cssi/SciSciGPT-SciSciNet huggingface dataset:
Renal biopsy and pregnancy.

Abstract Objective: Our aim was to review our experience with renal biopsy in pregnancy. Study Design: We reviewed 18 renal biopsies performed during pregnancy or in the immediate postpartum period at the University of North Carolina. Indications, histopathologic findings, complications, and neonatal outcome were reviewed for each case. Results: Fifteen patients underwent biopsy during the antepartum period and 3 in the postpartum period. Only 5 patients had the classic histopathologic preeclamptic lesion glomeruloendotheliosis confirmed. There were 7 identifiable renal hematomas after biopsy; 2 patients required blood transfusion. There were 4 intrauterine fetal deaths in this series; it is presumed that none were a result of the biopsy. Conclusion: Renal biopsy in pregnancy is a morbid procedure and should be considered only if it offers the opportunity to make a diagnosis other than severe preeclampsia in a patient remote from term. (Am J Obstet Gynecol 2001;184:1093-6.)
Development of procedures for early screening of smoking cessation medications in humans

Candidate medications for smoking cessation may be screened more efficiently if initial evaluations in humans combine the practical advantages of laboratory studies with the clinical validity of clinical trials, such as by increasing participants' "quit motivation" during brief testing. We manipulated "intrinsic" quit motivation by recruiting smokers who either did intend to quit soon ("treatment seekers," N = 47) or did not ("nonseekers," N = 93), and "extrinsic" quit motivation by providing or not providing reinforcement for abstinence ($12/day). All the subjects smoked as they would usually do during weeks 1 and 3, and tried to quit during weeks 2 and 4 using either a nicotine patch (21 mg) or a placebo patch, in accordance with the crossover design of the study. The nicotine patch increased abstinence in treatment seekers but not in nonseekers. Reinforcement had a main effect on abstinence but did not moderate the effects of the nicotine patch or treatment-seeking status. Intrinsic, but not extrinsic, quit motivation of participants may enhance the validity of brief tests of medication efficacy for smoking cessation.
Verifications of Design Equations of Beams Externally Strengthened with FRP Composites

Based on the test information available in the literature since 1990, a comprehensive database is assembled for an extensive survey of existing studies on the flexural behavior of reinforced concrete beams externally strengthened with fiber-reinforced polymer FRP composites. Beam dimensions, material properties concrete, steel reinforcement, FRP composites, etc., and corresponding flexural responses such as failure modes, moment capacities, and so on, are collected in this database. The purpose of this database is to verify the design formulas presented in ACI 440.2R-02, Guide for the Design and Construction of Externally Bonded FRP Systems for Strengthening Concrete Structures. The performance of some other simple strength design models is investigated based on the same database and compared with that of the ACI model, which is found to have the least scattered prediction compared to others. Finally, a modified maximum strain FRP equation is recommended.
A Distribution-Free Multivariate Sign Test Based on Interdirections

Abstract Distribution-free tests are investigated for the one-sample multivariate location problem. Counts, called interdirections, which measure the angular distance between two observation vectors relative to the positions of the other observations, are introduced. These counts are invariant under nonsingular linear transformations and have a small-sample distribution-free property over a broad class of population models, called distributions with elliptical directions, which includes all elliptically symmetric populations and many skewed populations. A sign test based on interdirections is described, including, as special cases, the two-sided univariate sign test and Blumen's bivariate sign test. The statistic is shown to have a limiting χ2 p null distribution and, because it is based on interdirections, it is also seen to be invariant and to have a small-sample distribution-free property. Pitman asymptotic relative efficiencies and a Monte Carlo study show the test to perform well compared with Hotell...
Breathe softly, beetle: Continuous gas exchange, water loss and the role of the subelytral space in the tenebrionid beetle, Eleodes obscura

Abstract Flightless, diurnal tenebrionid beetles are commonly found in deserts. They possess a curious morphological adaptation, the subelytral cavity (an air space beneath the fused elytra) the function of which is not completely understood. In the tenebrionid beetle Eleodes obscura, we measured abdominal movements within the subelytral cavity, and the activity of the pygidial cleft (which seals or unseals the subelytral cavity), simultaneously with total CO2 release rate and water loss rate. First, we found that E. obscura has the lowest cuticular permeability measured in flow-through respirometry in an insect (0.90 μg H2O cm−2 Torr−1 h−1). Second, it does not exhibit a discontinuous gas exchange cycle. Third, we describe the temporal coupling between gas exchange, water loss, subelytral space volume, and the capacity of the subelytral space to exchange gases with its surroundings as indicated by pygidial cleft state. Fourth, we suggest possible mechanisms that may reduce respiratory water loss rates in E. obscura. Finally, we suggest that E. obscura cannot exchange respiratory gases discontinuously because of a morphological constraint (small tracheal or spiracular conductance). This “conductance constraint hypothesis” may help to explain the otherwise puzzling phylogenetic patterns of continuous vs. discontinuous gas exchange observed in tracheate arthropods.
Stoichiometry of the Interaction between the Major Histocompatibility Complex-Related Fc Receptor and Its Fc Ligand†

The neonatal Fc receptor (FcRn) transports immunoglobulin G (IgG) across epithelia, providing passive immunity and protecting serum IgG from degradation. For both functions, FcRn binds to IgG at the acidic pH of intracellular vesicles (pH </= 6.5) and releases IgG at the basic pH of the bloodstream (pH approximately 7.4). Crystallographic studies show that rat FcRn can interact with the Fc portion of IgG in a repeating array in which FcRn dimers are bridged by Fc fragments to create an "oligomeric ribbon" with a 2n:n stoichiometry. The stoichiometry of the interaction between soluble FcRn and Fc has been reported as either 2:1 for rat FcRn [Huber et al. (1993) J. Mol. Biol. 230, 1077-1083] or 1:1 for mouse FcRn [Popov et al. (1996) Mol. Immunol. 33, 521-530]. To ascertain the reasons for this difference, we analyzed complexes formed in solution between soluble rat or mouse FcRn and Fc. Using a gel-filtration assay under nonequilibrium conditions, we find that both forms of FcRn produce 2:1 receptor-ligand complexes, but that alterations of the carbohydrate moieties on mouse FcRn can result in an apparent stoichiometry of 1:1. However, under equilibrium conditions, all forms of FcRn make complexes with a 2:1 stoichiometry. We conclude that rat and mouse FcRn share the same general ligand binding properties but that small differences in affinities can produce apparent differences under nonequilibrium conditions.
Public Response to Prison Siting Perceptions of Impact on Crime and Safety

In recent decades, prison populations and prison construction both have increased dramatically bringing issues related to prison siting to the forefront. Although the Not in My Backyard (NIMBY) syn...
Lymphography in mycosis fungoides

Extracutaneous involvement has been recognized as a major cause of death in mycosis fungoides. Clinical data suggest that in certain types of mycosis fungoides, patients who present with benign changes in lymph nodes, such as dermatopathic lymphadenitis, are at high risk of later development of lymph node involvement with disease. It seems, therefore, important to identify these conditions as well as true involvement with lymphoma, in all lymph node bearing areas at risk. Lymphography was performed in 28 patients with various stages of mycosis fungoides. The radiographic findings and the correlation with lymphadenopathy and histologic findings in other lymph node bearing areas are described. Lymphography in mycosis fungoides is capable of identifying abnormalities in para-aortic and iliac lymph nodes.
Optimal tool inspection intervals using a process control approach

SUMMARY In machining operations, it is often necessary to remove a cutting tool for inspection and maintenance to reduce the probability of failure during machining. In this paper, a tool replacement model patterned after a cost model for the design of control charts is developed which yields inspection intervals of equal length.
School health centers and primary care for adolescents: A review of the literature

In 1991 the Office of Technology Assessment concluded that school-based health centers (SBHCs) are "the most promising recent innovation to address the health and related needs of adolescents." Numerous researchers and government studies report that these centers increase adolescents access to health services. Although the past 25 years have seen a rapid growth in school health centers (SHCs) from the first in 1970 to a reported 623 sites nationally in fall 1994 these centers are still not operating extensively in the United States. Data from the Center for Population Options reveal that 418 SBHCs operated during the 1991-1992 school year. Of these 330 were in high schools providing services to 270000 students or approximately 2% of the estimated 13.2 million U.S. students enrolled in grades 9-12 during the same year. National health care reform proposals induding legislation proposed by President Clinton and Senator Kennedy in 1994 supported an expanded role for SHCs as an integral part of an improved health care system of services for children and adolescents. Direct federal funding for such centers became available in 1994 from the Bureau of Primary Care and the Maternal Child Health Bureau HRSA without enactment of proposed health care reform legislation. In 1994 $11.9 million in federal Maternal and Child Health (MCH) Block Grant funds and $25.2 million in state revenues were used to support SBHCs. (excerpt)
The Measles Virus Hemagglutinin β-Propeller Head β4-β5 Hydrophobic Groove Governs Functional Interactions with Nectin-4 and CD46 but Not Those with the Signaling Lymphocytic Activation Molecule

Wild-type measles virus (MV) strains use the signaling lymphocytic activation molecule (SLAM; CD150) and the adherens junction protein nectin-4 (poliovirus receptor-like 4 [PVRL4]) as receptors. Vaccine MV strains have adapted to use ubiquitous membrane cofactor protein (MCP; CD46) in addition. Recently solved cocrystal structures of the MV attachment protein (hemagglutinin [H]) with each receptor indicate that all three bind close to a hydrophobic groove located between blades 4 and 5 (β4-β5 groove) of the H protein β-propeller head. We used this structural information to focus our analysis of the functional footprints of the three receptors on vaccine MV H. We mutagenized this protein and tested the ability of individual mutants to support cell fusion through each receptor. The results highlighted a strong overlap between the functional footprints of nectin-4 and CD46 but not those of SLAM. A soluble form of nectin-4 abolished vaccine MV entry in nectin-4- and CD46-expressing cells but only reduced entry through SLAM. Analyses of the binding kinetics of an H mutant with the three receptors revealed that a single substitution in the β4-β5 groove drastically reduced nectin-4 and CD46 binding while minimally altering SLAM binding. We also generated recombinant viruses and analyzed their infections in cells expressing individual receptors. Introduction of a single substitution into the hydrophobic pocket affected entry through both nectin-4 and CD46 but not through SLAM. Thus, while nectin-4 and CD46 interact functionally with the H protein β4-β5 hydrophobic groove, SLAM merely covers it. This has implications for vaccine and antiviral strategies.
Transabdominal thin-gauge embryofetoscopy: A technique for early prenatal diagnosis and its use in the diagnosis of a case of Meckel-Gruber syndrome

OBJECTIVE: Our aim was to develop and evaluate a transabdominal endoscopic technique to visualize the embryo or fetus with thin-gauge needles and submillimetric fiberoptic endoscopes. METHODS: Under ultrasonographic guidance, an 18- or 19-gauge thin-wall needle was introduced into the uterus of 28 patients undergoing first-trimester or early second-trimester termination of pregnancy. A 0.7 mm endoscope was threaded through the lumen of the needle after removal of the stylet. Visualization of the embryo-fetus was attempted before 14 weeks' gestation ( n = 20). From 16 to 20 weeks ( n = 8), the needle and endoscope were directed to the placental insertion of the umbilical cord, and a cordocentesis was performed. RESULTS: Excellent visualization of the surface anatomy of fetuses from 7 to 13 weeks was obtained in 85% of cases (17/20). A diagnosis of Meckel-Gruber syndrome was made at 11 weeks' menstrual age by visualizing postaxial polydactyly and an occipital encephalocele. Endoscopically assisted cordocentesis allowed visualization of the lumen of the umbilical vein and of the blood flow within it. CONCLUSION: Endoscopic visualization of the embryo or fetus can be performed transabdominally in the first trimester with small needle-delivered endoscopes. This represents a clear advantage over previous endoscopic approaches to the human pregnancy. Potential applications of this technique include a precise description of fetal anatomy and physiologic features, diagnosis of anomalies, and therapeutic fetal interventions.
The Global Financial Crisis: Explaining Cross-Country Differences in the Output Impact

We provide one of the first attempts at explaining the differences in the crisis impact across developing countries and emerging markets. Using cross-country regressions to explain the factors driving growth forecast revisions after the eruption of the global crisis, we find that a small set of variables explain a large share of the variation in growth revisions. Countries with more leveraged domestic financial systems and more rapid credit growth tended to suffer larger downward revisions to their growth outlooks. For emerging markets, this financial channel trumps the trade channel. For a broader set of developing countries, however, the trade channel seems to have mattered, with countries exporting more advanced manufacturing goods more affected than those exporting food. Exchange-rate flexibility clearly helped in buffering the impact of the shock. There is also some -weaker-evidence that countries with a stronger fiscal position prior to the crisis were hit less severely. We find little evidence for the importance of other policy variables.
Resolving power of time-reversed wave-front imaging devices

It is shown that, in general, the size of the image of a point source generated by time-reversed wave-front devices is governed by considerations similar to those determining the resolving power of lenses. If the device subtends an angle α at the image, then the image has a lateral dimension ~λ/sin α. However, in some cases, when α is large and the imaging device is thin or the laser beams have special polarizations, images several times larger might be obtained.
Simulation techniques and potentials for metals

Abstract The properties of both ordered and disordered metallic systems can be studied by standard simulation techniques, both static and dynamic, provided that interatomic potentials are available. For simple metals and their alloys, pair potentials are well justified for most properties and their functional form is well understood. However, the long-range nature of these potentials creates special problems for simulations which will be discussed. The remainder of the paper is devoted to transition metals and the problems of constructing potentials that can be used with confidence in computer simulations.
Mechanism of positive allosteric modulators acting on AMPA receptors

Ligand-gated ion channels involved in the modulation of synaptic strength are the AMPA, kainate, and NMDA glutamate receptors. Small molecules that potentiate AMPA receptor currents relieve cognitive deficits caused by neurodegenerative diseases such as Alzheimer's disease and show promise in the treatment of depression. Previously, there has been limited understanding of the molecular mechanism of action for AMPA receptor potentiators. Here we present cocrystal structures of the glutamate receptor GluR2 S1S2 ligand-binding domain in complex with aniracetam [1-(4-methoxybenzoyl)-2-pyrrolidinone] or CX614 (pyrrolidino-1,3-oxazino benzo-1,4-dioxan-10-one), two AMPA receptor potentiators that preferentially slow AMPA receptor deactivation. Both potentiators bind within the dimer interface of the nondesensitized receptor at a common site located on the twofold axis of molecular symmetry. Importantly, the potentiator binding site is adjacent to the "hinge" in the ligand-binding core "clamshell" that undergoes conformational rearrangement after glutamate binding. Using rapid solution exchange, patch-clamp electrophysiology experiments, we show that point mutations of residues that interact with potentiators in the cocrystal disrupt potentiator function. We suggest that the potentiators slow deactivation by stabilizing the clamshell in its closed-cleft, glutamate-bound conformation.
Zytotaxonomische Untersuchungen des Formenkreises Achillea millefolium (Asteraceae) in der DDR

Chromosomenzahl, Morphologie und Proazulengehalt von 70 Wildpopulationen und deren Kulturen (Wildmaterial: 210 Individuen, Kulturen: 300 Individuen) wurden untersucht. Auf Grund dieser Analysen wird das Vorkommen von A. setacea W. et K. (2n = 18), A. collina J. Becker ex Rchb. (2n = 36), A. millefolium L. s. str. (2n = 54) und A. pannonica Scheele (2n = 72) sowie das Vorkommen von Hybridformen (2n = 45 und 2n = 63) im Untersuchungsgebiet nachgewiesen. Die nordlichen Arealgrenzen von A. collina J. Becker ex Rchb. und A. pannonica Scheele werden fur das Untersuchungsgebiet prazisiert. Es wird ein Bestimmungsschlussel vorgelegt, wobei betont wird, das zur Determinierung polyploider Formen stets Merkmalsgruppen herangezogen werden mussen. Verpflanzungsversuche lassen vermuten, das eine Reihe morphologischer Merkmale modifikativ veranderlich sind. Die phylogenetische Entwicklung und die rezenten Beziehungen zwischen den Arten des A. millefolium-Formenkreises und zwischen weiteren Arten der Sect. Millefolium werden diskutiert und die taxonomische Bewertung der untersuchten Arten wird erortert. Die Zugehorigkeit bisher zweifelhafter Belege vom Bienitz, westlich von Leipzig zu A. millefolium L. s. str. wird auf Grund spezieller Untersuchungen, in die auch A. aspleniifolia Vent. einbezogen ist, aufgeklart. Chromosome numbers, morphology, and contents of proazulene of 70 populations (210 specimens) and of their transplantants (300 specimens) were investigated. The results indicate clearly the occurence of the following species: A. setacea W. et K. (2n = 18), A. collina J. Becker ex Rchb. (2n = 36), A. millefolium L. s. str. (2n = 54), A. pannonica Scheele (2n = 72). Hybrids in the area of investigation also occur (2n = 45, 2n = 63). Within the area investigated the northern limits of A. collina J. Becker ex Rchb. and A. pannonica Scheele are substantiated. A key to the species is given. It should be noted that only the characters in combination will allow an identification of the polyploid forms. The transplantations suggest that a number of morphological characters are subject to modification. Phylogenetics and present-day relations among the species of A. millefolium-complex and among other species of the sect. Millefolium as well as their taxonomic status are discussed. The identity with A. millefolium L. s. str. of a collection of specimens from the surroundings of Leipzig, which was hitherto questioned, is established by special investigations which also included A. aspleniifolia Vent.
On climatic anomalies: Atmospheric‐pressure problems

Climatology is a science of meteorological generalizations. Monthly means of temperature and monthly totals of precipitation are most often the only data climatologists make use of in their studies. Evidently so-called “normal” means of long series of observations give the best maps of temperature- and rainfall-distribution and, eventually, of the range of variations. Atmospheric pressure is very seldom taken into consideration.
Structural properties of ZnSySe1 − y/ZnSe/GaAs(0 0 1) heterostructures grown by photoassisted metalorganic vapor phase epitaxy

The compositional control of ZnS y Se 1-y has been investigated using photoassisted metalorganic vapor phase epitaxy (MOVPE), using the sources DMZn, DMSe, and DES, and irradiation from a mercury arc lamp. The solid-phase composition is not a simple function of the gas-phase composition, but depends on the absolute mole fractions of the reactants. Nonetheless, the characteristic is sufficiently gradual so that good compositional control is achieved. The photoassisted MOVPE technique has been used to produce Zns y Se 1-y /ZnSe/GaAs (001) heterostructures, and these structures have been studied using high-resolution X-ray diffraction. Both pseudomorphic and non-pseudomorphic ZnSe buffer layers were used. The ZnS y Se 1-y layers were grown with compositions in the range of 0.00 ≤ y ≤ 0.11, and were thick enough ( ∼ 2 μm) to be non-pseudomorphic. Threading dislocation densities in the ZnS y Se 1-y layers increase monotonically with the lattice mismatch (relative to the underlying GaAs substrate). The presence of the ZnSe buffer layer does not modify the lattice-matching condition for the minimum threading dislocation density. However, the absolute dislocation densities in the ZnS y Se 1-y layers are increased by the presence of a non-pseudomorphic ZnSe buffer, relative to the predictions of the glide model for the ZnSySe 1-y /GaAs (001) single heterostructure. This is due to the increased linear density of misfit dislocations at the ZnSySe 1-y /ZnSe interface. For structures with pseudomorphic buffer layers, threading dislocation densities in the ZnSySe 1-y material are less than those predicted by the single heterostructure theory. This is expected due to incomplete lattice relaxation in the ZnS y Se 1-y .
An aversive conditioning unit for ants

An apparatus is described for studying aversive conditioning in ants. The aversive stimulus is mechanically produced vibration. Responses are recorded automatically by an infrared photocell system.
Automatic feedback control of mechanical gas face seals via clearance control

A new analytical approach is presented for designing controllers to regulate the axial clearance of a coned-face flexibly mounted stator mechanical gas face seal. The seal axial clearance is controlled by regulating the back-pressure force acting on the stator. The controllers are systematically designed using a completely analytical seal system model in which the linearized gas film stiffness and damping properties are represented by a constitutive model. An algorithm based on this model is derived to calculate the critical axial clearance where the seal is marginally stable, and a stable reference axial clearance is chosen. Proportional and proportional-plus-integral controllers are designed and analytically studied in terms of closed-loop stability and speed of response using the system model. The controllers are verified using a full numerical simulation (including nonlinear effects) of the mechanical gas face seal system, and the results demonstrate the effectiveness of both controllers to maintain t...
A Late Holocene Paleoecological Record from Torrey Pines State Reserve, California

Paleoenvironments of the Torrey Pines State Reserve were reconstructed from a 3600-yr core from Los Penasquitos Lagoon using fossil pollen, spores, charcoal, chemical stratigraphy, particle size, and magnetic susceptibility. Late Holocene sediments were radiocarbon dated, while the historical sediments were dated using sediment chemistry, fossil pollen, and historical records. At 3600 yr B.P., the estuary was a brackish-water lagoon. By 2800 yr B.P., Poaceae (grass) pollen increased to high levels, suggesting that the rising level of the core site led to its colonization by Spartina foliosa (cord-grass), the lowest-elevation plant type within regional estuaries. An increase in pollen and spores of moisture-dependent species suggests a climate with more available moisture after 2600 yr B.P. This change is similar to that found 280 km to the north at 3250 yr B.P., implying that regional climate changes were time-transgressive from north to south. Increased postsettlement sediment input resulted from nineteenth-century land disturbances caused by grazing and fire. Sedimentation rates increased further in the twentieth century due to closure of the estuarine mouth. The endemic Pinus torreyana (Torrey pine) was present at the site throughout this 3600-yr interval but was less numerous prior to 2100 yr B.P. This history may have contributed to the low genetic diversity of this species.
Institutional Profile: The Center for Biomarker Research and Personalized Medicine at Virginia Commonwealth University: advancing psychiatric drug treatment

The Center for Biomarker Research and Personalized Medicine is a small, focused and technology-driven organization, sited within the School of Pharmacy on the Medical College of Virginia Campus of Virginia Commonwealth University. The Center was established in 2006, with a mission to improve understanding and treatment of psychiatric disease by employing the latest advances in molecular biology, informatics and statistics. We take the philosophy that large-scale, exploratory studies are crucial to achieve our aims because strong biological associations have been historically absent for psychiatric disorders. Our work follows two main streams: the first being disease biomarker research, such as discovering genes contributing risk for schizophrenia or depression. The second stream is the discovery of biomarkers for therapeutic drug response, where our genome-wide association studies of antipsychotic and antidepressant response have yielded multiple new leads. With the recent success of large-scale biologica...
A Technique for Reducing the Effect of Mutual Coupling in Adaptive Arrays

The degraded SINR and poor performance of adaptive arrays, when mutual coupling is taken into account, is well known. In this paper a method using tapped delay lines for reducing the effect of mutual coupling in adaptive arrays is developed. It is shown that the SINR will improve proportionally to the number of taps used for each element.
The Synthesis and Electrical Conductivity of Novel Mixed Ionic and Electronic Conductors in The Gd2GaSbO7-Gd2Zr2O7 Solid Solution

The synthesis and electrical conductivity of a novel solid solution pyrochlore Gd2GaSbO7 - Gd2Zr2O7 were studied as a function of x in Gd2(GaSb)1-xZr2xO7 (0 ≤ x ≤ 1). In this study, single phases with the pyrochlore structure were obtained in the range of x ≤ 0.2, while a garnet phase appeared as a minor second phase for x ≥ 0.3. In the x = 0.2 sample, evidence of the displacement of 48f oxygens towards the normally empty 8b site was suggested by Rietveld analysis. The total electrical conductivity of the pyrochlores was 2.6x 10−2 S/m for x = 0.0 and 6.0×10−3S/m for x = 0.2 at 1273 K, respectively. In addition, evidence for n-type semiconductivity was obtained for x = 0.2 under reducing conditions. Further studies are underway to identify the dominant carriers under oxidizing conditions.
Comparison of flying height measurement between multi-channel laser interferometer and the capacitance probe slider

The authors studied the dynamics of a capacitance probe slider by measuring the head-disk spacing during CSS (contact-start-stop) cycles and during steady-state flying. They measured the head-disk spacing with both the MCLI and the capacitance probe slider simultaneously and then attempted to correlate the spacing fluctuation results. They first determined the calibration factor by measuring the flying height and the change in the capacitance during the CSS cycle. As expected, it was observed that the change in the capacitance is a nonlinear function of the change in the spacing. However, it was also discovered that the same calibration factor determined by a CSS cycle cannot be applied to calibrate the spacing fluctuation measurements made during steady-state flying conditions. The disagreement is due to spacing averaging caused by the finite size of the capacitance pad. >
Relative to Quinine and Quinidine, Their 9-Epimers Exhibit Decreased Cytostatic Activity and Altered Heme Binding but Similar Cytocidal Activity versus Plasmodium falciparum

ABSTRACT The 9-epimers of quinine (QN) and quinidine (QD) are known to exhibit poor cytostatic potency against P. falciparum (Karle JM, Karle IL, Gerena L, Milhous WK, Antimicrob. Agents Chemother. 36:1538–1544, 1992). We synthesized 9- epi -QN (eQN) and 9- epi -QD (eQD) via Mitsunobu esterification-saponification and evaluated both cytostatic and cytocidal antimalarial activities. Relative to the cytostatic activity of QN and QD, we observed a large decrease in cytostatic activity (higher 50% inhibitory concentration [IC 50 s]) against QN-sensitive strain HB3, QN-resistant strain Dd2, and QN-hypersensitive strain K76I, consistent with previous work. However, we observed relatively small changes in cytocidal activity (the 50% lethal dose), similar to observations with chloroquine (CQ) analogues with a wide range of IC 50 s (see the accompanying paper [A. P. Gorka, J. N. Alumasa, K. S. Sherlach, L. M. Jacobs, K. B. Nickley, J. P. Brower, A. C. de Dios, and P. D. Roepe, Antimicrob. Agents Chemother. 57:356–364, 2013]). Compared to QN and QD, the 9-epimers had significantly reduced hemozoin inhibition efficiency and did not affect pH-dependent aggregation of ferriprotoporphyrin IX (FPIX) heme. Magnetic susceptibility measurements showed that the 9-epimers perturb FPIX monomer-dimer equilibrium in favor of monomer, and UV-visible (VIS) titrations showed that eQN and eQD bind monomer with similar affinity relative to QN and QD. However, unique ring proton shifts in the presence of zinc(II) protoporphyrin IX (ZnPIX) indicate that binding of the 9-epimers to monomeric heme is via a distinct geometry. We isolated eQN- and eQD-FPIX complexes formed under aqueous conditions and analyzed them by mass, fluorescence, and UV-VIS spectroscopies. The 9-epimers produced low-fluorescent adducts with a 2:1 stoichiometry (drug to FPIX) which did not survive electrospray ionization, in contrast to QN and QD complexes. The data offer important insight into the relevance of heme interactions as a drug target for cytostatic versus cytocidal dosages of quinoline antimalarial drugs and further elucidate a surprising structural diversity of quinoline antimalarial drug-heme complexes.
Input shapers for reducing overshoot in human-operated flexible systems

Input shaping is a command generation method for creating commands that result in low levels of residual vibration. The vibration reduction is accomplished by slightly increasing the acceleration and deceleration periods of the command. The increase in the deceleration period can lead to system overshoot. This paper presents a new class of Zero Overtravel (ZO) input shapers that are designed to reduce shaper-induced overtravel from human-operator commands. During the development of these new shapers, an expression for shaper-induced overtravel is introduced. This expression is used as an additional constraint in the input shaper design process to generate the ZO shapers. Experiments from a portable bridge crane verify the theoretical predictions.
Tidal Friction in the Earth-Moon System and Laplace Planes: Darwin Redux

Abstract The dynamical evolution of the Earth–Moon system due to tidal friction is treated here. George H. Darwin used Laplace planes (also called proper planes) in his study of tidal evolution. The Laplace plane approach is adapted here to the formalisms of W.M. Kaula and P. Goldreich. Like Darwin, the approach assumes a three-body problem: Earth, Moon, and Sun, where the Moon and Sun are point-masses. The tidal potential is written in terms of the Laplace plane angles. The resulting secular equations of motion can be easily integrated numerically assuming the Moon is in a circular orbit about the Earth and the Earth is in a circular orbit about the Sun. For Earth–Moon distances greater than ∼10 Earth radii, the Earth’s approximate tidal response can be characterized with a single parameter, which is a ratio: a Love number times the sine of a lag angle divided by another such product. For low parameter values it can be shown that Darwin’s low-viscosity molten Earth, M. Ross’s and G. Schubert’s model of an Earth near melting, and Goldreich’s equal tidal lag angles must all give similar histories. For higher parameter values, as perhaps has been the case at times with the ocean tides, the Earth’s obliquity may have decreased slightly instead of increased once the Moon’s orbit evolved further than 50 Earth radii from the Earth, with possible implications for climate. This is contrast to the other tidal friction models mentioned, which have the obliquity always increasing with time. As for the Moon, its orbit is presently tilted to its Laplace plane by 5.2°. The equations do not allow the Moon to evolve out of its Laplace plane by tidal friction alone, so that if it was originally in its Laplace plane, the tilt arose with the addition of other mechanisms, such as resonance passages.
Impact of a Conjugate Vaccine on Community-Wide Carriage of Nonsusceptible Streptococcus pneumoniae in Alaska

Background. Streptococcus pneumoniae is a leading cause of invasive bacterial disease and pneumonia among children. Antimicrobial resistance among pneumococci has increased in recent years and complicates treatment. The introduction of heptavalent pneumococcal conjugate vaccine (PCV7) could reduce acquisition of antimicrobial-resistant pneumococci. Methods. We obtained 1350 nasopharyngeal swabs for culture from 1275 children aged 3-59 months presenting at 3 clinics in Anchorage, Alaska, during the winters of 2000, 2001, and 2002, as PCV7 was being introduced into the routine immunization schedule. We recorded the frequency of use of antibiotics as well as the dates of doses of PCV7 for enrolled children. We used multivariate logistic regression modeling to identify independent risk factors for overall carriage of pneumococci and carriage of PCV7-type pneumococci, cotrimoxazole-nonsusceptible (COT-NS) pneumococci, or penicillin-nonsusceptible (PCN-NS) pneumococci. Results. The proportion of children who were up-to-date for age, with respect to PCV7 vaccination, increased from 0% in 2000 to 55% in 2002. Carriage of PCV7-type pneumococci decreased by 43% (P<.0001). Risk of carriage of PCV7-type pneumococci was lower in 2002 than in 2000, independent of vaccination status, suggesting an indirect effect of vaccination. Carriage of COT-NS, but not PCN-NS, pneumococci also decreased (38%; P =.02), not only among vaccinated children but also among unvaccinated children without recent use of antibiotics. Conclusions. Introduction of PCV7 into the routine infant immunization schedule in a community with a high prevalence of antimicrobial-resistant pneumococci appears to reduce transmission of PCV7 vaccine serotypes and COT-NS pneumococci but has no impact on overall carriage of pneumococci or carriage of PCN-NS pneumococci.
A HYBRID SPECTRAL/FINITE VOLUME METHOD FOR VISCOUS FLOWS

Abstract This paper presents a hybrid spectral/finite volume method for steady-state compressible viscous flows. The method is evaluated for accuracy via test cases for various Mach numbers. The domain is divided into a viscous region and an inviscid region. The viscous region uses the full Navier-Stokes equations, while the inviscid region employs the Euler equations. A high order Chebyshev collocation spectral method is developed for the viscous region to resolve boundary layers. This method avoids the dense grids needed by finite-volume methods to resolve the viscous areas. A low order finite-volume method based on a Lax-Wendroff type scheme is employed for the inviscid region. A special interface formulation is developed for coupling the spectral with the finite-volume method. Comparisons with analytic results as well as convergence histories are presented.
Sovereignty and International Order

. Sovereignty may be threatened by obligations and relations with other nations, states or powers from either an “internal” or “external” perspective. In this paper, I argue that these obligations and relationships may be compatible with a state's sovereignty if we understand the proper nature of authoritative relationships. This requires a model of “rational authority” which places emphasis on the first-person perspective of the subjects to authority.
Physics-based compact models for insulated-gate field-effect biosensors, landau-transistors, and thin-film solar cells

As the future of Moore's law appear uncertain, semiconductor electronics is being reinvented with a broader focus on energy efficient 3D computing, flexible electronics, biosensors, energy harvesting, etc. These devices are gradually being integrated onto the CMOS fabric as ‘More-than-Moore’ components, with transformative impact on consumer electronics. Unfortunately, a lack of physics-based, experimentally validated, numerically stable, well-documented compact models makes integration of these components in a CMOS design flow difficult. In this paper, we describe physics-based compact models for three very different components that are likely to be integrated in future systems, namely, FET-based nanobiosensors for pH sensing, Landau-transistors for low-power electronics, and thin-film solar cells for energy harvesting. Our physics-based approach should inspire the community to develop similar models for other emerging devices, so as to make their integration onto CMOS platform a routine affair.
Reproductive risk factors in relation to molecular subtypes of breast cancer: Results from the nurses' health studies

Several intrinsic breast cancer subtypes, possibly representing unique etiologic processes, have been identified by gene expression profiles. Evidence suggests that associations with reproductive risk factors may vary by breast cancer subtype. In the Nurses' Health Studies, we prospectively examined associations of reproductive factors with breast cancer subtypes defined using immunohistochemical staining of tissue microarrays. Multivariate-adjusted Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Over follow-up, we identified 2,063 luminal A, 1,008 luminal B, 209 HER2-enriched, 378 basal-like and 110 unclassified tumors. Many factors appeared associated with luminal A tumors, including ages at menarche (p(heterogeneity) = 0.65) and menopause (p(heterogeneity) = 0.05), and current HT use (p(heterogeneity) = 0.33). Increasing parity was not associated with any subtype (p(heterogeneity) = 0.76), though age at first birth was associated with luminal A tumors only (per 1-year increase HR = 1.03 95%CI (1.02-1.05), p(heterogeneity) = 0.04). Though heterogeneity was not observed, duration of lactation was inversely associated with risk of basal-like tumors only (7+ months vs. never HR = 0.65 95%CI (0.49-0.87), ptrend = 0.02), p(heterogeneity) = 0.27). Years between menarche and first birth was strongly positively associated with luminal A and non-luminal subtypes (e.g. 22-year interval vs. nulliparous HR = 1.80, 95%CI (1.08-3.00) for basal-like tumors; p(heterogeneity) = 0.003), and evidence of effect modification by breastfeeding was observed. In summary, many reproductive risk factors for breast cancer appeared most strongly associated with the luminal A subtype. Our results support previous reports that lactation is protective against basal-like tumors, representing a potential modifiable risk factor for this aggressive subtype.
Developmental Origins of and Covariation Between Metric and Nonmetric Cranial Traits

Determination of how the underlying cause(s) of variation in metric and nonmetric skeletal traits compare has remained elusive despite active research (Bennett 1965 ; Berry and Berry 1967 ; Kellock and Parsons 1970; Rightmire 1972 ; Corruccini 1976 ; Cheverud et al. 1979 ; Cheverud and Buikstra 1982 ; Richtsmeier et al. 1984 ; Hartl et al. 1995 ). This question has been of particular importance to anthropologists trying to measure the biological or the genetic distance between populations, using fragmentary skeletal material (Berry and Berry 1967 ; Kellock and Parsons 1970 ; Rightmire 1972 ; Konigsberg 1988 ; Ishida and Dodo 1993 ; Prowse and Lovell 1996 ; Gonzalez-Jose et al. 2001 ; Hallgrimsson et al. 2004, and others).
The role of the U.S. judicial branch during the long war: Drone courts, damage suits, and freedom of information act (FOIA) requests

The current U.S. practice of using drones to engage in overseas killings raises difficult legal questions with incredibly high stakes. The fate of potential targets and collateral damage hangs in the balance along with grave concerns about national and foreign security
Mutation induction by difunctional alkylating agents in Neurospora crassa.

The genetic characterization of ad-3 mutants of Neurospora crassa induced by two carcinogenic difunctional alkylating agents, 1,2,4,5-diepoxypentane (DEP) and 1,2,7,8-diepoxyoctane (DEO), has shown that point mutations at the ad-3B locus have similar complementation patterns. In addition to the induction of point mutations, DEP induces a low frequency (7.5%) of multilocus deletions, whereas DEO induces an extremely high frequency (42.0%). The distribution of the different classes of ad-3 mutants and the frequency of multilocus deletion mutants among DEP-induced mutants are not significantly different from those induced by the monofunctional alkylating agents EI, EMS and ICR-177 at comparable forward-mutation frequencies. Moreover, the frequencies of DEP-induced ad-3B mutants showing allelic completion or having nonpolarized complementation patterns are similar to those of ad-3B mutants induced by monofunctional agents. It is suggested, therefore, that the mechanism of mutation-induction by DEP in N. crassa is similar to that of monofunctional alkylating agents. Mutation-induction by DEO probably results both from the mechanism of action of monofunctional alkylating agents and from inter-strand cross-linkage of the DNA molecule by the two functional epoxy groups.
A protocetid cetacean from the Eocene of South Carolina

Kellogg (1936, p. 242) described “an imperfectly preserved dorsal vertebra” from Texas, which he assigned to the primitive cetacean genus Protocetus. McLeod and Barnes (1990), however, were the first to report unequivocal protocetid remains from the Atlantic Coastal Plain. Since then, Hulbert and Petkewich (1991) and Hulbert (1993) have noted a well-preserved skeleton of a protocetid cetacean from middle Eocene deposits in Georgia. The purpose of this note is to report the recent discovery of additional protocetid remains from the coastal plain of South Carolina and to discuss their stratigraphic and biostratigraphic context.
Economic Efficiency and the Law: Distinguishing Form from Substance

This essay is written for a Festschrift to commemorate Jurgen Backhaus’s contribution to law and economics in recognition of his long service as Editor of the European Journal of Law and Economics. Scholars of law and economics have long been intrigued by the possibility that legal processes operate to promote economic efficiency. This essay probes the problematical character of the efficiency claim. This appraisal operates by refracting the efficiency claim through Pareto (The Mind and Society: A Treatise on General Sociology, Harcourt Brace, New York, 1935 [1923]) distinction between logical and nonlogical action. What results from this refraction is recognition that economic efficiency is an objectively meaningful concept only inside a model of competitive equilibrium. Outside that model, economic efficiency depends on the perspective of a theorizing subject. Economic efficiency pertains to the form of an argument but not to its substance. Efficiency claims are Paretian derivations and not refutable hypotheses.
Zinc Bis(Amide) Compounds Evaluated as Designed Precursors for Site-Selective P-type Doping of ZnSe

Zinc selenide doped with nitrogen deposited by organometallic vapor phase epitaxy (OMVPE) is one example which leads to a material that produces a blue emission. However, the effective incorporation of the nitrogen dopant into the zinc selenide lattice has not yet resulted in the demanded efficiency. One potential solution involves the design of a precursor introducing the nitrogen dopant bonded to zinc that survives the thermal decomposition process. Several new zinc bis (amide) compounds with the general formula Zn[N(R)(R′)] 2 have been synthesized. Investigations into the thermal decomposition mechanisms of these compounds have provided insight into the potential usefulness of the designed precursor in the preparation of ZnSe:N.
Correction: Brewer, G.J. Copper-2 Ingestion, Plus Increased Meat Eating Leading to Increased Copper Absorption, Are Major Factors Behind the Current Epidemic of Alzheimer’s Disease. Nutrients 2015, 7(12), 10053–10064

On page 10055, line 10, of the original publication [1] it was incorrectly stated that “However, this argument is invalid because in 1911, half the population of France was 60 or older”.[...]
The Relative Activity of the Soluble Lipase and Lipase Liberated during Autolysis of Certain Rapidly Growing Tubercle Bacilli. Studies in Acid-Fast Bacteria. VII

In the previous article,' experiments were recorded which demonstrated that an active fat-splitting ferment was present in solution in broth cultures of a variety of acid-fast bacilli. These experiments were carried out in such a manner as to be roughly quantitative, and the activity of the lipase, as determined by these experiments, was found to be very considerable. It is a matter of importance to determine whether these lipases are excreted by these acid-fast bacilli as exoferments, or whether they are bound up in the bodies of the bacteria, and appear in solution only when the bacteria have autolyzed (endoferments). Carrikre2 has described a thermolabile lipase in the organisms of a six-months-old culture of the tubercle bacillus; his observations suggest that this lipase was an endo-ferment and that even minute amounts of culture medium destroy or inactivate it. This observation is not in harmony with the results presented above, for the lipase of the acid-fast bacteria described there was present and active in the culture medium, and it was thermostabile. It is possible, however, that the lipase, which is demonstrable in younger cultures of tubercle bacilli, may have disappeared, as the cultures were incubated for a longer period, without affecting the activity of a second thermolabile endo-lipase which is locked up within the bacteria themselves. The following observations were undertaken with a view of determining the relative amounts of lipase, respectively, in the culture medium and in the bodies of the bacteria grown in the culture medium. The cultures (various acid-fast bacilli) were of unequal ages, as indicated in Table 1. Various degrees of autolysis of the bacteria, therefore, must have taken place, depending on the strain of organism studied and the length of incubation.
Environmental initiatives for physicians.

Physicians have a professional and moral responsibility to speak out about the environment's effect on health--particularly those hazards, such as smoking, that can be prevented, writes the U.S. surgeon general.
Surgical Outcome in Focal Cortical Dysplasia

The predictors of surgical outcome and relevance of pathological severity were determined in 166 consecutive patients with intractable epilepsy and focal cortical dysplasias treated surgically at Konkuk University Medical Center, and National University Hospital, Seoul, Korea.