cssi/SciSciGPT-SciSciNet huggingface dataset:
Distinct modes of mitochondrial metabolism uncouple T cell differentiation and function

Activated CD4 T cells proliferate rapidly and remodel epigenetically before exiting the cell cycle and engaging acquired effector functions. Metabolic reprogramming from the naive state is required throughout these phases of activation1. In CD4 T cells, T-cell-receptor ligation—along with co-stimulatory and cytokine signals—induces a glycolytic anabolic program that is required for biomass generation, rapid proliferation and effector function2. CD4 T cell differentiation (proliferation and epigenetic remodelling) and function are orchestrated coordinately by signal transduction and transcriptional remodelling. However, it remains unclear whether these processes are regulated independently of one another by cellular biochemical composition. Here we demonstrate that distinct modes of mitochondrial metabolism support differentiation and effector functions of mouse T helper 1 (TH1) cells by biochemically uncoupling these two processes. We find that the tricarboxylic acid cycle is required for the terminal effector function of TH1 cells through succinate dehydrogenase (complex II), but that the activity of succinate dehydrogenase suppresses TH1 cell proliferation and histone acetylation. By contrast, we show that complex I of the electron transport chain, the malate–aspartate shuttle and mitochondrial citrate export are required to maintain synthesis of aspartate, which is necessary for the proliferation of T helper cells. Furthermore, we find that mitochondrial citrate export and the malate–aspartate shuttle promote histone acetylation, and specifically regulate the expression of genes involved in T cell activation. Combining genetic, pharmacological and metabolomics approaches, we demonstrate that the differentiation and terminal effector functions of T helper cells are biochemically uncoupled. These findings support a model in which the malate–aspartate shuttle, mitochondrial citrate export and complex I supply the substrates needed for proliferation and epigenetic remodelling early during T cell activation, whereas complex II consumes the substrates of these pathways, which antagonizes differentiation and enforces terminal effector function. Our data suggest that transcriptional programming acts together with a parallel biochemical network to enforce cell state. Genetic, pharmacological and metabolomics experiments reveal that the malate–aspartate shuttle and mitochondrial citrate export support the differentiation of mouse T helper 1 cells, whereas succinate dehydrogenase enforces their terminal effector function.
The 2020 Lasker Awards and the COVID-19 Pandemic

In this Viewpoint, the chair of the 2020 Lasker Medical Research Awards reflects on the history of the award program and its recipients as a stand-in for the 20
Vulnerable top-of-permafrost ground ice indicated by remotelysensed late-season subsidence

Abstract. Ground ice is foundational to the integrity of Arctic ecosystems and infrastructure. However, we lack fine-scale ground ice maps across almost the entire Arctic, chiefly because ground ice cannot be observed directly from space. Focusing on northwestern Alaska, we assess the suitability of late-season subsidence from Sentinel-1 satellite observations as a direct indicator of vulnerable excess ground ice at the top of permafrost. The idea is that, towards the end of an exceptionally warm summer, the thaw front can penetrate materials that were previously perennially frozen, triggering increased subsidence if they are ice rich. For locations independently determined to be ice rich, the late-season subsidence in an exceptionally warm summer was 4–8 cm (5th–95th percentile), while it was lower for ice-poor areas (−1–2 cm). The distributions overlapped by 2 %, demonstrating high sensitivity and specificity for identifying top-of-permafrost excess ground ice. The strengths of late-season subsidence include the ease of automation and its applicability to areas that lack conspicuous manifestations of ground ice, as often occurs on hillslopes. One limitation is that it is not sensitive to excess ground ice below the thaw front and thus the total ice content. Late-season subsidence can enhance the automated mapping of vulnerable permafrost ground ice, complementing existing (predominantly non-automated) approaches based on largely indirect associations with vegetation cover and periglacial landforms. Improved ground ice maps will prove indispensable for anticipating terrain instability in the Arctic and sustainably stewarding its ecosystems.
The Impact of Inverter Dead-Time in Single-Phase Wireless Power Transfer Systems

In this article, the effect of the dead-time on a single-phase wireless power transfer (WPT) system is studied in detail. In practice, the dead-time is always placed between the complementary switching pulses of the inverter phase-leg. At higher operating frequencies, the dead-time issues in the resonant inverter become critical, especially as the power level increases. The detailed analysis of the dead-time on a WPT system is discussed for different operating conditions of the inverter duty-cycle and power factor. The switching characteristics of the WPT system inverter are analyzed, and the notch phenomenon that appears at the output of the inverter is also discussed. A notch equation based on the observations is derived to predict the notch occurrence during the system operation. Furthermore, the mathematical expressions are presented for different notch conditions. Subsequently, the effect of the notches on the sensitivity and the power transfer of the series–series compensated WPT system is analyzed. Finally, the approach is verified experimentally on an 8-kW WPT system prototype, and the results are compared with the theoretical analysis.
Rare Earth Recycling: Forecast of Recoverable Nd from Shredder Scrap and Influence of Recycling Rates on Price Volatility

This manuscript quantifies the recoverability of the rare earth (RE) element neodymium from shredder scrap during the next two decades and provides a forecast of recycling rates until 2034 based on these calculations. In combination with this forecast, an analysis of historical price and recycling trends for several critical (i.e., platinum group metals, zinc, tantalum, cobalt, antimony, and tungsten) and non-critical materials (i.e., tin, chromium, gold, and copper) results in general conclusions for the future price volatility of REs in dependence on expected recycling rates.
Solvability in infinite horizon optimization

We give necessary and sufficient conditions for finite detection of an optimal initial decision for infinite horizon optimization under a broad set of assumptions and provide an algorithm that is guaranteed to solve every solvable problem under these assumptions. We illustrate the theory and algorithms developed with applications in production planning.
What Does an Argument Culture Look Like

A strong argument culture is characterized by at least five productive tensions, between: commitment and contingency, partisanship and restraint, personal conviction and sensitivity to the audience, reasonableness and subjectivity, and decision and non-closure. Differences in how communities manage these tensions explain why there are multiple argument cultures and, hence, why we need to understand arguing both within and among different cultures. The paper elaborates these five productive tensions, offers some examples of argument cultures that negotiate them in various ways, and considers what it means to argue across cultures in a world that is both increasingly diverse and increasingly atomized.
Exploiting the transients of adaptation for RoQ attacks on Internet resources

We expose an unorthodox adversarial attack that exploits the transients of a system's adaptive behavior, as opposed to its limited steady-state capacity. We show that a well orchestrated attack could introduce significant inefficiencies that could potentially deprive a network element from much of its capacity, or significantly reduce its service quality, while evading detection by consuming an unsuspicious, small fraction of that element's hijacked capacity. This type of attack stands in sharp contrast to traditional brute-force, sustained high-rate DoS attacks, as well as recently proposed attacks that exploit specific protocol settings such as TCP timeouts. We exemplify what we term as reduction of quality (RoQ) attacks by exposing the vulnerabilities of common adaptation mechanisms. We develop control-theoretic models and associated metrics to quantify these vulnerabilities. We present numerical and simulation results, which we validate with observations from real Internet experiments. Our findings motivate the need for the development of adaptation mechanisms that are resilient to these new forms of attacks.
Giant nonlinear processes in plasmonic metasurfaces

Nonlinear metasurfaces based on coupling locally-enhanced plasmonic response to intersubband transitions of multi-quantum-wells have recently provided second-order susceptibilities several orders of magnitude larger than any other non-linear flat structure measured so far. Here, we demonstrate that a proper design of the plasmonic metasurface inclusions can dramatically enhance the overall non-linear response of the structure. The optimized metasurfaces are then applied to achieve efficient second-harmonic generation (SHG) and differential frequency generation (DFG) in the infrared and terahertz frequency bands, respectively. In case of low-power impinging beams (≈1W), our simulations predict large conversion efficiencies of around 0.8% and 0.01% for SHG and DFG, outperforming previously reported efficiencies in 1–2 orders magnitude and confirming the suitability of this type of plasmonic metasurfaces as a highly-efficient flat platform for non-linear photonics.
Reassessing the “Race to the Bottom” in State Welfare Policy

On the assumption that poor people migrate to obtain better welfare benefits, the magnet hypothesis predicts that a state's poverty rate increases when its welfare benefit rises faster than benefits in surrounding states. The benefit competition hypothesis proposes that states lower welfare benefits to avoid attracting the poor from neighboring states. Previous investigations, which yield support for these propositions, suffer from weaknesses in model specification and methodology. We correct these deficiencies in a simultaneous equation model including a state's poverty rate and its benefit level for AFDC (Aid to Families with Dependent Children) as endogenous variables. We estimate the model using pooled annual data for the American states from 1960 to 1990 and find that a state's poverty rate does not jump significantly when its welfare payments outpace benefits in neighboring states. Furthermore, there is no evidence of vigorous benefit competition among states: states respond to decreases in neighbor...
Solution-grown small-molecule organic semiconductor with enhanced crystal alignment and areal coverage for organic thin film transistors

Drop casting of small-molecule organic semiconductors typically forms crystals with random orientation and poor areal coverage, which leads to significant performance variations of organic thin-film transistors (OTFTs). In this study, we utilize the controlled evaporative self-assembly (CESA) method combined with binary solvent system to control the crystal growth. A small-molecule organic semiconductor,2,5-Di-(2-ethylhexyl)-3,6-bis(5″-n-hexyl-2,2′,5′,2″]terthiophen-5-yl)-pyrrolo[3,4-c]pyrrole-1,4-dione (SMDPPEH), is used as an example to demonstrate the effectiveness of our approach. By optimizing the double solvent ratios, well-aligned SMDPPEH crystals with significantly improved areal coverage were achieved. As a result, the SMDPPEH based OTFTs exhibit a mobility of 1.6 × 10−2 cm2/V s, which is the highest mobility from SMDPPEH ever reported.
Doxorubicin cardiotoxicity: Prevention of congestive heart failure with serial cardiac function monitoring with equilibrium radionuclide angiocardiography in the current era

Congestive heart failure (CHF) is among the most serious toxicities of doxorubicin, a potent cancer chemotherapeutic agent. Serial left ventricular ejection fraction (LVEF) monitoring during doxorubicin therapy for preventing CHF was proposed over 20 years ago. The current utility and cost-effectiveness of this approach in the present era are not known. Clinical and follow-up data of 265 patients with cancer (age, 53 ± 14 years; 76% women) undergoing doxorubicin chemotherapy with serial equilibrium radionuclide angiocardiography (ERNA) monitoring (≥2 studies) were analyzed retrospectively. Patients with a normal baseline LVEF (≥50%) and a 10% or greater point fall in LVEF to a final value of less than 50% during doxorubicin therapy were considered “at risk” for CHF (n = 41). Over 679 ± 426 days of follow-up, 7 patients (2.6%) had CHF develop and 90 (34%) died (all cancer-related deaths, with none due to CHF). A comparison of “at-risk” (n = 41 [15%]) and “low-risk” (n = 224 [85%]) groups showed a higher incidence of CHF (12% vs 0.9%, P < .0001), lower baseline LVEF (58% ± 8% vs 64% ± 8%, P < .0001), lower value for the lowest LVEF (42% ± 8% vs 57% ± 7%, P < .0001), and higher rate of cancer-related deaths (59% vs 29%, P = .0003) in the former despite similar cumulative doxorubicin dose (304 ± 124 mg/m2 vs 284 ± 110 mg/m2, P not significant). There were no differences in age, gender, cancer type, and co-morbidity. Cost analysis showed the overall cost of ERNA studies to be lower than the 1-year cost of caring for additional cases of CHF that would potentially be prevented by routine LVEF monitoring. An incipient fall in LVEF detected on serial ERNA during doxorubicin therapy provides an appropriate and cost-effective approach for predicting and preventing impending CHF. Use of this approach was associated with a low incidence of CHF (2.6%) and no CHF-related mortality in this study. (J Nucl Cardiol 2003;10:132-9.)
Oxidation of cobaltite: Part II. kinetics

A kinetics study has been performed on cobaltite to understand the oxidation processes over a temperature range of 573 to 1173 K using a thermogravimetric method. The results show that oxidation of cobaltite occurs in two stages. In the first stage, which occurs between 823 and 913 K, the majority of the sulfur is removed. However, the arsenic remains in the lattice of the reacted region. A pore-blocking kinetic model yields a satisfactory fit to these experimental data. At higher temperatures, there is a concurrent release of As and S from the crystal lattice of CoAsS. The shrinking-core kinetic model is applicable. Complementary X-ray diffraction and scanning electron microscopic analyses on these partially oxidized samples support the kinetic models. The effects of partial pressure of oxygen and particle size on roasting have been evaluated.
The boiling-point and pressure [1]

A VERY convenient lecture experiment to show that the boiling-point of liquids is lowered by diminishing the pressure of the surrounding medium, may be made with one of Ducretet's carbon-dioxide tubes. The lower part of the tube contains the CO2 in the liquid condition, while the upper part is, of course, filled with the same body in the gaseous state. By subjecting this upper half of the tube to a jet of ether spray, the pressure of the inclosed gas will gradually diminish, and after a few seconds the liquid below will enter into brisk ebullition.
Mild anxiogenic effects of nicotine withdrawal in mice

Increased anxiety is one of the symptoms of nicotine withdrawal that may lead to relapse. Previous studies have shown that nicotine withdrawal affects anxiety-like behavior in different tests of anxiety in humans and rats. However, relatively few studies have focused on the anxiogenic effect of nicotine withdrawal in mice. The present study investigated the effect of nicotine withdrawal on anxiety-like behavior in DBA/2J and C57BL/6J mouse strains in the light-dark box, acoustic startle response, and prepulse inhibition tests. An initial experiment showed that nicotine administration of 12 or 24 mg/kg/day (free base) for 14 days did not result in significant effects during withdrawal in startle, prepulse inhibition, or light-dark box, but there was a trend towards an anxiogenic effect in the light-dark box 24 h, but not 1 or 4 h, after cessation of nicotine administration. A subsequent study was therefore performed, with minipumps delivering saline, 24 mg/kg/day nicotine, or 48 mg/kg/day nicotine (free base), for 14 days. The pumps were removed, and the mice were tested 24 h after cessation of nicotine administration. Cessation of administration of 48 mg/kg/day nicotine free base in C57BL/6J mice resulted in increased anxiety-like behavior in the light-dark box, while the behavior of DBA/2J mice was unaffected. The acoustic startle response and prepulse inhibition were also unaffected in both strains. In conclusion, the present data show that nicotine withdrawal is mildly anxiogenic in C57BL/6J mice under the conditions used in the present experiments.
FLOW MODELING OF A POWER‐LAW FLUID IN A FULLY‐WIPED, CO‐ROTATING TWIN‐SCREW EXTRUDER

The two-dimensional flow theory of a power law fluid in a fully-wiped co-rotating twin-screw extruder was investigated under steady-state, isothermal conditions. The important distinction between this approach and previously published theories (Denson and Hwang 1980; Booy 1980; Wang and White 1989; Lai-Fook et al. 1989, 1991) is that actual boundary conditions were used instead of boundary conditions based on the parallel plate model developed for single screw extruders. The generalized screw curves constructed for both double-lead and single-lead screw elements were similar in shape to those published for single screw extruders with rectangular channels. Noticeable increases in the closed discharge pressure and the open discharge flow rate were observed, which are the result of the screw geometry. Experimental results with corn meal were in agreement with theoretical predictions for single-lead screw elements. Theoretical predictions for double-lead screw elements using the new solution also showed reasonable agreement with experimental data from published literature after the incorporation of the intermeshing effect.
Predicting Planets in Known Extrasolar Planetary Systems. III. Forming Terrestrial Planets

Recent results have shown that many of the known extrasolar planetary systems contain regions that are stable for both Earth-mass and Saturn-mass planets. Here we simulate the formation of terrestrial planets in four planetary systems, 55 Cancri, HD 38529, HD 37124, and HD 74156, under the assumption that these systems of giant planets are complete and that their orbits are well determined. Assuming that the giant planets formed and migrated quickly, terrestrial planets may form from a second generation of planetesimals. In each case, Moon- to Mars-sized planetary embryos are placed in between the giant planets and evolved for 100 Myr. We find that planets form relatively easily in 55 Cnc, with masses up to 0.6 M⊕ and, in some cases, substantial water content and orbits in the habitable zone. HD 38529 is likely to support an asteroid belt, but no terrestrial planets of significant mass. No terrestrial planets form in HD 37124 and HD 74156, although in some cases 1-2 lone embryos survive for 100 Myr. If migration occurred later, depleting the planetesimal disk, then massive terrestrial planets are unlikely to form in any of these systems.
Variation in chemical and physical properties during leaf development in california bay tree (Umbellularia californica): Predictions regarding palatability for deer

Changes in several chemical and physical characteristics of California Bay Tree,Umbellularia californica, foliage in both new growth and mature leaves were measured from the spring flush (April) until bud set and dormancy in autumn (October). Five sequential leaf developmental stages were described, with leaves passing through Stages One to Four during a growing season, and remaining in Stage Five after winter dormancy (i.e. second year of growth). Monoterpenoid total yield (mg all monoterpenoids/g LDW) increased from very low levels in Stage One to high levels in Stages Four and Five. Monoterpenoid composition (% of total yield by individual compounds) was highly variable among the developmental stages; however, concentrations of the four most abundant compounds, sabinene, 1,8 cineole, pinocarvone and umbellulone, all increased from Stages One to Four. Over winter, the concentrations (mg individual compound/g LOW) of pinocarvone dropped and umbellulone rose dramatically in leaf Stage Five, while the total yield did not change. Total nitrogen content decreased from Stage One to Stage Five. Total nonstructural carbohydrate did not vary statistically among the leaf developmental stages. Leaf specific weight, per cent moisture, and leaf toughness also increased with leaf development. From these results we predictU. californica foliage palatability for Blacktailed Deer.
Transformation of the Community Colleges for the 21st Century

Clark Kerr (cited in Brint & Karabel, 1989) called the community college the great educational innovation of 20th-century American higher education. From its humble beginnings in the early 1900s to the present day, the community college has become a critical component of the educational system. Today well over 5 million students enroll (44% of all U.S. undergraduates) in over 1,100 public 2-year colleges in all 50 states (Phillippe, 1998). The emphasis on achieving mobility through education, particularly higher education, is distinctly American. To this day no other society sends as many of its young people to colleges and universities as the United States does. At the center of this ef-
The value of bronchoalveolar lavage and bronchial washings in the diagnosis of invasive pulmonary aspergillosis.

The objective of this study was to clarify conflicting reports of the sensitivity and specificity of bronchoalveolar lavage or bronchial washings for diagnosing invasive pulmonary aspergillosis. The studywas a retrospective review of 300 consecutive patients in a tertiary referral centre subjected to 343 fiberoptic bronchoscopic procedures for the evaluation of pulmonary infiltrates. Classification of paired fungal culture and cytologic examination of bronchoalveolar lavage or bronchial washing fluidaccording to clinical, radiographic, histological and autopsy evidence of invasive pulmonary aspergillosis. One-hundred and fifteen deaths occurred, with a 58% autopsy rate. A diagnosis of invasive pulmonary aspergillosis was made in 21 immunosuppressed patients with 16 deaths. Bronchoalveolar lavage cytology showed aspergillus in 19 specimens (invasive pulmonary aspergillosis in 16), cultures yielded aspergillus in 41 (invasive pulmonary aspergillosis in ten), with both tests positive in nine. Cytology sensitivity was 64.0%, specificity 99.1 %, positive predictive value84.2%, and negative predictive value 97.2%. Culture sensitivity was 40.0%, specificity 90.3%, positive predictive value 24.4%, and negative predictive value 95.0%. Concordant cytology and culture sensitivity was 32.0%, specificity 99.7%, positive predictive value 88.9%, and negative predictive value 94.9%. In conclusion, when characteristic hyphae are visualized in bronchoalveolar lavage specimens from immunosuppressed patients with compatible clinical data, it is advisable to treatfor presumptive invasive pulmonary aspergillosis.
Pharmacokinetics and Side Effects of Milrinone in Infants and Children After Open Heart Surgery

UNLABELLED We investigated the pharmacokinetics and side effects of milrinone in infants and children (< or = 13 yr) after open heart surgery in this prospective, open-label study. Milrinone binding to cardiopulmonary bypass (CPB) circuitry was also examined in out two groups. Children in the small dose group (n = 11) received two 25-microg/kg boluses with a final infusion rate of 0.5 microg kg(-1) x min(-1); those in the large dose group (n = 8) received a 50-microg/kg bolus and a 25-microg/kg bolus with a final infusion rate of 0.75 microg x kg(-1) x min(-1). Blood samples for milrinone concentration were drawn 30 min after each bolus, at steady state, and after discontinuing the milrinone infusion. Pharmacokinetics were evaluated using traditional and nonlinear mixed effects modeling analysis. Milrinone kinetics best fit a two-compartment model. Steady-state plasma levels in the small and large dose groups were within the adult therapeutic range (113 +/- 39 and 206 +/- 74 ng/mL, respectively). The volumes of distribution (Vbeta) in infants (0.9 L/kg) and children (0.7 L/kg) were not different, but infants had significantly lower milrinone clearance (3.8 vs 5.9 mL x kg(-1) x min(-1)). Thrombocytopenia (defined as platelet count < or = 100,000 mm(-3)) occurred in 58%, and the risk increased significantly with duration of infusion. Tachyarrythmias were noted in two patients. Milrinone did not bind to CPB circuitry. We conclude that milrinone is cleared more rapidly in children than in adults. The major complication was thrombocytopenia. IMPLICATIONS Most pediatric dosing is based on data published for adults. Infants and children have kinetics that differ from adults. We studied the distribution of I.V. milrinone in infants and children after open heart surgery. Milrinone had a larger volume of distribution and a faster clearance in infants and children than in adults, and dosing should be adjusted accordingly.
Synthesis of 3′-deoxynucleosides III. Synthesis of 9-(3-deoxyaldofuranosyl) adenines derived from 3-deoxy-D-mannose and 3-deoxy-D-galactose

The diisopropylidene derivative of 3-deoxy-D-mannose was selectively hydrolyzed to 1,2-O-isopropylidene-3-deoxy-D-mannofuranose. In one series of reactions, this compound was converted via benzoylation and acetolysis to a suitably blocked sugar, which on condensation with chloromercuri-6-benzamidopurine (using titanium tetrachloride), followed by deacylation, yielded 9-(3-deoxy-α-D-mannofuranosyl) adenine. In a second series of reactions, 1,2-O-isopropylidene-3-deoxy-D-mannofuranose was converted through periodate oxidation and borohydride reduction to the corresponding derivatives of 3-deoxy-D-arabinose, convertible by the above standard reactions to 9-(3-deoxy-α-D-arabinofuranosyl)adenine. Inversion of 1,2-O-isopropylidene-5,6-di-O-methanesulfonyl-3-deoxy-D-galactofuranose with sodium benzoate led to 5,6-di-O-benzoyl-1,2-O-isopropylidene-3-deoxy-L-mannofuranose from which 9-(3-deoxy-α-L-mannofuranosyl) adenine was similarly prepared.
Laser Spectroscopy of a Halocarbocation in the Gas Phase: CH2I+

We report the first gas-phase observation of the electronic spectrum of a simple halocarbocation, CH2I+. The ion was generated rotationally cold (Trot ∼ 20 K) using pulsed discharge methods and was...
Reinstatement of cocaine seeking induced by drugs, cues, and stress in adolescent and adult rats

Rationale In human and animal studies, adolescence marks a period of increased vulnerability to the initiation and subsequent abuse of drugs. Adolescents may be especially vulnerable to relapse, and a critical aspect of drug abuse is that it is a chronically relapsing disorder. However, little is known of how vulnerability factors such as adolescence are related to conditions that induce relapse, triggered by the drug itself, drug-associated cues, or stress.
Nonparametric Regression With Missing Outcomes Using Weighted Kernel Estimating Equations.

We consider nonparametric regression of a scalar outcome on a covariate when the outcome is missing at random (MAR) given the covariate and other observed auxiliary variables. We propose a class of augmented inverse probability weighted (AIPW) kernel estimating equations for nonparametric regression under MAR. We show that AIPW kernel estimators are consistent when the probability that the outcome is observed, that is, the selection probability, is either known by design or estimated under a correctly specified model. In addition, we show that a specific AIPW kernel estimator in our class that employs the fitted values from a model for the conditional mean of the outcome given covariates and auxiliaries is double-robust, that is, it remains consistent if this model is correctly specified even if the selection probabilities are modeled or specified incorrectly. Furthermore, when both models happen to be right, this double-robust estimator attains the smallest possible asymptotic variance of all AIPW kernel...
Isomeric specificity of diphenylmethylpiperidine in the production of rat pancreatic islet cell toxicity.

Abstract The relationship between chemical structure and the pancreotoxic potential of positional isomers of diphenylmethylpiperidine was investigated in rats. The chemical synthesis of these compounds and their N -methylated analogs is reported. Oral administration of 4-diphenylmethylpiperidine and its N -methylated derivative (130 and 260 μmoles/kg) to rats for 14 days resulted in hyperglycemia, reduced pancreatic insulin content and the formation of large vacuoles in the cytoplasm of pancreatic islet cells. No effect on beta cell morphology or insulin content was observed after administration of 2- and 3-diphenylmethylpiperidine and their N -methylated analogs.
Photoacoustic spectroscopy for chemical detection

ABSTRACT The Global War on Terror has made rapid detection and identif ication of chemical and biolog ical agents a priority for Military and Homeland Defense applications. Reliable real-time detection of these threats is complicated by our enemys use of a diverse range of materials. Therefore, an adaptable platform is necessa ry. Photoacoustic spectroscopy (PAS) is a useful monitoring technique that is well suited for trace detection of gaseous me dia. This method routinely exhibits detection limits at the parts-per-billion (ppb) or sub-ppb range. The versatility of PAS also allows for the investigation of solid and liquid analytes. Current research utilizes quantum cascade lasers (QCLs) in combination with an air-coupled solid-phase photoacoustic cell design for the detection of condensed phase material films deposited on a surface. Furthermore, variation of th e QCL pulse repetition rate allows for id entification and molecular discrimination of analytes based solely on photoacoustic spectra collected at different film depths. Keywords: Photoacoustic spectroscopy, quantum cascade laser, solid-phase, depth profiling
Determining design wind loads for work zone traffic-control devices

Proper traffic control and delineation are critical to achieving safety in work zones. In addition to being crashworthy, a barricade or temporary sign support should have the ability to withstand anticipated service loads. If a barricade or temporary sign support fails or overturns, it cannot perform its intended function and the safety of the work zone may be compromised. Currently, no guidance is provided on the service loads that should be used in the design of these work zone devices. Recommendations are provided for design wind loads for work zone traffic-control devices. The results from field trials indicate that truck-induced wind loading is not a critical design issue for barricades and barricades with signs. The recommendations are thus based on an analytical determination of design wind speeds associated with different recurrence intervals that correspond to the duration of work zone activities. Analytical case studies are presented for two common barricade designs, with consideration given to both structural capacity and overturn. Guidance on the amount of ballast required to prevent overturn is provided as a function of wind speed, barricade length, and sign mounting height.
Anti-Inflammatory Therapy in Chronic Disease: Challenges and Opportunities

A number of widespread and devastating chronic diseases, including atherosclerosis, type 2 diabetes, and Alzheimer’s disease, have a pathophysiologically important inflammatory component. In these diseases, the precise identity of the inflammatory stimulus is often unknown and, if known, is difficult to remove. Thus, there is interest in therapeutically targeting the inflammatory response. Although there has been success with anti-inflammatory therapy in chronic diseases triggered by primary inflammation dysregulation or autoimmunity, there are considerable limitations. In particular, the inflammatory response is critical for survival. As a result, redundancy, compensatory pathways, and necessity narrow the risk:benefit ratio of anti-inflammatory drugs. However, new advances in understanding inflammatory signaling and its links to resolution pathways, together with new drug development, offer promise in this area of translational biomedical research.
Feedback-mediated cancer therapy: a FRET-based nanoreporter approach

A theranostic nanoparticle system was developed by integrating a chemotherapeutic agent with an “activatable” fluorescent tracer. The system signals tumor death by monitoring the activity of caspase-3, a product of apoptosis, and can therefore screen the treatment sensitivity of a particular tumor. The polymer nanoparticles (Poly [isobutylene-alt-maleic anhydride]) were formed through reprecipitation and contained paclitaxel, a chemotherapy drug, and fluorescein isothiocyanate, a fluorescent dye. The dye’s fluorescence was quenched through Forster resonance energy transfer (FRET) by a quencher that was connected to the dye by a peptide chain. With sizes ranging from 200-250 nm, the nanoparticles were stable for two weeks. The nanoparticles were tested in vitro with responsive Lewis Lung Carcinoma (LLC) cells and taxane-resistant cells. Upon cell death by paclitaxel exposure, caspase-3 cleaved the peptide chain connecting the dye and the quencher, causing the system to fluoresce. When LLC cells were treated with the system, the nanoreporters fluoresced, but when resistant cells were tested, and when the drug was removed from the system, the nanoreporters did not fluoresce. Since the system screens if a drug can successfully kill a particular tumor, it offers a novel and promising approach to personalized medicine.
Defect Donor and Acceptor in GaN

High-energy (0.7{endash}1MeV) electron irradiation in GaN grown on sapphire produces shallow donors and deep or shallow acceptors at equal rates, 1{plus_minus}0.2 cm{sup {minus}1}. The data, in conjunction with theory, are consistent only with the shallow donor being the N vacancy, and the acceptor the N interstitial. The N-vacancy donor energy is 64{plus_minus}10 meV, much larger than the value of 18meV found for the residual donor (probably Si) in this material. The Hall-effect measurements also reveal a degenerate n -type layer at the GaN/sapphire interface which must be accounted for to get the proper donor activation energy. {copyright} {ital 1997} {ital The American Physical Society}
Role of genetics in resistance to type 1 diabetes

Background A single nucleotide polymorphism in the mitochondrial gene encoding NADH dehydrogenase subunit 2 (mt-ND2) has been associated with reduced incidence of human type 1 diabetes (T1D). We identified the orthologue of this mitochondrial single nucleotide polymorphism in mouse and using NOD mouse models linked this genetic polymorphism to T1D resistance. The mechanism how this single nucleotide polymorphism affects the development of diabetes is studied using mouse models and beta cell lines. Methods The impact of this single nucleotide polymorphism on mitochondrial function and resistance to reactive oxygen species was assessed. For these studies we measured oxygen consumption by isolated mitochondria under different doses of nitric oxide. In addition, alloxan sensitivity of beta cell lines was tested using the MTT method to measure cell survival. Results mt-Nd2a is associated with protection against mouse T1D and alloxan-induced diabetes. Mice with mt-Nd2a exhibited resistance to transfer of diabetes by single clone of diabetogenic CD4+ or CD8+ T cells. Beta cell line with mt-Nd2a resist in vitro attack of diabetogenic CD8+ cytotoxic T cells, as well as free radicals generated by alloxan; isolated mitochondria with mt-Nd2a showed lower reactive oxygen species production and were more resistant to nitric oxide. Conclusion mt-Nd2a protects against T1D in mouse models. The protection is at beta cell level and is associated with resistance against reactive oxygen species-mediated damage and death. Copyright © 2011 John Wiley & Sons, Ltd.
Investigating the Interaction Between Folic Acid and Folate Binding Protein at the Single Molecule Level

The folic acid-folate receptor recognition interaction has been exploited for targeted drug delivery, yet the detailed mechanism of this binding is unknown. Here, atomic force microscopy was employed to measure the folic acid-folate binding protein interaction. After conjugating a flexible poly(ethylene glycol) linker to folic acid and attaching this to an AFM tip, a controlled mechanical force was applied to disrupt the binding interaction. The amount of force required to cause rupture at various force loading rates were measured. The rupture force dependency on the loading rate characterizes the energy landscape of the single molecule interaction between folic acid and folate binding protein. Control experiments were performed to ascertain the specificity of the FA-FBP single molecule interaction. The use of dynamic force spectroscopy to investigate the details of this binding interaction provides new insight to guide the design of folate receptor-targeting molecules.
Continuous monitoring of critically III patients with transcutaneous oxygen and carbon dioxide and conjunctival oxygen sensors

Transcutaneous (PtcO 2 ) and conjunctival (PcjO 2 ) oxygen tensions and transcutaneous (PtcCO 2 ) carbon dioxide tension were serially measured in 31 critically ill patients. Sixteen patients maintained a normal or greater blood pressure and 15 patients were severely hypotensive (MAP 2 and PaO 2 , PcjO 2 and PaO 2 , and PtcCO 2 and PaCO 2 were significant, with correlation coefficients (r values) of 0.62, 0.48, and 0.73, respectively. In hemodynamically unstable patients, there was poor correlation between PtcO 2 , PcjO 2 , PtcCO 2 , and arterial blood gas values. In the severely hypotensive patients, however, PtcO 2 and PcjO 2 were sensitive real-time monitors of peripheral perfusion and tissue oxygen delivery. Increases in PcjO 2 and PtcO 2 occurred within three minutes in patients who regained a palpable blood pressure from a pulseless baseline. PtcO 2 fell one to five minutes after the loss of blood pressure in patients whose clinical condition deteriorated in the emergency department. Decreases in PcjO 2 from previously stable levels occurred over three to four minutes before loss of blood pressure. Transcutaneous and conjunctival sensors can be used as continuous monitors of respiratory status in hemodynamically stable patients. In severely hypotensive patients and during cardiopulmonary resuscitation, these sensors no longer accurately reflect arterial blood gases, but act as sensitive real-time monitors of cardiac function and peripheral perfusion. PcjO 2 can detect deterioration of clinical state before alterations in blood pressure occur.
On the efficiency gains from imposing symmetry constraints in demand systems

Abstract This paper presents an easy to apply formula which can be used to assess the efficiency gains from imposing symmetry constraints on a system of demand equations. The interrelationship of the correlation between errors and the correlation between variables is shown to have a significant impact on efficiency gains. Standard results on efficiency gains from seemingly unrelated regression are shown to be inapplicable.
Chemical Wave Logic Gates

Logic gates based on chemical wave propagation in geometrically constrained excitable media are demonstrated in a Belousov−Zhabotinsky membrane system. The catalyst of the reaction is printed in specific predetermined patterns with geometries designed to provide various logic operations. Computational studies of the serial coupling of elements to form multicomponent gates and general chemical wave circuitry are presented.
Oxygen consumption and lipid content in red and white muscles of Antarctic fishes.

Antarctic nototheniid fishes have red muscle which is restricted to the pectoral girdle region of the body. The muscle masses articulate the pectoral fins whose movement propels the fish during sustained low speed cruising. Both the rate of oxygen consumption and lipid content are higher in the red muscle masses than in white muscle. Electron microscope observations reveal large numbers of lipid droplets and mitochondria arranged in close association with one another. These findings support the hypothesis that red muscle is used for long, sustained swimming motion, and that lipid, rather than glycogen, is the main energy source for this activity.
Physicochemical properties of whey protein-stabilized emulsions as affected by heating and ionic strength.

Corn oil-in-water emulsions (19.6 wt%; d 32 0.6 μm) stabilized by 2 wt% whey protein isolate (WPI) were prepared with a range of pH (3-7) and salt concentrations (0-100 mM NaCl). These emulsions were heated between 30 and 90°C and their particle size distribution, rheological properties and susceptibility to creaming measured. Emulsions had a paste-like texture around the isoelectric point of WPI (pH 5) at all temperatures, but tended to remain fluid-like at pH >6 or <4. Heating caused flocculation in pH 7 emulsions between 70 and 80°C (especially at high salt concentrations), but had little effect on pH 3 emulsions. Flocculation increased emulsion viscosity and creaming. Results were interpreted in terms of colloidal interactions between droplets.
Lichtenstein vs anterior preperitoneal prosthetic mesh placement in open inguinal hernia repair: A prospective, randomized trial

Male veterans with unilateral primary inguinal hernia, classified intraoperatively as Gilbert Type III or IV, were randomized to subaponeurotic (Lichtenstein, n=126) or preperitoneal (Read-Rives, n=121) repair under general or spinal anesthesia. The two groups of patients were comparable in age, body weight index, comorbidities, and size and type of hernia. Of the 247 patients enrolled, 224 were followed for at least 2 years (median 82 months, range 24–110 months), 16 were lost to follow-up, and seven died from causes unrelated to the surgery. The average operative time of the Read-Rives repair was 9 min longer than that of the Lichtenstein repair. There were no wound infections, and the frequencies of other short- and long-term complications were low and similar in the two groups. Six patients developed hernia recurrence, five in the Lichtenstein group (4.3%), and one in the Read-Rives group (<1%), (P=0.21). Both anterior repairs are associated with low postoperative morbidity and recurrence rates. The Lichtenstein repair is technically easier and less time consuming. There is no statistically significant difference in the recurrence rate between the two repairs.
Roles of Perceived Provider Cultural Sensitivity and Health Care Justice in African American/Black Patients’ Satisfaction with Provider

The present study tests a refined first component of the Patient-Centered Culturally Sensitive Health Care (PC-CSHC) Model—the evidence supported component that links perceived provider cultural sensitivity to patient satisfaction with provider care and identifies trust of provider as the mediator of this linkage. The refined first component of the PC-CSHC Model tested in the present study is novel in that it includes the three dimensions of provider cultural sensitivity and includes perceived provider impartiality (fairness), a core aspect of perceived health care justice, as a mediator in addition to trust of provider (the other core aspect of perceived health care justice). Study participants were 298 African American/Black primary care clinic patients with low household incomes. Mediation analyses revealed that the three dimensions of patients’ perceived provider cultural sensitivity were significant predictors of the participating patients’ reported satisfaction with their provider, and that some of these predictive relationships were partially mediated by (1) patients’ perceived provider impartiality (fairness), and (2) patients’ trust of their provider. Implications of these findings for providers’ interactions with patients, development of the PC-CSHC Model, and the roles of psychologists in facilitating patient-provider interactions are discussed.
Buckling analysis of laminated composite plates

Abstract Over the past few years, fibre-reinforced laminates have been found to be highly desirable for aerospace structural applications. This paper is concerned with one of the problem areas connected with these applications; namely, the stability of midplane symmetric, laminated composite plates. The results of plate buckling analyses performed by means of the BENST module of the PLANS system of finite element structural analysis programs are presented. These analyses involve a wide variation in laminate orthotropic and material axis orientation and a number of plate aspect ratios and support conditions. The efficacy of the BENST finite element program is demonstrated by comparison with published results. Peak buckling loads for simply supported plates at material axes orientation other than the plate principal axes are predicted for laminate material properties ranging from mildly orthotropic to severely orthotropic. This indicates that the common design practice of calculating simply supported plate buckling levels by applying a ‘knock down’ factor to existing clamped plate data may often be unnecessarily conservative. Also included in this paper are details on the finite element method implemented in BENST and the development of the expressions that permit the calculation of laminate effective material properties from the properties of the individual layers.
Metabolism of [3H]serotonin in the marine mollusc,Aplysia californica

The fate of serotonin was studied in several tissues of the marine mollusc, Aplysia californica. When isolated nervous tissue was bathed in [3H]serotonin, two radioactive derivatives were formed; both appeared to be sugar conjugates: the first, possibly of glucuronic acid, and the second, of a more complex sugar moiety. When [3H]serotonin was injected directly into cell bodies of identified neurons, both serotonergic and non-serotonergic, only the conjugate which behaved as the glucuronide was formed. [3H]Serotonin was also converted only to this substance during incubation with isolated heart, kidney and hemolymph. Metabolic activity of the blood resided within cellular elements. No evidence of oxidative deamination was found in any tissue. In contrast to serotonin, however, [3H]tryptamine was readily oxidized to indoleacetic acid by nervous tissue.