cssi/SciSciGPT-SciSciNet huggingface dataset:
The Nature of the Binding of Inhibitors to Pepsin and the Kinetics of Inhibited Peptic Hydrolysis of N-Acetyl-l-phenylalanyl-l-tyrosine

Abstract A quantitative study of the inhibition of the pepsin-catalyzed hydrolysis of acetyl-l-phenylalanyl-l-tyrosine at pH 2 and 37° is reported. Comparison of the inhibition constants and the -ΔF° values for 43 compounds that are structurally related to pepsin substrates allows those characteristics which dominate binding of inhibitor to enzyme at pH 2 to be ascertained. The results indicate that compounds are bound to pepsin principally by hydrophobic forces. The -ΔF° values are of a magnitude consistent with the view that more than a single amino acid residue of pepsin is directly involved in the binding of an inhibitor molecule to the enzyme. The kinetics of inhibition show that 1 molecule of inhibitor is bound per molecule of enzyme at low concentrations of inhibitor, and that at higher concentrations the kinetics is consistent with the binding of 2 inhibitor molecules. Two alternative mechanisms are presented that are consistent with the kinetic observations. One implies that inhibitor and substrate bind to different regions of the enzyme; the other implies that both bind to the substrate-binding region of the active center of the enzyme.
Decision Support in Healthcare Supply Chain Management and Pharmaceutical Inventory Control

This exploratory research examines the pharmaceutical inventory control practices of a local area hospital and demonstrates the utility of two alternative quantitative approaches. Pharmaceuticals represent a large cost factor for most hospitals due to the significant costs of these products and the storage and control requirements. The hospital stores drugs in the Central Pharmacy and at various Care Units (CUs) throughout the hospital and employs advanced technology to manage inventory and automate the ordering processes at these local storage units. This research examines current hospital policies, employs quantitative methods to improve upon these practices, and provides a decision support tool that allows managers to quickly understand operational, tactical, and strategic implications of changes in the formulary (pharmaceutical product mix available in hospital). This decision support tool affords managers the opportunity to improve management practices and the capacity to support negotiations with stakeholders on issues related to the formulary.
Nontuberculous lymphadenopathy in children: using the evidence to plan optimal management.

Nontuberculous mycobacterial (NTM) lymphadenopathy in children is managed and seen by surgeons and paediatricians. Despite a wealth of literature (but only one randomised controlled trial [1]) publications continue to express uncertainty about the optimal management of these lesions [2]. This review explores the literature to provide a practical, evidence-based approach to their management.
Biological Micro- and Nanotribology: Nature’s Solutions

Introduction.- Physical Principles of Micro- and Nanotribology.- Biological Frictional and Adhesive Systems.- Frictional Devices of Insects.- Microscale Test Equipment.- Nanoscale Probe Techniques.- Microscopy Techniques.- Samples, Sample Preparation and Tester Setup.- Case Study I: Indentation and Adhesion.- Case Study II: Friction.- Case Study III: Material Properties.- Outlook.- Appendix
A Broadband Planar N-Way Combiner/Divider

The experimental and predicted performance of the new broadband planar N-way combiner/divider is presented. The advantage of this combiner/divider over those previously published is that it can be realized in a planar structure. Experimental data on the planar combiner/divider for N=4 and N =7 indicates an average isolation of 20 dB between the N ports from 8 to 12 GHz, and compares favorably with analytic predictions.
Racial/ethnic differences in report of drug testing practices at the workplace level in the U.S.

Background and Objectives It is unknown whether racial/ethnic differences in report of workplace drug testing persist when analyzed within and across various occupations. We sought to examine the association between worker demographics, workplace characteristics, and report of employment in a workplace that performs drug testing. Methods We performed a cross-sectional study of the 2008–2010 National Survey on Drug Use and Health examining the relationship between race/ethnicity and report of workplace drug testing among employed, white, black, or Hispanic respondents ≥18 years old. In logistic regression analysis, we adjusted for demographic, occupational, and other relevant variables and performed stratified analyses among three specific occupations. Results Among 69,163 respondents, 48.2% reported employment in a workplace that performs drug testing. On multivariable analysis, younger age, male sex, black race, income greater than $20,000, completion of high school and non-urban residence were associated with report of drug testing at one's workplace among the full sample as were non-white collar occupation, work in medium or large workplace, and absence of other substance abuse/dependence. In stratified analyses, black race was associated with report of workplace level drug testing among executive/administrative/managerial/financial workers and technicians/related support occupations; Hispanic ethnicity was associated with the outcome among technicians/related support occupations. Conclusions Racial/ethnic differences in report of workplace drug testing exist within and across various occupations. These differences have important public health implications deserving further study. Scientific Significance Increased report of drug testing where racial/ethnic minorities work highlights the potential bias that can be introduced when drug testing policies are not implemented in a universal fashion. (Am J Addict 2014;23:357–362)
Waging a Living: Career Development and Long-Term Employment Outcomes for Young Adults with Disabilities:

Youth with disabilities face many barriers in making the transition from high school to stable long-term employment. Researchers used case study methodology to examine the career development process and postschool employment outcomes for a sample of individuals with disabilities who were working in living wage occupations 7 to 10 years after exiting high school. Key influences on initial post-high school placement included (a) participation in work experience, (b) transition services and supports, and (c) family support and expectations. Ongoing career advancement was supported by a combination of factors including (a) participation in postsecondary education or training; (b) steady work experiences; and (c) a set of personal attributes, including self-efficacy and persistence. These themes were present across all participants, but specific experiences and outcomes varied by gender.
Retrieval of mass and sizes of particles in sandstorms using two MODIS IR bands: A case study of April 7, 2001 sandstorm in China

[1] A thermal infrared remote sensing retrieval method developed by Wen and Rose [1994], which retrieves particle sizes, optical depth, and total masses of silicate particles in the volcanic cloud, was applied to an April 07, 2001 sandstorm over northern China, using MODIS. Results indicate that the area of the dust cloud observed was 1.34 million km2, the mean particle radius of the dust was 1.44 μm, and the mean optical depth at 11 μm was 0.79. The mean burden of dust was approximately 4.8 tons/km2 and the main portion of the dust storm on April 07, 2001 contained 6.5 million tons of dust. The results are supported by both independent remote sensing data (TOMS) and in situ data for a similar event in 1998. This paper demonstrates that Wen and Rose's retrieval method could be successfully applied to past and future sandstorm events using IR channels of AVHRR, GOES or MODIS.
Minimally invasive posterior lumbar fusion techniques

Minimally invasive approaches for lumbar spinal fusion have advanced considerably over the past decade. The underlying goal of these procedures is to perform a successful arthrodesis while minimizing destruction to normal soft tissues. In this manner, it is anticipated that patients will experience a reduction in postoperative pain, improved physiologic muscle function, and better cosmesis when compared with standard open spinal surgery. Contemporary techniques for minimally invasive posterior lumbar pedicle-screw fusion can be categorized as true percutaneous, through a tubular dilator retractor, and muscle splitting. Each of these approaches is associated with specific advantages and drawbacks.
Damage identification through generalized correlations between measurements

Several data-driven features have recently proven to be successful at detecting damage in structures. Some of these features, developed within the context of their state space attractors, highlight dynamics-specific changes without relying on model-specific forms or assumptions such as linearity. Features such as generalized interdependence and state space prediction error can also be formulated such that they provide information about generalized correlations between time series. Therefore, in addition to damage indications, these features can also provide details about the location of damage in a structure by comparing dynamical differences between measurements. This work proposes a framework for establishing such an analysis procedure that can detect presence, extent, location, and/or type of damage in a structure from a single feature. This approach is validated on a multi-degree of freedom oscillator.
Influence of measured freestream disturbances on hypersonic boundary-layer transition

Free stream disturbances influence on hypersonic boundary layer transition Reynolds number in heated and unheated flows
Neuropathology of Central Nervous System Arterial Syndromes. Part I: The Supratentorial Circulation

The objective of this review is to illustrate the principal cerebrovascular arterial pathoanatomical syndromes using the unique collection of whole brain sections in the Raymond Escourolle Neuropathology Laboratory at Salpetriere in Paris. The arterial supratentorial syndromes are presented in Part I; the infratentorial and spinal cord syndromes will be presented subsequently in Part II. No attempt is made to be all-inclusive in the review of the literature; rather, we cite only those bibliographic references that are historically noteworthy and with some exceptions that particularly emphasize the neuropathologic rather than radiographic/imaging aspects of the vascular syndromes. From these studies and our own archival material, we have synthesized the salient clinicopathologic aspects of the individual syndromes.
FLUORO-LIGAND PROMOTION OF C-H ACTIVATION

Ethylene dehydrogenates Ir(H)2FL2 (L = PtBu2Ph) to give the metalated species 1 and 2. These metalated species catalyze the exchange of deuterium from C6D6 to ethylene, and to tBu and ortho phenyl sites of coordinated L. This exchange is proposed to benefit from π-donation from F to Ir.
Data collection and analysis strategies for phMRI.

Abstract Although functional MRI traditionally has been applied mainly to study changes in task-induced brain function, evolving acquisition methodologies and improved knowledge of signal mechanisms have increased the utility of this method for studying responses to pharmacological stimuli, a technique often dubbed “phMRI”. The proliferation of higher magnetic field strengths and the use of exogenous contrast agent have boosted detection power, a critical factor for successful phMRI due to the restricted ability to average multiple stimuli within subjects. Receptor-based models of neurovascular coupling, including explicit pharmacological models incorporating receptor densities and affinities and data-driven models that incorporate weak biophysical constraints, have demonstrated compelling descriptions of phMRI signal induced by dopaminergic stimuli. This report describes phMRI acquisition and analysis methodologies, with an emphasis on data-driven analyses. As an example application, statistically efficient data-driven regressors were used to describe the biphasic response to the mu-opioid agonist remifentanil, and antagonism using dopaminergic and GABAergic ligands revealed modulation of the mesolimbic pathway. Results illustrate the power of phMRI as well as our incomplete understanding of mechanisms underlying the signal. Future directions are discussed for phMRI acquisitions in human studies, for evolving analysis methodologies, and for interpretative studies using the new generation of simultaneous PET/MRI scanners. This article is part of the Special Issue Section entitled ‘Neuroimaging in Neuropharmacology’.
The effect of nicotine on intestinal serotonin levels.

Total mucosal serotonin from the stomach fundus (SF), pyloric antrum (PA), mid jejunum (MJ) and ascending colon (AC) of the rat was partially depleted in vivo by a ‘smoking dose’ (100 μg/kg) of nicotine hydrogen tartrate intravenously. Maximal depletion occurred as follows: SF 43% at 15 sec, PA 41% at 20 sec, MJ 45% at 30 sec and AC 34% at 15 sec. These were highly significant (P < 0.001). Recovery was apparent in 10–30 min. Intraperitoneal nicotine gave similar results, however, due to delayed drug absorption the depleting effect occurred later (60–300 sec), was of smaller magnitude (average 30%), and was of a longer duration (20–60 min).
Force-directed geographical load balancing and scheduling for batch jobs in distributed datacenters

This work focuses on the load balancing and scheduling problem for batch jobs considering a cloud system comprised of geographically dispersed, heterogeneous datacenters. Each batch job is modeled using a directed acyclic graph of heterogeneous tasks. Load balancing and scheduling of batch jobs with loose deadlines results in operational cost reduction in the cloud system due to availability of renewable energy sources in datacenters' site and time of use dependent energy pricing in utility companies. A solution for load balancing and scheduling problem based on the force-directed scheduling approach is presented that considers the online application workload and limited resource and peak power capacity in each datacenter. The simulation results demonstrate significant operational cost decrease (up to 40%) using the proposed algorithm with respect to a greedy solution.
The demand for cheese in the United States: The role of household composition

Cheese consumption has been expanding at a time when demand for other dairy products has remained relatively constant. To examine factors affecting this demand, a Heckman sample selection model is used to obtain at-home demand function parameter estimates for several cheese varieties. Within this model, cheese adult equivalence scales (CAES) are used to quantify the relationship between age/gender distribution of household members and cheese consumption. Significant variation in cheese adult equivalent profiles was found for the cheese types analyzed.
Acute transient myositis of childhood

Six cases of acute transient myositis, mainly affecting the calf muscles in school age children, are described. Each had a viral prodromal illness usually involving the upper respiratory tract; one was recovering from varicella. Serum creatine phosphokinase was markedly elevated in all six children and most had a leucopaenia at the time of diagnosis. Recovery was spontaneous, with a simultaneous fall in creatine phosphokinase.
Theory of broadband heteronuclear decoupling in multispin systems

Abstract The Waugh theory of broadband decoupling in NMR for I-S spin - 1 2 pairs is extended to arbitrary spin systems. It is shown that complete decoupling is achieved over a certain bandwidth if the irradiation scheme generates an average Hamiltonian for the I spins whose eigenvectors and eigenvalues are independent of resonance offset. If the observed S spins are only weakly coupled, it is possible to calculate the resulting spectrum directly from the offset dependence of the average Hamiltonian of the isolated I-spin system under the influence of the periodic decoupling sequence. The treatment applies to indirectly observed multiple-quantum transitions as well as to directly observable single-quantum resonance lines.
Using the Particle Swarm Optimization Algorithm for Robotic Search Applications

This paper describes the experimental results of using the particle swarm optimization (PSO) algorithm to control a suite of robots. In our approach, each bot is one particle in the PSO; each particle/bot makes measurements, updates its own position and velocity, updates its own personal best measurement (pbest) and personal best location (if necessary), and broadcasts to the other bots if it has found a global best measurement/position. We built three bots and tested the algorithm by letting the bots find the brightest spot of light in the room. The tests show that using the PSO to control a swarm can successfully find the target, even in the presence of obstacles
Regionalized Temperature Variations in the Upper 400 km of the Earth's Mantle

Tectonically regionalized variations in the temperature of the upper 400 km of the Earth's mantle are estimated from analysis of global seismic travel-time data catalogued by the International Seismological Centre (ISC). Seismic parameter profiles are determined from estimates of P and S velocities obtained by tau inversion, and summary phase diagrams for the olivine and pyroxene- garnet subsystems are constructed in conjunction with a thermodynamic potential formulation.
Kin selection, social structure, gene flow, and the evolution of chimpanzees

Hypotheses about chimpanzee social behavior, phylogeography, and evolution were evaluated by noninvasive genotyping of free-ranging individuals from 20 African sites. Degrees of relatedness among individuals in one community were inferred from allele-sharing at eight nuclear simple sequence repeat (SSR) loci. Males are related on the order of half-siblings, and homozygosity is significantly increased at several SSR loci compared to Hardy-Weinberg expectations. These data support the kin-selection hypothesis for the evolution of cooperation among males. Sequence variation patterns at two mitochondrial loci indicate historically high long-distance gene flow and clarify the relationships among three allopatric subspecies. The unexpectedly large genetic distance between the western subspecies, Pan troglodytes verus, and the other two subspecies suggests a divergence time of about 1.58 million years. This result, if confirmed at nuclear loci and supported by eco-behavioral data, implies that P. t. verus should be elevated to full species rank.
Evolution of Geometric Sensitivity Derivatives from Computer Aided Design Models

The generation of design parameter sensitivity derivatives is required for gradient-based optimization. Such sensitivity derivatives are elusive at best when working with geometry defined within the solid modeling context of Computer-Aided Design (CAD) systems. Solid modeling CAD systems are often proprietary and always complex, thereby necessitating ad hoc procedures to infer parameter sensitivity. A new perspective is presented that makes direct use of the hierarchical associativity of CAD features to trace their evolution and thereby track design parameter sensitivity. In contrast to ad hoc methods, this method provides a more concise procedure following the model design intent and determining the sensitivity of CAD geometry directly to its respective defining parameters.
Special issue: reconciling the supply of and demand for research in the science of science and innovation policy

The articles in this special issue emerged from a joint United States/Norwegian meeting held in May 2009 in Oslo, Norway, that considered how science policy research does (or does not) support the information needs of science policy decision makers and steps that might be taken to improve such connections. The central question of the workshop was: How can scholars who study science and innovation policy contribute more effectively to the needs of policy makers facing decisions about science and innovation policy? Efforts to address these questions from a range of perspectives are found in the following five articles. Since science and innovation policy encompass an enormous diversity of issues and processes, matched by an equally numerous and diverse set of agencies and actors who conceive, advocate, and implement science and innovation policies, John Marburger III, science advisor to President George W. Bush 2001–2009, raises the question, ‘‘How Can Scholars who Study Science and Innovation Policy Contribute More Effectively to the Needs of Policy Makers Facing Decisions About Science and Innovation Policy?’’ in his introductory editorial essay, which is published posthumously. In the remaining research-oriented pieces, Magnus Gulbrandsen begins by addressing the challenges of establishing and maintaining legitimacy in hybrid organizations like research institutes that must complete in arenas where science and non-science as well public and private values collide in his article ‘‘Research institutes as hybrid organizations: central challenges to their legitimacy,’’ Barry Bozeman, Catherine P. Slade, and Paul Hirsch follow this by proposing a conceptual model that encourages more systematic analysis of social equity in science policy in their article, ‘‘Inequity in the distribution of science and technology outcomes: A conceptual model.’’ Nathaniel Logar calls into question the utility of existing theories that are meant to guide the creation of usable science and technology products from federal research projects in ‘‘Scholarly science policy models and real policy, RSD for SciSIP in US Mission Agencies.’’ Finally, Shobita Parthasarathy identifies differences in the US and European patent offices and how public interest is treated in the different processes of decision
Replication Fork Stability Is Essential for the Maintenance of Centromere Integrity in the Absence of Heterochromatin

The centromere of many eukaryotes contains highly repetitive sequences marked by methylation of histone H3K9 by Clr4(KMT1). This recruits multiple heterochromatin proteins, including Swi6 and Chp1, to form a rigid centromere and ensure accurate chromosome segregation. In the absence of heterochromatin, cells show an increased rate of recombination in the centromere, as well as chromosome loss. These defects are severely aggravated by loss of replication fork stability. Thus, heterochromatin proteins and replication fork protection mechanisms work in concert to prevent abnormal recombination, preserve centromere integrity, and ensure faithful chromosome segregation.
A radioautographic study of the state of the parental DNA in bacteriophage T2 infected cells

Bacteriophage T2 was grown in the presence of [3H]thymine, labeling its DNA, and was used to infect Escherichia coli B. The purpose of these experiments was to obtain information on the configuration of the phage DNA within the host cell. To obtain better resolution, before infection the bacteria were subjected to a low dose of ultraviolet radiation, to stimulate their growth into filaments, cells several times the length of the normal cell. A radioautographic method was used to investigate the state of the infecting DNA. The infected complexes were fixed on slides, covered with sensitive emulsion and examined microscopically after suitable exposure and development. The distribution of grains, considered to represent the position of the phage DNA, was determined at several times during the infection cycle. The results indicate that the phage DNA starts out in a compact form and gradually spreads throughout the host cell. The spread appears to begin before the onset of phage DNA synthesis and replication and is not inhibited by the presence of 5-fluorodeoxy-uridine in the medium. These results support the conjectures that an initially localized and gradually spreading phage-synthesizing pool exists which might have an effect on recombinant formation, and that the observed stabilization to 32P decay with increasing time in the latent period could be due, at least in part, to a configurational change in the DNA of the infecting phage.
Phase transitions in a driven lattice gas with repulsive interactions.

We study a lattice gas with repulsive nearest-neighbor interactions driven to steady state by an external electric field E. Using Monte Carlo techniques on a two-dimensional system, we find, in the E-T plane, a line of second-order transitions joining a line of first-order ones, at a point which is probably tricritical. From a field theoretical model, we show that the operator associated with E is naively irrelevant for critical behavior. This expectation is borne out by the Monte Carlo result \ensuremath{\beta}=(1/8.
Meta-optimizing semantic evolutionary search

A powerful heuristic allowing many optimization problems of interest to be solved quickly is to attempt decomposition – breaking problems down into smaller subproblems that may be solved independently. For example, the hierarchical Bayesian optimization algorithm (hBOA) [5] dynamically learns a problem decomposition in terms of solution parameters. The effectiveness of this approach hinges on the existence of some compact and reasonably correct decomposition in the space (of decompositions, not solutions). Difficulty arises when no such decomposition exists, or when an effective decomposition cannot be formulated directly as a model over solution parameters. In other words, how successfully an optimization algorithm can exploit neardecomposability depends on how clever an encoding has been chosen by humans to represent the problem. I posit that the characteristics of program spaces and the typically chaotic mapping from programs to outputs tend to scramble problems – even if the mapping from program outputs to fitness levels is nearly decomposable, the overall problem will not be (in terms of parameters of program spaces). MOSES (meta-optimizing semantic evolutionary search) [4] is a new estimation-of-distribution approach to program evolution. Distributions are not estimated over the entire space of programs. Rather, a novel representationbuilding procedure that exploits domain knowledge is used to dynamically select program subspaces for estimation over. This leads to a system of demes consisting of alternative representations (i.e. program subspaces) that are maintained simultaneously and managed by the overall system. The hBOA is applied to learn new programs within
Thiosulfate reductase as a chlorate reductase in Salmonella typhimurium

The contribution of thiosulfate reductase to chlorate sensitivity in Salmonella typhimurium was examined. Electrophoresed extracts of nitrate-grown cells of both the wild type and a chlC mutant were shown to contain chlorate reductase activity of the same relative mobility as a thiosulfate reductase activity which was present in the chlC mutant, but not in the wild-type grown under these conditions. A mutation is phs, which is essential for thiosulfate reductase by S. typhimurium, was shown to confer some chlorate resistance in the wild-type background and to increase the chlorate resistance obtained with a chlC mutation. Finally, thiosulfate in the anaerobic growth medium was shown to protect a chlC mutant growing in the presence of chlorate, but it did not protect the wild type. The results are consistent with a picture in which thiosulfate reductase can function as a chlorate reductase in both the wild-type and chlC backgrounds, although its capacity to reduce thiosulfate is diminished by the presence of an active nitrate reductase encoded by chlC.
The transmembrane domains of ErbB receptors do not dimerize strongly in micelles.

The epidermal growth factor receptors (erbB) constitute an important class of single pass transmembrane receptors involved in the transduction of signals important for cell proliferation and differentiation. Receptor association is a key event in the signal transduction process, but the molecular basis of this interaction is not fully understood. Previous biochemical and genetic studies have suggested that the single transmembrane helices of these receptor proteins might play a role in stabilizing the receptor complexes. To determine if the erbB transmembrane domains could provide a driving force to stabilize the receptor dimers, we carried out a thermodynamic study of these domains expressed as C-terminal fusion proteins with staphylococcal nuclease. Similar fusion constructs have been used successfully to investigate the oligomerization and association thermodynamics of a number of transmembrane sequences, including that of glycophorin A. Using SDS-PAGE analysis and sedimentation equilibrium analytical ultracentrifugation, we do not find strong, specific homo or hetero-interactions between the transmembrane domains of the erbB receptors in micellar solutions. Our results indicate that any preferential interactions between these domains in micellar solutions are extremely modest, of the order of 1 kcal mol−1 or less. We applied a thermodynamic formalism to assess the effect of weakly interacting TM segments on the behavior of a covalently attached soluble domain. In the case of the ligand-bound EGFR ectodomain, we find that restriction of the ectodomain to the micellar phase by a hydrophobic TM, even in the absence of strong specific interactions, is largely sufficient to account for the previously reported increase in dimerization affinity.
Kalirin-7 is a Key Player in the Formation of Excitatory Synapses in Hippocampal Neurons

Kalirin-7 (Kal7), a major isoform of Kalirin in the adult rodent hippocampus, is exclusively localized to the postsynaptic side of mature excitatory synapses in hippocampal neurons. Kal7 interacts with multiple PDZ domain-containing proteins through its unique PDZ binding motif. Overexpression of Kal7 increases spine density and spine size, whereas reduction of endogenous Kal7 expression by small hairpin RNA (shRNA) causes a decrease in synapse number and spine density in cultured hippocampal neurons. Hippocampal CA1 pyramidal neurons of Kal7 knockout (Kal7KO) mice show decreased spine density, spine length, synapse number, and postsynaptic density (PSD) size in their apical dendrites; are deficient in long-term potentiation (LTP); and exhibit decreased frequency of spontaneous excitatory postsynaptic current (sEPSC). Kal7 plays a key role in estrogen-mediated spine/synapse formation in hippocampal neurons. Kal7 is also an essential determinant of dendritic spine formation following chronic cocaine treatment. Kal7 plays a key role in excitatory synapse formation and function.
Injection of GTP-binding protein or cyclic GMP phosphodiesterase hyperpolarizes retinal rods

Light-induced activation of cyclic GMP phosphodiesterase (PDE) in the outer segments of vertebrate rod photoreceptors has been suggested as a step in the transduction process linking the absorption of light by rhodopsin with a hyperpolarization of the plasma membrane1–3. Activation of PDE is mediated by a ‘GTP-binding protein’ (G). As a result of interaction with a rhodopsin photoproduct (possibly metarhodopsin II380), this GTP-binding protein exchanges a previously bound GDP for a GTP4,5. This ‘GTP-charged’ protein (GGTP) is thought to activate PDE through an interaction in which an inhibitory protein is released from PDE6–8. Assays of PDE activity in vitro have demonstrated that the hydrolysis of cyclic GMP occurs within milliseconds of light onset9, which suggests that this process is rapid enough to be an intermediate step in transduction. To test this idea electrophysiologically, we have injected purified GTP-binding protein that was binding a hydrolysis-resistant analogue of GTP, guanylyl imidodiphosphate (p(NH)ppG), termed Gp(NH)ppG, as well as partially purified PDE, into toad rod outer segments while recording membrane voltage. We report here that injection of either of these biochemically active proteins induces a reversible hyperpolarization of the rod membrane, while injection of inactive proteins seems to have no effect on membrane voltage.
Morphologic features of the vectorcardiographic T loop in arteriosclerotic heart disease.

Abstract The vectorcardiographic appearance of the highly magnified T loop of 80 patients with arteriosclerotic heart disease was studied and compared with that of 20 normal subjects. The severity of the arteriosclerotic heart disease was evaluated by coronary arteriography. The following indicators were found to be characteristic of the subjects with arteriosclerotic heart disease and were considered to be abnormal: 1. 1. The T loop angle was outside the normal range in about half the cases, and was projected in a direction other than anterior, inferior and to the left in 50 per cent. 2. 2. A wide QRS-T angle was found in the frontal and horizontal planes in about half of the cases. 3. 3. A length/width ratio of 3.0 or less, considered abnormal in our study, was found in 39 per cent of the cases. 4. 4. Open T loops were found in the frontal plane in 36 per cent, in the horizontal plane in 47 per cent, and in the sagittal plane in 35 per cent. 5. 5. Terminal delay in the inscription of the T loop was considered abnormal and was noted in 41 per cent of the cases of arteriosclerotic heart disease. The rotation of the T loop and its relation to the rotation of the QRS loop appeared to have no significance in the diagnosis of arteriosclerotic heart disease.
PIE-FCCS Study of the Effects of Polycationic Macromolecules on Phosphatidylserine and Phosphatidylinositol Phosphate Lipid Mobility

The interaction between proteins and anionic lipids in the plasma membrane is a common motif in cell communication at the plasma membrane. Such interactions can gate membrane protein function and have also been proposed to sequester membrane lipids during quiescent phases of signaling. To date, however, the molecular structure and dynamics of the lipid-protein interface is poorly understood. To isolate these interactions in a biophysical assay, we have investigated the behavior of a polycationic polymer, quaternized polyvinylpyridine (QPVP), on supported lipid bilayers doped with tail-labeled phosphatidylserine (PS) or phosphatidylinositol phosphate (PIP) lipids. To measure the mobility and association of the lipid and adsorbed polymer, we use a time-resolved fluorescence technique, pulsed interleaved excitation fluorescence cross-correlation spectroscopy (PIE-FCCS). PIE-FCCS is a dual-color fluorescence spectroscopy that translates fluctuations in fluorescence signal into a measurement of diffusion and co-localization. With PIE-FCCS we have investigated the polymer adsorption-dependent translational mobility of the lipids and systematically studied the influence of lipid head-group charge and solvent ionic strength. Our results indicate that alteration of anionic lipid lateral mobility is dependent on the net charge of the lipid head group and is significantly screened by the ionic strength of the solution. At physiological salt concentration we observe that the lipid lateral mobility is nearly unaffected by mobile, adsorbed polymers and that there is no evidence of stable lipid-polymer complexes.
Herbal medicine research and global health: an ethical analysis

Governments, international agencies and corporations are increasingly investing in traditional herbal medicine research. Yet little literature addresses ethical challenges in this research. In this paper, we apply concepts in a comprehensive ethical framework for clinical research to international traditional herbal medicine research. We examine in detail three key, underappreciated dimensions of the ethical framework in which particularly difficult questions arise for international herbal medicine research: social value, scientific validity and favourable risk-benefit ratio. Significant challenges exist in determining shared concepts of social value, scientific validity and favourable risk-benefit ratio across international research collaborations. However, we argue that collaborative partnership, including democratic deliberation, offers the context and process by which many of the ethical challenges in international herbal medicine research can, and should be, resolved. By "cross-training" investigators, and investing in safety-monitoring infrastructure, the issues identified by this comprehensive framework can promote ethically sound international herbal medicine research that contributes to global health.
Clinician statements and family satisfaction with family conferences in the intensive care unit

Objectives:The quality of family-clinician communication in the intensive care unit is often inadequate, but little is known about specific clinician communication behaviors that might improve family satisfaction. In this exploratory analysis, we hypothesized that clinicians’ communication behaviors
Single logarithm effects in electron-positron annihilation

Abstract We show that the inclusion of the single logarithmic terms in the perturbative treatment of the energy-energy correlation at large collinearity angles makes the introduction of nonperturbative hadronization effects crucial to describe the experimental data at the present energies. It is unlikely that further perturbative corrections will change this result.
An analytical method for predicting plastic flow in notched fiber composite materials

An analytical system was developed for prediction of the onset and progress of plastic flow of oriented fiber composite materials in which both externally applied complex stress states and stress raisers were present. The predictive system was a unique combination of two numerical systems, the “SAAS II” finite element analysis system and a micromechanics finite element program. The SAAS II system was used to generate the three-dimensional stress distributions, which were used as the input into the finite element micromechanics program. Appropriate yielding criteria were then applied to this latter program. The accuracy of the analytical system was demonstrated by the agreement between the analytically predicted and the experimentally measured flow values of externally notched tungsten wire reinforced copper oriented fiber composites, in which the fiber fraction was 50 vol pct.
Hyperthermia-enhanced indocyanine green delivery for laser-induced thermal ablation of carcinomas

AbstractPurpose: Intravenous administration of indocyanine green (ICG) dye can effectively convert near-infrared (NIR) laser light into heat and enhance thermal injury of blood vessels; however, there is no selective uptake of ICG by the tumour compared to the other tissues, which impacts the therapeutic ratio of this strategy unless uptake can be selectively increased in tumour tissue. Here we investigated the use of local hyperthermia prior to intravenous ICG administration to enhance ICG uptake in tumour tissue, thereby enhancing laser thermal ablation of solid tumours. Methods: Murine SCK breast or SCCVII head and neck tumours were treated with a 755-nm laser light either alone or with prior intravenous administration of 4 mg/kg ICG and/or local tumour hyperthermia at 42.5 °C for 60 min. Retention of ICG was quantified using a NIR animal imaging system. Treatment effects were assessed by growth delay and histology. Results: ICG accumulation in the heated tumours was 1.23-fold greater on average compar...
A 0.8/2.4 GHz Tunable Active Band Pass Filter in InP/Si BiCMOS Technology

A tunable active band pass filter (BPF) has been designed in a chip-scale heterogeneous integration technology, which intimately integrates InP HBTs on a deep scaled CMOS technology. The BPF test chip consists of a programmable gain amplifier (PGA), a BPF core, and a buffer. The chip features a frequency tuning range from 0.8 to 2.4 GHz with 150 MHz pass band and four gain steps: 0, 6, 12, and 16 dB. The BPF core employs active-RC architecture for high linearity by leveraging the >300 GHz fT of InP HBTs and the programmability of CMOS. The test chip occupies 1.7×1.25 mm2 area including pads and draws 85/110 mA from a 3.5 V power supply for 0.8/2.4 GHz bands, respectively. In addition, it demonstrates out-of-band IIP3s of 21.97/16.87 dBm for 0.8/2.4 GHz bands at the high gain mode, which suggests the BPF core delivers 37.97/32.87 dBm out-of-band IIP3s.
Microcrack coalescence and macroscopic crack growth initiation in brittle solids

The problem studied in this paper concerns the analytical estimation of the effect of microcracking on crack growth initiation in brittle solids. Particular attention is given to the counteracting effects of toughness degradation and shielding by macrocracking. with a view to determining the range of dominance of each mechanism. Crack growth initiation by coalescence with microcracks is studied with the aid of a cohesive zone model. The extent of shielding of the crack tip by the intervening microcracks is estimated under isotropic damage conditions. A comparison of these effects reveals that, were the crack capable of growing within its plane, the toughness enhancement derived from shielding would be almost exactly counterbalanced by the reduction of toughness in the microcracked material. However, if microcrack deflection is taken into account levels of toughening consistent with experimental data are computed.
Correlation of Microbiologic Findings and 67Gallium Scans in Patients with Pulmonary Infections

Of 63 patients with proven or disproven infections in the lung, 58 (92 percent) had excellent positive or negative correlation with the lung scan obtained using radioactive 67gallium citrate. Diagnosis was established by transtracheal aspiration, thoracocentesis, needle aspiration, or biopsy of the lung. Included were 15 patients with anaerobic infections of the lung, 12 with infective endocarditis with emboli, nine with tuberculosis, six with pneumococcal infections, five with carcinoma, four with fungal infections, three with pulmonary involvement secondary to abdominal sepsis, two with pneumonia due to Mycoplasma, and seven with other diseases. The uptake of 67gallium was increased in anaerobic infections, pneumococcal pneumonia, malignant neoplasms, systemic lupus erythematosus, sarcoid, coccidioidomycosis, and septic pulmonary emboli due to endocarditis. The 67gallium scans were normal in four of nine patients with pulmonary tuberculosis. With this exception, increased uptake of 67gallium occurred in all culture-proven pulmonary infections. When infection is suspected and routine cultures are negative, increased uptake of 67gallium in the lung indicates active disease and warrants additional diagnostic procedures.
A noncentral limit theorem for quadratic forms of Gaussian stationary sequences

We examine the limit behavior of quadratic forms of stationary Gaussian sequences with long-range dependence. The matrix that characterizes the quadratic form is Toeplitz and the Fourier transform of its entries is a regularly varying function at the origin. The spectral density of the stationary sequence is also regularly varying at the origin. We show that the normalized quadratic form converges inD[0, 1] to a new type of non-Gaussian self-similar process, which can be represented as a Wiener-Ito integral onR2.
Housing Policy for Persons With Severe Mental Illness

Homelessness among persons with severe mental illness is a visible manifestation of deeply flawed public policies. This article critically assesses research to date on housing and related policies for the homeless mentally ill and recommends that future research target three strategic areas: (i) housing subsidies; (ii) landlord reluctance to rent to persons with mental illness, thereby solving one of their major problems in accessing housing; and (iii) appropriate housing and service mix for this heterogeneous population; that is, answering the longstanding threshold policy question of what housing and service mixes work best and for whom.
Variation in growth of infants with a single ventricle.

Objective The study goal was to evaluate interstage growth variation among sites participating in the National Pediatric Cardiology Quality Improvement Collaborative registry caring for infants with hypoplastic left heart syndrome and to identify nutritional practices common among sites achieving best growth outcomes. Study design This was a retrospective analysis of infants in the registry who had presented due to their superior cavopulmonary connection (SCPC) and whose surgical site had enrolled ≥4 eligible patients in the registry. The primary outcome variable was weight-for-age z-score (WAZ) change between Norwood discharge and presentation for SCPC (interstage period). Blinded, structured interviews were performed with each site regarding site-specific nutritional practices. Practices common among sites with positive interstage WAZ changes were identified. Results Sixteen centers enrolled 132 infants from December 2008 through December 2010. Median age at SCPC was 5 months (2.6-12.6), and median interstage WAZ change was −0.29 (−3.2 to 2.3). Significant variation in WAZ changes among sites was demonstrated ( P P = .002). Conclusions Considerable variation exists in interstage growth among patients receiving care at these 16 surgical sites. Standardization of interstage nutritional management with focus on best nutritional practices may lead to improved growth in this high-risk population of infants.
Aqueous two-phase system patterning of detection antibody solutions for cross-reaction-free multiplex ELISA

Accurate disease diagnosis, patient stratification and biomarker validation require the analysis of multiple biomarkers. This paper describes cross-reactivity-free multiplexing of enzyme-linked immunosorbent assays (ELISAs) using aqueous two-phase systems (ATPSs) to confine detection antibodies at specific locations in fully aqueous environments. Antibody cross-reactions are eliminated because the detection antibody solutions are co-localized only to corresponding surface-immobilized capture antibody spots. This multiplexing technique is validated using plasma samples from allogeneic bone marrow recipients. Patients with acute graft versus host disease (GVHD), a common and serious condition associated with allogeneic bone marrow transplantation, display higher mean concentrations for four multiplexed biomarkers (HGF, elafin, ST2 and TNFR1) relative to healthy donors and transplant patients without GVHD. The antibody co-localization capability of this technology is particularly useful when using inherently cross-reactive reagents such as polyclonal antibodies, although monoclonal antibody cross-reactivity can also be reduced. Because ATPS-ELISA adapts readily available antibody reagents, plate materials and detection instruments, it should be easily transferable into other research and clinical settings.
Probing carbon micropore size distribution by nucleus independent chemical shift

Abstract Accurate determination of micropore size distribution is a challenging problem especially of subnanometer-sized micropores. Here, a simple room temperature method is introduced for determining micropore size distribution of activated carbons based on 1H nuclear magnetic resonance (NMR) of adsorbed water under magic angle spinning (MAS). The observed NMR peak shift is determined by the mechanism of nucleus independent chemical shift (NICS). Density functional theory computation of NICS yields a quantitative relationship between the observed peak shift and the micropore size. This relationship provides a direct link between the 1H MAS NMR lineshape and micropore size distribution. Such NICS NMR porometry technique is shown to be useful for characterizing micropore structures of highly carbonized activated carbons.