cssi/SciSciGPT-SciSciNet huggingface dataset:
Magnetoresistive biosensors for quantitative proteomics

Quantitative proteomics, as a developing method for study of proteins and identification of diseases, reveals more comprehensive and accurate information of an organism than traditional genomics. A variety of platforms, such as mass spectrometry, optical sensors, electrochemical sensors, magnetic sensors, etc., have been developed for detecting proteins quantitatively. The sandwich immunoassay is widely used as a labeled detection method due to its high specificity and flexibility allowing multiple different types of labels. While optical sensors use enzyme and fluorophore labels to detect proteins with high sensitivity, they often suffer from high background signal and challenges in miniaturization. Magnetic biosensors, including nuclear magnetic resonance sensors, oscillator-based sensors, Hall-effect sensors, and magnetoresistive sensors, use the specific binding events between magnetic nanoparticles (MNPs) and target proteins to measure the analyte concentration. Compared with other biosensing techniques, magnetic sensors take advantage of the intrinsic lack of magnetic signatures in biological samples to achieve high sensitivity and high specificity, and are compatible with semiconductor-based fabrication process to have low-cost and small-size for point-of-care (POC) applications. Although still in the development stage, magnetic biosensing is a promising technique for in-home testing and portable disease monitoring.
Improving the Specificity of Cardiac Biomarkers-The Early Development of Cardiac Troponin I (cTnI) Assays.

Featured Article: Adams JE III, Bodor GS, Davila-Roman VG, Delmez JA, Apple FS, Ladenson JH, Jaffe AS. Cardiac troponin I: a marker with high specificity for cardiac injury. Circulation 1993;88:101–6.2 By the late 1980s, it was clear that there were frequent increases of creatine kinase-muscle–brain (CK-MB)3 in patients with renal failure, hypothyroidism, pulmonary embolism, and a variety of skeletal muscle pathologies. Thus, there were often questions about whether such increases were due to the release from tissues other than the heart and especially from skeletal muscle where there is reexpression of B-chain CK protein in response to injury. These questions made the triage of patients with increased CK-MB values difficult, especially when conjoint skeletal muscle and cardiac muscle injury was present as is common postoperatively (1). Because of these difficulties, there was interest in developing more clinically specific cardiac markers. Initially, cardiac troponin T (cTnT) was introduced, but there were questions related to its clinical specificity. These questions subsequently were found to result from antibody cross-reactivity with skeletal muscle troponin, and that problem was …
Oxidative Stress in Systemic Lupus Erythematosus: Causes, Consequences, and Treatment

Abstract The causes of systemic lupus erythematosus (SLE) are unknown; however, the pathogenesis is attributed, at least in part, to compartmentalized oxidative stress within the immune system. The accumulation of mitochondria is considered a primary source of increased production of reactive oxygen intermediates (ROI) in T cells. In turn, ROI generate diffusible inflammatory lipid hydroperoxides, which spread oxidative stress to other intracellular organelles and through the bloodstream. Biomarkers of oxidative stress correlate with disease activity and mediate organ damage. Oxidation triggers the autoantigenicity of host proteins and triggers autoimmunity. Depletion of the intracellular antioxidant, glutathione, leads to the activation of the mechanistic target of rapamycin that skews lineage specification in T cells. Importantly, the depletion of glutathione can be reversed by N-acetylcysteine with remarkable safety and promising therapeutic efficacy. In contrast, deficient generation of ROI in phagocytic cells may lead to the persistence of infectious organisms that may stimulate innate immune signaling and thus enhance autoimmunity.
Smoothly Varying Injected Neutral Beam Voltage and Current Provides New Capability on the DIII-D Tokamak

A significant engineering upgrade of the DIII-D neutral beam system has recently completed, providing ability to smoothly and independently vary the beam voltage and current. This enables greater control of the injected beam power, torque, and plasma instability drive for fusion experiments. Modifications to the high-voltage equipment and the plasma control system were made and tested over the last year to allow beam energy to vary by as much as 20 kV over a 0.5-s period anywhere within the 45–85 kV operating range of the beams. The beam current can be made to track the voltage (keeping the perveance constant), or the current and voltage can be varied independently (scanning the perveance). The smooth variation of beam energy avoids the extremely perturbative effects of pulsewidth modulation, the only tool previously used for regulating the injected neutral beam power. With independent control of voltage and current, the beam ion velocity space can be tailored to facilitate new experiments that explore, for example, the detrimental effects of Alfven eigenmodes. These modes are driven by energetic particles and can possibly be avoided in steady-state scenarios by timely variation of the beam energy while maintaining constant input power. A description of the modifications made to the power supply and beam controls will be presented, as well as some initial physics results employing the new variable beam energy system.
From “Scrub Players Playing on a Vacant Lot” to the Big Leagues: Ontarian and Victorian Educational Constructions of the Imperial Relationship

This chapter is a comparative study of the treatment of the British Empire in Ontarian and Victorian textbooks and curricula. A major emphasis in the chapter is the portrayal of Canadian and Australian involvement in the British Empire/Commonwealth, which comprised a central component of their national identities in educational materials. Authors and educators emphasized the importance of the imperial relationship through the 1950s, though many intellectuals recognized Britain’s declining status and world importance. By the 1960s, however, educators could no longer ignore the waning importance of Britain and the empire in the face of an accelerated program of decolonization. The collapse of the British Empire was a catalyst for major reforms in education in both Ontario and Victoria as educators struggled to find a new focus for the national identity.
Cardinal Utility and Decision Making under Uncertainty

In the expected utility theory developed by von Neuman and Morgenstern (1947) (See also Marschak, 1950), cardinal utility indices for an individual corresponding to a finite set of prizes {x1,...,xi,...,xn}, are derived from the ordering by the individual of the probability distributions over the set of prizes. It is shown that if the ordering of these probability distributions satisfies certain, so called, rationality conditions or rules,1 then cardinal utility indices uv i, constant up to positive affine transformations, can be assigned to the prizes xi such that the individual orders the probability distributions as if he or she were maximizing the expected value of the utilities uv i. According to some interpretations of the expected utility theory, the cardinal utility function uv i(xi) = uv i represents a joint effect of the attitude toward risk’of the individual and his or her “utility” or satisfaction of the prizes. There is no need, therefore, according to these interpretations of the theory, to assume the actual reality of utility as a cardinal magnitude under riskless conditions thus by-passing the controversy of cardinality versus ordinality where the existence in riskless conditions of utility as cardinal magnitude and the need to use it in economic theory are the main issues.
Regulation of Thyroid Hormone Metabolism in the Brain

In recent years, it has become apparent that most of the 3,5,3’ — triiodothyronine (T3) present in the cerebral cortical nuclei is derived from local thyroxine (T4) to T3 conversion. In this discussion, I will review our knowledge of the processes by which this situation arises and how it might serve to protect the brain from thyroid hormone deficiency in circumstances where serum T4 is reduced, such as occurs in hypothyroidism or in iodine deficiency. The review will include the enzymology of the brain deiodinases and how they respond to alterations in thyroid status, as well as our knowledge of their anatomical and cellular localization. In addition, the various levels of adaptation of thyroid hormone economy in the hypothyroid neonatal rat brain will be examined. Considerable knowledge has accumulated in this area over the last eight years. The interested reader should supplement the information in the discussion with the bibliographic citations and especially a recent comprehensive volume reviewing the subject of thyroid hormone metabolism (1).
Synthesis of 18F-Fluorobenzylguanidine analogues via SNAr substitution

1510 Objectives 124I/123I-MIBG have a limited capacity of sequential imaging of hNET-expressing cells in patients. Garg et al have shown that hydrophilic 18F-MFBG (or PFBG) is recognized and transported by hNET-expressing cells (Nucl Med Bio, 21:97-101, 1994). However, the radiosynthesis of 18F-MFBG (or PFBG) is a multi-step, labor intensive and time-consuming reaction that has impeded wider use of these tracers in the clinic. To simply the radiosynthesis, we designed and synthesized a novel diaryliodonium salt precursors in order to facilitate a two-step, one pot radiosynthesis. Methods Diaryliodonium salts precursors were synthesized from commercially available Iodobenzyl ethyl amine in three steps. These intermediate products were characterized by MS and [1H]NMR. Using anhydrous kryptofix-K18F as the starting material, fluorination was optimized by varying temperature (60oC to 130oC) and solvent (DMF and AcCN). After hydrolysis, 18F-MFBG (or PFBG) was purified by semipreparative HPLC. In-vitro evaluation was performed with hNET-expressing C6 and C6-WT cells. Results Stable diaryliodonium salts were obtained with an over-all yield of 40%, and further characterization confirmed the expected structures. 18F-MFBG (or PFBG) was prepared successfully in 1 hour with a radiochemical yield of 20% (decay-corrected). Radiochemical purity of both radiotracers is greater than 99%. In-vitro studies showed that 18F-MFBG (or PFBG) specifically accumulated in C6-hNET cells, which can be competitively blocked with an excess of MIBG. Conclusions Meta and para-118F-Fluorobenzylguanidines were synthesized successfully in a two-step reaction using diaryliodonium salts. In-vitro results showed that these agents are promising for imaging hNET reporter gene expression, and will likely have clinical application for PET imaging of neuroendocrine tumors
Energetic Nitroaromatic Transients and Their Role in Controlling the Sensitivity of Explosives

In the elucidation of initiation mechanisms of explosives it is important to identify and characterize the chemical reactivity of the energetic transient species formed via electronic or thermal excitation. Electronic excitation of s-TNB in aerated protic solvents generates a transient species the yield of which is a function of oxygen concentration. Spectroscopic and kinetic data suggest the formation of a complex between s-TNB and oxygen. Electronic excitation of mono- and dinitronaphthalenes leads to their lowest excited triplet states. The chemical reactivity of these states for hydrogen abstraction, electron and proton transfer was studied as a function of intramolecular charge distribution. This is the only known study which demonstrates by direct observation the high chemical reactivity of the excited states of nitroaromatics. Electronic excitation of s-TNT2 indicates a photochemically induced isomerization leading to an aci-quinoid transient in nonpolar solvents or its conjugate base in polar solvents. Identification of these transients was based on spectroscopic and kinetic data. The knowledge derived from these studies led to the discovery that proton abstractors, such as NaOH, KI, and (CH3) 4NB3H8, known as QMB3, induce deflagration in molten s-TNT. Furthermore, elucidation of the mechanism of the extensive sensitization of s-TNT by additives such as QMB3 and NaOH became possible. These findings seem to be extremely valuable towards understanding and possibly controlling the sensitivity of explosive materials.
Role of Infectious Agents on Development of Esophageal Carcinomas

Comprising two primary histological subtypes, esophageal squamous cell carcinoma and esophageal adenocarcinoma, esophageal cancer remains among the most aggressive forms of human malignancy. Despite advances in our understanding of the genetic landscape of esophageal cancer, patient outcomes remain poor, suggesting that cell extrinsic factors may influence disease pathogenesis. Interest in defining roles for infectious agents in esophageal carcinogenesis is rapidly emerging as an increasing number of clinical studies have linked various pathogens with esophageal cancer. Here, we review the current literature characterizing bacterial, viral, fungal and parasitic pathogens in the esophagus in the context of homeostasis and carcinogenesis. We discuss global changes in the microbial composition of the esophagus and adjacent organs as they relate to esophageal cancer. We further provide a comprehensive overview of the relationship between specific pathogens, including Helicobacter pylori, Herpesviridae and Human Immunodeficiency Virus, and esophageal cancer.
RRAM Solutions for Stochastic Computing

Stochastic computing is a low-cost form of computing. To perform stochastic computing, inputs need to be converted to stochastic bit streams using stochastic number generators (SNGs). The random number generation presents a significant overhead, which partially defeats the benefits of stochastic computing. In this work, we show that stochastic computing can be implemented in memory, through temporally varying resistive RAM (RRAM) devices. We can take advantage of the temporal variations in the resistance switching of RRAM devices for stochastic computing. By adopting a group write approach, an RRAM memory can be used to generate random bit streams and reshuffle bit streams, accomplishing two essential functions for stochastic computing without expensive SNGs. We demonstrate in-memory stochastic computing in two test applications, a gradient descent solver and a k-means clustering processor.
Treatment of a 4-Part Proximal Humeral Fracture with a Concomitant Glenoid Fracture in an Elderly Patient: A Case Report.

Case Reported here is a single case of a highly comminuted fracture of the proximal aspect of the humerus with substantial humeral head displacement and a concomitant glenoid fracture encompassing >20% of the glenoid width. The fractures were treated simultaneously with reverse total shoulder arthroplasty and open reduction and internal fixation, respectively. Conclusion The 1-year follow-up demonstrated excellent pain control and a good functional outcome, with no signs of instability or implant complications.
Derivation of a new drive/coast motor driver model for real-time brushed DC motor control, and validation on a MIP robot

Brushed DC motors are usually driven with PWM forcing in one of two modes: drive/brake or drive/coast. That is, at the low state of the PWM forcing profile, the motor driver will either “brake” the motor with its own back EMF, or allow the motor to “coast” (i.e., spin freely). Drive/brake motor drivers, which are by far the most common, may be represented by a Multilevel Four-Quadrant DC Chopper model, while drive/coast motor drivers may be represented by two independent Bipolar Two-Quadrant DC Chopper models. Conveniently, when averaged over the PWM duty cycle, drive/brake motor drivers are accurately modeled as linear systems over their entire operational range. On the other hand, drive/coast motor drivers, when averaged over the PWM duty cycle, exhibit significant nonlinear behaviors that are dependent on factors such as inductance, PWM frequency, and rotor speed. Though there are some existing partial derivations of drive/coast motor driver models, no comprehensive, experimentally-validated modeling approaches appropriate for feedback control applications over the full dynamic range of the motor could be readily found in the literature. In this paper, we derive a practical nonlinear model of a drive/coast motor driver, validate this model using a motor dynamometer, and demonstrate a real-time implementation of this model on a Mobile Inverted Pendulum (MIP) robot.
Adult palliative care in the USA: information-seeking behaviour patterns.

Objective Acceptance of palliative care (PC) in the USA has increased in recent decades with the growing number of recommendations for adoption from professional organisations. However, there are prevalent public misperceptions of PC that may prevent broader utilisation. This study seeks to identify the primary sources for PC information, which may help identify sources of misperception and improve PC messaging. Methods We analysed the 2018 Health Information National Trends Survey (HINTS), a representative survey of USA population knowledge regarding cancer-related information. This is the first iteration to include questions on PC. Prevalence of preferred PC information sources was estimated; multivariable logistic regression invoking stepwise variable selection was used to determine associations with information-seeking behaviour. Results Our study cohort consisted of 1127 American adults who were familiar with PC. Overall, 59.3% and 34.0% relied primarily on healthcare providers and internet or printed media, respectively. In stepwise regression models of seeking information from healthcare providers, predictors and their relative contributions to the multivariable model were higher education attainment (58.7%), age ≥60 years (21.5%) and female sex (15.0%). Higher income was the most robust predictor (35.1%) of reliance on internet and printed media for information, followed by being currently married (26.2%). Conclusions Overall, American adults rely on healthcare providers and media for PC information, with significant sociodemographic differences in information-seeking behaviour. These findings may be used to inform strategies to promote accurate PC awareness.
Measuring Law Faculty Scholarly Impact by Citations: Reliable and Valid for Collective Faculty Ranking

No single metric of faculty scholarly activity can fully capture every individual contribution. For that reason, evaluating a single professor’s scholarly work requires a nuanced, multifaceted, and individually focused assessment. However, for a contemporary sketch of the collective scholarly impact of a law school faculty, citation measurements in the legal literature are both reliable and valid. The new Heald-Sichelman study of citations in the HeinOnline database confirms the reliability of the multiyear results of the Leiter-Sisk Scholarly Impact Ranking based on the Westlaw journals database. Despite using a different law journal database, counting citations differently, including pre-tenure faculty, and even adding download statistics into the mix, the Heald-Sichelman ranking correlates powerfully at 0.88 with the most recent Leiter-Sisk ranking. An objective citation measurement is time-sensitive and corresponds to informed awareness of law school faculty developments around the country. A citation-based ranking thus is a valid, if imperfect, proxy for faculty scholarly impact on a national scale. With appropriate qualifications and necessary adjustments, a citation-based ranking should be considered in any evaluation of the overall quality of a law school faculty. For the U.S. News ranking of American law schools, an up-to-date, citation-based ranking would have considerable merit as an objective forward-directed control to the subjective past-looking academic reputation survey.
Pediatric limb salvage after severe thermal injury

Abstract Fourth-degree burns represent a significant challenge due to the exposure of delicate tissues (i.e., neurovascular structures, bones, joints) and complications (i.e., infection and graft loss). In addition to the typical challenges of significant tissue loss associated with fourth-degree burns, this is the first case report to describe a large-volume lymphatic leak of the extremity. We treated the lymphatic leak with bowel rest, parenteral nutrition, Octreotide, collagen matrix, and negative-pressure vacuum-assisted closure (V.A.C.®) therapy.
Evaluating Methods for Enabling Continuous Operation in Dynamic WiFi Direct Networks

Designing protocols for optimizing and controlling Mobile Ad Hoc Networks (MANETs) has been an active subject of research for many years; however, the autonomous configuration and maintenance of MANETs remains an open problem. WiFi Direct, a WiFi-Alliance standard facilitating peer-to-peer communication without the need for traditional WiFi access points, has been adopted on a variety of platforms including, phones, tablets, printers, smart TVs, and many other Linux based operating systems. Nevertheless, current WiFi Direct implementations rely on human intervention to restore connectivity in the event of a network failure. This work evaluates several of our previously proposed schemes for the autonomous creation and maintenance of WiFi Direct groups with the goal of quickly restoring communication when the network fails. We compare two methods for reforming a network with an approach that maintains two simultaneous WiFi Direct groups, allowing for the diversion of traffic when one of the groups fails. Each method is implemented and evaluated on a testbed of Raspberry Pi 3B single board computers making use of external wireless cards. Finally, we present scenarios that highlight the strengths and weaknesses of each method.
Generalising indirect defence and resistance of plants

Indirect defence, the adaptive top-down control of herbivores by plant traits that enhance predation, is a central component of plant-herbivore interactions. However, the scope of interactions that comprise indirect defence and associated ecological and evolutionary processes has not been clearly defined. We argue that the range of plant traits that mediate indirect defence is much greater than previously thought, and we further organise major concepts surrounding their ecological functioning. Despite the wide range of plant traits and interacting organisms involved, indirect defences show commonalities when grouped. These categories are based on whether indirect defences boost natural enemy abundance via food or shelter resources, or, alternatively, increase natural enemy foraging efficiency via information or alteration of habitat complexity. The benefits of indirect defences to natural enemies should be further explored to establish the conditions in which indirect defence generates a plant-natural enemy mutualism. By considering the broader scope of plant-herbivore-natural enemy interactions that comprise indirect defence, we can better understand plant-based food webs, as well as the evolutionary processes that have shaped them.
Homemaking: Radical Nostalgia and the Construction of a South Asian Diaspora: by Anindya Raychaudhuri, London/New York, Rowman & Littlefield International, 2018, 202 pp., £24.95 (paperback), ISBN 978-1783482634

In Homemaking: Radical Nostalgia and the Construction of a South Asian Diaspora, Anindya Raychaudhuri forwards nostalgia as the means through which South Asians in diaspora create a sense of home a...
Role of Hypercoagulable Studies in Cryptogenic Stroke: A Retrospective Study

Introduction: Hypercoagulable states are recognized, although uncommon, etiology of ischemic stroke especially in young adults under the age of 40 and children. Currently, there are no specific guidelines related to screening patients for inherited thrombophilia who are diagnosed with ischemic stroke without any identifiable risk factors. Typically, patients to be screened for thrombophilia will have prior unexplained thromboembolic events. We evaluated the association between thrombophilia and cryptogenic stroke and the role of serologic and genetic testing to establish the diagnosis. Material and methods: We performed a retrospective study through a review of EHR of patients diagnosed with ischemic stroke at our hospital between 2015- 2019 with laboratory testing for thrombophilia. The primary outcome was to identify any positive association between thrombophilia and cryptogenic stroke. The secondary outcome was to identify any change in clinical management based on thrombophilia testing results. Results: Among 35 patients included, who had an average age of 58.5 years ± 16.37 years with 36.6% under the age of 55 and 63.3% above the age of 55. Sex distribution was 40% female and 60%, male. Of 35 patients who had thrombophilia studies ordered, 9 patients had at least one positive thrombophilia test identified but none of them had any resultant change in management. 2 patients had protein C deficiency, 3 patients had protein S deficiency and 4 patients had antithrombin III deficiency, however, they were measured during the acute phase and were not repeated as an outpatient. None of the patients were found to have any Factor V and PT gene G20210A gene mutation. Lupus anticoagulant, antiphospholipid antibodies, homocysteine level were not uniformly tested. Conclusion: Only 8% of all patients who had thrombophilia testing had at least one positive study with no change in clinical management. We concluded that there is a poor correlation between inherited thrombophilia and cryptogenic stroke. The majority of our patients who had worked up done were above the age of 55 years who didn't display any symptom of thrombophilia previously. It raises a question of reflexive and inappropriate testing in the absence of clear guidelines for thrombophilia workup in the setting of cryptogenic stroke. Disclosures No relevant conflicts of interest to declare.
A Portrait in Four Movements: The Chicago Symphony Under Barenboim, Boulez, Haitink, and Muti: by Andrew Patner, edited by John R. Schmidt and Douglas R. Shadle, Chicago, IL, University of Chicago Press, 2019, 255 pp., $27.50 (hardback), ISBN 978-0-226-60991-1

The rich history of the Chicago Symphony Orchestra, the third oldest among the group that has traditionally been known as the “Big Five” of the United States, dates back to 1891. There are a few bo...
Supply Voltage Dependence of Ring Oscillator Frequencies for Total Ionizing Dose Exposures for 7-nm Bulk FinFET Technology

Total ionizing dose (TID) effects at the 7-nm bulk FinFET node are characterized through changes in ring oscillator (RO) frequencies and current as a function of $V_{\mathrm {DD}}$ to model delay and power degradations in digital circuits. At the 7-nm node, tests show that gate delay decreased, and power consumption increased as TID increased. Percent increase in parameter degradations shows an inverse relationship with supply voltage, while percent increase in power consumption shows a direct relationship with supply voltage. Annealing at room temperature did not affect degradations. Circuit-level degradations for the 7-nm technology were less than 1% after TID exposure of 380 krad(SiO2). These TID exposure results will provide insight to designers about circuit-level parameters of interest concerning the 7-nm technology node.
With No Lysine Kinase 1 Promotes Right Ventricular Dysfunction Via Glucotoxicity

ObjectivesInvestigate how WNK1 inhibition modulates glucotoxicity, mitochondrial/peroxisomal protein regulation and metabolism, and right ventricular (RV) function in pulmonary arterial hypertension (PAH). Determine how hypochloremia impacts RV function in PAH patients. BackgroundIn PAH-induced RV failure, GLUT1/GLUT4 expression is elevated, which increases glucose uptake and glycolytic flux to compensate for mitochondrial dysfunction. However, the resultant consequences of the glucose-mediated post-translational modifications (PTM), protein O-GlcNAcylation/glycation in RV failure are understudied. WNK1, a chloride-sensitive kinase, increases GLUT1/GLUT4 expression in skeletal muscle, but its regulation in RV dysfunction is unexplored. MethodsRats were treated with WNK463 (small molecule WNK inhibitor) or vehicle starting two weeks after monocrotaline injection. Immunoblots quantified protein abundance/PTMs. Mitochondrial/peroxisomal proteomics and global metabolomics evaluated glucose metabolism and mitochondrial/peroxisomal function. Pulmonary vascular and cardiac histology, echocardiography, and pressure-volume loop analysis quantified RV function and PAH severity. Finally, the relationship between hypochloremia, a WNK1-activating state, and RV function was evaluated in 217 PAH patients. ResultsWNK463 decreased WNK1/GLUT1/GLUT4 expression, normalized glucose metabolite levels, which dampened excess protein O-GlcNAcylation/glycation. Integration of RV mitochondrial/peroxisomal proteomics and metabolomics identified fatty acid oxidation (FAO) as the most dysregulated metabolic pathway. WNK463 enhanced FAO as demonstrated by increased expression of mitochondrial FAO proteins and normalization of RV acylcarnitines. WNK463 reduced glutaminolysis induction and lipotoxicity, two secondary consequences of diminished FAO. WNK463 augmented RV systolic and diastolic function independent of pulmonary vascular disease severity. In PAH patients, hypochloremia resulted in more severe RV dysfunction. ConclusionsWNK463 combated RV glucotoxicity and impaired FAO, which directly improved RV function. HighlightsO_LISmall molecule inhibition of WNK1 (WNK463) signaling mitigates upregulation of the membrane glucose channels GLUT1 and GLUT4, restores levels of several glucose metabolites, and normalizes protein O-GlcNAcylation and glycation in the RV. C_LIO_LIQuantitative proteomics of RV mitochondrial enrichments shows WNK463 treatment prevents downregulation of mitochondrial enzymes in the tricarboxylic acid cycle, fatty acid oxidation pathway, and the electron transport chain complexes. C_LIO_LIIntegration of proteomics and metabolomics analysis reveals WNK463 reduces glutaminolysis induction and lipotoxicity due to impaired fatty acid oxidation C_LIO_LIWNK463 augments RV systolic and diastolic function independent of PAH severity. C_LIO_LIHypochloremia, a condition of predicted WNK1 activation, in PAH patients results in more severe RV dysfunction. C_LI
Sub-Arcsecond Mid-Infrared Observations of NGC 6240: Limitations of AGN-Starburst Power Diagnostics

In order to examine the relative importance of powerful starbursts and Compton-thick AGNs in NGC 6240, we have obtained mid-infrared images and low-resolution spectra of the galaxy with sub-arcsecond spatial resolution using the Keck Telescopes. Despite the high spatial resolution (~200 pc) of our data, no signature of the hidden AGNs has been detected in the mid-infrared. The southern nucleus, which we show provides 80-90% of the total 8-25 um luminosity of the system, has a mid-infrared spectrum and a mid-/far-infrared spectral energy distribution consistent with starbursts. At the same time, however, it is also possible to attribute up to 60% of the bolometric luminosity to an AGN, consistent with X-ray observations, if the AGN is heavily obscured and emits mostly in the far-infrared. This ambiguity arises because the intrinsic variation of properties among a given galaxy population (e.g., starbursts) introduces at least a factor of a few uncertainty even into the most robust AGN-starburst diagnostics. We conclude that with present observations it is not possible to determine the dominant power source in galaxies when AGN and starburst luminosities are within a factor of a few of each other.
Should I Stay or Should I Go Now: Late Establishment and Low Site Fidelity as Alternative Territorial Behaviors

In species in which males defend territories for breeding, males may differ in territorial behavior; alternative behaviors among territorial males are not well understood. In our long-term study of partially-migratory song sparrows, we have observed that most territorial males establish territories before females begin nesting and remain site-faithful both within and between breeding seasons; however, some males establish territories later in the season (late establishers) and/or change territory locations either within or between seasons (movers). Whether late establishment or moving are equally successful strategies for territory defense, or best-of-bad-job options, is not known. Here, we compare the frequencies of these behaviors to demographic variables over a 9-yr period and compare lifetime tenure and early season nesting success for males who differ in site fidelity and timing of territory establishment. Across years, late establishing was negatively correlated with the return rate of previously territorial males; moving was positively correlated with the number of occupied territories at the start of the breeding season (territory density). While moving was independent of number of years on territory, late territory establishment only occurred in a male’s first year as a territory holder. Of 88 males, 25% established their first territory late, primarily in undefended space; 31% moved. Late and early establishers did not differ in lifetime tenure; movers, however, had longer lifetime tenure than site-faithful males. Among early establishers, movers and non-movers did not differ in the number of successful early nests/year or number of young fledged/year; among late establishers, however, movers had significantly higher early nesting success by both measures. Late establishers who moved had higher early season nesting success and higher early season nesting success/year than site-faithful early establishers. Thus, individual variation in the timing of territory establishment and site fidelity may be facultative alternative territorial strategies.
Fluorescence excitation and imaging of single molecules near dielectric-coated and bare surfaces: a theoretical study.

Summary Microscopic fluorescent samples of interest to cell and molecular biology are commonly embedded in an aqueous medium near a solid surface that is coated with a thin film such as a lipid multilayer, collagen, acrylamide, or a cell wall. Both excitation and emission of fluorescent single molecules near film-coated surfaces are strongly affected by the proximity of the coated surface, the film thickness, its refractive index and the fluorophore’s orientation. For total internal reflection excitation, multiple reflections in the film
Experimental Leptospira interrogans serovar Kennewicki infection of horses.

Background: Little information is available about experimental induction of leptospirosis in horses. Objectives: Determine serologic, hematologic responses of horses to Leptospira interrogans serovar Kennewicki infection. Animals: Four adult horses seronegative for leptospirosis. Methods: Experimental and observational study. Horses were challenged with an equine isolate of L. interrogans serovar Kennewicki at 2 different doses and different inoculation sites. After challenge, the horses were monitored for 60 days. Blood, urine, and aqueous humor samples were collected at intervals until euthanasia 60 days after infection. Results: Pyrexia (39.3–40°C) occurred as early as 1 day after challenge with 10 × 108Leptospira divided equally between topical ocular and intraperitoneal injection in 2 horses. Leptospires were recovered from the blood and urine but not from the aqueous humor of the 2 febrile horses. The sera of all 4 challenged horses developed microscopic agglutination test antibody after challenge and remained relatively constant for 21 days. Titer to cross-reacting strains declined earlier than titer to the challenge strain. Conclusions: Clinical disease in experimentally infected horses can be mild or inapparent in Leptospira infected horses. Repeated serologic testing can allow recognition of the infecting serovar. In febrile horses, Leptospira can be isolated from blood while isolation from the urine can occur after fever has subsided.
Effects of cations and propranolol on a fluorescent phospholipid incorporated into brain synaptosome membranes.

Dimethylaminonaphthalenesulfonyl-phosphatidylserine (DNS-PS), a fluorescent phospholipid, was incorporated into rat brain synaptosomes by a procedure utilizing the chaotropic agent sodium perchlorate. This procedure caused only minor changes in the electron microscopic appearance and protein composition of the membranes. Perchlorate treatment alone altered the activity of selected enzymes such as acetylcholinesterase and monoamine oxidase, but the insertion of DNS-PS within the membrane had only minor effects on the specific activities of synaptosomal enzymes. The fluorescence emission maximum of the membrane-bound DNS-PS was shifted to a slightly longer wavelength by addition of 100 mM NaCl or KCl, and the polarization of fluorescence decreased. The addition of 10 mM CaC12 shifted the emission maximum to a shorter wavelength, increased relative fluorescence 10-20%, and increased the polarization of fluorescence. Energy transfer from aromatic residues of membrane proteins to the DNS moiety was increased 11% by CaCl2, while MgCl2 had little effect, suggesting that Ca2+ may decrease the intermolecular distance between aromatic amino acids of membrane proteins and the fluorescent phospholipid. The beta adrenergic blocking agent propranolol reversed the changes caused by calcium and displaced at least a portion of the bound cation from the membrane.
Lamotrigine extends lifespan but compromises health span in Drosophila melanogaster

The discovery of life extension in Caenorhabditis elegans treated with anticonvulsant medications has raised the question whether these drugs are prospective anti-aging candidate compounds. The impact of these compounds on neural modulation suggests that they might influence the chronic diseases of aging as well. Lamotrigine is a commonly used anticonvulsant with a relatively good adverse-effects profile. In this study, we evaluated the interaction between the impacts of lamotrigine on mortality rate, lifespan, metabolic rate and locomotion. It has been proposed in a wide range of animal models that there is an inverse relationship between longevity, metabolic rate, and locomotion. We hypothesized that the survival benefits displayed by this compound would be associated with deleterious effects on health span, such as depression of locomotion. Using Drosophila as our model system, we found that lamotrigine decreased mortality and increased lifespan in parallel with a reduction in locomotor activity and a trend towards metabolic rate depression. Our findings underscore the view that assessing health span is critical in the pursuit of useful anti-aging compounds.
Theory and Strategy in the Study of Cultural Adaptability

This evolutionary theory is also a functional theory in the sense that it involves the basic functional thesis that (1) institutions are mechanisms of social interaction which serve the continued life of the society, and (2) all parts of the social system must form an integrated whole so that changes in one part require adjustments in others. In addition, the functional theory stresses the priority of some aspects of society over others. To translate a theme from George Orwell's Animal Farm, all social institutions are basic, but some are more basic than others. That is to say, some aspects of the situation have immediate, direct, and consistent influences on the total structure of society, whereas others are peripheral. We do not deny that art and economy are related, nor even that art might change the economy of a society; however, it is more likely and more frequent that the economy changes the art. Furthermore, certain areas of life activity lie closer to such external factors as environment or such internal ones as technical change and are therefore more vulnerable to their pressures.
Alternatives to the Perfectly Matched Layer for Waveguide Simulation Using the FDFD Method

One of the most widely utilized absorbing boundaries for the finite difference frequency domain (FDFD) method is the perfectly matched layer (PML); however, this boundary is not ideal, as it significantly increases the computational complexity of a simulation. We compare three alternatives to the PML for modal solution using the FDFD method: the Higdon absorbing boundary condition, the complementary operators method, and the transparent absorbing boundary. These methods are integrated into an FDFD algorithm and applied to a well-known ridge waveguide test structure. The errors introduced by the absorbing boundaries are quantified in terms of propagation constant error and modal distortion, and compared to reported results using the PML.
Cyclophilin A Modulates Processing of Human Immunodeficiency Virus Type 1 p55Gag: Mechanism for Antiviral Effects of Cyclosporin A

Abstract The molecular chaperone cyclophilin A (Cyp A) modulates human immunodeficiency virus type 1 (HIV-1) infectivity through its interactions with Gag structural proteins. The molecular mechanism for CypA in HIV-1 replication is not known. We studied chaperone effects on Gag precursor processing using cyclosporin A (CsA) to bind CypA and prevent its interaction with p55 Gag . CsA treatment inhibited p55 Gag processing in extracellular virus-like particles produced from COS cells. We confirmed the effect of CsA on Gag processing by examining virions produced from CEMx174 cells infected with HIV-1 LAI . Particles accumulated in the presence of CsA displayed mostly immature virion morphology and lacked condensed capsids. CsA has a direct effect on HIV-1 Gag processing that implicates CypA as having an important role in the maturation of HIV-1 particles.
Inverse relationship between Sr isotope diversity and rate of oceanic volcanism has implications for mantle heterogeneity

Cohen and O'Nions1 noted that basalts from the Mid-Atlantic Ridge (MAR) display greater diversity of Pb, Nd and Sr isotopes than do basalts from the East Pacific Rise (EPR). They attributed this difference not to greater isotopic heterogeneity beneath the MAR, but rather to more effective mixing (to eradicate heterogeneity) beneath the EPR. Allegre et al.2 reached the same conclusion on the basis of isotope data including noble gas isotopic data. To test this idea further, I compare here the average spreading rate of nine portions of the mid-ocean ridge system with the measured 87Sr/86Sr diversity of basalts. This shows that the maximum observed 87Sr/86Sr diversity is inversely proportional to spreading rate. Furthermore, globally averaged eruption rates for mantle-derived rocks of intra-oceanic island arcs, ocean islands and the mid-ocean ridge system exhibit a negative correlation with 87Sr/86Sr diversity. These results suggest that the upper mantle is everywhere heterogeneous on a small scale and that the extent of observed heterogeneity is a function of mixing. Independent geophysical and petrological evidence for the existence of steady-state crustal magma chambers beneath fast-spreading ridges and their absence below slow spreading ridges favours this hypothesis because mixing is enhanced by the presence of a magma chamber. Alternatively, mixing during melt production in the mantle, during melt segregation or during ascent could also result in the observed patterns if the degree of mixing is related to eruption rate. Large heterogeneities (mantle plumes?) are required to explain why isotopic variations are well correlated geographically in some places but not in others.
Highlights from the American College of Cardiology Annual Scientific Session 2005: March 6 to 9, 2005, Orlando, Florida.

Background: The biological basis of using antioxidant supplements, including a-tocopherol (vitamin E), to prevent the initiation and progression of cardiovascular disease (CVD) is based on the oxidative-modification hypothesis, according to which peroxidation of lowdensity lipoprotein (LDL) cholesterol is the initiator of atherosclerosis. Supplementation of antioxidants capable of inhibiting the lipid peroxidation could lead to reduction in the risk of a first major cardiovascular event (MACE) as well as in the progression of established atherosclerotic disease. High doses of vitamin E can block lipid peroxidation and have additional effects that might reduce the risk of coronary heart disease (CHD). Epidemiologic cohort studies have suggested that vitamin E supplementation may prevent CVD and cancer. However, randomized, controlled trials have focused primarily on individuals with existing CHD, with inconsistent results. In fact, the actual value of vitamin E for primary prevention of CVD has been controversial. A metaanalysis of 7 trials of vitamin E, with a daily dose ranging from 50 to 800 IU and long-term follow-up of 1.4 to 12 years, included 81788 patients in either primary or secondary prevention. Compared with control, supplements of vitamin E did not provide survival benefit or significantly decrease risk of cardiovascular death or cerebrovascular accident. Furthermore, another large
A Practical Fast Fourier Transform (FFT)-Based Implementation For Image Correlation

Presented here is a simple, easily implemented method for an FFT-based implementation of image cross-correlation which provides for the proper normalization required to obtain useful, easily interpreted output. The results are applied to character recognition. The algorithm is structured such that the data is processed in a highly parallel fashion in order to facilitate a fast, efficient hardware implementation. A discussion is made of the relative merits of using this method.
Down-regulation of hypothalamic 5-HT1A receptors in morphine-abstinent rats.

Abstract The effects of morphine tolerance-dependence and abstinence on 5-HT 1A receptors in brain regions and spinal cord of the rat were determined. Tolerance to and physical dependence on morphine was induced in male Sprague-Dawley rats by implanting six morphine pellets (each containing 75 mg of morphine free base) during a seven day period. Two groups of rats were used for binding studies. In one group the pellets were left intact (tolerant-dependent) and in the other they were removed (abstinent). Rats were killed, and spinal cords and brains were excised. Brain was dissected into seven regions (amygdala, hippocampus, hypothalamus, striatum, midbrain, pons + medulla and cortex). 5-HT 1A receptors were characterized by using [ 3 H]8-hydroxy-di-n-propylaminotetralin ([ 3 H]DPAT) as the ligand and unlabelled 5-HT to determine the non-specific binding. In morphine and placebo tolerant-dependent rats the binding of [ 3 H]DPAT to 5-HT 1A receptors in brain regions and spinal cord did not differ. The B max value of [ 3 H]DPAT in the hypothalamus of morphine abstinent rats was decreased by 61.9%. No change in B max value was observed in other brain regions and spinal cord. The K d values were unaffected. Subcutaneous administration of DPAT produced hypothermia in rats from which pellets had been removed. The intensity of DPAT-induced hypothermic response was greater in morphine abstinent rats as compared to placebo abstinent rats. Since DPAT is believed to have a major action on the presynaptic 5-HT neurons, it is concluded that in morphine abstinent rats 5-HT 1A receptors are down-regulated in hypothalamus, but in morphine tolerant-dependent rats they are unaffected.
An extension of hetenyi's method through the use of macaulay brackets

In the second form of (15), the effect of depletion is accounted for explicitly in the leading term by an appropriate change of the expansion parameter. Numerical solutions of (7) for cesium and sodium ionization, which were based on five ionized trace species (N0, Cs, or Na, 02~, 0~, e~), five neutral air species (02, N2, 0, N, NO), and a ten-reaction system for the ionization process, were compared with (15). The comparison showed that the leading term of the second form of (15) agreed within 5% with all the results of the more elaborate calculations over a range of 0 to 99.5% ionization. Explicitly