cssi/SciSciGPT-SciSciNet huggingface dataset:
Chemical Shift and Its Uses as an Electronic Parameter in Structure-Activity Correlations

Abstract Apparent correlations are found between the N-H chemical shifts of congeneric series of compounds and the dipole moments of the molecules, such as lactams and thiolactams, cyclic ureas and thioureas. When there is a high degree of correlation, either the N-H chemical shift or the dipole moment of the molecule can be used as an electronic parameter in correlating the biological activity with the chemical structure. In a series of substituted salicylaldehydes the Hammett σ constant gives better correlation with the biological activity than the O-H chemical shift. This is probably due to the anisotropic effect of the substituent besides the electronic effect. Other factors affecting the N-H chemical shift, e.g. intramolecular hydrogen-bonding of nitrosoureas and the deshielding effect of a benzene ring, in o-phenyleneureas are also presented. In spite of the limitations, the chemical shifts of many compounds can be obtained very easily, therefore, their uses in structure-activity correlations deserv...
Glucose biosensor based on immobilization of glucose oxidase in platinum nanoparticles/graphene/chitosan nanocomposite film.

The bionanocomposite film consisting of glucose oxidase/Pt/functional graphene sheets/chitosan (GOD/Pt/FGS/chitosan) for glucose sensing is described. With the electrocatalytic synergy of FGS and Pt nanoparticles to hydrogen peroxide, a sensitive biosensor with a detection limit of 0.6M glucose was achieved. The biosensor also has good reproducibility, long-term stability and negligible interfering signals from ascorbic acid and uric acid comparing with the response to glucose. The large surface area and good electrical conductivity of graphene suggests that graphene is a potential candidate as a sensor material. The hybrid nanocomposite glucose sensor provides new opportunity for clinical diagnosis and point-of-care applications.
Renormalization in quantum mechanics.

We implement the concept of Wilson renormalization in the context of simple quantum-mechanical systems. The attractive inverse square potential leads to a $\ensuremath{\beta}$ function with a nontrivial ultraviolet stable fixed point and the Hulthen potential exhibits both ultraviolet and infrared stable fixed points. We also discuss the implementation of the Wilson scheme in the broader context of one-dimensional potential problems. The possibility of an analogue of Zamolodchikov's $C$ function in these systems is also discussed.
The impact factor: its place in Garfield's thought, in science evaluation, and in library collection management

This paper is a response to that of Vanclay, who proposes, that since the impact factor (IF) is so seriously flawed, Thomson Reuters should either correct the measure or--preferably--no longer publish it and restrict itself to journal certification. It is argued here that Vanclay's analysis is itself seriously flawed, because he appears totally ignorant of the thought structure of Eugene Garfield, IF's creator. As a result, Vanclay appears unaware of the importance of total cites and the close connection of IF with review journals, where the paradigms of science are defined. This paper's author agrees that IF is a defective measure, analyzing its defects from the perspective of the frequency theory of probability, on which modern inferential statistics is based. However, he asserts that abandoning it would be counterproductive because of its demonstrated ability--even with its defects--to identify small important journals like review journals, giving it an important role in science evaluation and library collection management.
Identification of the Actinobacillus pleuropneumoniae Leucine-Responsive Regulatory Protein and Its Involvement in the Regulation of In Vivo-Induced Genes

Actinobacillus pleuropneumoniae is a gram-negative bacterial pathogen that causes a severe hemorrhagic pneumonia in swine. We have previously shown that the limitation of branched-chain amino acids (BCAAs) is a cue that induces the expression of a subset of A. pleuropneumoniae genes identified as specifically induced during infection of the natural host animal by using an in vivo expression technology screen. Leucine-responsive regulatory protein (Lrp) is a global regulator and has been shown in Escherichia coli to regulate many genes, including genes involved in BCAA biosynthesis. We hypothesized that A. pleuropneumoniae contains a regulator similar to Lrp and that this protein is involved in the regulation of a subset of genes important during infection and recently shown to have increased expression in the absence of BCAAs. We report the identification of an A. pleuropneumoniae serotype 1 gene encoding a protein with similarity to amino acid sequence and functional domains of other reported Lrp proteins. We further show that purified A. pleuropneumoniae His6-Lrp binds in vitro to the A. pleuropneumoniae promoter regions for ilvI, antisense cps1AB, lrp, and nqr. A genetically defined A. pleuropneumoniae lrp mutant was constructed using an allelic replacement and sucrose counterselection method. Analysis of expression from the ilvI and antisense cps1AB promoters in wild-type, lrp mutant, and complemented lrp mutant strains indicated that Lrp is required for induction of expression of ilvI under BCAA limitation.
Oxide mobility enhancement due to bias sputtering in perpendicular recording media

This study addresses some consideration of oxide mobility in two types of oxide composite perpendicular media A (CoCrPt-SiO2) and B (FePt-MgO). The effects of bias sputtering on the morphology of the deposited composite film was examined. Results show that although the preferential sputtering seems different, the enhanced grain separation in the biased films is similar for the two media, which suggests that biasing is generally effective in driving the segregation. This is ascribed to an increase in Ar ion bombardment of the substrate during bias sputtering, which helps to increase mobility of the oxide molecules on the growing surface such that they reach grain boundaries.
Detecting Subgroups in Online Discussions by Modeling Positive and Negative Relations among Participants

A mixture of positive (friendly) and negative (antagonistic) relations exist among users in most social media applications. However, many such applications do not allow users to explicitly express the polarity of their interactions. As a result most research has either ignored negative links or was limited to the few domains where such relations are explicitly expressed (e.g. Epinions trust/distrust). We study text exchanged between users in online communities. We find that the polarity of the links between users can be predicted with high accuracy given the text they exchange. This allows us to build a signed network representation of discussions; where every edge has a sign: positive to denote a friendly relation, or negative to denote an antagonistic relation. We also connect our analysis to social psychology theories of balance. We show that the automatically predicted networks are consistent with those theories. Inspired by that, we present a technique for identifying subgroups in discussions by partitioning singed networks representing them.
Vertebral Augmentation After Recent Randomized Controlled Trials: A New Rise in Kyphoplasty Volumes

Abstract Purpose In 2009, the results of two randomized controlled trials refuting the effectiveness of vertebroplasty compared with sham procedures were published in a leading journal. The purpose of the present study was to evaluate the impact of these randomized trials on subsequent volume and utilization rates of vertebral augmentation (VA) in the United States. Methods Using nationwide Medicare Part B databases, Current Procedural Terminology, version 4, codes for thoracic and lumbar vertebroplasty and kyphoplasty were studied from 2006 to 2013 (codes 22520 to 22525). The total volumes of procedures were determined and utilization rates were calculated. Volumes and rates by provider specialty were also studied. Results The total volume of VA procedures peaked in 2008 at 101,807 and thereafter fell steadily to 80,940 in 2013. The utilization rates per 100,000 beneficiaries also showed a similar trend. Radiologists performed the largest number of VA procedures in 2013 (33,618 procedures [42%]), followed by orthopedic surgeons (19,886 procedures [25%]). After 2009, vertebroplasty volumes decreased sharply. Kyphoplasty volumes increased in 2011, after an initial decrease in 2010. The divergent trend in the volumes of the two procedures persisted through 2013. Conclusions After the publication of the two trials' results in 2009, vertebroplasty volumes and rates decreased sharply. However, there is an emerging trend toward performing more kyphoplasty procedures, mitigating the decrease in total volume of VA procedures. Radiologists have the strongest role in performing these procedures among all medical specialties.
Dry sliding of Cu–15 wt%Ni–8 wt%Sn bronze: Wear behaviour and microstructures

Abstract Dry sliding wear of Cu–15Ni–8Sn (in wt%) bronze against a stainless steel 440C counter surface is investigated using a pin-on-disc tester in air and flowing Ar gas. The microstructure of the debris, the worn surface and the subsurface of the pin have been characterized using X-ray diffraction, scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy dispersive spectroscopy (EDS) and X-ray photoelectron spectroscopy. The debris is found to comprise of particles of Fe 2 O 3 and CuO phases, in addition to bronze particles. EDS analysis of the debris revealed that bronze picked up Fe and Cr elements from the stainless steel while the Fe 2 O 3 particles picked up Cu, Ni and Sn elements from the pin, attesting the mechanical mixing of chemical species during the wear process. Cross-section SEM of the worn pin revealed a highly deformed subsurface layer, capped by a thin layer separating the outer surface and the deformed layer. Cross-sectional TEM investigations of the capped layer revealed it to be a set of mechanically mixed layers (MML) comprising nanograins with varying grain size and composition. SEM micrographs also revealed the formation of subsurface cracks in the vicinity of the interface between the deformed subsurface layer and the capping layer. Wear processes are discussed in the light of these microstructural observations, combined with wear rate and friction coefficient measurements.
Elemental mercury exposure: An evidence-based consensus guideline for out-of-hospital management

The objective of this guideline is to assist poison center personnel in the out-of-hospital triage and initial management of patients with suspected exposures to elemental mercury. An evidence-base...
Robust tests for the bullwhip effect in supply chains with stochastic dynamics

This paper analyzes the bullwhip effect in single-echelon supply chains driven by arbitrary customer demands and operated nondeterministically. The supply chain, with stochastic system parameters, is modeled as a Markovian jump linear system. The paper presents robust analytical conditions to diagnose the bullwhip effect and bound its magnitude. The tests are independent of the customer demand. Examples are given. Ordering policies that pass these tests, and thus avoid the bullwhip effect in random environments for arbitrary customer demands, are shown to exist. The paper also presents possible extensions to multi-echelon chains.
Investigation of current percolation characteristics in coated conductors

The IBAD and RABiTS coated conductors are investigated by variable temperature scanning laser microscopy (VTSLM). In 50 /spl mu/m scanning step images, IBAD samples appear to have more uniform current distribution than RABiTS samples, which can be related to the smaller grain sizes in IBAD. The images of IBAD samples taken with higher resolution reveal feather-like clusters with 40-150 /spl mu/m in diameter. In RABiTS, the shape and size of percolation clusters are clear and do not change between high and low resolution images, and they are estimated to be 50-150 /spl mu/m. VTSLM images prove that the current percolation in the transition region is due to the combination of the grain boundary network and the critical temperature variation. At the temperature below the critical temperature, the images of VTSLM show that the current bottleneck area causes the major local dissipation limiting I/sub c/. We also find that the dissipation areas have lower T/sub c//sup */ and high /spl delta/V/sub m/, an important characteristic shared among all the lower J/sub c//sup */ areas.
Analysis of on-chip inductance effects using a novel performance optimization methodology for distributed RLC interconnects

This work presents a new and computationally efficient performance optimization technique for distributed RLC interconnects based on a rigorous delay computation scheme. The new optimization technique has been employed to analyze the impact of line inductance on the circuit behaviour and to illustrate the implications of technology scaling on wire inductance. It is shown that reduction in the driver capacitance and output resistance with scaling makes deep submicron (DSM) designs increasingly susceptible to inductance effects. Also, the impact of inductance variations on performance has been quantified. Additionally, the impact of the wire inductance on catastrophic logic failures and IC reliability issues have been analyzed.
Design of Conical Steel Wind Turbine Towers Manufactured with Automated Spiral Welding

One of the barriers to reducing the cost of wind-generated energy is the cost of manufacturing wind turbine towers which are usually designed with conical steel shells. Such towers are currently manufactured manually at centralized plants and then transported in sections to the installation site. The necessity of transporting these sections often limits the base diameter of large tower designs, requiring an increased use of material when compared to an optimized (i.e. least-weight) design. A new manufacturing technology, based on an adaptation of spiral welding, enables on-site and automated fabrication of taller, more economical towers. On-site fabrication precludes transport-based limits that currently inhibit turbine size and automated fabrication enables production at lower cost than other methods. Spiral welding is a mature technology in the pipeline industry where resistance to internal and external pressures is the primary loading mode, however, for wind turbine towers, flexure is the primary loading mode and the design of spirally-welded tubes for this application is not fully established. Moreover, this application of spiral welding requires requires larger diameter-to-thickness ratios than are currently used in the pipeline industry. This paper examines existing design standards for slender shells and assesses their applicability to shells manufactured by spiral welding. The research considers two limit states, local buckling and fatigue, and emphasizes the differences in imperfections and weld details between traditional turbine towers and those manufactured with spiral welding.
Differential Engagement of Modules 1 and 4 of Vascular Cell Adhesion Molecule-1 (CD106) by Integrins α4β1 (CD49d/29) and αMβ2 (CD11b/18) of Eosinophils

We have studied adhesion of eosinophils to various forms of vascular cell adhesion molecule 1 (VCAM-1, CD106), an integrin counter-receptor implicated in eosinophil recruitment to the airway in asthma. Full-length 7d-VCAM-1, with seven immunoglobulin-like modules, contains integrin-binding sites in modules 1 and 4. The alternatively spliced six-module protein, 6d-VCAM-1, lacks module 4. In static assays, unactivated purified human blood eosinophils adhered similarly to recombinant soluble human 6d-VCAM-1 and 7d-VCAM-1 coated onto polystyrene microtiter wells. Further experiments, however, revealed differences in recognition of modules 1 and 4. Antibody blocking indicated that eosinophil adhesion to 6d-VCAM-1 or a VCAM-1 construct containing only modules 1–3, 1–3VCAM-1, is mediated by α4β1 (CD49d/29), whereas adhesion to a construct containing modules 4–7, 4–7VCAM-1, is mediated by bothα4β1 andαMβ2 (CD11b/18). Inhibitors of phosphoinositide 3-kinase, which block adhesion of eosinophils mediated by αMβ2, blocked adhesion to 4–7VCAM-1 but had no effect on adhesion to 6d-VCAM-1. Consistent with the antibody and pharmacological blocking experiments, eosinophilic leukemic cell lines lacking αMβ2 did not adhere to 4–7VCAM-1 but did adhere to 6d-VCAM-1 or 1–3VCAM-1. Activation of eosinophils by interleukin (IL)-5 enhanced static adhesion to 6d-VCAM-1, 7d-VCAM-1, or 4–7VCAM-1; IL-5-enhanced adhesion to all 3 constructs was blocked by anti-αMβ2. Adhesion of unstimulated eosinophils to 7d-VCAM-1 under flow conditions was inhibited by anti-α4 or anti-αM. IL-5 treatment decreased eosinophil adhesion to 7d-VCAM-1 under flow, and anti-αM had the paradoxical effect of increasing adhesion. These results demonstrate that αMβ2 modulatesα4β1-mediated eosinophil adhesion to VCAM-1 under both static and flow conditions.
SHARC: A streaming model for FPGA accelerators and its application to Saliency

Reconfigurable hardware such as FPGAs are being increasingly employed for accelerating compute-intensive applications. While recent advances in technology have increased the capacity of FPGAs, lack of standard models for developing custom accelerators creates issues with scalability and compatibility. We present SHARC — Streaming Hardware Accelerator with Run-time Configurability, for an FPGA-based accelerator. This model is at a lower-level compared to existing stream processing models and provides the hardware designer with a flexible platform for developing custom accelerators. The SHARC model provides a generic interface for each hardware module and a hierarchical structure for parallelism at multiple levels in an accelerator. It also includes a parameterization and hierarchical run-time reconfiguration framework to enable hardware reuse for flexible yet high throughput design. This model is very well suited for compute-intensive applications in areas such as real-time vision and signal processing, where stream processing provides enormous performance benefits. We present a case-study by implementing a bio-inspired Saliency-based visual attention system using the proposed model and demonstrate the benefits of run-time reconfiguration. Experimental results show about 5X speedup over an existing CPU implementation and up to 14X higher Performance-per-Watt over a relevant GPU implementation.
Use of Rapamycin Slows Progression of Cardiac Transplantation Vasculopathy

Background— Cardiac transplantation vasculopathy is the leading cause of late death in heart transplantation recipients. Rapamycin is an immunosuppressant drug with potent antiproliferative and antimigratory effects. We investigated whether rapamycin could prevent progression of graft vasculopathy in 46 patients (age, 54±10 years; 4.3±2.3 years after transplantation) with severe disease. Methods and Results— At annual cardiac catheterization, patients were randomly assigned to treatment with rapamycin (n=22) versus continued current immunosuppression (n=24). Clinical characteristics including recipient age and sex, underlying cause of congestive heart failure, donor age and sex, and ischemic time were recorded. Cardiac catheterization was graded with the use of a semiquantitative scale and repeated annually. Clinically significant adverse events were defined as death, need for angioplasty or bypass surgery, myocardial infarction, and a >25% worsening of the catheterization score. These events were monitor...
Salt-soluble elastin from lathyritic chicks

The isolation of a salt-soluble homogeneous elastin from the aortas of lathyritic chicks by chromatography on DEAE-cellulose and salt precipitation is described. These new techniques, as well as some previously published by other workers, were evaluated with the help of antiserum raised in sheep against insoluble chick elastin. The purified elastin was very basic and behaved in a predictable manner in coacervation studies. The protein migrated in sodium dodecyl sulphate–polyacrylamide gels as a single band moving slightly faster than pyruvate kinase (mol.wt. 57000).
FABRICATION OF TARGETS FOR PROTON FOCUS CONE FAST IGNITION EXPERIMENTS

The fast ignition concept is a proposed method to reach fusion by two separate processes. The task of the first process is the compression of fuel and the second is the ignition of the compressed fuel by a rapid and directed energy deposition. One delivery method of this energy can be in the form of focused proton beams and this type of fast ignition target will be discussed. The target designs consisted of gold and plastic cones with a curved proton-generating surface (aluminum) within the cone and very close to the tip. The challenges of the given target specifications led to a new cone design consisting of a cone base and cone tip made in two pieces with the proton generating surface sandwiched between. The fabrication of these targets consisted of several steps and processes that included making PAMS shell mandrels, sputter coating deposition, electroplating, precision machining, chemical etching, and target assembly.
Detecting Speculative Language Using Syntactic Dependencies and Logistic Regression

In this paper we describe our approach to the CoNLL-2010 shared task on detecting speculative language in biomedical text. We treat the detection of sentences containing uncertain information (Task1) as a token classification task since the existence or absence of cues determines the sentence label. We distinguish words that have speculative and non-speculative meaning by employing syntactic features as a proxy for their semantic content. In order to identify the scope of each cue (Task2), we learn a classifier that predicts whether each token of a sentence belongs to the scope of a given cue. The features in the classifier are based on the syntactic dependency path between the cue and the token. In both tasks, we use a Bayesian logistic regression classifier incorporating a sparsity-enforcing Laplace prior. Overall, the performance achieved is 85.21% F-score and 44.11% F-score in Task1 and Task2, respectively.
Kissing-loop interaction between 5′ and 3′ ends of tick-borne Langat virus genome ‘bridges the gap’ between mosquito- and tick-borne flaviviruses in mechanisms of viral RNA cyclization: applications for virus attenuation and vaccine development

Insertion of microRNA target sequences into the flavivirus genome results in selective tissue-specific attenuation and host-range restriction of live attenuated vaccine viruses. However, previous strategies for miRNA-targeting did not incorporate a mechanism to prevent target elimination under miRNA-mediated selective pressure, restricting their use in vaccine development. To overcome this limitation, we developed a new approach for miRNA-targeting of tick-borne flavivirus (Langat virus, LGTV) in the duplicated capsid gene region (DCGR). Genetic stability of viruses with DCGR was ensured by the presence of multiple cis-acting elements within the N-terminal capsid coding region, including the stem-loop structure (5'SL6) at the 3' end of the promoter. We found that the 5'SL6 functions as a structural scaffold for the conserved hexanucleotide motif at its tip and engages in a complementary interaction with the region present in the 3' NCR to enhance viral RNA replication. The resulting kissing-loop interaction, common in tick-borne flaviviruses, supports a single pair of cyclization elements (CYC) and functions as a homolog of the second pair of CYC that is present in the majority of mosquito-borne flaviviruses. Placing miRNA targets into the DCGR results in superior attenuation of LGTV in the CNS and does not interfere with development of protective immunity in immunized mice.
Marriage, Family, and Divorce

The family is generally considered to be the basic building block on which social order is founded. Yet, even with all the attention that social scientists and others have given it, the family remains perhaps one of the least understood institutions, especially in modern times, because “family” comes in new variations, not the least of which are families headed by homosexual couples.
Experimental transmission and pathogenesis of immunodeficiency syndrome in cats

We describe the identification, experimental transmission, and pathogenesis of a naturally occurring powerfully immunosuppressive isolate of feline leukemia virus (designated here as FeLV-FAIDS) which induces fatal acquired immunodeficiency syndrome (AIDS) in 100% (25 of 25) of persistently viremic experimentally infected specific pathogen- free (SPF) cats after predictable survival periods ranging from less than 3 months (acute immunodeficiency syndrome) to greater than one year (chronic immunodeficiency syndrome), depending on the age of the cat at time of virus exposure. The pathogenesis of FeLV-FAIDS-induced feline immunodeficiency disease is characterized by: a prodromal period of largely asymptomatic viremia; progressive weight loss, lymphoid hyperplasia associated with viral replication in lymphoid follicles, lymphoid depletion associated with extinction of viral replication in lymphoid follicles, intractable diarrhea associated with necrosis of intestinal crypt epithelium, lymphopenia, suppressed lymphocyte blastogenesis, impaired cutaneous allograft rejection, hypogammaglobulinemia, and opportunistic infections such as bacterial respiratory disease and necrotizing stomatitis. The clinical onset of immunodeficiency syndrome correlates with the replication of a specific FeLV-FAIDS viral variant, detected principally as unintegrated viral DNA, in bone marrow, lymphoid tissues, and intestine. Two of seven cats with chronic immunodeficiency disease that survived greater than 1 year after inoculation developed lymphoma affecting the marrow, intestine, spleen, and mesenteric nodes. Experimentally induced feline immunodeficiency syndrome, therefore, is a rapid and consistent in vivo model for prospective studies of the viral genetic determinants, pathogenesis, prevention, and therapy of retrovirus-induced immunodeficiency disease.
Sex-dependence of anxiety-like behavior in cannabinoid receptor 1 (Cnr1) knockout mice

Epidemiological data suggest women are at increased risk for developing anxiety and depression, although the mechanisms for this sex/gender difference remain incompletely understood. Pre-clinical studies have begun to investigate sex-dependent emotional learning and behavior in rodents, particularly as it relates to psychopathology; however, information about how gonadal hormones interact with the central nervous system is limited. We observe greater anxiety-like behavior in male mice with global knockout of the cannabinoid 1 receptor (Cnr1) compared to male, wild-type controls as measured by percent open arm entries on an elevated plus maze test. A similar increase in anxiety-like behavior, however, is not observed when comparing female Cnr1 knockouts to female wild-type subjects. Although, ovariectomy in female mice did not reverse this effect, both male and female adult mice with normative development were sensitive to Cnr1 antagonist-mediated increases in anxiety-like behavior. Together, these data support an interaction between sex, potentially mediated by gonadal hormones, and the endocannabinoid system at an early stage of development that is critical for establishing adult anxiety-like behavior.
The Priority of Attention: Intentionality for Automata

IT (intentionality) is the major stumbling block to the claim that machines could one day possess true intelligence. The question is not whether machines would be able to produce outputs indistinguishable from those of a person, as proponents of "artificial intelligence" have traditional ly maintained.1 Searle has shown, rather, that the real question is whether machines could ever be conscious of objects in the way we know ourselves to be.2 That would seem to make it, at least in part, a phenomenological problem. By means of microphenomenology, then, I shall try to show that the basic structure of IT, as detected in reflection, can be analyzed in terms of an even more primitive factor, FA (focal attention). Since attentional processes can be correlated with neurological selectivi y, it will be argued that any machine constructed to perform such processes would be capable of IT. I shall, in short, attempt to support the possibility of creating automata capable of intentional activities by trying to describe how they oc cur in ourselves.3 The term 'intentionality' has many meanings. But the sense of IT in which we ought to be interested, given the question of artificial intelligence, is the "ofness" or "aboutness" that thought processes are said to bear to their objects.4 When I reflect on such processes in myself I find them to be a "grasping" or understanding of something that somehow transcends the process. To say the object "transcends" the process is only to say it presents itself as independent of the process, not that it necessarily "exists," since it could be anything from a dream to an abstraction.5 The task before us, then, is to explain how processes of FA can both a) perform the office of rendering their contents intelligible, and b) present themselves as correlated with objects entirely distinct from those processes. I shall try to make the case that certain attentional strategies are sufficient for man or machine to accomplish both of those requisites, intelligibility and transcendence.
Effect of oral thiamine administration on thiamine content of the Stool.

SummaryThe daily oral administration of 5 mg of thiamine hydrochloride in tablet form to 12 young and 21 old individuals was followed by an increase of the fecal thiamine excretion corresponding to one—half to three—fourths of the thiamine dose given. The fecal excretion of thiamine returned to the original level after the thiamine supplementation had been discontinued.
Enzyme Architecture: Optimization of Transition State Stabilization from a Cation–Phosphodianion Pair

The side chain cation of R269 lies at the surface of l-glycerol 3-phosphate dehydrogenase (GPDH) and forms an ion pair to the phosphodianion of substrate dihydroxyacetone phosphate (DHAP), which is buried at the nonpolar protein interior. The R269A mutation of GPDH results in a 110-fold increase in Km (2.8 kcal/mol effect) and a 41 000-fold decrease in kcat (6.3 kcal/mol effect), which corresponds to a 9.1 kcal/mol destabilization of the transition state for GPDH-catalyzed reduction of DHAP by NADH. There is a 6.7 kcal/mol stabilization of the transition state for the R269A mutant GPDH-catalyzed reaction by 1.0 M guanidinium ion, and the transition state for the reaction of the substrate pieces is stabilized by an additional 2.4 kcal/mol by their covalent attachment at wildtype GPDH. These results provide strong support for the proposal that GPDH invests the 11 kcal/mol intrinsic phosphodianion binding energy of DHAP in trapping the substrate at a nonpolar active site, where strong electrostatic interacti...
A Novel Approximation to Dynamic Time Warping allows Anytime Clustering of Massive Time Series Datasets.

Given the ubiquity of time series data, the data mining community has spent significant time investigating the best time series similarity measure to use for various tasks and domains. After more than a decade of extensive efforts, there is increasing evidence that Dynamic Time Warping (DTW) is very difficult to beat. Given that, recent efforts have focused on making the intrinsically slow DTW algorithm faster. For the similarity-search task, an important subroutine in many data mining algorithms, significant progress has been made by replacing the vast majority of expensive DTW calculations with cheap-to-compute lower bound calculations. However, these lower bound based optimizations do not directly apply to clustering, and thus for some realistic problems, clustering with DTW can take days or weeks. In this work, we show that we can mitigate this untenable lethargy by casting DTW clustering as an anytime algorithm. At the heart of our algorithm is a novel data-adaptive approximation to DTW which can be quickly computed, and which produces approximations to DTW that are much better than the best currently known linear-time approximations. We demonstrate our ideas on real world problems showing that we can get virtually all the accuracy of a batch DTW clustering algorithm in a fraction of the time.
Injectable Bioglass as a Potential Substitute for Injectable Polytetrafluoroethylene

AbstractInjectable polytetrafluoroethylene (Teflon) and collagen have inherent problems that may prevent their long-term success. In search of a different injectable biomaterial we confirmed in rabbits the safety of injected Bioglass* particles suspended in sodium hyaluronate. A second study was performed testing the ability of the Bioglass suspension to increase urethral resistance in pigs. Bioglass particles in suspension have the potential to substitute for polytetrafluoroethylene or collagen in the treatment of urinary incontinence or vesicoureteral reflux.
Advances in Underwater Acoustic Networking

This chapter contains sections titled: Introduction Communication Architecture Basics of Underwater Communications Physical Layer Medium Access Control Layer Network Layer Cross-Layer Design Experimental Platforms UW-Buffalo: An Underwater Acoustic Testbed at the University at Buffalo Conclusions References
Precommitment, Cash Transfers, and Timely Arrival for Birth: Evidence from a Randomized Controlled Trial in Nairobi Kenya.

Maternal and neonatal mortality rates in the slums of Nairobi, Kenya are among the highest in the world. Mounting evidence suggests that delivering in a facility is not enough to ensure mortality reductions: women must deliver in high-quality facilities and arrive early enough for appropriate care if complications arise. We designed an RCT combining labeled cash transfers and pre-commitment incentives to encourage earlier and more effective delivery facility choice and to promote earlier facility arrival. We find that the intervention improves planning, increases delivery at the desired facility, and encourages more timely arrival at delivery facilities.
Constructing the Antiracial City: City Planning and Antiracialism in the 21st Century

This study asks: How does racism continue to shape city spaces in the 21st century marked by more subtle forms of new racism or antiracialism? This article performs a rhetorical analysis of the city of Cleveland’s urban planning documents from the early 2000s to explore how rhetorics of contemporary urban planning rely on a form of neoliberal racism or antiracialism to at once recognize race while eliding the relevance of racism in the construction of urban spaces. Three strategies—market logic, hegemonic memory, and multiculturalism—give appeal to the plan by giving voice to issues of race, diversity, and even urban inequality while filtering out the more complex issue of structural racism.
Computer Vision–Based Model for Moisture Marks Detection and Recognition in Subway Networks

AbstractMoisture marks (wet areas) are significant defects that may develop on the surfaces of subway structures as a result of water leakage through soil. The detection and assessment of moisture ...
Sprouting angiogenesis induces significant mechanical heterogeneities and ECM stiffening across length scales in fibrin hydrogels.

Abstract Matrix stiffness is a well-established instructive cue in two-dimensional cell cultures. Its roles in morphogenesis in 3-dimensional (3D) cultures, and the converse effects of cells on the mechanics of their surrounding microenvironment , have been more elusive given the absence of suitable methods to quantify stiffness on a length-scale relevant for individual cell-extracellular matrix (ECM) interactions. In this study, we applied traditional bulk rheology and laser tweezers-based active microrheology to probe mechanics across length scales during the complex multicellular process of capillary morphogenesis in 3D, and further characterized the relative contributions of neovessels and supportive stromal cells to dynamic changes in stiffness over time. Our data show local ECM stiffness was highly heterogeneous around sprouting capillaries, and the variation progressively increased with time. Both endothelial cells and stromal support cells progressively stiffened the ECM, with the changes in bulk properties dominated by the latter. Interestingly, regions with high micro-stiffness did not necessarily correlate with remodeled regions of high ECM density as shown by confocal reflectance microscopy. Collectively, these findings, especially the large spatiotemporal variations in local stiffness around cells during morphogenesis in soft 3D fibrin gels, underscore that characterizing ECM mechanics across length scales. provides an opportunity to attain a deeper mechanobiological understanding of the microenvironment's roles in cell fate and tissue patterning.
Use of argon to measure gas exchange in turbulent mountain streams

Abstract. Gas exchange is a parameter needed in stream metabolism and trace gas emissions models. One way to estimate gas exchange is via measuring the decline of added tracer gases such as sulfur hexafluoride ( SF6 ). Estimates of oxygen ( O2 ) gas exchange derived from SF6 additions require scaling via Schmidt number (Sc) ratio, but this scaling is uncertain under conditions of high gas exchange via bubbles because scaling depends on gas solubility as well as Sc. Because argon ( Ar ) and O2 have nearly identical Schmidt numbers and solubility, Ar may be a useful tracer gas for estimating stream O2 exchange. Here we compared rates of gas exchange measured via Ar and SF6 for turbulent mountain streams in Wyoming, USA. We measured Ar as the ratio of Ar : N2 using a membrane inlet mass spectrometer (MIMS). Normalizing to N2 confers higher precision than simply measuring [ Ar ] alone. We consistently enriched streams with Ar from 1 to 18 % of ambient Ar concentration and could estimate gas exchange rate using an exponential decline model. The mean ratio of gas exchange of Ar relative to SF6 was 1.8 (credible interval 1.1 to 2.5) compared to the theoretical estimate 1.35, showing that using SF6 would have underestimated exchange of Ar . Steep streams (slopes 11–12 % ) had high rates of gas exchange velocity normalized to Sc=600 ( k600 , 57–210 m d−1 ), and slope strongly predicted variation in k600 among all streams. We suggest that Ar is a useful tracer because it is easily measured, requires no scaling assumptions to estimate rates of O2 exchange, and is not an intense greenhouse gas as is SF6 . We caution that scaling from rates of either Ar or SF6 gas exchange to CO2 is uncertain due to solubility effects in conditions of bubble-mediated gas transfer.
Interaction of ICa with INa/Ca2 [Ca++]i and Ca++ binding proteins in frog atrium: a theoretical study.

The sarcoplasmic reticulum (S-R) of cells from the atrium of the bullfrog (Rana catesbeiana) is not involved in the cyclic uptake and release of calcium under normal physiological conditions. Consequently, bullfrog atrial cells provide a system in which the interactions between the “L”-type calcium current (ICa), sodium-calcium exchange current (INa/Ca) and intracellular Ca++ binding proteins (calmodulin and two different classes of Ca++ binding sites on troponin: TCa, a calcium-specific binding site thought to be responsible for phasic tension generation, and TMg, a Ca++−Mg++ competitive binding site) may be examined in isolation from complications arising from S−R uptake and release. A Hodgkin and Huxley type model1 incorporating INa/Ca and intracellular Ca++ binding sites has been used to examine the potential interactions between these different mechanisms during the cardiac action potential.
Use of Tourniquets in Mass Casualty Incidents and “Stop the Bleed” Program

The use of tourniquets, as a temporary procedure to control extremity bleeding, may be life saving. For many years, the use of tourniquets was banned from civilian prehospital protocols for management of limb hemorrhage due to concerns for complications, mainly loss of limbs. Military studies published by the Israeli, Americans, and British in the past 15 years, show that tourniquets are effective to control bleeding in the battlefield, are associated with minor complications and no limb loss. These outcomes were replicated in civilian studies as well. Recently, the advanced trauma life support (ATLS®) course introduced tourniquet use as an alternative for management of limb hemorrhage, when direct pressure fails to control bleeding. Nevertheless, in some situations when improvised tourniquets (cloths, ropes, ties) are applied by untrained bystanders, the opposite effect may occur, and the bleeding may increase. Therefore, tourniquet application should be limited to trained personnel. Untrained bystanders should be allowed to hold pressure directly on the bleeding site until trained personnel arrive. The “Stop the Bleed” training program, recently introduced by the American College of Surgeons (ACS), should increase the number of bystanders trained to control the bleeding until EMS arrives.
Developing Pediatric Patient Safety Research Priorities.

Pediatric patient safety and a focused, relevant research agenda are top priorities for both advancing the health of children and guiding health care providers and systems on impactful changes in which to invest. In 1999, the Institute of Medicine launched a national conversation on patient safety with the To Err Is Human 1 report. From this seminal point, the research agenda on patient safety has proliferated, producing evidence-based advances to address key patient safety risks, such as central-line bloodstream infections. Health care providers and systems now routinely focus on mitigating patient safety risks with these efforts, garnering attention at the bedside and up to board rooms. Despite the acceleration in activity over the past 20 years, our efforts for children have lacked a unified direction and need a meaningful and inclusive pediatric patient safety research agenda. In their article entitled “Priorities for Pediatric Patient Safety Research,” Hoffman et al2 reinvigorate this discussion and provide a foundational starting point for this national journey toward the north star of meaningfully improving pediatric safety and child health more broadly. No child should be harmed while trying … Address correspondence to Marlene R. Miller, MD, MSc, Department of Pediatrics, University Hospitals Rainbow Babies and Children’s Hospital, 11100 Euclid Ave, Horvitz Tower Room 1606, Cleveland, OH 44106. E-mail: marlene.miller{at}uhhospitals.org
17 Spinal Cord Injury

In this chapter, we review the major aspects of spinal cord injury (SCI) and recent research about the condition and its concomitants. SCI is a relatively low-incidence but high-cost injury, with lifetime costs estimated to be well above the $1 million mark, and costs increase dramatically as the severity of injury increases. In addition, the National Spinal Cord Injury Statistical Center (NSCISC, 2010) reports life expectancies for individuals with a SCI continue to increase with advances in medical care. As individuals are living longer with SCI, the cost of ongoing care has also increased, with diminishing resources to provide care for acute medical interventions, rehabilitative care, and postdischarge management. The length of stay for inpatient rehabilitation following SCI is becoming increasingly shorter; thus more demands are placed on clinicians to provide a comprehensive rehabilitation experience in a fraction of the time. For example, the typical length of stay following an SCI in 1973 was 98 days compared to 2005, when the average length of stay was 37 days (NSCISC, 2010). With increased incidence and longevity, and decreases in the available financial support for medical rehabilitation, there is a greater need to understand the behavioral and social mechanisms that influence quality of life (QoL) following SCI. As such, we consider the psychological literature that concerns adjustment, quality of life, and service delivery in SCI rehabilitation, and we conclude with an overview of intervention strategies and issues in health and public policy that affect persons with SCI. Keywords: spinal cord injury; rehabilitation; secondary complications; disability
Chapter 29 International rules and institutions for trade policy

Publisher Summary This chapter describes the basic structure of international trade agreements as they exist in practice, explores theoretically the normative consequences of actual and alternative trade agreements, and offers some theoretically-based explanation for the structure of trade agreements. International trade agreements codify attempts by countries to mutually restrain the degree of trade intervention from what might otherwise obtain. Generally, they include three basic elements: substantive obligations; permissible exceptions to those obligations; and enforcement mechanisms. Through the provisions of a trade agreement countries, therefore, typically agree to mutually restrain both their baseline levels of trade intervention and their use of special protection, with the effectiveness of these restraints determined ultimately by the strength of the enforcement mechanisms in place. The chapter describes some of the major themes that characterize the behavior of trade intervention in their presence and discusses why and in what circumstances countries might wish to enter into international trade agreements. It also reviews the literature related to the collection of rules and institutions that define an international trade agreement and explains the issues of enforcement, along with the process of multilateral and bilateral liberalization.
Safety, Efficacy, and Cost of Four-Factor Prothrombin Complex Concentrate (4F-PCC) in Patients With Factor Xa Inhibitor-Related Bleeding: A Retrospective Study

Oral factor Xa (fXa) inhibitor-related bleeding is a concerning drug safety problem. There is considerable controversy surrounding available reversal strategies. The recently approved reversal agent andexanet alfa has limited data, an unclear safety profile, and imparts a substantial financial burden. This has led to the off-label use of four-factor prothrombin complex concentrates (4F-PCC) for this indication. This study aimed to assess the safety and efficacy of 4F-PCC for the management of major bleeding related to oral fXa inhibitors. This observational, retrospective study included adult patients admitted from 2014 to 2018 who received 4F-PCC (Kcentra®) for fXa inhibitor-related major bleeding. Efficacy was assessed using criteria described by Sarode et al. Secondary outcomes included the incidence of thromboembolism, mortality, and a cost analysis comparing 4F-PCC to andexanet alfa for reversal of oral fXa inhibitors. Thirty-one patients received 4F-PCC for major bleeding associated with apixaban (55%) or rivaroxaban (45%). Intracranial hemorrhage (58%) and pericardial effusion (16%) accounted for the majority of bleeding events. Most patients received a single weight-based 4F-PCC dose of 25 units/kg (38.7%) or 50 units/kg (51.6%). Effective hemostasis was achieved in 80.6% of patients. Five patients (16%) died due to acute bleeding and no thromboembolic events were observed. Administration of 4F-PCC was effective for most patients requiring emergent reversal of anticoagulation with apixaban or rivaroxaban and was associated with a low risk of thromboembolic events. Considerable cost differences limit the use of andexanet alfa and may warrant further study of 4F-PCC for fXa inhibitor reversal.