cssi/SciSciGPT-SciSciNet huggingface dataset:
Pharmacogenetics and the Development of Personalized Approaches for Combination Therapy in Asthma

Asthma is a common, chronic disease of the airways that is treated with a combination of different therapies. The combination of LABA and ICS therapy results in a synergistic interaction that is efficacious in improving asthma symptom control; however, genetic variation has the potential to alter therapeutic efficacy. Both agents mediate complex molecular pathways consisting of gene variation that has been investigated with the analysis of candidate genes in the β2-adrenergic receptor and glucocorticoid pathway. These pharmacogenetic studies have been limited to retrospective analyses of clinical trial cohorts and a small number of prospective, genotype-stratified trials. More recently, genome-wide association studies in combination with replication in additional cohorts and in vitro cell-based models have been used to identify novel pathway-related pharmacogenetic variations. This review of the pharmacogenetics of the β2-adrenergic receptor and glucocorticoid pathways highlights the genotypic effects of variation in multiple genes from interacting pathways which may contribute to differential responses to inhaled beta agonists and glucocorticoids. As our understanding of these genetic mechanisms improves, panels of biomarkers may be developed to determine which combination therapies are the most effective with the least risk to an individual asthma patient. Before we can usher in an era of personalized medicine for asthma, it is first important to improve our ability to analyze large volumes of genetic data in large clinical trial cohorts using a combination of study designs, analytical methods, and in vitro functional studies.
Memory-based versus on-line processing : Implications for attitude strength

Three experiments tested whether the manner in which attitudes are created—through on-line or memory-based processing—can impact the resultant strength of those attitudes. In each study, participants were presented with 20 behavioral statements about a person named Marie. Whereas some participants were asked to continually evaluate Marie based upon each sentence and then report their overall evaluation (on-line processing), others were asked to focus on the sentence structure and to evaluate Marie only after they had read all the sentences (memory-based processing). Even when controlling for attitude accessibility, attitudes created through on-line processing were stronger than attitudes created through memory-based processing: Experiment 1 showed that participants in the on-line condition felt more certain of their attitudes, Experiment 2 showed that on-line attitudes were better predictors of participants’ evaluative preferences, while Experiment 3 showed that on-line attitudes manifested stronger attitude–behavioral intention correspondence.
Metabolic activation and cytotoxicity of cyclophosphamide in primary cultures of postnatal rat hepatocytes

Abstract We have developed a model of primary cultures of postnatal rat hepatocytes to characterize the metabolic activation of xenobiotics to toxic intermediates and to study the mechanism(s) by which these chemicals produce cellular injury. This model was employed to investigate the cytochrome P-450 mediated biotransformation of cyclophosphamide (CP) to cytotoxic metabolites that nonspecifically alkylate DNA and cellular proteins. The parenchymal cells were isolated by an in situ collagenase perfusion technique and cultured for 24 hr prior to drug treatment. The cultures were then exposed to CP concentrations ranging from 1 × 10 −4 M to 1 × 10 −3 M for 24 hr. Initial studies indicated minimal toxicity to non-replicating parenchymal hepatocytes maintained in ornithine-supplemented, arginine-deficient medium. The addition of arginine permitted the overgrowth of fibroblasts in the same culture system. These fibroblasts then became the target of alkylating CP metabolites produced by the par-enchymal cells. By day 3 after CP administration, cell number and total protein per dish decreased by over 40 percent. The morphology of the cultures changed dramatically because of fibroblast destruction. The cytotoxicity to dividing fibroblasts was eliminated by administering 2-diethylaminoethyl-2, 2-diphenylvalerate hydrochloride (SKF 525-A), an inhibitor of the cytochrome P-450 monooxygenase system, to the co-cultures treated with CP. The alkylating metabolites of CP produced by the parenchymal cells and released into the culture medium were quantitated by reacting aliquots of medium from CP-treated cells with 4-( p -nitrobenzyl)pyridine. These results provide both direct and indirect evidence of drug metabolism in cultured cells and suggest that this co-culture system can be utilized to evaluate the metabolic activation of xenobiotics.
Special considerations for the use of insulin in older adults.

AbstractObjective: The goal of this article is to provide guidance in prescribing insulin for older adults. Background: The prevalence of diabetes increases with age, with almost 30% of the elderly population diagnosed with this metabolic disorder. Along with the well-documented microvascular and microvascular complications of diabetes, older adults are at increased risk of numerous other complications, such as dementia, risk of falling, frailty, and incontinence. Data Synthesis: Whether designing a new insulin regimen or adjusting an existing regimen, many factors must be considered; these include advantages and disadvantages of each insulin option; adverse events, particularly hypoglycemia and increased risk of falls; and comorbid conditions. When assessing insulin options for older adults, a thorough evaluation of key features, such as the pharmacokinetics and timing of administration in relation to meals, along with cost, will assist clinicians in selecting an appropriate regimen. Hypoglycemia and ris...
Intramolecular hydride transfer and cyclization of 5-oxo-Na-tosyl-14,21 -dehydrosecodine

Abstract 5-Oxo-Na-tosyl-14,21-dehydrosecodine (8) was prepared by bromination of 6 followed by double dehydrobromination with ethyl aluminum dichloride in HMPA. When a dilute solution of 8 was heated, 10 was formed via intramolecular hydride transfer and cyclization.
The Sorghum Photoperiod Sensitivity Gene, Ma3, Encodes a Phytochrome B

The Ma3 gene is one of six genes that regulate the photoperiodic sensitivity of flowering in sorghum (Sorghum bicolor [L.] Moench). The ma3R mutation of this gene causes a phenotype that is similar to plants that are known to lack phytochrome B, and ma3 sorghum lacks a 123-KD phytochrome that predominates in light-grown plants and that is present in non-ma3 plants. A population segregating for Ma3 and ma3 was created and used to identify two randomly amplified polymorphic DNA markers linked to Ma3. These two markers were cloned and mapped in a recombinant inbred population as restriction fragment length polymorphisms. cDNA clones of PHYA and PHYC were cloned and sequenced from a cDNA library prepared from green sorghum leaves. Using a genome-walking technique, a 7941-bp partial sequence of PHYB, was determined from genomic DNA from ma3 sorghum. PHYA, PHYB, and PHYC all mapped to the same linkage group. The Ma3-linked markers mapped with PHYB more than 121 centimorgans from PHYA and PHYC. A frameshift mutation resulting in a premature stop codon was found in the PHYB sequence from ma3 sorghum. Therefore, we conclude that the Ma3 locus in sorghum is a PHYB gene that encodes a 123-kD phytochrome.
Modeling runtime enforcement with mandatory results automata

This paper presents a theory of runtime enforcement based on mechanism models called mandatory results automata (MRAs). MRAs can monitor and transform security-relevant actions and their results. The operational semantics of MRAs is simple and enables straightforward definitions of concrete MRAs. Moreover, the definitions of policies and enforcement with MRAs are simple and expressive. Putting all of these features together, we argue that MRAs make good general models of runtime mechanisms, upon which a theory of runtime enforcement can be based. We develop some enforceability theory by characterizing the policies deterministic and non-deterministic MRAs can and cannot enforce.
Intracellular Delivery of Quantum Dot−Protein Cargos Mediated by Cell Penetrating Peptides

We utilize cell penetrating peptide functionalized QDs as specific vectors for the intracellular delivery of model fluorescent protein cargos. Multiple copies of two structurally diverse fluorescent proteins, the 27 kDa monomeric yellow fluorescent protein and the 240 kDa multichromophore b-phycoerythrin complex, were attached to QDs using either metal-affinity driven self-assembly or biotin-Streptavidin binding, respectively. Cellular uptake of these complexes was found to depend on the additional presence of cell-penetrating peptides within the QD-protein conjugates. Once inside the cells, the QD conjugates were mostly distributed within endolysosomal compartments, indicating that intracellular delivery of both QD assemblies was primarily driven by endocytotic uptake. Cellular microinjection of QD-fluorescent protein assemblies was also utilized as an alternate delivery strategy that could bypass the endocytic pathway. Simultaneous signals from both the QDs and the fluorescent proteins allowed verification of their colocalization and conjugate integrity upon delivery inside live cells. Due to their intrinsic fluorescence properties, this class of proteins provides a unique tool to test the ability of QDs functionalized with cell penetrating peptides to mediate the intracellular delivery of both small and large size protein cargos. Use of QD-peptide/fluorescent protein vectors may make powerful tools for understanding the mechanisms of nanoparticle-mediated drug delivery.
Limited versus severe Wegener's granulomatosis: baseline data on patients in the Wegener's granulomatosis etanercept trial.

Objective To report baseline data on 180 patients with Wegener's granulomatosis (WG) enrolled in the WG Etanercept Trial (WGET), and to examine demographic and clinical differences between patients with limited disease and those with severe disease. Methods Definitions of limited and severe disease were agreed upon by consensus of the investigators at a pretrial meeting and were incorporated into the protocol as a stratification criterion. These data were applied prospectively to the WGET patient cohort, based on clinical features and the intention to treat patients according to disease activity. Data related to disease onset, date of diagnosis, clinical features, antineutrophil cytoplasmic antibody assays, tissue biopsy findings, and other medical history were collected on a baseline medical history form. Physician-investigators from each center participated in the development of this form, and all were certified in its use prior to the start of the trial. Selected data on patients who were screened for the trial but were not enrolled were also collected. Results Several significant differences between the limited and severe disease subsets were observed. Patients with limited disease were nearly a decade younger at disease onset compared with patients with severe disease. Thirty-three percent of patients with severe disease were women, compared with 58% of those with limited disease. Despite their younger age at symptom onset, patients with limited disease tended to have longer disease duration, a greater likelihood of experiencing exacerbation of previous disease following a period of remission, and a higher prevalence of destructive upper respiratory tract disorders at the time of enrollment (e.g., saddle-nose deformity). Patients with limited WG were less likely than those with severe disease to have antibodies to either proteinase 3 or myeloperoxidase. Patients with severe disease had a higher likelihood of previous thyroid disease, particularly either Graves' disease or Hashimoto thyroiditis, suggesting the possibility of different pathogenetic factors within these disease subsets. Other observed differences between these subsets, such as the greater frequency of alveolar hemorrhage in the severe disease group, were related to the a priori definitions of limited and severe disease. Conclusion There are significant differences between patients with limited WG and those with severe WG with regard to sex, age, the likelihood of recurrent disease, the risk of damage in certain organ systems, and, possibly, etiologic factors. These differences (and perhaps other differences that are currently unrecognized) in patient subsets may have implications for mechanisms of pathogenesis, prognosis, response to treatment, and the design of future clinical investigations.
Use of hyperspectral remote sensing for detection and monitoring of chemical and biological agents: a survey

This paper surveys the potential use of hyperspectral imaging technology for standoff detection of chemical and biological agents in terrorism defense applications. In particular it focuses on the uses of hyperspectral imaging technology to detect and monitor chemical and biological attacks. In so doing it examines current technologies, their advantages and disadvantages, and investigates the possible role of hyperspectral imaging for homeland security applications. The study also addresses and provides applicable solutions for several of the potential challenges that currently create barriers to the full use of hyperspectral technology in the standoff detection of likely available chemical and biological agents.
Adoptive Transfer of Ex Vivo HO-1 Modified Bone Marrow–derived Macrophages Prevents Liver Ischemia and Reperfusion Injury

Macrophages play a critical role in the pathophysiology of liver ischemia and reperfusion (IR) injury (IRI). However, macrophages that overexpress antioxidant heme oxygenase-1 (HO-1) may exert profound anti-inflammatory functions. This study explores the cytoprotective effects and mechanisms of ex vivo modified HO-1-expressing bone marrow–derived macrophages (BMDMs) in well-defined mouse model of liver warm ischemia followed by reperfusion. Adoptive transfer of Ad-HO-1-transduced macrophages prevented IR-induced hepatocellular damage, as evidenced by depressed serum glutamic-oxaloacetic transaminase (sGOT) levels and preserved liver histology (Suzuki scores), compared to Ad-β-gal controls. This beneficial effect was reversed following concomitant treatment with HO-1 siRNA. Ad-HO-1-transfected macrophages significantly decreased local neutrophil accumulation, TNF-α/IL-1β, IFN-γ/E-selectin, and IP-10/MCP-1 expression, caspase-3 activity, and the frequency of apoptotic cells, as compared with controls. Unlike in controls, Ad-HO-1-transfected macrophages markedly increased hepatic expression of antiapoptotic Bcl-2/Bcl-xl and depressed caspase-3 activity. These results establish the precedent for a novel investigative tool and provide the rationale for a clinically attractive new strategy in which native macrophages can be transfected ex vivo with cytoprotective HO-1 and then infused, if needed, to prospective recipients exposed to hepatic IR–mediated local inflammation, such as during liver transplantation, resection, or trauma.
Optimization of heat exchanger designs in metal hydride based hydrogen storage systems

Abstract Design of the heat exchanger in a metal hydride based hydrogen storage system influences the storage capacity, gravimetric hydrogen storage density, and refueling time for automotive on-board hydrogen storage systems. The choice of a storage bed design incorporating the heat exchanger and the corresponding geometrical design parameters is not obvious. A systematic study is presented to optimize the heat exchanger design using computational fluid dynamics (CFD) modeling. Three different shell and tube heat exchanger designs are chosen. In the first design, metal hydride is present in the shell and heat transfer fluid flows through straight parallel cooling tubes placed inside the bed. The cooling tubes are interconnected by conducting fins. In the second design, heat transfer fluid flows through helical tubes in the bed. The helical tube design permits use of a specific maximum distance between the metal hydride and the coolant for removing heat during refueling. In the third design, the metal hydride is present in the tubes and the fluid flows through the shell. An automated tool is generated using COMSOL-MATLAB integration to arrive at the optimal geometric parameters for each design type. Using sodium alanate as the reference storage material, the relative merits of each design are analyzed and a comparison of the gravimetric and volumetric hydrogen storage densities for the three designs is presented.
The robot management system: a framework for conducting human-robot interaction studies through crowdsourcing

Human-Robot Interaction (HRI) is a rapidly expanding field of study that focuses on allowing non-roboticist users to naturally and effectively interact with robots. The importance of conducting extensive user studies has become a fundamental component of HRI research; however, due to the nature of robotics research, such studies often become expensive, time consuming, and limited to constrained demographics. In this work, we present the Robot Management System (RMS), a novel framework for bringing robotic experiments to the web. We present a detailed description of our open-source system and describe an initial trial of the RMS as a means of conducting user studies. Using a series of navigation and manipulation tasks with a PR2 robot, we compare three user study conditions: users that are co-present with the robot, users that are recruited to the university laboratory but control the robot from a different room, and remote web-based users. Our findings show little statistical differences between usability patterns across these groups, validating the use of web-based crowdsourcing techniques for certain types of HRI evaluations.
Structural evidence for dikes beneath silicic domes, Medicine Lake Highland Volcano, California

Three types of structural geologic evidence have been used to determine the geometry of conduits that supplied magma to rhyolite flows and domes. For the Medicine Lake Highland Volcano, vent alignments, ground-crack geometry, and the distribution of flow banding, surface fracture patterns, and remelted zones on dome surfaces help us to conclude that dikes rather than pipe-like conduits fed these 1,100-yr-old extrusions. Solidified remains of the tops of some of these dikes may be as shallow as 30 m below the surface. Conduit geometry is an important factor in understanding and forecasting silicic eruptions and in siting geothermal wells.
Preexposure to ozone blocks the antigen‐induced late asthmatic response of the canine peripheral airways

The influence of exposure of the airways to ozone on acute allergic responsiveness has been investigated in several species. Little is known, however, about the effect of this environmental pollutant on the late asthmatic response (LAR) in animals in which it is exhibited. The purpose of this study was to evaluate this effect in the canine peripheral airways and to assess the potential role of mast cells in modulating the effect. A series of experiments on seven mongrel dogs demonstrated that the numbers of mast cells at the base of the epithelial region of small subsegmental airways exposed to 1 ppm ozone for 5 min were significantly (p less than .01) increased 3 h following exposure compared to air exposed or nonexposed control airways. In a second series of experiments performed on eight additional mongrel dogs with inherent sensitivity to Ascaris suum antigen, antigen aerosol was administered to the sublobar segment 3 h following ozone preexposure when mast cell numbers were presumed to be increased. These experiments were performed to determine whether ozone preexposure could enhance the late-phase response to antigen by virtue of acutely increasing the number of mast cells available to bind the antigen. Four of the eight dogs tested displayed a late-phase response to antigen following air-sham preexposure. In these four dogs, simultaneous ozone preexposure of a contralateral lobe completely blocked the late-phase response to antigen. These results indicate that the consequences of a single exposure to ozone persist beyond its effects on acute antigen-induced bronchoconstriction and extend to the complex processes involved with the late response. This attenuating effect of ozone is seen under conditions where mast-cell numbers in the airways are increased above baseline levels.
Uptake and bioconversion of stereoisomeric dipeptide prodrugs of ganciclovir by nanoparticulate carriers in corneal epithelial cells.

AbstractPurpose: The objective of this study is to investigate cellular uptake of prodrug-loaded nanoparticle (NP). Another objective is to study bioconversion of stereoisomeric dipeptide prodrugs of ganciclovir (GCV) including L-Val-L-Val-GCV (LLGCV), L-Val-D-Val-GCV (LDGCV) and d-Val-l-Val-GCV (DLGCV) in human corneal epithelial cell (HCEC) model.Methods: Poly(D,L-lactic-co-glycolic acid) (PLGA) NP encapsulating prodrugs of GCV were formulated under a double emulsion method. Fluorescein isothiocyanate isomer–PLGA conjugates were synthesized to fabricate biocompatible fluorescent PLGA NP. Intracellular uptake of FITC-labeled NP was visualized by a fluorescent microscope in HCEC cells.Results: Fluorescent PLGA NP and non-fluorescent NP display similar hydrodynamic diameter in the range of 115–145 nm with a narrow particle size distribution and zeta potentials around −13 mV. Both NP types showed identical intracellular accumulation in HCEC cells. Maximum uptake (around 60%) was noted at 3 h for NP. Cellula...
Elastic π± + 3He scattering

Abstract Differential cross sections have been measured at θ ≈20–120° at 50, 100 and 200 MeV. Salient features of the angular distributions are Coulomb interference effects at 50 MeV and clear spin-flip contributions to π − compared to π + scattering in the angular region of θ ≈80° dominated by the πN p-wave minimum. Comparison with optical model calculations account for the data up to 200 MeV while this first-order scattering theory misses conspicuous features of data at 295 MeV.
Serum lipid profiles in major depression with clinical subtypes, suicide attempts and episodes

Abstract Background We tried to report the data between serum lipid profiles and major depression with different clinical subtypes, with or without suicide attempts, and with single episode or recurrent episodes. Method During a 2-year period, a total of 168 participants (109 patients with major depression and 59 subjects in a healthy control group) were recruited in this study. Blood samples for serum lipid profiles in all participants were collected. Data analysis was performed by using an analysis of covariance (ANCOVA) with body mass index (BMI) adjustment. Results The data showed that there were no significant differences of any kind in serum lipid profiles between depressive patients with melancholic feature or atypical feature, with or without suicide attempts nor between depressive patients with single episode or recurrent episodes. Conclusion The results suggested there were no serum lipid profiles used as biological markers to distinguish the clinical subtypes, suicide attempts and episodes in patients with major depression.
The case for ratio dependence in trophic ecology

It can be argued that predation is the fundamental process of ecology. It follows that ecologists must understand how the predation rate depends on the populations involved, of both predator and prey, to understand the behavior of food webs. The theme of this book is that this dependence has been largely misunderstood, with consequences for ecological theory and its applications. In particular, in most current predator–prey and food web models, the per capita predation rate, or predator functional response, is assumed to be a function of prey density alone, and is thus termed prey-dependent (PD).
Factors affecting speech discrimination test difficulty.

Changes in item and overall test difficulty of speech discrimination and intelligibility tests were examined as a function of: carrier phrase, talker, reutterances by a talker, and level of accompa...
Functional analysis of untreated and reconstucted posterior cruciate ligament injuries

Twenty patients with old ruptures of the PCL were analyzed. Ten patients were untreated, and ten patients had reconstruction of the PCL with the medial head of the gastrocnemius. The patients' gait was analyzed using high speed photography, footswitches, electromyography, and force plate. Patients were studied while walking, running, and stair-climbing. A Cybex muscle strength evaluation was also performed. Clinically, all patients had moderate to severe posterior instability. Five of the 20 patients also had posterolateral instability. Cybex testing showed quadriceps deficits in both reconstructed and untreated groups when comparing involved and uninvolved limbs. The reconstructed group also had deficits on hamstring Cybex testing. Footswitch data showed only minimal abnormalities. Gait velocity of walking was 91% of normal with a normal cadence. There was no significant difference in the single limb support times between the involved and uninvolved limbs in walking, fast walking, or running. The photometric data showed a tendency for increased knee flexion during the midstance phase of the gait cycle in comparing involved and uninvolved limbs. The knee flexion angles during midstance were similar in the patients with posterior instability when compared to the patients with the additional posterolateral instability. Force plate data showed decreased foot-floor reaction in the untreated group during terminal stance while walking. Similar findings were found in the reconstructed group during running.(ABSTRACT TRUNCATED AT 250 WORDS)
The magnetic phase diagram of amorphous FexPd82−xSi18, 2⩽x⩽25

Abstract The magnetic phase diagram of the metallic glasses Fe x Pd 82− x Si 18 , 2⩽ x ⩽25, is presented. Transitions from spin glass to weak ferromagnetism with composition and temperature are associated with the composition dependent heterogeneity of the rapidly quenched materials.
Sex steroids increase cholesterol 7α-hydroxylase mRNA in nonhuman primates

Abstract One mechanism that may account for our prior observation that oral contraceptives decrease the hepatic cholesterol concentration independently of the low-density lipoprotein (LDL) receptor in sexually intact nonhuman primates is that sex hormones increase biliary cholesterol secretion by increasing hepatic mRNA abundance for cholesterol 7α-hydroxylase, the rate-limiting enzyme in the conversion of cholesterol into bile acids. To examine the independent effect of estrogen, progestin, and combined estrogen and progestin on the hepatic cholesterol concentration and cholesterol 7α-hydroxylase mRNA abundance, 34 ovariectomized adult female cynomolgus monkeys were fed a moderately atherogenic diet for 12 weeks with either oral conjugated equine estrogen ([CEE] n = 8), medroxyprogesterone acetate ([MPA] n = 9), or combined CEE + MPA (n = 9) and compared with a control group (n = 8) that did not receive exogenous sex hormones. After 12 weeks, hepatic cholesterol was significantly lower in CEE-treated (6.2 ± 1.2 mg/g liver) and CEE + MPA-treated (6.4 ± 0.9 mg/g liver) animals compared with the control (12.6 ± 1.9 mg/g liver) and MPA-treated (14.6 ± 1.6 mg/g liver) groups. Hepatic cholesterol 7α-hydroxylase mRNA abundance was significantly increased in CEE-treated (0.553 ± 0.08 pg/μg RNA), MPA-treated (0.734 ± 0.12 pg/μg RNA), and CEE + MPA-treated (0.487 ± 0.07 pg/μg RNA) animals compared with the controls (0.318 ± 0.03 pg/μg RNA). There was no significant difference in the plasma LDL cholesterol concentration and hepatic LDL receptor mRNA abundance between the groups. These data support but do not prove the hypothesis that low-dose oral estrogen induces an increase in cholesterol 7α-hydroxylase mRNA abundance, which is correlated with biliary cholesterol secretion and may result in depletion of hepatic cholesterol.
2,6-Dichlorophenol, the sex pheromone of the Rocky Mountain wood tick,Dermacentor andersoni Stiles and the American dog tick,Dermacentor variabilis (Say)

2,6-Dichlorophenol is the only active sex attractant component detected in the extracts of the Rocky Mountain wood tick,Dermacentor andersoni Stiles and the American dog tick,Dermacentor variabilis (Say). It elicits from the male of each species a hierarchy of responses culminating in copulation. This compound probably occurs generally throughout the metastriate Ixodidae. 2,6-Dibromophenol, an artifact, also elicits the same sexual responses from the wood tick, but phenol andp-cresol do not.
Voltage assisted perpendicular write head

A novel perpendicular write head design is proposed. In this design, an active stress is applied in synchronization with the write current waveform by applying voltage across electrostrictive material adjacent to the head yoke and pole tip. With sufficient stress magnitude, a planar magnetic anisotropy can be induced perpendicular to the head air-bearing surface via the natural magnetostrictive effect in high moment magnetic materials. The dynamically induced magnetic anisotropy, synchronized to the write current transition, can significantly enhance the write efficiency and, more importantly, improve cross-track write field gradient and ensure zero head remanence.
Minerals and Precious Stones of Brazil by Carlos Cornejo and Andrea Bartonrelli. Solaris Cultural Publications, São Paulo, Brazil. 2010; 704 pages; $120 (hardbound)

This interesting and beautifully illustrated book is long overdue, filling the previous gaping void represented by the lack of a comprehensive English-language work on the collector minerals and ge...
Focus groups as a human dimensions research tool: Three illustrations of their use

Through a discussion of our experiences with focus groups in Michigan, we illustrate the application of focus groups in human dimensions research. Focus groups aided in hypothesis generation and de...
Dwell Time And Maximum Likelihood Analysis Of Single Molecule Disulfide Bond Reduction Events While Under A Stretching Force

We study the effects of force on the enzymatic disulfide bond reduction by human thioredoxin (hTRX) in an engineered polyprotein with precise number of disulfide bonds. Single polyprotein molecules are stretched by a cantilever of the Atomic Force Microscope (AFM) in the force-clamp (FC-AFM) mode. Each single disulfide reduction is accurately detected from stepwise increases in the molecule's length vs time (FC traces). Previous FC-AFM studies with E. Coli thioredoxin have proposed two simultaneously occurring disulfide reduction mechanisms producing the overall reduction rate to decrease and then increase with increasing pulling force. In contrast, for the human thioredoxin (hTRX) the overall reduction rate only decreases with a pulling force up to a plateau at forces larger than 300 pN. Here, at each clamping force (100 pN - 400 pN) we collect a large number (> 500 events) of long (>50 s) FC traces. We analyze the data by exponential fits to the ensemble of FC traces and logarithmic histograms of the times elapsed to the actual reduction events (dwell times). Our results demonstrate two force decelerated reduction pathways in 100 pN - 200 pN merging into one apparent pathway in 300 pN - 400 pN. The faster pathway is strongly force dependant and predominates at low forces. The latter one is slower and very weakly force dependant. Next, we apply the maximum likelihood methods (MLM) to fit the FC dwell-time sequences. The MLM confirms the presence of two independent reaction pathways in the whole set of investigated forces. We attribute the faster pathway to a Michaelis-Menten type mechanism with a force-dependant catalytic step. We speculate that the mostly force-independent pathway may represent an electron-tunneling mechanism of reduction.
Chromosome preparations of bone marrow cells without prior in vitro culture or in vivo colchicine administration.

Bone marrow (about 0.5 ml) from au erythropoietic region is freed of blood clots by washing 1-3 min in 1 μg/ml colchicine solution (2-3 ml) and then soaking 1-2 hr at 20-30° C in a second change. For mammalian or avian marrows, the colchicine is made up in phosphate-buffered (pH 7) physiological NaCl solution; for amphibian, Ringer's A solution. Next the specimens are soaked about 20 min in a hypotonic solution as follows: for mammalian, 1% Na-citrate; for avian, a 1:4 dilution of the buffered NaCl solution by distilled water; and for amphibian, Ringer's A-distilled water, 1:1. Then they are heated in a mixture of 2% orcein in 45% acetic acid and 1 N HCl, 9:1. Immediately after heating, squash preparations are made with 2% acetic-orcein in the usual manner. An alternative method is to dissociate the marrow cells by agitating after colchicine treatment. Then, recovering the cells between changes by low-speed centrifugation, to carry out the hypotonic treatment and subsequent fixation in Carnoy's solution I...
Hepatic blood flow in the moderately hypothermic state.

Summary Direct total hepatic blood flow measurements were made in near-normothermic and moderately hypothermic dogs. At an average body temperature of 29.3° C., the mean flow was 27.5 cc./kg./min., as compared with a mean flow of 40.9 cc./kg./min. at a temperature of 36.6°C. Utilizing other data from this laboratory, it is evident that with moderate body hypothermia total hepatic flow decreases proportionately less than do cardiac output and hepatic arterial flow.
Putting together a scientific team: collaborative science.

One of the most enjoyable parts of a science career is collaborative team experiences and developing life-long social networks. When the hypothesis being tested requires innovative efforts greater than any single laboratory, collaboration becomes an essential component for success – everyone is a stakeholder and trust is the driving force.
Temporal pattern of regional left ventricular wall motion in patients with segmental early relaxation

The purpose of this investigation was to describe the temporal pattern of regional left ventricular (LV) wall motion in patients with segmental early relaxation (SER). Segmental early relaxation was demonstrated angiographically in seven patients undergoing diagnostic cardiac catheterization because of chest pain. In all patients, early relaxation of only the anterolateral wall was observed. The temporal pattern of regional wall motion was assessed from ventriculograms, obtained in the right anterior oblique projection, by measuring the lengths of the anterolateral minor axis chord and the corresponding diaphragmatic minor axis chord. The onset of lengthening of the anterolateral chord preceded that of the diaphragmatic chord by 110 ± 10 msec. Maximal shortening of the anterolateral chord during systole was 43 ± 4% and was coincident with a 32 ± 4% shortening of the diaphragmatic chord. During early relaxation, shortening of the anterolateral chord diminished to 17 ± 4% (P <.01); and was coincident with a 35 ± 4% shortening of the diaphragmatic chord (P <.05). Early relaxation of the anterolateral wall was followed by a transient augmentation of shortening of the anterolateral chord to 29 ± 3% (P <.001), whereas shortening of the diaphragmatic chord diminished to 32 ± 4%. Subsequently both chords returned to their initial end-diastolic lengths. These preliminary observations indicate that early lengthening of the anterolateral segment is followed by a transient rebound of shortening which was only present in the segment that manifested early relaxation.
Super obese 33-week parturient undergoing an urgent laparoscopic bowel resection: A case report and review of anesthetic implications

Approximately two percent of women undergo non-obstetric surgery during their pregnancies. The following case report describes the anesthetic management of a super obese parturient in her third trimester of pregnancy undergoing urgent laparoscopic (converted to open) bowel resection. Such a case, which has not been previously reported, has multiple clinical implications for both mother and fetus and was further complicated by super obesity (BMI>50) and laparoscopy. The anesthetic implications for this patient population are reviewed.
Plasma concentrations and electrocardiographic alterations after repetitive administration of propoxyphene to dogs

Abstract Propoxyphene hydrochloride was administered orally to four dogs every 8 hr for 19 days. Initial doses of 20 mg/kg were increased to 60 mg/kg in 5 to 15 mg/kg increments every 3 to 4 days. At the conclusion of the experiments animals were ambulatory although signs of toxicity including anorexia, sedation, tremors, and emesis were noted periodically throughout the study. Slight elevations in alkaline phosphatase and serum glutamate pyruvate transaminase values were also observed. Plasma concentrations of propoxyphene (P) (2.3±0.5 μg/ml) and norpropoxyphene (NP) (18.4±4.7 μg/ml), its major metabolite, were markedly elevated over those observed with a single near-lethal dose administered to naive dogs (P, 0.83 μg/ml; NP, 2.56 μg/ml). Tissue concentrations of P and NP were in excess of plasma concentrations showing marked tissue accumulation of both compounds. Electrocardiograms (ECG) showed an increase in PR interval after the first dose of propoxyphene. Doses from 20 to 45 mg/kg produced no further lengthening of the PR interval. Only when dogs were receiving 60 mg/kg (three times daily) were further changes in this interval observed, along with alterations in the QRS complex and T wave portions of the ECG. The average heart rate of these dogs was not significantly altered during the course of the study. At necropsy, mild superficial focal erosions in the mucosa of the stomach and upper small intestine were noted. No other histological changes were observed. These results demonstrated that in the dog, high plasma and tissue concentrations of P and NP can occur without causing significant toxic or lethal effects.
A decentralized ID algorithm for detecting slow-fast oscillations in power systems from overwhelming volumes of phasor data

As the number of sensors, namely Phasor Measurement Units or PMUs, in the US power transmission grid scales up into the thousands within the next few years, the current state-of-the-art centralized data processing architecture will no longer be sustainable, and decentralized algorithms must be developed instead. In this paper we propose such an algorithm for one of the most critical applications in power system monitoring- namely, modal decomposition of swing dynamics for detecting slow and fast oscillation modes in the system with evaluation of their respective damping factors. Given a multiple set of coherent generation clusters in the system, we first use data from all PMU sources to calculate the oscillatory modes, their damping and participation in a centralized fashion. Next, we categorize the PMUs into several disjoint sets, and use the data from each of these sets to evaluate the modal frequencies for the entire system individually, assuming that the network has a connected topology guaranteeing system observability. A global estimate for any specific eigenvalue of interest is then computed from the geometric mean of those obtained from the disjoint estimation, and analytical expressions are derived to indicate how this geometric mean, representing the ‘fused distributed solution’ compares to the centralized solution. A discussion on how the output nodes in the network should be chosen appropriately contingent on the topological structure of the network, in order to minimize the error between the two estimates is also presented. We illustrate our results with prototype power system network models inspired by two well-known transfer paths in the US west coast grid.
Islet Cell Antibody-Positive Relatives with Human Leukocyte Antigen DQA110102, DQB110602: Identification by the Diabetes Prevention Trial-Type 11

The presence of human leukocyte antigen (HLA) haplotype DQA1*0102, DQB1*0602 is associated with protection from type 1 diabetes. The Diabetes Prevention Trial-type 1 has identified 100 islet cell antibody (ICA)-positive relatives with this protective haplotype, far exceeding the number of such subjects reported in other studies worldwide. Comparisons between ICA+ relatives with and without DQB1*0602 demonstrated no differences in gender or age; however, among racial groups, African-American ICA+ relatives were more likely to carry this haplotype than others. The ICA+ DQB1*0602 individuals were less likely to have additional risk factors for diabetes [insulin autoantibody (IAA) positive or low first phase insulin release (FPIR)] than ICA+ relatives without DQB1*0602. However, 29% of the ICA+ DQB1*0602 relatives did have IAA or low FPIR. Although half of the ICA+ DQB1*0602 relatives had a high risk second haplotype, this was not associated with the additional risk factors for diabetes. Hispanic ICA+ individ...
Saturation Kinetics of Acetic Acid Transport through Perfluorosulfonated Ion-Exchange Membranes

Abstract Permeation of acetic acid through perfluorosulfonated polymeric membranes exhibit Michaelis-Menten-type saturation kinetics characterized by a maximum flux for permeating species. It is postulated that the saturation kinetics is probably a result of the solubility of acetic acid reaching a maximum limit in the membrane.
The challenge of measurement science, part 2 [President's perspectives]

In this paper the challenges on measurement science are discussed, new technologies, such as the internet, gaming, and the smart grid, can be more exciting than measurement science to the latest generation of students, academics, and practitioners. The science of measurement has been thoroughly investigated over the past two hundred years, which might breed complacency and potentially contempt. No series of failures or catastrophes have occurred that can be attributed to issues within measurement science.
SILENCE AND MEMORY IN CRIMINOLOGY—THE AMERICAN SOCIETY OF CRIMINOLOGY 2009 SUTHERLAND ADDRESS*

Two recent American Society of Criminology presidential addresses have identified as a key problem the fact that criminology lacks a history. In this address, I ask why criminology (in contrast to closely related fields) has generated so few studies of its past; I also identify some results of this failure and discuss why intellectual fields need a sense of their origins and development. History molds individual and collective identities; it lays a foundation for sociologies of knowledge; it encourages reflexivity, teaches us where our ideas came from, and gives us a sense of where we are going. To encourage historical work, I propose an overall framework for understanding the evolution of criminology, reaching back to the late eighteenth century and continuing into the present. My overall framework is that of scientific modernism, within which I identify the following three primary phases: exploratory modernism, confident modernism, and agonistic modernism. In conclusion, I suggest ways to stimulate histories of science in the field of criminology.
Numerical Study of Aerodynamic Performance of Film Cooling With Backward Injection Holes

Film cooling has been successfully used in cooling gas turbine components that are exposed to very high temperature environments. One main disadvantage of using film cooling is the aerodynamic losses associated. To address to the needs of obtaining uniform cooling in the downstream regions, backward injection of coolant has proved to be effective. However, there is a need to understand the aerodynamic behaviors of jet and mainstream flows in order to design effective configurations with this scheme of injecting coolant. In this work, the underlying aerodynamic principles of backward injection are studied numerically. All simulations are conducted with Fluent, a commercial CFD software. Results show that the classical counter rotating vortex found in simple cylindrical holes are not seen in the case of backward injections. Backward injection results in reduced coolant requirements and elimination of complex hole designs to avoid jet lift-off.Copyright © 2013 by ASME
Writing as a Linguistic Problem.

This article presents a psycholinguistic view of writing that focuses on the processes of translating concepts into sentences. The current research emphasis on planning is discussed in terms of its theoretical roots in artificial intelligence models of planning and the limited applicability of such models for writing. A case is made for viewing writing not only as a planning problem but as a linguistic problem that can benefit from work in reading and speech production.
Convection-Enhanced Delivery for Targeted Delivery of Antiglioma Agents: The Translational Experience

Recent improvements in the understanding of glioblastoma (GBM) have allowed for increased ability to develop specific, targeted therapies. In parallel, however, there is a need for effective methods of delivery to circumvent the therapeutic obstacles presented by the blood-brain barrier and systemic side effects. The ideal delivery system should allow for adequate targeting of the tumor while minimizing systemic exposure, applicability across a wide range of potential therapies, and have existing safe and efficacious systems that allow for widespread application. Though many alternatives to systemic delivery have been developed, this paper will focus on our experience with convection-enhanced delivery (CED) and our focus on translating this technology from pre-clinical studies to the treatment of human GBM.
Inventory of Data Sources for Estimating Health Care Costs in the United States

Objective: To develop an inventory of data sources for estimating health care costs in the United States and provide information to aid researchers in identifying appropriate data sources for their specific research questions. Methods: We identified data sources for estimating health care costs using 3 approaches: (1) a review of the 18 articles included in this supplement, (2) an evaluation of websites of federal government agencies, non profit foundations, and related societies that support health care research or provide health care services, and (3) a systematic review of the recently published literature. Descriptive information was abstracted from each data source, including sponsor, website, lowest level of data aggregation, type of data source, population included, cross-sectional or longitudinal data capture, source of diagnosis information, and cost of obtaining the data source. Details about the cost elements available in each data source were also abstracted. Results: We identified 88 data sources that can be used to estimate health care costs in the United States. Most data sources were sponsored by government agencies, national or nationally representative, and cross-sectional. About 40% were surveys, followed by administrative or linked administrative data, fee or cost schedules, discharges, and other types of data. Diagnosis information was available in most data sources through procedure or diagnosis codes, self-report, registry, or chart review. Cost elements included inpatient hospitalizations (42.0%), physician and other outpatient services (45.5%), outpatient pharmacy or laboratory (28.4%), out-ofpocket (22.7%), patient time and other direct nonmedical costs (35.2%), and wages (13.6%). About half were freely available for downloading or available for a nominal fee, and the cost of obtaining the remaining data sources varied by the scope of the project. Conclusions: Available data sources vary in population included, type of data source, scope, and accessibility, and have different strengths and weaknesses for specific research questions.
On the equivalence between the Kaiser-Hamming sharpening procedure and the McClellan transformation for FIR digital filter design

In this correspondence it is shown that the Kaiser-Hamming procedure for sharpening the response of a symmetric one-dimensional FIR digital filter and the transformation design method for two-dimensional FIR filters, (originally due to McClellan) are mathematically equivalent. The different viewpoints concerning this common idea suggest generalizations to both approaches.