnet or gopher session. Identifies Web directories that lead users to OPACs with Web form searching.
A Global Census of Fission Yeast Deubiquitinating Enzyme Localization and Interaction Networks Reveals Distinct Compartmentalization Profiles and Overlapping Functions in Endocytosis and Polarity

Ubiquitination and deubiquitination are reciprocal processes that tune protein stability, function, and/or localization. The removal of ubiquitin and remodeling of ubiquitin chains is catalyzed by deubiquitinating enzymes (DUBs), which are cysteine proteases or metalloproteases. Although ubiquitination has been extensively studied for decades, the complexity of cellular roles for deubiquitinating enzymes has only recently been explored, and there are still several gaps in our understanding of when, where, and how these enzymes function to modulate the fate of polypeptides. To address these questions we performed a systematic analysis of the 20 Schizosaccharomyces pombe DUBs using confocal microscopy, proteomics, and enzymatic activity assays. Our results reveal that S. pombe DUBs are present in almost all cell compartments, and the majority are part of stable protein complexes essential for their function. Interestingly, DUB partners identified by our study include the homolog of a putative tumor suppressor gene not previously linked to the ubiquitin pathway, and two conserved tryptophan-aspartate (WD) repeat proteins that regulate Ubp9, a DUB that we show participates in endocytosis, actin dynamics, and cell polarity. In order to understand how DUB activity affects these processes we constructed multiple DUB mutants and find that a quintuple deletion of ubp4 ubp5 ubp9 ubp15 sst2/amsh displays severe growth, polarity, and endocytosis defects. This mutant allowed the identification of two common substrates for five cytoplasmic DUBs. Through these studies, a common regulatory theme emerged in which DUB localization and/or activity is modulated by interacting partners. Despite apparently distinct cytoplasmic localization patterns, several DUBs cooperate in regulating endocytosis and cell polarity. These studies provide a framework for dissecting DUB signaling pathways in S. pombe and may shed light on DUB functions in metazoans.
GLC Determination of (–)-l-Cyclopropylmethyl-4-(3-trifluoromethylthio-5H-dibenzo[a,d]cyclohepten-5-ylidene)piperidine in Human Plasma and Urine

Abstract (–) – 1 – Cyclopropylmethyl – 4 - (3 - trifluoromethylthio-5 H -dibenzo[a,d]cyclohepten-5-ylidene)piperidine (MK-160) was extracted from human plasma and urine with petroleum ether and quantitated by GLC using a nitrogen-sensitive detector. A homologue of the drug served as the internal standard. The method is specific for the drug in the presence of potential metabolites and is capable of measuring concentrations in plasma as low as 6 ng/ml.
A model of negotiated transfer pricing

Abstract A large majority of firms employ negotiated transfer pricing, yet this method of decentralization remains largely unexplored. This study develops a model of negotiated transfer pricing incorporating private divisional information, as this is the setting where decentralization is most compelling. The firm designs a compensation system utilizing divisional performance evaluation and negotiated transfer pricing. A dynamic bargaining model is employed to capture managerial negotiations. The study demonstrates that the firm can design managerial-compensation schemes and bargaining infrastructures so that the negotiated transfer-pricing structure allows it to reach the upper bound on available profits.
Histone deacetylase inhibitors are potent inducers of gene expression in latent EBV and sensitize lymphoma cells to nucleoside antiviral agents

Induction of EBV lytic-phase gene expression, combined with exposure to an antiherpes viral drug, represents a promising targeted therapeutic approach to EBV-associated lymphomas. Short-chain fatty acids or certain chemotherapeutics have been used to induce EBV lytic-phase gene expression in cultured cells and mouse models, but these studies generally have not translated into clinical application. The recent success of a clinical trial with the pan-histone deacetylase (pan-HDAC) inhibitor arginine butyrate and the antiherpes viral drug ganciclovir in the treatment of EBV lymphomas prompted us to investigate the potential of several HDAC inhibitors, including some new, highly potent compounds, to sensitize EBV+ human lymphoma cells to antiviral agents in vitro. Our study included short-chain fatty acids (sodium butyrate and valproic acid); hydroxamic acids (oxamflatin, Scriptaid, suberoyl anilide hydroxamic acid, panobinostat [LBH589], and belinostat [PXD101]); the benzamide MS275; the cyclic tetrapeptide apicidin; and the recently discovered HDAC inhibitor largazole. With the exception of suberoyl anilide hydroxamic acid and PXD101, all of the other HDAC inhibitors effectively sensitized EBV+ lymphoma cells to ganciclovir. LBH589, MS275, and largazole were effective at nanomolar concentrations and were 104 to 105 times more potent than butyrate. The effectiveness and potency of these HDAC inhibitors make them potentially applicable as sensitizers to antivirals for the treatment of EBV-associated lymphomas.
Human Immunodeficiency Virus, Type 1 Protease Substrate Specificity Is Limited by Interactions between Substrate Amino Acids Bound in Adjacent Enzyme Subsites

The specificity of the retroviral protease is determined by the ability of substrate amino acid side chains to bind into eight individual subsites within the enzyme. Although the subsites are able to act somewhat independently in selection of amino acid side chains that fit into each pocket, significant interactions exist between individual subsites that substantially limit the number of cleavable amino acid sequences. The substrate peptide binds within the enzyme in an extended anti-parallel beta sheet conformation with substrate amino acid side chains adjacent in the linear sequence extending in opposite directions in the enzyme-substrate complex. From this geometry, we have defined both cis and trans steric interactions, which have been characterized by a steady state kinetic analysis of human immunodeficiency virus, type-1 protease using a series of peptide substrates that are derivatives of the avian leukosis/sarcoma virus nucleocapsid-protease cleavage site. These peptides contain both single and double amino acid substitutions in seven positions of the minimum length substrate required by the retroviral protease for specific and efficient cleavage. Steady state kinetic data from the single amino acid substituted peptides were used to predict effects on protease-catalyzed cleavage of corresponding double substituted peptide substrates. The calculated Gibbs' free energy changes were compared with actual experimental values in order to determine how the fit of a substrate amino acid in one subsite influences the fit of amino acids in adjacent subsites. Analysis of these data shows that substrate specificity is limited by steric interactions between pairs of enzyme subsites. Moreover, certain enzyme subsites are relatively tolerant of substitutions in the substrate and exert little effect on adjacent subsites, whereas others are more restrictive and have marked influence on adjacent cis and trans subsites.
Efficacy and safety of hypoglycemic drugs in children with type 2 diabetes mellitus

Study Objectives. To assess the characteristics of children with type 2 diabetes mellitus and to determine the efficacy and safety of drug therapies for this disease in this population. Design. Retrospective review of medical records. Setting. Endocrinology specialty clinic at a tertiary teaching children's hospital. Patients. Forty-two children and adolescents with type 2 diabetes examined between January 1996 and December 2001. Measurements and Main Results. Demographic information, presenting signs and symptoms, drug history, and laboratory values were obtained in all patients. Presenting signs and symptoms were similar to those seen in adults. Patients were initially treated with metformin (14.3%), sulfonylureas (14.3%), insulin (31.0%), or combination therapy (14.3%). Most drug regimens decreased hemoglobin A1c (A1C) levels. Overall, patients treated with drugs had a significant decrease in A1C values, from 10.6% ± 2.7% (mean ± SD) before treatment to 8.0% ± 2.0% at 3.2–52.9 months of treatment (p<0.001). Adverse reactions attributed to drugs included hypoglycemia and gastrointestinal distress. Conclusion. Drug therapy appears to be effective in lowering A1C values in pediatric patients, although further prospective trials are necessary to determine optimal drug therapy in this population.
NUMERICAL SOLUTIONS OF OPTIMAL CONTROL FOR THERMALLY CONVECTIVE FLOWS

We study the numerical solution of optimal control problems associated with two-dimensional viscous incompressible thermally convective flows. Although the techniques apply to more general settings, the presentation is confined to the objectives of minimizing the vorticity in the steady state case and tracking the velocity field in the non-stationary case with boundary temperature controls. In the steady state case we develop a systematic way to use the Lagrange multiplier rules to derive an optimality system of equations from which an optimal solution can be computed; finite element methods are used to find approximate solutions for the optimality system of equations. In the time-dependent case a piecewise-in-time optimal control approach is proposed and the fully discrete approximation algorithm for solving the piecewise optimal control problem is defined. Numerical results are presented for both the steady state and time-dependent optimal control problems.
Interregional comparative advantage models in developing agriculture

This paper emphasizes the importance of agronomic and institutional constraints in the formulation of interregional programing models. Two versions of a linear programming model (17 regions and 25 crops) with different objective functions but identical specification, tailored to characteristics of Egyptian agriculture, are constructed. The objective is to test the position taken in earlier studies that in overpopulated less developed countries, the resulting cropping plans would be highly similar, if not identical, whether gross revenue or net revenue is maximised. Significant variations in land allocation patterns, and consequently substantial differences in gains, were found.
Improved Synthesis of 1‐Benzenesulfinyl Piperidine and Analogs for the Activation of Thioglycosides in Conjunction with Trifluoromethanesulfonic Anhydride*

An improved protocol for the large‐scale production of 1‐benzenesulfinyl piperidine and other sulfinamides is described. It is demonstrated that 1‐benzenesulfinyl pyrrolidine and N,N‐diethyl benzenesulfinamide function analogously to 1‐benzenesulfinyl piperidine in the trifluoromethanesulfonic anhydride‐mediated activation of thioglycosides, and that their less crystalline nature enables them to be used at −78°C as opposed to the −60°C required to keep 1‐benzenesulfinyl piperidine in solution. N,N-Dicyclohexyl benzenesulfinamide does not activate thioglycosides in combination with trifluoromethanesulfonic anhydride, which is attributed to its greater steric bulk. * Dedicated with respect to the memory of Professor Jacques H. Van Boom.
Investing in innovation to enable global competitiveness: The case of Portugal

Abstract The concept of leveraged innovation to create wealth within regions, countries and economies is not a new concept. Competitiveness of regions in the increasingly global economy now requires not only that innovation be present within a regional economy, but also that mechanisms exist to effectively transfer those developed innovations from the research laboratory to the marketplace. It is surmised that increased innovation, and the transfer of this innovation, can lead to increased prosperity of regions (Porter). As such, many developing countries around the world are looking at investments in innovation as a means to spur regional economic development and wealth creation while preserving national competitiveness. That said, innovation investment is by no means an exact science. Historically, typical “innovation investments” have been focused on “tangible” capital infrastructure projects such as the establishment of incubators and science parks. While many regions point to the existence of such tangible innovation assets as proof of investment in innovation, it has been discovered that in some cases, an investment in the capacity building of human networks to engage in technology transfer and commercialization related activities can act as a stronger facilitator for the transformation of economies and produce a larger return on investment in innovation for the country. Given not only Portugal's, but other regions throughout the EU-Zone, recent financial and economic woes, it bears examination on whether investing in the innovation and technology transfer knowledge and “know how” of key human networks within a struggling economy is a worthwhile investment for financially struggling countries during the current times of fiscal crisis.
Macropinocytosis is decreased in diabetic mouse macrophages and is regulated by AMPK.

Macrophages (MΦs) utilize macropinocytosis to integrate immune and metabolic signals in order to initiate an effective immune response. Diabetes is characterized by metabolic abnormalities and altered immune function. Here we examine the influence of diabetes on macropinocytosis in primary mouse macrophages and in an in vitro diabetes model. The data demonstrate that peritoneal MΦs from diabetic (db/db) mice had reduced macropinocytosis when compared to MΦs from non-diabetic (db/+) mice. Additionally, MΦs cultured in hyperglycemic conditions were less adept at macropinocytosis than those cultured in low glucose. Notably, AMP-activated protein kinase (AMPK) activity was decreased in MΦs cultured in hyperglycemic conditions. Activation of AMPK with leptin or 5-aminoimidazole-4-carboxamide-1-β-riboside (AICAR) increased macropinocytosis and inhibition of AMPK with compound C decreased macropinocytosis. Taken together, these findings indicate that MΦs from diabetic mice have decreased macropinocytosis. This decrease appears dependent on reduced AMPK activity. These results demonstrate a previously unrealized role for AMPK in MΦs and suggest that increasing AMPK activity in diabetic MΦs could improve innate immunity and decrease susceptibility to infection.
Mechanical Wheelchair Propulsion System for Patients With Arthrogryposis

Arthrogryposis is a congenital disorder characterized by extreme joint stiffness that inhibits strength and flexibility in upper and lower extremities. Cases vary in severity, but this research focuses on those in which patients require a wheelchair for mobility. Currently, two conventional designs exist: mechanical and electric wheelchairs. For most arthrogryposis patients, existing mechanical wheelchairs are insufficient for independent propulsion as their joints are severely impaired, prohibiting them from reaching the outer handrails on the wheels and expending enough force to propel and steer. Existing devices that improve the mechanical advantage of wheelchairs are insufficient for the needs of these patients who have very limited and specific ranges of motions, which are not compatible with the required force inputs. Though electric wheelchairs allow independent mobility, they are expensive to maintain and not easily portable, limiting their use by socioeconomically disadvantaged patients.Arthrogryposis patients require a lightweight, portable and durable mechanical wheelchair that takes advantage of the user’s specific strengths, and is easily maneuvered in all directions without assistance. A design is presented for a socioeconomically disadvantaged teenage client with arthrogryposis. After taking data regarding the ranges of motion and strength of the client, a new propulsion system was designed and retrofitted to a conventional wheelchair. Prototye I has been tested and a second-generation design which fits the needs of a wider audience suffering from arthrogryposis is presented.Copyright © 2012 by ASME
The average span of self-avoiding walks on two- and three-dimensional lattices

Abstract The “span” of a walk is defined as its maximum extent in a given direction and for “random walks” of n steps it is known that the average span 〈 d n 〉 is proportional to n 1 2 in one, two and three dimensions. The span of “self-avoiding walks” on two- and three-dimensional lattices is investigated by the ratio method using exact 〉 d n 〉 values for finite n . Assuming the asymptotic form 〈 d n 〉 ≈ n δ we find: δ = 0.775 ± 0.010 in two dimensions (square and triangular lattices) and δ = 0.662 ± 0.005 (presumably δ = 2 3 ) in three dimensions (simple cubic and face-centred cubic lattices). The simple conjecture δ = 1 2 γ where γ is the exponent involved in the asymptotic form of the mean square end-to-end distance 〈 r 2 n 〉 ≈ n γ , seems ruled out. Higer moments of the span as well as its relation to the surface tension of chain molecules are briefly discussed.
High-speed deposition of RE123 film with large current capacity by hot-wall type PLD system

Abstract We have studied a hot-wall heating system to produce GdBa 2 Cu 3 O y (GdBCO) films with large critical currents ( I c ) at a high production rate by a pulsed-laser-deposition (PLD) method. GdBCO films fabricated at a production rate of 30 m/h under the optimized conditions, especially a distance of 95 mm between the target and the substrate (T–S), exhibited high critical current densities ( J c ) of about 3 MA/cm 2 and I c over 300 A at a thickness of 1–2 μm. Furthermore, long GdBCO tapes prepared by repeated depositions at each tape-passing speed of 80 m/h showed uniform I c distribution along the longitudinal direction, because the hot-wall system enabled to stabilize temperature within a few degrees at 800 °C. A 170 m long tape with I c over 600 A was successfully fabricated at a production rate of 16 m/h using a laser power of 360 W.
PNEUMONIA, BRONCHITIS AND PULMONARY CHANGES WITH AGE: POSTOPERATIVE PULMONARY COMPLICATIONS

Successful pulmonary defense against inhaled irritants depends on a positive balance between rate of clearance or inactivation of injurious particles and their rate of deposition. Deposition is governed by numbers of particles, their aerodynamic size and density, and geometry of airways. Clearance and inactivation depend largely on the mucociliary blanket in the airways and alveolar macrophages at the alveolar level. The function of both is depressed by many deleterious influences, some of which relate directly to surgery.
Anion Effects on the Kinetics of Mercury Underpotential Deposition on Au(111) Electrodes

The kinetics and mechanism of mercury underpotential deposition (UPD) on Au(111) electrodes have been investigated in the presence and absence of strongly interacting anions including bi-sulfate, chloride, and acetate. In the absence of strongly interacting anions, i.e. in perchloric acid, the mercury UPD process is largely controlled by mercury−gold surface interactions. The presence of sulfuric acid in the supporting electrolyte alters the kinetics of the initial and final stages of mercury deposition/dissolution. The presence of two well-ordered structures at potentials below (a mercurous sulfate √3×√19 structure) and above (a √3×√7 bi-sulfate structure) mercury deposition leads to the appearance of two pairs of sharp spikes in the cyclic voltammogram. Analysis of the current transients obtained for deposition and dissolution processes reveals that three different processes are taking place during the adsorption/desorption of the mercury bi-sulfate layer: adsorption/desorption processes governed by La...
Precise Molecular Constants for the6Li2A1Σ+u–X1Σ+gSystem by Sub-Doppler Polarization Spectroscopy

Abstract We report here new and more accurate molecular constants from sub-Doppler polarization spectroscopy of the A 1 Σ + u –X 1 Σ + g system of 6 Li 2 using single mode cw dye lasers. These new constants cover the range of vibrational levels from v ″ = 0–8 in the ground state and v ′ = 0–24 in the excited state. New molecular constants and RKR potential energy curves for the A 1 Σ + u and X 1 Σ + g states are given. The T e value for the A 1 Σ + u state is 14068.043(34) cm −1 . The analysis indicates that there is a noticeable breakdown of the Born–Oppenheimer approximation for the 6 Li 2 and 7 Li 2 isotopomers.
Genetic evidence for similar negative regulatory domains in the yeast transcription activators GAL4 and LAC9

The GAL4 protein of Saccharomyces cerevisiae and the LAC9 protein of Kluyveromyces lactis are transcription activator proteins with similar structure and function. Greatest similarity occurs in the C region near the carboxy terminus, where 16 of 18 amino acids are identical. The function of the C region is unclear. Here we show that the structural similarity is reflected in functional similarity. Single amino acid changes in the C region of GAL4 and LAC9 create a similar phenotype: constitutive gene expression. In S. cerevisiae the constitutive phenotype caused by GAL4 mutants can be abolished by overproduction of GAL80. These results support a model in which the C region of GAL4 and LAC9 constitute similar negative regulatory domains that interact with GAL80 in S. cerevisiae and an unidentified GAL80 homolog in K. lactis. This protein-protein interaction prevents expression of the galactose operon in the uninduced state.