cssi/SciSciGPT-SciSciNet huggingface dataset:
Specific MDR1 P-Glycoprotein Blockade Inhibits Human Alloimmune T Cell Activation In Vitro

MDR1 P-glycoprotein (P-gp), the multidrug resistance-associated transmembrane transporter, is physiologically expressed by human peripheral immune cells, but its role in cell-mediated immunity remains poorly understood. Here, we demonstrate a novel role for P-gp in alloantigen-dependent human T cell activation. The pharmacologic P-gp inhibitor tamoxifen (1–10 μM) and the MDR1 P-gp-specific mAb Hyb-241 (1–20 μg/ml), which detected surface P-gp on 21% of human CD3+ T cells and 84% of CD14+ APCs in our studies, inhibited alloantigen-dependent, but not mitogen-dependent, T cell proliferation in a dose-dependent manner from 40–90% (p 85% inhibition (p < 0.01) of IL-2, IFN-γ, and TNF-α production in 48-h MLR coculture supernatants. Addition of recombinant human IL-2 (0.1–10 ng/ml) restored proliferation in tamoxifen-treated cocultures. Pretreatment of purified CD4+ T cells with Hyb-241 mAb before coculture resulted in inhibition of CD4+ T cellular IFN-γ secretion. Also, blockade of P-gp on allogeneic APCs inhibited IL-12 secretion. Taken together these results demonstrate that P-gp is functional on both CD4+ T cells and CD14+ APCs, and that P-gp blockade may attenuate both IFN-γ and IL-12 through a positive feedback loop. Our results define a novel role for P-gp in alloimmunity and thus raise the intriguing possibility that P-gp may represent a novel therapeutic target in allograft rejection.
Price of flexibility in intelligent interfaces

Flexibility and customizability are central to the perceived advantages of the growth in technological powers. However, these and other vectors of technological change, when used clumsily, create new burdens and complexities for beleaguered human practitioners responsible for achieving goals within some field of activity. 'Intelligent interfaces' are sometimes seen as solutions to the growing demands of highly technological and highly automated fields of activity. However, data from a variety of sources indicates that an exclusively technology-driven approach to the development of intelligent interfaces is likely to provide the illusion of assistance while creating a new layer of burdens and complexities. It is necessary to understand the difference between two types of flexibility in cognitive artifacts: (a) flexibilities that increase practitioners' ranges of adaptive responses to the variability in the field of activity, and (b) flexibilities that simply create new burdens on practitioners, especially at high tempos or high criticality periods.
Review: Systemic treatment of advanced colorectal cancer: Tailoring therapy to the tumor:

Colorectal cancer is a prevalent disease in Western countries. While prevention through screening is the best approach to combat the development of colorectal cancer through the removal of precursor adenomas, many patients present with advanced disease that will require surgery and systemic therapy to improve survival. With reference to systemic therapy, the median survival of patients with metastatic colorectal cancer (those with tumor spread to lymph nodes or distant sites) has improved over the past three decades due to the introduction of 5-fluorouracil (5-FU), its subsequent biomodulation, and the addition other chemotherapeutic agents. There is now evidence that the biology of the colorectal tumor, in addition to the stage of colorectal cancer, may predict response to 5-FU-based therapy. More recently, systemic biological therapies that target signaling processes for tumor growth, such as epidermal growth factor receptor, and vascular endothelial growth factor, are also effective in improving patient survival with metastatic colorectal cancer. The use of a combination of systemic therapies that include chemotherapy and biologic therapy should continue to increase patient survival with metastatic colorectal cancer through appropriately designed clinical trials. Treatments based on the biology of the colorectal tumor also need to be examined through clinical trials.
Odor and chemesthesis from exposures to glutaraldehyde vapor

Assessment of olfactory and chemesthetic sensitivity (feel, sensory irritation) to vapor of glutaraldehyde in young adult females. For chemesthetic sensitivity, assessment included the variable of duration, with focus on whether concentrations initially too low to evoke feel in the eye or upper airway might do so in exposures up to 15 min. Experiment 1 probed sensitivity with forced-choice testing of detection over ranges of concentrations appropriate to three endpoints: odor, feel in the eye, and feel in the nose. A subject participated in hours of testing per endpoint to yield enough data to erect a psychometric (concentration-response) function. Exposure in Experiment 1 entailed use of a vapor-delivery system that stimulated sites of interest separately. Exposure in Experiment 2 occurred in the ambient environment of a chamber, with the sites stimulated simultaneously. In that case, subjects rated confidence by the minute that they felt the presence of vapor in the eyes, nose, and throat during exposures of 15 minutes to 35, 50, 75, and 100 ppb, a blank, and an odor control of mild heptane. In Experiment 1, the typical subject achieved 50% detection (threshold) of odor at 0.3 ppb. The typical subject achieved 50% detection of feel in the eye and nose at 390 and 470 ppb, respectively. Psychometric functions for feel showed much sharper dependence on concentration than those for odor. In Experiment 2, confidence in detection of feel migrated progressively away from no—with certainty toward the zone of uncertainty, with bigger change when the exposures contained any glutaraldehyde. The ratings of confidence failed, however, to show distinguish among these concentrations. Glutaraldehyde has much higher odor potency than previously thought. Its green-apple odor should signal presence of the vapor at levels more than a 100-fold below any that might evoke sensory irritation in brief exposures. Exposures that start decidedly below irritating (100 ppb and below) seem unlikely to turn irritating over time. Although the effects from these concentrations differentiated themselves from those of air and an odor control, they exhibited none of the concentration dependence seen for sensations of feel. They seemed likely driven by the penetrating odor of glutaraldehyde.
Properties and structures of the influenza and HIV fusion peptides on lipid membranes: implications for a role in fusion.

The fusion peptides of HIV and influenza virus are crucial for viral entry into a host cell. We report the membrane-perturbing and structural properties of fusion peptides from the HA fusion protein of influenza virus and the gp41 fusion protein of HIV. Our goals were to determine: 1), how fusion peptides alter structure within the bilayers of fusogenic and nonfusogenic lipid vesicles and 2), how fusion peptide structure is related to the ability to promote fusion. Fluorescent probes revealed that neither peptide had a significant effect on bilayer packing at the water-membrane interface, but both increased acyl chain order in both fusogenic and nonfusogenic vesicles. Both also reduced free volume within the bilayer as indicated by partitioning of a lipophilic fluorophore into membranes. These membrane ordering effects were smaller for the gp41 peptide than for the HA peptide at low peptide/lipid ratio, suggesting that the two peptides assume different structures on membranes. The influenza peptide was predominantly helical, and the gp41 peptide was predominantly antiparallel β-sheet when membrane bound, however, the depths of penetration of Trps of both peptides into neutral membranes were similar and independent of membrane composition. We previously demonstrated: 1), the abilities of both peptides to promote fusion but not initial intermediate formation during PEG-mediated fusion and 2), the ability of hexadecane to compete with this effect of the fusion peptides. Taken together, our current and past results suggest a hypothesis for a common mechanism by which these two viral fusion peptides promote fusion.
Multiresolution order-statistic CFAR techniques for radar target detection

Order-Statistic Constant False-Alarm Rate (OS-CFAR) processing provides an adaptive threshold to distinguish targets from clutter returns in radar detection. In traditional OS-CFAR, ordered statistics from a fixed-size reference window surrounding the cell under test (CUT) provide an estimate of the mean clutter power. We investigate adapting the reference window size as a function of the observed data in order to obtain robust detection performance in nonhomogeneous clutter environments. Goodness-of-fit tests are used to select the adaptive reference window size. Unlike traditional OS-CFAR, computationally e±cient multiscale OS-CFAR based on this approach must be modified to include the CUT in the reference window. The effects of CUT inclusion are investigated. Preliminary results suggest that CUT-inclusive OS-CFAR with adaptive window size performs well in nonhomogeneous clutter environments of varying size. These results point to the feasibility of computationally efficient multi-scale OS-CFAR.
Role of CD8+ and CD4+ T cells in the rejection of murine intestinal allografts

A MAJOR factor preventing the more widespread clinical application of intestinal transplantation is the unusual frequency and severity of allograft rejection. Using a murine model of intestinal transplantation, we have previously shown that allograft rejection was dependent on ab, but not gd, T cells and that this rejection could be significantly inhibited by tacrolimus, an immunosuppressive agent with potent anti-T-cell properties. In this study, the murine model was used to examine further the role of CD8 and CD4 T cells in the rejection of intestinal allografts.
The Differential Effects of Teaching Addition Through Strategy Instruction Versus Drill and Practice to Students With and Without Learning Disabilities

Forty-two second-grade general education students and 42 students with learning disabilities (LD) were taught basic, one-digit addition facts (e.g., 5 + 3 = _). Students received instruction via (a) a minimum addend strategy, (b) drill and practice, or (c) control. The effectiveness of the two methods was measured through students' accuracy and latency scores on a posttest and a transfer task (e.g., 5 + 3 + 7 =_). Students with LD improved significantly only in the strategy condition, as compared to drill-and-practice and control conditions, whereas general education students improved significantly both in the strategy and the drill-and-practice conditions as compared to the control condition. However, in the transfer task, students from all groups became significantly more accurate only in the strategy condition, while all students were significantly faster than their control group peers regardless of teaching method. The implications for teachers' differential choices of methods of instruction for students with different learning characteristics are discussed.
Regional patterns of biological soil crust lichen species composition related to vegetation, soils, and climate in Oregon, USA

Abstract Biological soil crusts are ecosystem engineers in arid and semi-arid habitats; they affect soil chemistry, stability, and vegetation. Little is known about regional variation in biotic crust communities of North America. We explored how biotic crust lichen community composition and richness are related to vascular plant, soil and climate characteristics in Oregon. In 59 0.4-ha plots, we found 99 biotic crust lichen species, one-third of which were observed only once. Biotic crust lichen communities rich in cyanolichens characterized Juniperus stands whereas warm grasslands were home to regionally uncommon species including Texosporium sancti-jacobi and Rhizocarpon diploschistidina. We discerned biotic crust communities in sandy Artemisia tridentata ssp. wyomingensis sites from those loamy A. arbuscula sites. Hotspots of biotic crust lichen species richness were geographically scattered, weakly negatively associated with abundance of shrubs of disturbed sites , Gutierrezia and Chrysothamnus. The sites with lowest biotic crust lichen richness were heavily grazed, burned plots with Gutierrezia in the grassy north; unstable steep talus slopes at the center of the study area; and sandy, grazed sites with Chrysothamnus in the southern portion of our region. Overall, regional patterns in biotic crust lichen communities were strongly associated with vegetation, soils, and climate.
SIGACT News Complexity Theory Column 10

We survey techniques and results obtained over the past thirty years for space-bounded probabilistic computation. We use a common framework for the study of both finite-state automata and logarithmic-space-bounded Turing machines. In particular, we present recent advances on space-efficient deterministic simulation of probabilistic automata.
Metal-catalyzed degradation and racemization of amino acids in iron sulfate brines under simulated martian surface conditions

Abstract Recent lines of evidence indicate that Mars may have been substantially warmer and wetter, raising questions about whether the planet’s surface was once more conducive to the possibility of life. To better constrain the extent of preservation of ancient amino acid biosignatures, the effects of metal ions and UV radiation were investigated with respect to the rates of diagenesis of amino acids in metal-rich sulfate brines. Individual experimental results indicate that the oxidation rates of amino acids loosely followed trends characteristic of a radiolytic oxidation mechanism that is dependent on variations in side-chain constituents. Relative rates of racemization only show a limited dependence on the presence of metals; overall, rates of racemization in the presence of metals in solution are an order of magnitude slower than oxidation and both are several orders of magnitude faster than previously reported. This increase in rate constant is indicative of an extremely efficient catalytic enhancement of this destructive diagenetic pathway. These findings imply that chiral life-detection strategies should focus on specific geochemical environments that exhibit relatively slow rates of both degradation and racemization. Episodic liquid water during periods of increased water activity on the martian surface may have significant implications for the oxidation of organic matter through secondary diagenetic reactions and may act as a leveling mechanism for organic compounds.
Generation of pulses with negative group velocities via four-wave mixing in 85 Rb

We generate pairs of superluminal pulses via four-wave mixing. A relative pulse peak advancement of the seed pulses of > 50% is demonstrated. Generated conjugate pulses can propagate with negative group velocities of up to ν g = −1/880c.
Prenatal alcohol exposure delays the development of the cortical barrel field in neonatal rats

In-utero alcohol exposure produces sensorimotor developmental abnormalities that often persist into adulthood. The rodent cortical barrel field associated with the representation of the body surface was used as our model system to examine the effect of prenatal alcohol exposure (PAE) on early somatosensory cortical development. In this study, pregnant female rats were intragastrically gavaged daily with high doses of alcohol (6 gm/kg body weight) throughout the first 20 days of pregnancy. Blood alcohol levels were measured in the pregnant dams on gestational days 13 (G13) and G20. The ethanol treated group (EtOH) was compared to the normal control chowfed (CF) group, nutritionally matched pairfed (PF) group, and cross-foster (XF) group. Cortical barrel development was examined in pups across all treatment groups from G25, corresponding to postnatal day 2 (P2), to G32 corresponding to P9. The EtOH and control group pups were weighed, anesthetized, and perfused. Brains were removed and weighed with, and without cerebellum and olfactory bulbs, and neocortex was removed and weighed. Cortices were then flattened, sectioned tangentially, and stained with a metabolic marker, cytochrome oxidase (CO) to reveal the barrel field. Progression of barrel development was distinguished into three categories: (a) absent, (b) cloudy barrel-like pattern, and (c) well-formed barrels with intervening septae. The major findings are: (1) PAE delayed barrel field development by one or more days, (2) the barrel field first appeared as a cloudy pattern that gave way on subsequent days to an adult-like pattern with clearly demarcated intervening septal regions, (3) the barrel field developed differentially in a lateral-to-medial gradient in both alcohol and control groups, (4) PAE delayed birth by one or more days in 53% of the pups, (5) regardless of whether pups were born on G23 (normal expected birth date for non-alcohol controls) or as in the case for the alcohol-delayed pups born as late as G27, the barrel field was never present at birth suggesting the importance of postnatal experience on barrel field development, and (6) PAE did not disrupt the normal barrel field pattern, although both total body and brain weights were compromised. These findings suggest that PAE delays the development of the somatosensory cortex (SI); such delays may interfere with timing and formation of cortical circuits. It is unknown whether other nuclei along the somatosensory pathway undergo similar delays in development or if PAE selectively disrupts cortical circuitry.
Notes on infinite determinants of Hilbert space operators

Abstract We present a novel approach to obtaining the basic facts (including Lidskii's theorem on the equality of the matrix and spectral traces) about determinants and traces of trace class operators on a separable Hilbert space. We also discuss Fredholm theory, “regularized” determinants and Fredholm theory on the trace ideals, l p(p
Effect of corticosterone administration at varying levels on leucine oxidation and whole body protein synthesis and breakdown in adrenalectomized rats.

Abstract Adrenalectomized rats were implanted with pellets containing corticosterone in proportions varying from 0% to 100%, plus cholesterol. Stable levels of plasma corticosterone resulted, varying from close to zero (I) to physiologic (II) to supraphysiologic (III). Whole body protein synthesis (S) was measured during fasting by a technique involving injection of [1-14C]-leucine, analysis of expired air for 14CO2, and measurement of urinary excretion of urea N plus ammonia N(C). Whole body breakdown (B) during fasting was calculated as the sum of S and C. C rose progressively from I to III, but fractional oxidation of 14C leucine was lowest in II. Both S and B were markedly reduced in I and maximal in II. In III, S fell but B remained high. Thus variations in glucocorticoid levels above and below physiologic exert profound effects on leucine oxidation and protein turnover, involving effects on both synthesis and breakdown.
Orientational asymmetries in small-field optokinetic nystagmus in human infants

Optokinetic nystagmus (OKN) is a pattern of reflexive eye movements which occurs when portions of the visual field are in continuous motion. Gratings moving at 7 deg/s either horizontally (left or right) or vertically (up or down) were presented on a viewing screen subtending 30 degrees by 22 degrees. Horizontal (HOKN) and vertical (VOKN) OKN were recorded under binocular viewing conditions from infants and adults. Eye movements were recorded by means of an infrared corneal reflection eye movement recorder. OKN to horizontal and vertical stimuli was different in pattern for infants. Infants' HOKN was of significantly higher frequency and lower amplitude than their VOKN. Infants below 4 months of age also showed an asymmetry within VOKN between upward and downward stimulus motion, with markedly lower gains and more variable slow phase following movements for downward moving stimuli. No differences were found in HOKN to the right and left. There was also no evidence of a build-up of slow phase velocity over time. Infants' fast phases showed peak velocity/amplitude relationships like those of adults, and like those of infant saccades recorded in a previous study of infants' fast eye movements. Across all directions of stimulus movement, infants had lower slow phase gains and OKN frequencies, and larger slow phase amplitudes than adults. The characteristics of infants' OKN are discussed in relation to those observed in other species and in adult clinical patients with eye movement disorders.
Epidemiology of carpal tunnel syndrome in patients with single versus multiple trigger digits.

Purpose Previous studies have identified the association between trigger digit and carpal tunnel syndrome (CTS). However, whether the presence of multiple trigger digits affects the prevalence of CTS is unknown. The purpose of this study was to determine the incidence of carpal tunnel symptoms in patients treated for single versus multiple trigger digits. Methods We performed a retrospective review of 300 patients treated for trigger digit by injection or surgical release and recorded CTS symptoms, signs, and treatment for either the ipsilateral or contralateral hand documented within 24 months before trigger digit treatment and for an average of 35 months (range, 7– 66 mo) after treatment. Patients were categorized as having single (n = 160) or multiple (n = 140) trigger digits. Binary logistic regression modeled risk factors for development of CTS. Patient age, sex, number of trigger digits (single or multiple), and presence of diabetes, gout, thyroid disease, or thumb osteoarthritis were considered independent variables. Results A total of 58 of 140 patients (41%) who presented with multiple trigger digits exhibited concomitant carpal tunnel symptoms, compared with 26 of 160 (16%) patients who presented with a single trigger digit. Significant independent predictors of CTS associated with trigger digits in the final regression model included multiple trigger digits (odds ratio=3.6; subjects with multiple trigger digits had significantly higher odds of carpal tunnel presentation than subjects with a single trigger digit) and diabetes (odds ratio=1.9; diabetic subjects had significantly higher odds of carpal tunnel presentation than nondiabetics). Conclusions A greater than 3-fold increase in the relative risk of CTS development exists in patients undergoing treatment for multiple trigger digits, compared with those undergoing treatment for a single trigger digit. Awareness of this association may aid in the early diagnosis and treatment of CTS in patients presenting with multiple trigger digits. Type of study/level of evidence Prognostic III.
Monoclonal antibody to calmodulin: development, characterization, and comparison with polyclonal anti-calmodulin antibodies

Specific anti-calmodulin rabbit polyclonal and murine monoclonal antibodies have been produced with a thyroglobulin-linked peptide corresponding to amino acids 128-148 of bovine brain calmodulin. The monoclonal antibody is IgG-1 with kappa light chains. Both sets of antibodies recognize native vertebrate calmodulin, with the polyclonal antibody exhibiting an approximately fourfold higher sensitivity than the monoclonal antibody in a radioimmunoassay. The affinity of both polyclonal and monoclonal antibodies is approximately 2.5-fold higher for Ca(2+)-free calmodulin than for Ca(2+)-calmodulin. Other selected members of the calmodulin family (S100, troponin, and parvalbumin) do not exhibit significant cross-reactivity with the monoclonal antibody. Troponin and S100 beta displace some 125I-calmodulin from the polyclonal antibody, but require at least 900-fold excess concentration. The monoclonal antibody recognizes intact vertebrate calmodulin in solution and also on solid-phase. In addition, plant calmodulin and some forms of post-translationally modified calmodulin (phosphorylated or glycated) bind the monoclonal antibody. The affinity of the monoclonal antibody is approximately 5 x 10(8) liters/mol determined by displacement of 125I-calmodulin. On dot blotting the sensitivity for vertebrate calmodulin is 50 pg. The epitope for the monoclonal antibody is in the carboxyl terminal region (residues 107-148) of calmodulin. This highly specific anti-calmodulin monoclonal antibody should be a useful reagent in elucidating the mechanism by which calmodulin regulates intracellular metabolism.
Dissipative particle dynamics simulation of poly(ethylene oxide)–poly(ethyl ethylene) block copolymer properties for enhancement of cell membrane rupture under stress

Abstract Magnetic Fluid Hyperthermia (MFH) is an encouraging cancer treatment involving superparamagnetic nanoparticles coated with bio-active molecules. When placed in an oscillating magnetic field, the particles release heat into the tumor environment. The generally accepted mechanism of cell death is through hyperthermia, but it is plausible that destruction of the cell through mechanical means could also play a significant role. In this study, we examine mechanical disruption of a model cell membrane in the presence of a representative magnetic nanoparticle coating, the copolymer poly(ethylene oxide)–poly(ethyl ethylene) (PEO–PEE). Our goal is to determine the effect of polymer properties on the mechanical rupture of a cell membrane under stress. Using dissipative particle dynamics, we create an interacting system of dipalmitoylphosphatidylcholine lipids, PEO–PEE polymers, and water and apply an incremental tension until bilayer rupture occurs. Our findings show that the optimal structure of the block copolymers to enhance rupture is relatively short polymers with a hydrophobic–hydrophilic–hydrophobic block structure containing a high hydrophilic content. Additionally, we compare the energy necessary to rupture a cell membrane with the magnetostatic energy of magnetic nanoparticles in MFH and our results indicate that nanoparticle sizes of the order of those currently used in standard MFH treatment produce enough energy for mechanical rupture, thus suggesting that mechanical means may be exploited in MFH to enhance the destruction of tumor cells.
Gender and textbooks: Women writers of elementary readers, 1880–1950

Between 1880 and 1950, the role of women as authors of elementary readers flowered and faded. From 1880 to 1915, female authorship dominated. Over the next fifteen years female authorship withstood the challenge of the scientific movement in education. Women’s role as solo authors declined, however, during the Depression, World War II and the postwar years. These changes are explained by the deteriorating environment for female professionalism, changes in the concept of reading expertise, the expanded role of publishers in textbook development, and the differences between men and women in opportunities for graduate study.
Concise review: the role of hematopoietic stem cell transplantation in the treatment of acute myeloid leukemia.

Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative option for patients with acute myeloid leukemia (AML). Our understanding of the biology of leukemic stem cells has continued to improve over the last decade and risk stratification using cytogenetics and molecular markers have improved our ability to select patients who would benefit from allogeneic transplantation. Results of HSCT have also improved substantitally, extending the potential application of allogeneic transplant to more patients. This review discusses the theoretical aspects of transplant, analyzes clinical results, and provides recommendations for the use of HSCT in AML. Further study of the biology of leukemic stem cells and the role for HSCT is necessary to optimize outcomes in AML patients. STEM CELLS 2012;30:1581–1586
Prolactin secretion in posterior pituitary lobectomized rats: differential effects of 5-hydroxytryptophan and ether

Abstract The objective of this study was to determine whether the posterior pituitary mediates the prolactin (PRL) releasing activities of serotonin and ether. Ovariectomized (OVEX) rats were subjected to posterior pituitary lobectomy (LOBEX) or sham surgery (SHAM). Either 1 or 12 days after surgery, rats were injected i.v. with 20 mg/kg b. wt. of 5-hydroxytryptophan (5-HTP), which is a precursor of serotonin. A second group of rats was exposed to ether vapors for 10 min. Blood was collected from a jugular cannula before and after the treatments and analyzed for PRL. On either 1 or 12 days after surgery, injection of 5-HTP increased plasma PRL levels 5–10 fold in both LOBEX and SHAM rats. This was followed by a decline to preinjection levels within 60–90 min. LOBEX and SHAM male rats which were injected i.p. with 50 mg/kg b. wt. of 5-HTP, also showed marked and similar elevations of plasma PRL levels 12 days after surgery. Exposure of OVEX rats to ether elicited a 2–3 fold rise in plasma PRL levels only on day 1, but not on day 12, after LOBEX. The ether-induced rise in PRL was similar in SHAM rats tested on both days. These results indicate that the 5-HTP-induced rise in plasma PRL levels is independent of the posterior pituitary, regardless of the sex, the route of drug administration or the length of time after surgery. In contrast, the PRL response to ether stress is diminished within 12 days after LOBEX. The evidence that the PRL responses to 5-HTP and to ether might be mediated via different neuronal mechanisms is discussed.
Brief paper: Estimating the region of attraction for large-scale systems with uncertainties

In this paper, a new approach is proposed for estimating regions of attraction for large-scale dynamic systems. In designing control laws for such systems, it is essential to incorporate the underlying information structure constraints while keeping the number of optimization variables at a minimum. The proposed method successfully accomplishes both of these objectives. It is computationally efficient, and can produce decentralized control laws without imposing structural constraints on the Lyapunov function (a feature that can considerably improve the quality of the estimate). The design algorithm is based on linear matrix inequalities and can easily accommodate various types of uncertainties in the system model. An example with 300 states is provided to demonstrate the suitability of this approach for large, sparse systems.
Derivatives of 1,1′-bis(diphenylphosphino)ferrocene (dppf): Electrochemistry, complexation and the X-ray structures of 1,1′-bis(diphenylphosphino)osmocene (dppo) and [PdCl2(dppo)]

Abstract The oxidative electrochemistry of 1,1′-bis(diphenylphosphino)osmocene (dppo) and 1,1′-bis(diphenylarsino)ferrocene (dpaf) was studied in dichloromethane with tetrabutylammonium hexafluorophosphate as the supporting electrolyte. The [MCl2(P∩P)] (M = Pd or Pt; P∩P = dppo or 1,1′-bis(diphenylphosphinoindenyl)iron) complexes were prepared, studied electrochemically and the X-ray structures of dppo and [PdCl2(dppo)] were determined.
Withdrawal of Inhaled Nitric Oxide from Nonresponders after Short Exposure

INTRODUCTION: Inhaled nitric oxide has been approved by FDA for treatment of hypoxic respiratory failure in term and near-term neonates. The safety of withdrawing NO in patients who fail to respond is a major concern. OBJECTIVE: To obtain further insight into the safety of withdrawing NO in patients who do not initially respond to this therapy, the charts of patients enrolled at our center in the Neonatal Nitric Oxide Study (NINOS) were reviewed. Oxygenation indices (OI) before, during and after exposure to NO or placebo were compared. METHODS: The charts of 110 neonates who received NO or placebo within the NINOS trial guidelines from 1995 to 1999 were reviewed. Arterial blood gases of nonresponders before, during and after a 30-minute exposure to different doses of NO or placebo were analyzed. RESULTS: For both high-dose and 20 ppm nonresponders who received NO, there was no significant change in OI from baseline after withdrawing NO. For patients receiving placebo, there was a significant increase in OI following a 30-minute exposure to placebo. CONCLUSIONS: NO has been shown to be effective in the treatment of neonatal respiratory failure; however, not all recipients demonstrate clinical improvement. This study showed that withdrawing NO in nonresponders did not cause increased respiratory morbidity when NO exposure was limited to 30 min. Differences between our results and others showing refractory hypoxia after withdrawing NO may be due to different durations of NO exposure and, possibly, its effect on endogenous NO metabolism.
Topological hypercovers and 1-realizations

We show that if U * is a hypercover of a topological space X then the natural map hocolim U * → X is a weak equivalence. This fact is used to construct topological realization functors for the 1-homotopy theory of schemes over real and complex fields. In an appendix, we also prove a theorem about computing homotopy colimits of spaces that are not cofibrant.
Large variations in balloon ascent rate over Hawaii

[1] A sequence of nine weather balloons were launched recently over the island of Hawaii during the nights of 12, 13, and 17 December, 2002, providing measurements of ascent rate, horizontal wind speed and direction, temperature, and other quantities. The measurements show short intervals of altitude with a large increase in ascent rate, occurring only near the tropopause, indicating regions of strong upward air velocity at this location. The large ascent rates correlate well to the strength of a jet stream, and with the presence of a local critical level, indicating mountain waves as the primary cause. No corresponding decreases in ascent rate were measured, suggesting strong three-dimensional effects.
WHAT IS QUANTITATIVE REASONING? DEFINING THE CONSTRUCT FOR ASSESSMENT PURPOSES

In order to create fair and valid assessments, it is necessary to be clear about what is to be measured and how the resulting data should be interpreted. For a number of historical and practical reasons described in this paper, adequately detailed statements with both a theoretical and empirical base do not currently exist for the construct of quantitative reasoning for use in assessments. There is also no adequate explanation of the important differences between assessments that measure quantitative reasoning constructs and those that are intended to measure achievement in related mathematical content areas. The literature in psychology, psychometrics, philosophy, and education, while containing much that is relevant to the construct of quantitative reasoning, unfortunately does not provide materials that can be used in research and development to address such practical issues or to explain the basic nature of quantitative reasoning assessments. This paper briefly discusses the importance and use of constructs and the quantitative reasoning and standards literature. It then presents a statement about the construct of quantitative reasoning for assessment purposes within a construct validity framework that includes both a definition of the construct and threats to valid score interpretation. These threats are based on related but distinguishable constructs and other types of construct-irrelevant variance in the assessments.
Codon Usage Methods for Horizontal Gene Transfer Detection Generate an Abundance of False Positive and False Negative Results

Bacteria acquire new DNA in a process known as horizontal gene transfer (HGT). To investigate the evolutionary impact of this transfer of DNA, various methods have been developed to detect past HGT events. For example, codon usage-based methods detect the presence of transferred genes by identifying atypical patterns of codon usage. However, some inherited genes exhibit atypical codon usage and some transferred genes have codon usage patterns similar to those of the inherited genes. In this study, we used a comparative phylogenetic approach with Methylobacterium and Caulobacter species to demonstrate that even well-designed codon usage methods fail to detect many HGT events and generate a high rate of false positives (60–75 %) and false negatives (23–61 %). Therefore, we recommend caution when employing codon usage methods to identify transferred genes and suggest that the rapidly increasing availability of bacterial genome sequences makes the phylogenetic approach the method of choice.
Supercritical fluid extraction of aromatic contaminants from a sandy loam soil

Near-critical fluids and liquefied gases can achieve high efficiencies in the extraction of organic contaminants from soil. Adsorptive behavior of several polycyclic aromatic hydrocarbons (PAHs) from supercritical carbon dioxide (SC CO{sub 2}) onto sandy loam-type soil has been characterized. Data for the solubility of phenanthrene, anthracene, triphenylene, and perylene in SC CO{sub 2} demonstrates a strong relationship between solubility and the carbon number and angularity of the ring structure. Soil adsorption isotherms for these compounds are non-linear, and have been described using Freundlich and BET adsorption models. The slope of the adsorption isotherms has been correlated with PAH solubility on log-log coordinates. Addition of polar modifiers, e.g., water or methanol, dramatically reduces the PAH adsorption levels, indicating the importance of polar adsorption sites on soil surfaces.
A Calmodulin-Dependent Translocation Pathway for Small Secretory Proteins

Metazoans secrete an extensive array of small proteins essential for intercellular communication, defense, and physiologic regulation. Their synthesis takes mere seconds, leaving minimal time for recognition by the machinery for cotranslational protein translocation into the ER. The pathway taken by these substrates to enter the ER is not known. Here, we show that both in vivo and in vitro, small secretory proteins can enter the ER posttranslationally via a transient cytosolic intermediate. This intermediate contained calmodulin selectively bound to the signal peptides of small secretory proteins. Calmodulin maintained the translocation competence of small-protein precursors, precluded their aggregation and degradation, and minimized their inappropriate interactions with other cytosolic polypeptide-binding proteins. Acute inhibition of calmodulin specifically impaired small-protein translocation in vitro and in cells. These findings establish a mammalian posttranslational pathway for small-protein secretion and identify an unexpected role for calmodulin in chaperoning these precursors safely through the cytosol.
Observations of wave effects on inlet circulation

Abstract Observations of water levels, winds, waves, and currents in Katama Bay, Edgartown Channel, and Katama Inlet on Martha׳s Vineyard, Massachusetts are used to test the hypothesis that wave forcing is important to circulation in inlet channels of two-inlet systems and to water levels in the bay between the inlets. Katama Bay is connected to the Atlantic Ocean via Katama Inlet and to Vineyard Sound via Edgartown Channel. A numerical model based on the momentum and continuity equations that uses measured bathymetry and is driven with observed water levels in the ocean and sound, ocean waves, and local winds predicts the currents observed in Katama Inlet more accurately when wave forcing is included than when waves are ignored. During Hurricanes Irene and Sandy, when incident (12-m water depth) significant wave heights were greater than 5 m, breaking-wave cross-shore (along-inlet-channel) radiation stress gradients enhanced flows from the ocean into the bay during flood tides, and reduced (almost to zero during Irene) flows out of the bay during ebb tides. Model simulations without the effects of waves predict net discharge from the sound to the ocean both during Hurricane Irene and over a 1-month period with a range of conditions. In contrast, simulations that include wave forcing predict net discharge from the ocean to the sound, consistent with the observations.
The Effect of a Whey Protein Supplement on Bone Mass in Older Caucasian Adults.

Context: It has been assumed that the increase in urine calcium (Ca) that accompanies an increase in dietary protein was due to increased bone resorption. However, studies using stable Ca isotopes have found that dietary protein increases Ca absorption without increasing bone resorption. Objective: The objective of the study was to investigate the impact of a moderately high protein diet on bone mineral density (BMD). Design: This was a randomized, double-blind, placebo-controlled trial of protein supplementation daily for 18 months. Setting: The study was conducted at two institutional research centers. Participants: Two hundred eight older women and men with a body mass index between 19 and 32 kg/m2 and a self-reported protein intake between 0.6 and 1.0 g/kg participated in the study. Intervention: Subjects were asked to incorporate either a 45-g whey protein or isocaloric maltodextrin supplement into their usual diet for 18 months. Main Outcome Measure: BMD by dual-energy x-ray absorptiometry, body com...
Reduction mammaplasty and mastopexy in previously irradiated breasts.

Background: Little data exist on the safety of elective breast surgery following breast conservation therapy. Objectives: The authors evaluate their experience performing reduction mammaplasties and mastopexies in previously irradiated breasts. Methods: A retrospective chart review was conducted of all reduction mammaplasties and mastopexies in previously irradiated breasts performed by the 2 senior authors (MYN and SLS) from 1995 to 2012 (n = 18). Patient records were analyzed for demographics, perioperative and postoperative details, and complications. Results: During the study period, 12 reduction mammaplasties and 6 mastopexies were performed on breasts previously treated with breast conservation therapy. The average study participant age was 49.5 years, and average body mass index was 29. Average preoperative bra cup size was D/DD. One patient was a former smoker; 17 were nonsmokers. Eleven of the 18 patients had been previously treated with chemotherapy; average time between radiation therapy and surgery was 2.5 years. Average specimen weight in the 12 reduction mammaplasties was 623 g. Twenty-two percent (n = 4) of patients experienced a total of 5 minor complications; none required a return to the operating room. One patient (6%) experienced a major complication resulting in approximately 50% loss of breast tissue, which was reconstructed with a latissimus dorsi musculocutaneous flap. Seventeen patients (94%) had successful outcomes with preoperative goals achieved. Conclusions: In the previously irradiated breast, reduction mammaplasty and mastopexy should be approached with extra caution, but the surgeries may still be safely and successfully performed. Level of Evidence: 4 ![Graphic][1] [1]: /embed/inline-graphic-1.gif
Peer victimization and social alienation: predicting deviant peer affiliation in middle school.

Two prospective studies examined a theoretical model wherein exposure to victimization, resulting from early behavioral risk, heightens children's social alienation and subsequent deviant peer affiliation (DPA). Across Study 1 (298 girls, 287 boys; K–7th grade; 5–12 years) and Study 2 (338 girls, 298 boys; 2nd–6th grade; 8–12 years), children, parents, peers, and teachers reported on children's externalizing behavior and internalizing symptoms, peer victimization, social alienation, and DPA. Path analyses supported the proposed pathway: Peer victimization predicted social alienation, which then predicted DPA. Early externalizing behavior set this path in motion and made an independent contribution to DPA. This research identifies an important pathway through which externalizing behavior and consequent peer victimization launch children onto a risky social trajectory.
Analysis of septins across kingdoms reveals orthology and new motifs

Septins are cytoskeletal GTPase proteins first discovered in the fungus Saccharomyces cerevisiae where they organize the septum and link nuclear division with cell division. More recently septins have been found in animals where they are important in processes ranging from actin and microtubule organization to embryonic patterning and where defects in septins have been implicated in human disease. Previous studies suggested that many animal septins fell into independent evolutionary groups, confounding cross-kingdom comparison. In the current work, we identified 162 septins from fungi, microsporidia and animals and analyzed their phylogenetic relationships. There was support for five groups of septins with orthology between kingdoms. Group 1 (which includes S. cerevisiae Cdc10p and human Sept9) and Group 2 (which includes S. cerevisiae Cdc3p and human Sept7) contain sequences from fungi and animals. Group 3 (which includes S. cerevisiae Cdc11p) and Group 4 (which includes S. cerevisiae Cdc12p) contain sequences from fungi and microsporidia. Group 5 (which includes Aspergillus nidulans AspE) contains sequences from filamentous fungi. We suggest a modified nomenclature based on these phylogenetic relationships. Comparative sequence alignments revealed septin derivatives of already known G1, G3 and G4 GTPase motifs, four new motifs from two to twelve amino acids long and six conserved single amino acid positions. One of these new motifs is septin-specific and several are group specific. Our studies provide an evolutionary history for this important family of proteins and a framework and consistent nomenclature for comparison of septin orthologs across kingdoms.
Differential Localization of Protein Kinase C δ by Phorbol Esters and Related Compounds Using a Fusion Protein with Green Fluorescent Protein

Enzyme localization often plays a controlling role in determining its activity and specificity. Protein kinase C (PKC) has long been known to translocate in response to physiological stimuli as well as to exogenous ligands such as the phorbol esters. We report here that different phorbol derivatives and related ligands, selected for differences in chemical structure and profile of biological activity, induce distinct patterns of redistribution of PKC delta. Localization of a PKC delta-green fluorescent protein (GFP) fusion construct was monitored in living Chinese hamster ovary cells as a function of ligand, concentration, and time using confocal laser scanning microscopy. delta-PKC-GFP was expressed predominantly in the cytoplasm, with some in the nucleus and perinuclear region. Phorbol 12-myristate 13-acetate (PMA) induced plasma membrane translocation followed by slower nuclear membrane translocation. As the concentration of PMA increased, the proportion of nuclear to plasma membrane localization increased markedly. In contrast to PMA, bryostatin 1, a unique activator of PKC that induces a subset of PMA-mediated responses while antagonizing others, at all doses induced almost exclusively nuclear membrane translocation. Like PMA, the complete tumor promoter 12-deoxyphorbol 13-tetradecanoate induced plasma membrane and slower nuclear membrane translocation, whereas the inhibitor of tumor promotion 12-deoxyphorbol 13-phenylacetate, which differs only in its side chain, induced a distinctive distribution of PKC delta-GFP. Finally, the novel constrained diacylglycerol derivative B8-DL-B8 induced a slow Golgi localization. We speculate that differential control of PKC delta localization may provide an interesting strategy for producing ligands with differential biological consequences.
RSVP: A task, reading aid, and research tool

Computer presentation of text material is evaluated with respect to its efficiency relative to normal reading. All results are examined in light of the various task analyses associated with different variations on the technique. Finally, the utility of computer presentation as a research tool for investigating human information processing is addressed.