cssi/SciSciGPT-SciSciNet huggingface dataset:
Function and Regulation of Endothelin-1 and Its Receptors in Salt Sensitive Hypertension Induced by Sensory Nerve Degeneration

To determine the role of endothelin-1 (ET-1) and its receptors in salt-sensitive hypertension induced by sensory nerve degeneration, selective ET A antagonist (ABT-627) and ET B antagonist (A-192621) were used. Newborn Wistar rats were given vehicle or 50 mg/kg capsaicin subcutaneously on the first and second days of life. After the weaning period, male rats were divided into eight groups, and subjected to the following treatments for 2 weeks: control + normal salt diet (Con+NS, 0.5%), control + high salt diet (Con+HS, 4%), control + high salt diet + ABT-627 (Con+HS+ABT-627), control + high salt diet + A-192621 (Con+HS+A-192621), capsaicin + normal salt diet (Cap+NS), capsaicin + high salt diet (Cap+HS), capsaicin + high salt diet + ABT-627 (Cap+HS+ABT-627), capsaicin + high salt diet + A-192621 (Cap+HS+A-192621). Both ABT-627 (5 mg/kg/d) and A-192621 (30 mg/kg/d) were given by oral gavage twice a day. Mean arterial pressure (MAP, mm Hg) was higher in Con+HS+A-192621 (141±11) than in Con+NS (94±10), Con+HS (95±5), and Con+HS+ABT-627 (97±6) ( P P P P P A receptor prevents the development of salt sensitive hypertension induced by sensory nerve degeneration, indicating that activation of the ET A receptor by increased plasma ET-1 level contributes to elevation of blood pressure in this model. In contrast, blockade of the ET B receptor leads to an increase in blood pressure in both normal and sensory nerve degenerated rats fed a high salt diet. These results suggest that ET B plays an antihypertensive role in response to high salt intake under both normal and sensory nerve degenerated conditions.
Composition of a protein antifreeze from larvae of the beetle, Tenebrio molitor

A thermal hysteresis producing antifreeze protein was isolated from larvae of the beetle, Tenebrio molitor. This is the first thermal hysteresis protein purified from an insect. The specific activity of the Tenebrio antifreeze is somewhat greater than that of the fishes. The composition of the Tenebrio protein is quite different from those of the fish protein antifreezes. The most obvious difference is the lack of a large alanine component in the Tenebrio antifreeze. The significance of the differences are discussed.
Effects of H2O2 on the dogfish (Mustelus canis) ocular lens.

Abstract 1. The influence of in vitro exposure of dogfish ( Mustelus canis ) lenses to H 2 O 2 was studied. 2. Concentrations of H 2 O 2 greater than 10 −4 M caused opacities in the outer cortex of the lens within a few hr. 3. Evidence of protein aggregation within the lens and in extracted lens protein solutions was found. Dithiothreitol inhibits aggregation. 4. Little if any influence of H 2 O 2 was observed on 86 Rb exchange of the dogfish lens.
Maximizing Gathered Samples in Wireless Sensor Networks with Slepian-Wolf Coding

We consider an energy constrained wireless sensor network, with arbitrary number of nodes, where source nodes utilize Slepian-Wolf (SW) coding before transmission to a joint decoder. We investigate optimal and near-optimal SW coding rates, transmit powers, and transmit durations that maximize the number of collected samples during the network lifetime, subject to channel capacity, SW rate region, and residual energy constraints. We find optimal (near-optimal) closed-form solutions in the absence (presence) of an energy constraint at the joint decoder. We take into account the energy consumption of SW encoding and decoding and communication circuitry. Numerical results demonstrate the effectiveness of the proposed optimization, especially when the joint decoder is not energy constrained.
Purification of human alpha1-beta glycoprotein and study of its microheterogeneity and molecular variants

Alpha 1-beta glycoprotein (A1B) was purified to homogeneity from human plasma using a three-step procedure involving pseudo-ligand affinity chromatography on immobilized Cibacron Blue 3-GA, gel filtration chromatography on Sephadex G-200 and ion-exchange chromatography on DEAE Affigel Blue. The overall yield of the combined techniques was 31%. The major advantages of this technique include its conveniency, and the fact that no apparent alteration of the purified protein occurred as judged by the absence of modification of its physicochemical parameters. A1B appears to be present in normal plasma as a major form of Mr 70,000 daltons with extensive charge heterogeneity, together with minor components of higher Mr.
Detection of volatile and soluble general anesthetics using a fluorescence-based fiber optic sensor: recent progress in chemical sensitivity and noise sources

A fiber optic sensor for general anesthetics based on the phase transition of immobilized phospholipid vesicles is under development. Current work centers on evaluating the sensor response to different anesthetics and instrumentation design. The fluorescence of laurdan- doped liposomes is found to respond linearly to the infusible anesthetics thiopental sodium and Propofol. Preliminary experiments have been performed to determine sources of noise in the optical and electronic components of the sensor as it is now configured. One potential noise source is the liposome sample at the fiber tip; photobleaching and thermal fluctuations due to heating by the illuminating 360 nm radiation can affect measurement of the anesthetic level. Heating of the sample is a factor at high illumination levels, but photobleaching, which reduces the signal intensity, does not alter the intensity ratio upon which the anesthetic concentration measurement is based. Optical microscopy of fiber tips embedded in liposomes allows direct observation of the light intensity near the tip of the fiber despite the extreme turbidity of the suspension. Light intensity drops to less than 10% of its maximum intensity at the fiber tip within 300 micrometers . Further use of this technique should allow monitoring the effects of photobleaching on the spatial distribution of the liposomes responsible for the measured optical signal.
Escherichia coli strains with defined mutations which alter cellular permeability

We describe the construction and analysis of an isogenic series ofEscherichia coli K12 strains that vary in their outer membrane permeability. They carry mutations that alter the amount and the type of porin present in the outer membrane. The permeability profiles of these strains suggest that both the amount and the type of porin present in the outer membrane affects permeability. Several of the strains carry mutations that extend the permeability of the outer membrane to include a variety of compounds that are normally excluded from entering the cell.
Extracorporeal assist of anhepatic animals with liver slice perfusion

Summary Thin (0.5 to 1.0 mm) liver slices perfused with arterial blood have been used to provide temporary support of anhepatic pigs. The technic is far simpler than is whole liver perfusion. It reverses the electroencephalographic abnormalities, and other metabolic functions are restored, but as yet it is not sufficient to provide total support.
FREE AND CHROMATIN-ASSOCIATED MONO-, DI-, AND TRIMETHYLATION OF HISTONE H4-LYSINE 20 DURING DEVELOPMENT AND CELL CYCLE PROGRESSION

Methylation of specific amino acids in histone tails is responsible for packaging DNA into condensed, repressed chromatin, and into open chromatin that is accessible to the transcription machinery. Monomethylation and trimethylation of histone H4-lysine 20 (H4-K20) control the formation of repressed chromatin. Using antibodies that specifically recognize the three methyl marks of histone H4-K20, we characterized their regulation during the cell cycle and throughout development. We find free mono- and trimethylated histone H4-K20 in unfertilized Drosophila eggs and in S2 tissue culture cells. Soluble mono-. di-, and trimethylated H4-K20 are also found in HeLa cells. These soluble modified histones may represent a pool of free histones that can rapidly be incorporated into chromatin. The three methyl marks are each regulated differentially during development and their detection on western blots does not overlap with their detection on chromosomes. Monomethylated H4-K20 is detected on condensed chromosomes throughout development, while di- and trimethylated H4-K20 are detected on metaphase chromosomes at specific stages. Our results suggest that the detection of methylated H4-K20 on chromosomes may reveal chromatin packaging rather than the distribution of the methyl marks.
Expression of ionotropic glutamate receptor genes by P19 embryonal carcinoma cells.

Abstract P19 embryonal carcinoma cells can be induced to differentiate into neuron-like cells by retinoic acid. P19 neurons were recently shown to express both NMDA and non-NMDA type glutamate receptor-mediated currents and be susceptible to glutamate excitotoxicity. In this study, we used RT-PCR to survey differentiated P19 cultures for glutamate receptor transcript expression. The following transcripts were detected: at least one member of the GluR1-4 family, GluR5, GluR6, GluR7, KA1, KA2, NMDAR1, and NMDAR2B. Nuclease protection assays revealed a large quantitative induction of GluR6 transcripts following retinoic acid treatment. Ionotropic glutamate receptors are a fundamental and major feature of CNS neurons which are not expressed by the cell lines commonly used as experimental models for mammalian neurons. The present results show that P19 cells express multiple genes involved in glutamate receptor biology. Since the stem cells can be manipulated genetically, the system has the basic requirements for analyzing mechanisms involved in glutamate receptor gene expression.
Real-space order parameter in layered cuprate superconductors

We analyze the center-of-mass order parameter in [ital s]-wave and [ital d]-wave superconductors and find a large spatial dc term in the [ital s] wave but none in the [ital d] wave. Thus, the [ital d]-wave hypothesis may reconcile high-temperature superconductivity with Hohenberg's theorem. The center-of-mass order parameter has nodes at Cu sites and peaks at O sites with opposite signs at [ital x]- and [ital y]-bonded oxygens. At boundaries, it attains opposite amplitudes for [ital x] and [ital y] edges. A singular Ginzburg-Landau parameter at [ital T][sub [ital c]] is predicted, which suggests that the maximum energy gap opens quickly.
Conflict escalation in dyads with a history of territorial disputes

Purpose – Building on the steps to war model, this paper seeks to examine the impact that territorial Militarized Interstate Disputes (MID) have on the time it takes a dyad to go to war after it experiences its first MID.Design/methodology/approach – A model common to epidemiological research, the hazard model, is employed to examine the dyadic relationship from the time of the first MID forward. This is an improvement to dyadic analysis, as most research examines the characteristics of individual MIDs in isolation.Findings – Dyads with a history of territorial MIDs go to war much more quickly than dyads without a history of territorial MIDs. Future research should explore the relationship between territory, war, and power status to test the assertion that minor power states engage in power politics behavior less frequently.Practical implications – Conflict resolution measures need to be employed more quickly when states have unresolved territorial issues. Mediation generally does not occur quickly, which...
The effects of formaldehyde gas in a flow-through rat tracheal implant system.

Abstract A flow-through rat tracheal implant system is described which permits the quantitative and repetitive exposure of respiratory epithelia to test gaseous substances. To investigate the acute toxicity of formaldehyde gas with this new system, open-ended rat tracheal implants were exposed to the gas for 1 h twice a week for up to 8 weeks. The formaldehyde gas was generated from paraformaldehyde, mixed with humidified air and introduced into the lumens of the tracheal implants through microbore tubing. Concentrations of 4.1 ± 0.9, 8.1 ± 1.2 or 12.7 ± 1.5 ppm , were introduced into the trachea by passing an airstream moving at 50, 225 or 475 ml/min, respectively, over the paraformaldehyde heated to 42°C. These formaldehyde concentrations induced mucociliary hypertrophy and increasing amounts of atrophic, transitional and metaplastic epithelia in the tracheal mucosa.
The oxidative disposition of potassium cyanide in mice.

The role of oxidative metabolism in the disposition of potassium cyanide (KCN), was investigated in mice administered KCN, (4.6 mg/kg, s.c.) containing 4.5 microCi [14C]KCN. The expired pulmonary metabolites, [14C]hydrocyanic acid (HCN) and 14CO2, were collected and analyzed. Approximately 1% and 2% of the KCN dose was expired as [14C]HCN and 14CO2, respectively. Expiration of the pulmonary metabolites was decreased following pretreatment with sodium nitrite, sodium thiosulfate, oxygen, or a combination of cyanide antidotes. Treatment with hydrogen peroxide lowered the amount of [14C]HCN expired and did not alter the expiration of 14CO2. Treatment with 3-amino-1,2,4-triazole (catalase inhibitor), superoxide dismutase, or diethyldithiocarbamic acid (superoxide dismutase inhibitor) did not change the amount of [14C]HCN expired. However, superoxide dismutase significantly increased the amount of 14CO2 expired, whereas diethyldithiocarbamic acid decreased 14CO2 expiration. The results from these studies suggest that in vivo cyanide can be oxidized to CO2 and treatment with agents that alter the availability of endogenous superoxide and/or hydrogen peroxide can alter the rate of cyanide oxidation.
Non-alcoholic fatty liver disease: epidemiology, pathophysiology, diagnosis and treatment

Abstract Non-alcoholic fatty liver disease (NAFLD) in most of the world is the most common cause of liver disease in children and adolescents. The term NAFLD includes a spectrum of liver findings with macrovesicular steatosis, either in isolation, or with inflammation and evidence of cellular injury (non-alcoholic steatohepatitis), to cirrhosis. Particular factors responsible for progression of NAFLD from bland to more severe forms remain unknown. Multiple genetic and environmental risk factors are associated with increased risk for NAFLD including obesity, male gender, older age, Hispanic ethnicity or Asian race, and a positive family history. Non-invasive methods of investigation suggesting NAFLD include hepatic ultrasound and MRI, although definitive diagnosis is based on liver biopsy. The current standard of care for treatment of NAFLD is lifestyle modifications in the form of diet and exercise. Rigorous trials of additional treatment modalities such as antioxidants and insulin sensitizers are being explored.
Distribution of a non-conservative constituent in an estuary with application to the numerical simulation of dissolved silica in the San Francisco Bay

Abstract A simplified relation between the distribution of a non-conservative quantity and the distribution of salinity in an estuary is developed analytically from the conservation equations. The relation is tested against a numerical simulation of the same problem using a two-dimensional gravitational circulation model.
Skeletal effects of statins.

Objective: To review the skeletal effects of hydroxy-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins) and evaluate the use and potential benefit of statins in the management of osteoporosis. Methods: Background information on the topic of the effect of statins on bone and fracture risk is presented, and the pertinent published literature is reviewed. Results: Osteoporosis is the most common bone disease, affecting millions of people worldwide and leading to considerable morbidity, especially when it is not adequately managed. Although statins have primarily been known for their lipid-lowering effects, recent data have documented a potential association between statin use and improvement in fracture risk profile. Some statins have been shown to decrease bone-specific alkaline phosphatase or serum osteocalcin concentrations, but other studies have failed to demonstrate the beneficial effects of these agents. Therefore, additional studies should be undertaken to clarify the mechanism of act...
Topical Application of a Protein Kinase C Inhibitor Reduces Skin and Hair Pigmentation

To determine whether inhibition of PKC-β activity decreases pigmentation, paired cultures of primary human melanocytes were first pretreated with bisindolylmaleimide (Bis), a selective PKC inhibitor, or vehicle alone for 30 min, and then treated with TPA for an additional 90 min to activate PKC in the presence of Bis. Bis blocked the expected induction of tyrosinase activity by activation of PKC. Addition of a peptide corresponding to amino acids 501–511 of tyrosinase containing its PKC-β phosphorylation site, a presumptive PKC-β pseudosubstrate, gave similar results. To determine whether Bis reduces pigmentation in vivo , the backs of four shaved and depilated pigmented guinea pigs were UV irradiated with a solar simulator for 2 wk excluding weekends. Compared to vehicle alone, Bis (300 μM), applied twice daily to paired sites for various periods encompassing the irradiation period, decreased tanning. Bis also, although less strikingly, reduced basal epidermal melanin when topically applied twice daily, 5 d per wk, for 3 wk to shaved and depilated unirradiated skin. Moreover, topical application of Bis (100 μM) once daily for 9 d to the freshly depilated backs of 8-wk-old mice markedly lightened the color of regrowing hair. These results demonstrate that inhibiting PKC activity in vivo selectively blocks tanning and reduces basal pigmentation in the epidermis and in anagen hair shafts.
Dislocation Filtering in GaN Nanostructures

Dislocation filtering in GaN by selective area growth through a nanoporous template is examined both by transmission electron microscopy and numerical modeling. These nanorods grow epitaxially from the (0001)-oriented GaN underlayer through the ∼100 nm thick template and naturally terminate with hexagonal pyramid-shaped caps. It is demonstrated that for a certain window of geometric parameters a threading dislocation growing within a GaN nanorod is likely to be excluded by the strong image forces of the nearby free surfaces. Approximately 3000 nanorods were examined in cross-section, including growth through 50 and 80 nm diameter pores. The very few threading dislocations not filtered by the template turn toward a free surface within the nanorod, exiting less than 50 nm past the base of the template. The potential active region for light-emitting diode devices based on these nanorods would have been entirely free of threading dislocations for all samples examined. A greater than 2 orders of magnitude redu...
Optical bleaching of perovskite (CH3NH3)PbI3 through room-temperature phase transformation induced by ammonia

Ammonia induces a phase transformation of perovskite (CH3NH3)PbI3, leading to a rapid (<1 s) change in its color from brown to colorless (400–800 nm). This color change is reversed within seconds upon removing the NH3 source.
Proximity effect tunnelling as a probe of metallurgical processes in thin films

Abstract Electron tunnelling in a junction of the form Al-oxide-M1-M2, where M1, and M2, are metals at least one of which is a superconductor, reveals structure at the phonon frequencies of both M1 and M2. For thin films peaks in the phonon density of states from M1 appear as dips in d2 V/dI2 whereas peaks in the phonon density of states from M2 appear inverted. It is therefore possible to determine which metal is adjacent to the oxide and to monitor changes in this material as diffusion, alloying or formation of intermetallics take place in films as thin as 200 A.
Primacy Effects in Justice Judgments: Testing Predictions from Fairness Heuristic Theory.

We tested predictions from fairness heuristic theory that justice judgments are more sensitive to early fairness-relevant information than to later fairness-relevant information and that this primacy effect is more evident when group identification is higher. Participants working on a series of three tasks experienced resource failures that interfered with their productivity and always had the possibility of explaining problems to a supervisor. In a manipulation of the timing of fairness-relevant experiences, the supervisor refused to consider explanations on the first, second, or third of three work trials (but did consider explanations on the other two trials) or the supervisor never refused to hear the explanations. Prior to the work periods, the participants either had or had not undergone a manipulation designed to induce greater identification with the work group. As predicted, the timing of fairness-relevant experiences showed a primacy effect on fairness judgments and acceptance of authority in the high identification conditions and no evidence of such an effect in the low identification conditions. The implications of the findings for understanding the psychology of justice and for real-world justice phenomena are discussed.
Calculations of Cumulus Vertical Draft Velocities in Hurricanes from Aircraft Observations

Abstract In cumulus convective atmospheres the most significant length scale of vertical motion is of cumulus draft size—of horizontal lengths two to four orders of magnitude less than the synoptic scale and of magnitude one to three orders greater. This draft motion on scales between the gust and synoptic motion has been least investigated. The purpose of this paper is to propose a new method of calculating draft velocities from aircraft and present results of calculations with this method in hurricanes. An aircraft Doppler radio navigation instrument which is capable of measuring horizontal wind variations to a space resolution of a fraction of a nautical mile can be employed with other instruments to measure an aircraft's pitch angle changes. From this determination, along with other standard aircraft measurements such as radar and pressure altitude, power setting, etc., it is possible to make determinations of average vertical air motion to space resolutions of 0.4 to 0.7 nautical miles. Calculations ...
The α-Helical Domain of Gαt Determines Specific Interaction with Regulator of G Protein Signaling 9

RGS proteins (regulators of G protein signaling) are potent accelerators of the intrinsic GTPase activity of G protein alpha subunits (GAPs), thus controlling the response kinetics of a variety of cell signaling processes. Most RGS domains that have been studied have relatively little GTPase activating specificity especially for G proteins within the Gi subfamily. Retinal RGS9 is unique in its ability to act synergistically with a downstream effector cGMP phosphodiesterase to stimulate the GTPase activity of the alpha subunit of transducin, Galphat. Here we report another unique property of RGS9: high specificity for Galphat. The core (RGS) domain of RGS9 (RGS9) stimulates Galphat GTPase activity by 10-fold and Galphai1 GTPase activity by only 2-fold at a concentration of 10 microM. Using chimeric Galphat/Galphai1 subunits we demonstrated that the alpha-helical domain of Galphat imparts this specificity. The functional effects of RGS9 were well correlated with its affinity for activated Galpha subunits as measured by a change in fluorescence of a mutant Galphat (Chi6b) selectively labeled at Cys-210. Kd values for RGS9 complexes with Galphat and Galphai1 calculated from the direct binding and competition experiments were 185 nM and 2 microM, respectively. The gamma subunit of phosphodiesterase increases the GAP activity of RGS9. We demonstrate that this is because of the ability of Pgamma to increase the affinity of RGS9 for Galphat. A distinct, nonoverlapping pattern of RGS and Pgamma interaction with Galphat suggests a unique mechanism of effector-mediated GAP function of the RGS9.
Preliminary piloted simulation studies of the HL-20 lifting body

NASA Langley Research Center is developing a lifting body vehicle, designated the HL-20, as one option of the proposed Personnel Launch System for NASA's future manned access to space requirements. Data derived from wind-tunnel and computational fluid dynamics analyses of the conceptual design led to the derivation of a flight simulator model to investigate the potential flight characteristics of the HL-20. A simulation investigation was initiated to determine if satisfactory unpowered horizontal landings could be accomplished. Control law design and trajectory development were directed toward this end. The study uncovered several deficiencies subsequently corrected through design changes, and it validated the predicted subsonic aerodynamic properties. Expanding the investigation to the Mach 4 to Mach 1 regime revealed flight characteristics necessitating the development of innovative control techniques. This article will present the significant results uncovered to date by flight simulator evaluations of a lifting body class of vehicle, and will demonstrate the effectiveness of flight simulation as an integrated part of the conceptual design phase.
Homo- and hetero-epitaxial deposition of Au by surface limited redox replacement of Pb underpotentially deposited layer in one-cell configuration

Abstract This work reports on homo- and hetero-epitaxial Au deposition realized by surface limited redox replacement (SLRR) of Pb underpotentially deposited (UPD) layer by [AuCl4]− ions in one-cell configuration. An over-stoichiometric amount of deposited Au hinted at by the electrochemical quartz-crystal micro balance (EQCM) kinetic experiments and validated by separate pulse experiments has been attributed to reduction in each SLRR event of a pre-adsorbed layer of [AuCl4]− ions. This phenomenology, known as “spontaneous deposition”, along with strict control over the Pb UPD coverage enables a fine tunable epitaxial Au deposition in the sub-monolayer to monolayer range. After as little as one replacement event on Pt (1 1 1) the deposit displays a Pb UPD cyclic voltammetry (CV) curve as would be observed on an Au (1 1 1) substrate. High quality epitaxial Au has been grown for up to 40 SLRR events as evidenced by CV and ex situ scanning tunneling microscopy (STM). However, growth of thicker films yields a significant surface roughness evolution of 2.5 times. The thicker deposit features a dendritic structure when viewed via scanning electron microscopy. X-ray photoelectron spectroscopy shows less than 0.1 at% Pb in the Au deposit and rules out defect induced roughening. STM results suggest that the surface roughness is likely due to formation of Au islands that grow rapidly in vertical direction and serve eventually as seeds of the dendritic growth transition. Despite its complexity, SLRR of Pb by Au proves to be a viable method for quick and cost effective growth of continuous homo- or hetero-epitaxial Au ultra-thin films.
Use of Total Lymphocyte Count for Monitoring Response to Antiretroviral Therapy

The CD4 cell count has become a key laboratory measurement in the management of human immunodeficiency virus (HIV) disease. In ideal situations, HIV-infected persons are followed up longitudinally with serial CD4 cell counts to determine disease progression, risk for opportunistic infection, and the need for prophylactic or therapeutic intervention. However, the use of the CD4 cell count in resource-limited settings is often not possible because of lack of availability and high cost. Thus, other laboratory markers have been proposed as substitutes for the CD4 cell count. The data regarding the clinical utility of the total lymphocyte count (TLC) as a potential surrogate marker of immune function in patients with HIV disease are examined. The role of the TLC in the initiation of antiretroviral therapy and opportunistic infection prophylaxis, as well as the role of the TLC in monitoring the response to antiretroviral therapy, are also addressed.
Cardiomyocyte Ca2+ handling and structure is regulated by degree and duration of mechanical load variation.

Cardiac transverse (t)-tubules are altered during disease and may be regulated by stretch-sensitive molecules. The relationship between variations in the degree and duration of load and t-tubule structure remains unknown, as well as its implications for local Ca2+-induced Ca2+ release (CICR). Rat hearts were studied after 4 or 8 weeks of moderate mechanical unloading [using heterotopic abdominal heart–lung transplantation (HAHLT)] and 6 or 10 weeks of pressure overloading using thoracic aortic constriction. CICR, cell and t-tubule structure were assessed using confocal-microscopy, patch-clamping and scanning ion conductance microscopy. Moderate unloading was compared with severe unloading [using heart-only transplantation (HAHT)]. Mechanical unloading reduced cardiomyocyte volume in a time-dependent manner. Ca2+ release synchronicity was reduced at 8 weeks moderate unloading only. Ca2+ sparks increased in frequency and duration at 8 weeks of moderate unloading, which also induced t-tubule disorganization. Overloading increased cardiomyocyte volume and disrupted t-tubule morphology at 10 weeks but not 6 weeks. Moderate mechanical unloading for 4 weeks had milder effects compared with severe mechanical unloading (37% reduction in cell volume at 4 weeks compared to 56% reduction after severe mechanical unloading) and did not cause depression and delay of the Ca2+ transient, increased Ca2+ spark frequency or impaired t-tubule and cell surface structure. These data suggest that variations in chronic mechanical load influence local CICR and t-tubule structure in a time- and degree-dependent manner, and that physiological states of increased and reduced cell size, without pathological changes are possible.
A decision support system for the procurement of military equipment

The use of life-cycle costs in procurement is limited by the accuracy of cost estimates and assessments of availability risks under the conditions generating costs. Critical to these problems are the needs and responses of equipment to maintenance and repair. Using transition probabilities to define the relationships between serviceability and maintenance and repairs, this article develops a comprehensive decision support system for military procurement. It uses a dynamic programming model to determine the least-cost set of maintenance and repair decisions, where adjustments are included for warranty conditions, time value of money, the opportunity costs of equipment failure, and the end-of-cycle salvage values or disposal costs. The system allows users to define working and failed states, create their own rules or indicators of availability from estimates of state probabilities and establish thresholds of risk acceptability.
Enzymatic synthesis of polymers containing nicotinamide mononucleotide

Nicotinamide mononucleoside 5'-diphosphate in its reduced form is an excellent substrate for polynucleotide phosphorylase from Micrococcus luteus both in de novo polymerization reactions and in primer extension reactions. The oxidized form of the diphosphate is a much less efficient substrate; it can be used to extend primers but does not oligomerize in the absence of a primer. The cyanide adduct of the oxidized substrate, like the reduced substrate, polymerizes efficiently. Loss of cyanide yields high molecular weight polymers of the oxidized form. Terminal transferase from calf thymus accepts nicotinamide mononucleoside 5'-triphosphate as a substrate and efficiently adds one residue to the 3'-end of an oligodeoxynucleotide. T4 polynucleotide kinase accepts oligomers of nicotinamide mononucleotide as substrates. However, RNA polymerases do not incorporate nicotinamide mononucleoside 5'-triphosphate into products on any of the templates that we used.
Using State Pension Shocks to Estimate Fiscal Multipliers since the Great Recession

Has government spending raised income and employment since 2008? I use new data on state pension returns during the Great Recession to recover exogenous changes in spending. Instrumenting with these return shocks, I estimate that each dollar of windfall-financed spending raised local incomes by $1.43 and every additional $22,011 of spending created one contemporaneous job. These estimates are similar to those found in Shoag (2010) despite the non-overlapping datasets. Unlike Shoag (2010), however, the bulk of the employment increase post-2008 stems from decreases in unemployment rather than increased labor force participation.
Big Steel, Invention, and Innovation: Reply

I. The invention, 475. — II. The innovation: domestic lag, 475. — III. The innovation: international lag, 476. — IV. Explanation of the lag, 478. — V. Conclusion, 481.
Enhanced modulation of hypotension in endotoxemia by concomitant nitric oxide synthesis inhibition and nitric oxide scavenging.

Elevated nitric oxide (NO) levels appear to be a primary cause of the sepsis related hypotension. We tested a hypothesis that a concomitant NO synthesis inhibition (NOSI) and NO scavenging (NOSC) could effectively modulate this hypotension. Anesthetized SD rats were subjected to endotoxemic shock by intravenous administration of endotoxin (LPS; 10mg/Kg). Three hours post-LPS, the animals were randomly divided into three groups and infused with 25mg/Kg of N-amino-L-methyl ester (NAME; a NO synthesis inhibitor, N=4), 130 mg/Kg human hemoglobin (Hb; a NO scavenger, N=6), or a mixture of both (130mgHb/Kg and 25mg NAME/Kg, N=4). Changes in mean blood pressure (MBP) and erythrocyte and plasma nitrosyl Hb (HbNO) levels were followed. The initial MBP increase of the combined treatment was significantly greater than Hb or NAME alone (P<0.05, t-test) and was maintained significantly above the pre-treatment values (P<0.05, paired t-test) 2hrs after treatment. All post-LPS erythrocyte samples exhibited the characteri...
UNICOM: a construction/integration model of failures in action planning

The author's goal is to systematically break down UNICOM's knowledge base in a manner that explains UNIX performance for users at different levels of expertise. That is, they want to determine what aspects of the knowledge base must be deleted to simulate intermediate and novice performance. They report on the efforts to simulate UNIX command performance acquisition at both the group level, and at the level of individuals. They model tasks whose solutions cannot be precompiled, because familiar elements are put together in a novel fashion. It is presumed that subjects are not recalling fixed scripts from memory. Rather, they are producing action plans for each task. They describe UNIX performance data, and the UNICOM model, and then describe how the model accounts for the failure of less expert users to produce effective action plans. >
Adam Smith and the Circles of Sympathy: Perfectionism and social order

[A]lmost all worthwhile human life lies between the extremes that morality puts before us. Bernard Williams, Ethics and the Limits of Philosophy Smith's portraits in the last chapter of the “weak man” and the “wise and virtuous man” are ideal types. Most people fall somewhere in the middle. Like Cicero's De Officiis , which Smith characterized as a doctrine of “imperfect, but attainable virtues,” the Moral Sentiments seeks to describe the morality of ordinary people, to whom Smith variously referred as “tolerably good soldiers,” “commonly honest men,” the “mean,” the “many,” the “greater part,” the “crude,” the “mass,” the “vulgar,” the “coarse clay of mankind.” Cicero described the nature of his project in the following way: The duties that I discuss in these books are, then, those that the Stoics call “middle”. They are shared and widely accessible. In this chapter, I do four things. First, I argue that Smith was primarily concerned in the Moral Sentiments with describing and legitimating the morality of ordinary people for its stabilizing effects on modern society. This will mean, ultimately, that much of the perfectionist rhetoric in his thought should be bracketed from, or at least interpreted within, the central thrust of his practical morality, which was oriented around social order. Here I fundamentally agree with Joseph Crospey, Charles Griswold and Douglas Den Uyl, among others, that Smith was primarily concerned in the Moral Sentiments with social coordination.
The Need for More Autism Awareness in the Somali American Population

To the Editor: Autism spectrum disorder is diagnosed in 1 out of every 68 children (1 in 42 boys and 1 in 189 girls), and the prevalence has increased 20-fold to 30-fold since 1970.1 Studies have shown increased risk in identical twins. If parents have one child with autism spectrum disorder, they have a 2% to 18% chance of having another affected child. Prevalence varies in different racial and ethnic groups. In a Swedish study, the prevalence of autism spectrum disorder was 4 to 5 times higher in their Somalian immigrant population.2,3 According to the 2010 American Community Survey data, there are approximately 85 700 people with Somali ancestry in the United States. Approximately 25 000 (one third) live in a growing Minnesota population. A University of Minnesota study indicates higher rates of autism (1 in 32) in the Somali population.4 Autism spectrum disorder is challenging to diagnose, explain, and treat in a cross-cultural setting. We experienced these challenges recently in a Somali family with 3 children with autism spectrum disorder. The parents had not heard of autism or seen anyone with autism in their family or among friends. They asked why it happened in their family and whether their fourth child (a 2-year-old) would also be affected. County social services were arranged, but it will still be a difficult journey for the family, as they will be taking care of one child or another around the clock. Referral to an autism center proved most beneficial. Awareness of symptoms and treatment of autism spectrum disorder is critical for the Somali American population. This can be done through organizations supporting the Somali immigrant population, and more so by physicians who treat patients in the community. Increasing the services is needed to assist families through support, education, and care such as with the Center for Autism. We advocate for more awareness as a first step to promote healthier patients, families, and society.
Nonequilibrium Liquid Plasma Generation

In most cases, the electric breakdown of liquids is initiated by the application of high electric field on the electrode, followed by rapid propagation and branching of plasma channels. Typically, plasmas are only considered to exist through the ionization of gases, and typical production of plasmas in liquids has generated bubbles through heating or via cavitations and sustains the plasmas within those bubbles. The question appears: Is it possible to ionize the liquid without cracking and voids formation? We have demonstrated possibility of formation of nonequilibrium plasma in liquid phase and investigated the dynamics of excitation and quenching of nonequilibrium plasma in liquid water.
A History of the Rio Pongo: Time for a New Appraisal?

Forty-five years ago (1965), when some of us were beginning our studies of the history of the Upper Guinea coast, there existed only a few published general histories of Guinea-Conakry or region-based models to guide us. Andre Arcin's substantial works (1907 and 1911) provided original but awkward structures from which we could commence our work, but his monographs tended to be based heavily upon a colonial presence, a necessity to make sense of a complex colony, and a reliance upon oral traditions or other uncitationed sources, many of which could not be tested a half century later.1 Christopher Fyfe's comprehensive history of Sierra Leone had just been published in 1962. Fyfe's foremost emphasis was to chronicle the development of the Sierra Leone settlement and chart that colony's progress, but his extensive documentation was extraordinary in that it demonstrated the clear link between the "Northern Rivers" and British enterprise from Freetown and opened Britain's archives as sources of information about the history of these rivers in new and profound ways.2
Toward Individualized Breast Cancer Therapy: Translating Biological Concepts to the Bedside

The management of breast cancer has changed dramatically over the past 20 years. Based on gene expression profiles, or proteomics of three or four biomarkers, it is apparent that there are multiple subtypes with different clinical characteristics, clinical courses, and sensitivities to existing therapies. This manuscript reviews the management of hormone receptor-positive, human epidermal growth factor receptor 2-positive, and triple-negative breast cancers, emphasizing changes that have occurred in recent years and focusing on potential mechanisms of drug resistance. I also highlight strategies to prevent or overcome resistance to specific therapeutic agents. As a result of enhanced biological understanding of the molecular anomalies that drive the development, progression, and dissemination of breast cancer, a number of novel, molecularly targeted agents have been added to standard therapies. Chemotherapy, endocrine therapy, and targeted treatments have markedly reduced the risk for recurrence and mortality after primary treatment of breast cancer and have increased the 5- and 10-year survival rates. The challenges with novel therapeutics include the absence of accurate predictive biomarkers to identify those patient who will derive substantial benefit and those patients whose tumors are resistant to specific antitumor agents. As we move forward with increasing molecular segmentation of breast cancer and develop new, highly targeted agents, molecular diagnostics must accompany molecular therapeutics to implement the concept of personalized cancer therapy.
Mouse Mutants Reveal that Putative Protein Interaction Sites in the p53 Proline-Rich Domain Are Dispensable for Tumor Suppression

The stability and activity of tumor suppressor p53 are tightly regulated and partially depend on the p53 proline-rich domain (PRD). We recently analyzed mice expressing p53 with a deletion of the PRD (p53ΔP). p53ΔP, a weak transactivator hypersensitive to Mdm2-mediated degradation, is unable to suppress oncogene-induced tumors. This phenotype could result from the loss of two motifs: Pin1 sites proposed to influence p53 stabilization and PXXP motifs proposed to mediate protein interactions. We investigated the importance of these motifs by generating mice encoding point mutations in the PRD. p53TTAA contains mutations suppressing all putative Pin1 sites in the PRD, while p53AXXA lacks PXXP motifs but retains one intact Pin1 site. Both mutant proteins accumulated in response to DNA damage, although the accumulation of p53TTAA was partially impaired. Importantly, p53TTAA and p53AXXA are efficient transactivators and potent suppressors of oncogene-induced tumors. Thus, Pin1 sites in the PRD may modulate p53 stability but do not significantly affect function. In addition, PXXP motifs are not essential, but structure dictated by the presence of prolines, PXXXXP motifs that may mediate protein interactions, and/or the length of this region appears to be functionally significant. These results may explain why the sequence of the p53 PRD is so variable in evolution.
In vivo tear-film thickness determination and implications for tear-film stability

PURPOSE. Previous measurements of tear-film thickness in vivo are limited and cannot be easily applied in a clinical setting. A novel technique to measure tear-film thickness indirectly is introduced here, requiring only a slit lamp, video camera, and computer. A recent fluid mechanical theory relates tear-film thickness h, to the tear meniscus radius R, tear surface tension s, tear viscosity µ, and upper lid velocity U. This theory yields the result that h/R = 2.12 (µU/s) 2/3. All parameters except h/R are taken as known physical constants, and R was measured for each subject, allowing the above equation to establish h. Tear-film breakup was also evaluated and correlated with tear-film thickness. METHODS. A clinical study was performed in which aqueous tear-film thickness was determined for 45 subjects, including 24 non-lens subjects, 15 hydrogel contact lens wearers, and 6 RGP lens wearers. R was measured by instilling fluorescein dye in the form of an eyedrop and videotaping the tear meniscus in profil...
An efficient, pitch-aligned high-frequency regeneration technique for RELP vocoders

A technique for reducing the tonal noises due to harmonic misalignment in RELP vocoders is developed. The method, pitch-aligned high-frequency regeneration, is based upon frequency translation by modulation phenomena of the transmitted baseband signal. The method is reported to give the same tonal noise reduction as a full-band pitch prediction system. A reduced complexity version is implemented in a real-time, single TMS320-based vocoder.
Within-Family Variability in Representations of Past Relationships With Parents

Background. We examined within-family variation in siblings’ memories of experiences with parents and their associations with current positive and negative affect. Methods. Participants were 1,369 adults with at least 1 sibling, aged 26 – 74 years from 498 families in the MacArthur Study of Midlife in the United States ( M age = 47 years, 59% women, 94% White). Results. There was considerable variability in recalled maternal and paternal treatment across the dimensions of affection (intraclass correlation coeffi cients [ICCs] 0.33 and 0.41, respectively), discipline (ICCs 0.39 and 0.43), and confl ict (ICCs 0.24 and 0.26). In turn, recalled parental treatment, particularly affection, made unique contributions to current positive (ICC 0.12) and negative affect (ICC 0.08) over and above individual and familial level characteristics such as offspring demographic characteristics, extraversion and neuroticism, family structure, recalled early family environment, and parents’ current status. Conclusions. Results link adults’ memories of experiences with their parents in childhood to their current well-being and highlight the importance of considering within-family models for family theory .
Overcoming Insurance and Financial Risks for M&A

Business combinations face insurance and financial risks arising from the incomplete convergence of International Accounting Standards Board (IASB) and Financial Accounting Standards Board (FASB) rules. What are some practical solutions? The author of this article offers some answers. © 2014 Wiley Periodicals, Inc.
Anomalous impurity ion heating from Alfvénic cascade in the reversed field pinch

Anomalous ion and impurity heating in reversed field pinch plasmas is addressed. Previous work [N. Mattor et al., Comments Plasma Phys. Controlled Fusion 15, 65 (1992)], which calculated the heating of bulk ions by gyro and Landau resonances with turbulent fluctuations cascading from unstable tearing modes, is extended to impurity species measured in Madison symmetric torus (MST). The heavier mass of impurities allows gyro-resonant heating at lower frequencies where more energy is present in the fluctuations. A 0D transport model is used to examine heating rates under various time-dependent, experimental heating scenarios, such as a sawtooth crash. Impurity heating rates calculated for impurities found in MST are comparable to observed rates inferred in the impurity temperature rise during sawtooth events.
Paired professional development: a methodology for continued professional development in computer science

We describe a study group methodology called paired professional development (PPD) for use by faculty members for continuing education. The methodology brings exactly two colleagues together for cooperative study within a topic area over an extended period of time. Paired professional development is grounded in the practice of study groups, collaborative learning and high-impact educational practices, and is similar to pair programming in structure and benefits.