cssi/SciSciGPT-SciSciNet huggingface dataset:
Participation of transglutaminase in the activation of latent transforming growth factor β1 in aging articular cartilage

OBJECTIVE Transglutaminase (TGase) catalyzes the calcium-dependent crosslinking of polypeptide chains, resulting in posttranslational protein modifications that affect both intracellular and extracellular processes. We previously demonstrated a dramatic elevation of TGase activity levels in aging articular chondrocytes and postulated a role for TGase in the pathologic processes common in aging joints. In several cell systems, TGase participates in the activation of latent transforming growth factor beta (LTGFbeta). Since TGFbeta is a key factor in age-related cartilage diseases, the purpose of the present study was to determine whether TGase from aging articular chondrocytes participates in LTGFbeta activation. METHODS We measured the ability of old and young porcine articular chondrocytes to activate 10 ng/ml of LTGFbeta1 in the presence and absence of TGase inhibitors. The activity of plasmin, another key participant in LTGFbeta activation, was also measured. RESULTS Old chondrocytes activated 11+/-1.8% (mean +/- SD) of exogenous LTGFbeta1 at 6 hours, while young chondrocytes activated 4.2+/-0.5% of exogenous LTGFbeta1. The addition of 3 different TGase inhibitors suppressed active TGFbeta1 in the cell layer to levels that were 35-69% of control values in old chondrocytes and had no effect on young chondrocytes. The ability to suppress TGFbeta activation correlated with the ability of each of the TGase inhibitors to inhibit TGase activity. The activity of plasmin, which enzymatically activates LTGFbeta1, did not differ between young and old chondrocytes and was unaffected by TGase inhibition. CONCLUSION We report here a novel pathologic function for TGase in aging articular cartilage. This work supports a role for elevated TGase activity in age-related arthritis based in part on its participation in the activation of the critical growth factor TGFbeta in articular cartilage.
Chemical influences on adsorption-mediated self-propelled drop movement.

We report studies of reactive wetting employing droplets of a nonpolar liquid (decahydronaphthalene) on chemically patterned surfaces. The drops contain an n alkylamine that adsorbs onto surfaces exposing carboxylic acid groups and produces surfaces exposing methyl groups. The change in surface energy that occurs concurrent with the formation of an oriented monomolecular film of alkylamine during this process is sufficient to produce a self-propelled movement of decahydronaphthalene drops on the surface. We employed patterning to direct the movement of the drops on the surface, thereby allowing measurements of the relationships between the macroscopic fluidic behavior of the droplets and microscopic adsorption events. Specifically, we examined the effects of the unbalanced surface-tension force and the influences of adsorbate concentration on drop movement. In this latter case, both kinetic and thermodynamic arguments can be applied to describe the system. We compared the predictions from these two approaches by analyzing data from the present system and those reported by F. Domingues Dos Santos and T. Ondarcuhu [Phys. Rev. Lett. 75(16), 2972 (1975)] that exhibited opposite trends in behavior. The present analysis provides insight into the influence of chemical reaction kinetics on adsorption-mediated drop movement (i.e., reactive wetting).
Curcumin prevents HIV protease inhibitor ritonavir-induced vascular injury and superoxide anion production in porcine coronary arteries

Introduction: HIV protease inhibitor ritonavir (RTV) may induce vascular dysfunction through oxidative stress. The objective of this study was to determine whether a dietary antioxidant curcumin could prevent coronary arteries from RTV-induced injury. Methods: Porcine coronary arteries were incubated with RTV and/or curcumin for 24 hours. Vasomotor function was studied with a myograph tension system in response to thromboxane A2 analogue U46619 (contraction), and bradykinin (endothelium-dependent relaxation). Superoxide anion levels were determined by lucigenin enhanced chemiluminescence. Results: In response to U46619, the control vessels showed a 71% reduction (p < 0.001, t-test). The combination of RTV and curcumin showed a vessel tension similar to controls. In response to bradykinin, the control vessel rings relaxed by 70.80%, while RTV treated vessels only relaxed by 29.25%, which showed a 59% reduction as compared to controls (p < 0.001, t-test). Curcumin plus RTV showed 54.20% of vasorelaxation, respectively. Superoxide anion level in the RTV-treated group was increased by 47%, as compared to controls (P < 0.05, t-test). Curcumin treatment significantly inhibited RTV induced superoxide anion production. Conclusions: HIV protease inhibitor RTV significantly decreases smooth muscle cell contractivity and endothelium-dependent vasorelaxation, but increases superoxide anion production in porcine coronary arteries. Curcumin can effectively inhibit RTV-induced vascular injury and oxidative stress.
The role of technology in vascular surgery

Abstract This paper is based upon a plenary lecture presented at the opening of the International Vascular Symposium held in London in September 1981.
Stable isotope studies on Mono Lake (California). 1. d18 in lake sediments as proxy for climatic change during the last 15 years

Mono Lake is a hypersaline, alkaline lake in the Mono Basin located #at the eastern base of the Californian Sierra Nevada. Its lake-level history since 1912 has been recorded instrumentally, showing the decline of lake-surface elevations initiated by the 1941 artificial diversion of stream inflow. We have made high-resolution oxygen isotopic measurements on the total carbonate fraction of lake sediments and shown that the S’*O record parallels the lakelevel fluctuations rather well. The measurements were carried out on sediments that had been leached with deionized water to isolate the isotopic signals of the calcium carbonate from those of pore water and water-soluble carbonate salts in the sediment. Extending the S’“O record back in time, we found that lake level changed markedly during the past 150 yr, reflecting climatic variations and resultant runoff fluctuiitions. Lake levels were high around 1845, 1880, and 19 15 and low around 1860, 1900, and 1933. This study demonstrates that closed-basin lake sediment S180 provides an effective means of probing past precipitation variations in arid to semiarid regions such as the Great Basin in the western United States. Numerous attempts have been made to reconstruct paleolake levels on the basis of geological and stable isotopic evidence from which paleohydrological conditions have been inferred. Studies on closed-basin lakes in semiarid and tropical zones have contributed greatly to paleoclimatic research, particularly for the Late Pleistocene and the Holocene (e.g. Street-Perrott and Harrison 1985; Chivas et al. 1986; Gasse et al. 1991). Water entering closed-basin lakes via rain and runoff leaves by evaporation. Hence, fluctuations in lake level and volume should serve to indicate changes in the moisture budget associated with climatic change. Mono Lake, located in eastern California about 480 km north of Los Angeles (Fig. l), is the only terminal lake in the Mono Basin. Its present ratio of surface area (150 km2) to catchment area (2,072 km2) is -7 : 100, in contrast to the ratio of -33 : 100 for Lake Russell during the last glacial period (Russell 1889; Lajoie 1968; Mono Lake Committee 1981). Since 1912, the levels of Mono Lake have been measured by the U.S. Geological Survey (USGS) and the Los Angeles Department of Water and Power (LADWP) (Blevins et al. 1987). Since its historic high in 1915, the water level within the lake has fallen as a result of climatic changes. The lake level fall has been exacerbated by the diversion of inflow to the lake by LADWP ‘since 1941 and has caused a further increase in salinity and alkalinity. Dur
Preservation of prefrontal cortical volume in behaviorally characterized aged macaque monkeys.

Abstract Normal aging is frequently accompanied by a decline in cognitive capacities supported by the prefrontal cortex. The principal aim of the present study was to determine whether these impairments are coupled to morphometric alterations affecting the volume of the prefrontal cortex in an established nonhuman primate model. A large sample of 19 young (4–11 years old) and 40 aged (20–32 years old) rhesus monkeys was tested using a delayed response procedure known to require the functional integrity of area 46 of the prefrontal cortex. Aged monkeys displayed robust delayed response deficits that were specifically related to the demands of testing on memory. Modern stereological methods were then used to estimate the total volume of area 46 and the volume of layer I in brains from 21 young and aged monkeys. Prefrontal cortex volume was entirely preserved in the aged monkeys as a group and among the subset of aged subjects that displayed the most severe behavioral impairment. These findings indicate that gross morphometric alterations affecting cortical volume are unlikely to account for age-related decline in the information processing capacities of area 46 in primates. Taken together, current evidence instead suggests that changes in the functional connectivity of critical cortical circuits may contribute to normal cognitive aging.
The role of AMP-activated protein kinase in the action of ethanol in the liver.

Background & Aims: Our previous work has shown that ethanol induces the fatty acid synthesis pathway by activation of sterol regulatory element-binding protein 1 (SREBP-1). In the present study, we studied the mechanisms of this activation by identifying a new target of ethanol, AMP-activated protein kinase (AMPK). Methods: The effects of ethanol on AMPK, acetyl-CoA carboxylase (ACC), and SREBP-1 were assessed in rat hepatic cells and in the livers of ethanol-fed mice. Results: In rat hepatoma H4IIEC3 or McA-RH 7777 cell lines, ethanol-induced transcription of an SREBP-regulated promoter was suppressed by the presence of 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) or metformin, 2 known AMPK activators. Consistent with this, over expression of a constitutively active form of AMPK blocked the effect of ethanol, whereas coexpression of a dominant-negative form of AMPK augmented the effect. Moreover, activation of AMPK by metformin or AICAR largely blocked the ability of ethanol to increase levels of mature SREBP-1 protein. These findings suggest that the effect of ethanol on SREBP-regulated promoter activation was partially mediated through AMPK inhibition. We further demonstrated that AMPK was inhibited by ethanol in hepatic cells. In parallel, ethanol increased the activity of ACC and suppressed the rate of palmitic acid oxidation. Finally, feeding mice a low-fat diet with ethanol resulted in significantly reduced hepatic AMPK activity, increased ACC activity, and enhanced malonyl CoA content. Conclusions: Taken together, our findings suggest that AMPK may play a key role in regulating the effects of ethanol on SREBP-1 activation, fatty acid metabolism, and development of alcoholic fatty liver.
Afghanistan Historiography and Pashtun Islam: Modernization Theory's Afterimage

In contrast to major developments in general South Asian historiography, the historiography of modern Afghanistan has largely persisted as something of a scholarly throwback to the ‘modernization theory’ trend of the 1950s and 60s. The way Pashtun experiences of Islam have been treated in history writing draws heavily upon this larger modernization-oriented thematic, which in turn has existed in a dialectic with journalistic and policy-oriented writing. This article analyzes a number of scholarly works in which questions of Islam and social change in Pashtun polities form a major focus. The article focuses on works focusing on the pre-1979 situation, which has been examined only perfunctorily in works of authors employing more current analytical techniques. The article identifies a number of appropriate thematic questions in existing work which could improve our understanding of the cultural history of pre-1979 Islam in P ashtun areas of Afghanistan, and raises a fe w ne w questions worth investigating. The US has directly involved itself in the domestic politics of a jihad-torn Afghanistan off and on for around two and a half decades, especially the Pashtun-majority regions notorious in western public opinion for being the heartland of the Taliban movement. One might expect that during this time, US and western-based scholars would develop a sizable body of literature on the historical experience of Islam in Pashtun societies predating the war, and that this literature would have kept pace with contemporary trends in historiographical literature. Curiously, the opposite seems to be the case, perhaps in part because of the effects of the particularly closely linked nature of v arious intellectual genealogies in Afghanistan studies throughout the 19th and 20th centuries, and (often imperial) statist policy concerns generally. A reappraisal of the field might then be warranted, especially given the modest upswing in Afghan studies since the commencement of the latest, most overtly involved phase of US-spearheade d w estern in volvement beginning in 2001. Also around two and a half decades ago, Ranajit Guha published his seminal essay ‘The Prose of Counter-Insurgency’ in Subaltern Studies II. That journal devoted to the history of non-elites in India has since opened a number of doors in the social and cultural historiography of colonial South
Fast numerical solution of the finite-horizon optimal control problem for real-time applications

This paper uses a relaxation-based technique to solve the finite-horizon optimal control problem for real-time control applications, such as the motion control problem. The proposed technique is reliable, handles singularities well, and allows for fast computation and minimum solution error.
A lattice network for signal representation using Gaussian basis functions and max-energy paradigm

Describes two novel schemes for efficient representation of 1-D and 2-D signals using Gaussian basis functions (BFs). Special methods are required since the Gaussian functions are nonorthogonal. The first method employs a paradigm of maximum energy reduction interlaced with the A* heuristic search. The second method uses an adaptive lattice system to find the optimal projections of the BFs onto the signal, and a lateral-vertical suppression network to select the most efficient representation in terms of data compression. >
Software Stability in Software Reengineering

Legacy systems won't evolve well in today's modern computing environments without reengineering. Unfortunately, most reengineering projects are only concerned about whether the systems can be seamlessly integrated into the environments and usually ignore the quality in the improvement of the legacy systems. We all agree that it would be better to observe both integration and quality improvement implemented in the reengineering process. Software stability makes this possible in the reengineering process so that the new systems can run in a heterogeneous computing environment but also be stable enough to reduce the maintenance costs and efforts. In this paper, a connection between the stability modeling and reengineering process for legacy system is described. A preliminary study on techniques for building a better stable system will be presented although the techniques are still not very promising yet. We will also discuss the issues and challenges of applying software stability into the legacy reengineering process.
EP1 Disruption Attenuates End-Organ Damage in a Mouse Model of Hypertension

Prostaglandin E(2) is a major prostanoid found in the kidney and vasculature contributing to the regulation of blood pressure. The prostaglandin E(2) receptor EP1 has been shown to contribute to hypertension by mediating angiotensin II-dependent vasoconstriction, although its precise role is incompletely characterized. Disruption of the EP1 receptor in C57BL/6J mice reduced the incidence of mortality during severe hypertension induced by uninephrectomy, deoxycorticosterone acetate, and angiotensin II. Mortality was dependent on all components of the model. Death was a result of aortic aneurysm rupture or occurred after development of anasarca, each of which was reduced in EP1-/- mice. Mean arterial pressure was increased in treated EP1+/+ and EP1-/- mice; however, this elevation was significantly lower in EP1-/- mice. Blood pressure reduction via administration of hydralazine phenocopied EP1-/- mice. Thus, reduction in blood pressure by disruption of EP1 reduced incidence of mortality and decreased organ damage, suggesting that EP1 receptor blockade may be a viable target for antihypertensive therapy.
Multiple criteria decision support for software reuse: A case study

In practice, many factors must be considered and balanced when making software reuse decisions. However, few empirical studies exist that leverage practical techniques to support decision-making in software reuse. This paper reports a case study that applied SMART (Simple Multi-Attribute Rating Technique) to a company that considered reuse as an option of reengineering its web site. The company's reuse goal was set to maximize benefits and to minimize costs. After several rounds of rigorous analysis, the company identified the optimal reuse percentage, which was reusing 76–100% of the existing artifacts and knowledge. Our study shows that SMART is a valuable and practical technique that can be incorporated in an organization's software reuse program.
Effect of sodium linoleate infusion on plasma free fatty acids, glucose, insulin, and ketones in unanesthetized dogs.

By using a continuous-flow centrifuge to separate carotid artery blood into cells and plasma, sodium linoleate was infused into the jugular vein of five conscious dogs at a mean rate of 41.9 μEq. · kg. −1 · min −1 for ninety minutes without adverse side effects. Linoleate infusion quickly elevated plasma free fatty acid (FFA) levels to approximately 1.50 μEq./ml. and was accompanied by a rapid four- to sixfold increase in plasma immunoreactive insulin (IRI) which was sustained throughout the infusion. After thirty minutes of infusion, plasma glucose began to fall, ultimately declining 35 per cent from control levels. Plasma ketone levels rose to twice their control levels during linoleate infusion but were always less than 20 per cent of the ketone levels shown to be insulinogenic in dogs. Upon termination of the infusion, plasma FFA, IRI, and ketones fell quickly to control levels, while plasma glucose rose toward normal. The half-life of plasma linoleate, estimated from the infusion rate and the increment in plasma FFA during steady-state infusion, was 0.76 minute. This result, based on net flux, validates estimates based on tracer experiments. The similarity between the metabolic responses to linoleate infusion and those previously found to oleate suggests that these effects may be common to most physiologic long-chain FFA. Stimulation of insulin secretion by high levels of FFA could thus play a role in modulating lipolytic responses and changes in glucose metabolism accompanying such responses.
PRODUCTION OF A RABBIT ANTIMOUSE EOSINOPHIL SERUM WITH NO CROSS-REACTIVITY TO NEUTROPHILS

Antieosinophil serum (AES), obtained by immunizing rabbits with a highly purified suspension of mouse eosinophils, contains high titers of specific agglutinating and cytotoxic antibodies to eosinophils. Absorption with macrophages, lymphocytes, and neutrophils does not affect the antieosinophilic activity while it is markedly lowered by absorption with eosinophils. One dose of AES (0.1 ml) injected into mice with schistosomiasis mansoni caused a mean decrease in circulating eosinophils of 90% within 1 h which was maintained for 5 days, followed by gradual recovery. No other changes in the total or differential white cell counts were noted. In normal mice AES markedly depressed exudation of eosinophils in the peritoneal cavity after repeated saline stimulation. Some of the immunological and clinical implications of a monospecific AES are discussed.
Functional expression of TASK‐1/TASK‐3 heteromers in cerebellar granule cells

TASK-1 and TASK-3 are functional members of the tandem-pore K+ (K2P) channel family, and mRNAs for both channels are expressed together in many brain regions. Although TASK-1 and TASK-3 subunits are able to form heteromers when their complementary RNAs are injected into oocytes, whether functional heteromers are present in the native tissue is not known. Using cultured cerebellar granule (CG) neurones that express mRNAs of both TASK-1 and TASK-3, we studied the presence of heteromers by comparing the sensitivities of cloned and native K+ channels to extracellular pH (pHo) and ruthenium red. The single-channel conductance of TASK-1, TASK-3 and a tandem construct (TASK-1/TASK-3) expressed in COS-7 cells were 14.2 ± 0.4, 37.8 ± 0.7 and 38.1 ± 0.7 pS (–60 mV), respectively. TASK-3 and TASK-1/TASK-3 (and TASK-3/TASK-1) displayed nearly identical single-channel kinetics. TASK-3 and TASK-1/TASK-3 expressed in COS-7 cells were inhibited by 26 ± 4 and 36 ± 2 %, respectively, when pHo was changed from 8.3 to 7.3. In outside-out patches from CG neurones, the K+ channel with single channel properties similar to those of TASK-3 was inhibited by 31 ± 7 % by the same reduction in pHo. TASK-3 and TASK-1/TASK-3 expressed in COS-7 cells were inhibited by 78 ± 7 and 3 ± 4 %, respectively, when 5 μm ruthenium red was applied to outside-out patches. In outside-out patches from CG neurones containing a 38 pS channel, two types of responses to ruthenium red were observed. Ruthenium red inhibited the channel activity by 77 ± 5 % in 42 % of patches (range: 72–82 %) and by 5 ± 4 % (range: 0–9 %) in 58 % of patches. When patches contained more than three 38 pS channels, the average response to ruthenium red was 47 ± 6 % inhibition (n= 5). These electrophysiological studies show that native 38 pS K+ channels of the TASK family in cultured CG neurones consist of both homomeric TASK-3 and heteromeric TASK-1/TASK-3.
Fear and Loathing in Congress and the Courts: Immigration and Judicial Review

This paper examines the oil-and-water relationship of United States immigration policy and judicial review. The most famous illustration of this uneasy mix has been the so-called plenary power doctrine, under which the Supreme Court has explicitly accorded Congress unusual deference in matters that affect the admission or expulsion of aliens. A second illustration is consular absolutism, the lower court doctrine that bars judicial review of consular officers' visa denials. A third is the ferocious assault on judicial review of immigration decisions by Congress in 1996. Surprisingly, commentators have made no explicit attempt to link these three major developments. Yet they reflect, and possibly reinforce, a clear, albeit qualified, pattern of genuine discomfort ? on the parts of both Congress and the Judiciary ? with the notion of a significant judicial role in immigration matters. Moreover, these doctrines have had an immense combined effect on the evolution of modern immigration law. After summarizing and critiquing the stated doctrinal explanations for these developments, the paper explores why immigration regulation has bred such particularized antagonism to judicial review. It considers some of the external factors that operate on judges, the general unpopularity and political powerlessness of immigrants, and some generic costs of judicial review. The article also offers an explanation of why, despite those costs, judicial review is at least as critical in immigration cases as it is in any other legislative or administrative process. The justifications for review are rooted in justice, not in charity.
What the Unconstitutional Conditions Doctrine Can Teach Us About ERISA Preemption: Is it Possible to Consistently Identify 'Coercive' Pay-or-Play Schemes?

Two recent circuit court decisions - first Retail Industry Leaders Ass’n v. Fielder in the Fourth Circuit then Golden Gate Restaurant Ass’n v. San Francisco in the Ninth Circuit - have left far from clear the extent to which state-level employer pay-or-play health insurance schemes are valid in the face of an ERISA preemption challenge. Debate indeed continues as to whether the currently operative, but as yet unchallenged, pay-or-play law in Massachusetts is preempted. The Ninth Circuit reasoned in Golden Gate that the San Francisco scheme it upheld was distinguishable from the Maryland scheme the Fourth Circuit struck down because it did not coerce employers into increasing their ERISA health benefits, and therefore the decision created no circuit split. This Note argues that a coercion-centered test is unlikely to produce a consistent doctrine. To make this point, it analogizes to the unconstitutional conditions doctrine, in which courts have also tried to measure the coercive effect of economic incentive schemes but have failed to fashion a coherent test capable of producing predictable outcomes. Instead of focusing on coercion, courts can, with equal fidelity to the law, apply a rebuttable presumption against preemption to pay-or-play schemes which are part of comprehensive health reform initiatives. This approach provides a superior basis for distinguishing the Maryland and San Francisco schemes, and also leads to the predictable outcome that the Massachusetts pay-or-play law is not preempted.
Growth and oxygen-uptake responses of Cunninghamella echinulata on even-chain fatty acids.

During the past 4 decades there have been several reports on the ability of microorganisms to utilize individual fatty acids as sole sources of carbon and energy. In each case, where an attempt was made to grow one organism on all the fatty acids, a breach or gap in the series was observed; one, or perhaps several of the acids were not utilized for growth. The intermediate-chain-length acids (C,-C14) were generally found to be non-utilizable, and inhibitory to growth (Wyss et al., 1945). These same acids have also been reported to inhibit endogenous respiration (Rolinson, 1954). Early German workers termed this phenomenon "Fettsaureliicke," literally translated "fatty acid gap." Fettsaureliicke is a useful word to describe the fact that the acids in the middle of the
Scaling Law for Hysteresis Losses in Round Superconductors Magnetized by Alternating, Rotating or Elliptical Magnetic Fields

AC losses in an isolated superconducting round wire with a power-law electrical behavior produced by the combined effect of transverse alternating and rotating fields, i.e., an elliptical field, are investigated. The goal is to provide semianalytical expressions of the magnetization losses with a high enough reliability to be used in sizing code development or optimization methods. The fit expressions are based on data generated by means of a 2-D numerical model using the well-known and proved H-formulation. In the meantime, data processing allows for revealing a universal variable cn of utmost importance in magnetization loss calculation. This variable depends on the n-value of the power-law resistivity, and both the dimensionless magnetic field b* and frequency f*.
Study on New Reparation Technology for Ageing MV XLPE Cable

The paper briefly introduced the present situation of XLPE cable in early operation in China.The reason of occurring water tree deterioration for XLPE cable and the basic principle of restraining and eliminating water tree was also introduced.The working mechanism and the enforcement scheme on-the-spot for repairing ageing cable with water tree was described in detail.
Activation of diacylglycerol in cultured endothelial cells exposed to cyclic strain

Confluent bovine aortic endothelial cells (EC) were grown on flexible membranes and subjected to 10% average strain at 60 cycles/min for up to 500 s. A biphasic increase in diacylglycerol (DAG) occ...
Minireview: Epigenomic Plasticity and Vulnerability to EDC Exposures

The epigenome undergoes significant remodeling during tissue and organ development, which coincides with a period of exquisite sensitivity to environmental exposures. In the case of endocrine-disrupting compounds (EDCs), exposures can reprogram the epigenome of developing tissues to increase susceptibility to diseases later in life, a process termed "developmental reprogramming." Both DNA methylation and histone modifications have been shown to be vulnerable to disruption by EDC exposures, and several mechanisms have been identified by which EDCs can reprogram the epigenome. These include altered methyl donor availability, loss of imprinting control, changes in dioxygenase activity, altered expression of noncoding RNAs, and activation of cell signaling pathways that can phosphorylate, and alter the activity of, histone methyltransferases. This altered epigenomic programming can persist across the life course, and in some instances generations, to alter gene expression in ways that correlate with increased disease susceptibility. Together, these studies on developmental reprogramming of the epigenome by EDCs are providing new insights into epigenomic plasticity that is vulnerable to disruption by environmental exposures.
Charge Patterned Sequences form Helical Structures through Charge Neutralization

Many proteins with repeating blocks of oppositely charged residues form long single alpha helices (SAHs). The consensus sequence is a block of four Glu residues followed by a block of four Lys or Arg residues, (Glu4(Lys/Arg)4)n. The current working hypothesis is that SAHs are stabilized by i:i+4 salt bridges between opposite charges in consecutive helical turns. We test the merits of this hypothesis to understand the sequence-encoded preference for SAHs and the logic behind the failure of certain atomistic simulations in anticipating the preference for stable SAHs.In simulations with fixed charges the favorable free energy of solvation of charged residues and the associated loss of sidechain entropy hinders the formation of SAHs. We proposed that alterations to charge states induced by sequence context might play an important role in stabilizing SAHs. We tested this hypothesis using a (Glu4Lys4)n repeat protein and a simulation strategy that permits the substitution of charged residues with neutralized protonated or deprotonated variants of Glu / Lys. Our results predict that stable SAH structures derive from the neutralization of approximately half the Glu residues. These findings explain experimental observations and also provide a coherent rationale for the failure of simulations based on fixed charge models. Large-scale sequence analysis reveals that naturally occurring sequences often include “defects” in charge patterns such as Gln or Ala substitutions. This sequence-encoded incorporation of uncharged residues combined with neutralization of charged residues might tilt the balance toward alpha helical conformations.Our results highlight the need for developing robust methodologies for constant pH simulations that can be applied to sequences with high charge contents. They also highlight the need for generalizing bioinformatics predictors to account for sequence-encoded charge regulation that might influence disorder predictions for sequences with high fractions of charged residues.
Genomic and functional analysis of the host response to acute simian varicella infection in the lung.

Varicella Zoster Virus (VZV) is the causative agent of varicella and herpes zoster. Although it is well established that VZV is transmitted via the respiratory route, the host-pathogen interactions during acute VZV infection in the lungs remain poorly understood due to limited access to clinical samples. To address these gaps in our knowledge, we leveraged a nonhuman primate model of VZV infection where rhesus macaques are intrabronchially challenged with the closely related Simian Varicella Virus (SVV). Acute infection is characterized by immune infiltration of the lung airways, a significant up-regulation of genes involved in antiviral-immunity and a down-regulation of genes involved in lung development. This is followed by a decrease in viral loads and increased expression of genes associated with cell cycle and tissue repair. These data provide the first characterization of the host response required to control varicella virus replication in the lung and provide insight into mechanisms by which VZV infection can cause lung injury in an immune competent host.
Gibberellic acid affects growth and flowering of Philodendron‘Black Cardinal’

A single foliar spray of gibberellic acid (GA3) at concentrations of 125, 250, 500, or 1,000 mg L−1 induced flowering of Philodendron‘Black Cardinal’ (an interspecific hybrid developed from a series of crosses among P. wendlandii, hastatum, erubescens, imbe, fragrantissimum, and an unnamed species) in approximately 170 d. Percentage of plants induced and mean flower number per plant increased as GA3 concentrations increased. Compared to unsprayed plants, the number of new leaves decreased, petiole lengths of new leaves and length of the largest leaf increased, but leaf width was unaffected among sprayed plants. One hour before the spathe started to unfurl, spadix temperatures increased, and temperatures in the male portion of the spadix rose by 10 °C above ambient as the spathe fully opened. Elevated temperatures were recorded for about two hours and returned to ambient within five hours. Spathes remained open for about five hours. A creamy white spadix with a contrasting burgundy spathe resulted in more aesthetically pleasing plants than with foliage alone. Because of the short period of display, the open spathe would not increase additional ornamental value of Philodendron‘Black Cardinal’ in the marketplace. However, if breeding is the purpose of flowering induction, spathes should be cut away from the spadix to facilitate pollination.
Executive Director Perceptions of the Board and Implementation of Program Change

In a study of factors affecting the implementation of program change in an agency, the behavior of the board of directors is of great significance. The significance of the board in relationship to the degree to which the agency implements program changes is due to two factors. First, the board is the ultimate arbiter of which program changes will be implemented. Second, and perhaps of greater importance, the way in which the agency director perceives his board as operating will affect his own behavior regarding suggestions for program changes.
Wideband circularly polarized fan-shaped antenna on a HIS structure

A wideband circularly polarized antenna consisting of four section fan-shaped antenna is presented. A small square patch was placed at the center of structure to accommodate the power splitting with necessary phase shifting feeding circuitry. To achieve wideband circularly polarized (CP) radiation patterns, equal amplitude and sequentially rotating 0°, 90°, 180°, 270° phase difference between each section is required. A one to four way quadrifilar power divider chip was used to satisfy mentioned feeding condition. A mushroom electromagnetic band gap (EBG) structure was used as a high impedance surface (HIS) to convert the bidirectional radiation patterns to a directional one. The proposed antenna achieves an VSWR 2:1 impedance matching from 1.12 GHz to 1.61GHz (35% fractional bandwidth). The CP radiation pattern and axial ratio (AR) quality over the entire operating band is promising. This antenna shows a RHCP gain of more than 5dBic and AR below 1dB from 1.16GHz to 1.58GHz which covers the L-band satellite communication.
Variation in Free Radical Yields from U.S. Marketed Cigarettes.

Free radicals in tobacco smoke are thought to be an important cause of smoking-induced diseases, yet the variation in free radical exposure to smokers from different brands of commercially available cigarettes is unknown. We measured the levels of highly reactive gas-phase and stable particulate-phase radicals in mainstream cigarette smoke by electron paramagnetic resonance (EPR) spectroscopy with and without the spin-trapping agent phenyl-N-tert-butylnitrone (PBN), respectively, in 27 popular US cigarettes and the 3R4F research cigarette, machine-smoked according to the FTC protocol. We find a 12-fold variation in the levels of gas-phase radicals (1.2 to 14 nmol per cigarette) and a 2-fold variation in the amounts of particulate-phase radicals (44 to 96 pmol per cigarette) across the range of cigarette brands. Gas and particulate-phase radicals were highly correlated across brands (ρ = 0.62, p < 0.001). Both radicals were correlated with TPM (gas-phase: ρ = 0.38, p = 0.04; particulate-phase: ρ = 0.44, p ...
IS THERE A CARDIOMYOPATHY OF OBESITY? 10 YEAR LONGITUDINAL FOLLOW UP OF SEVERELY OBESE PATIENTS IN THE UTAH OBESITY STUDY

Background: The concept of a cardiomyopathy due to obesity is based mainly on relatively small cross sectional studies that are hampered by referral bias. Methods: We analyzed 254 severely obese subjects (BMI ≥ 35 kg/m2) participating in a longitudinal study of obesity and CV disease. All of the
Emergency Department Vital Signs and Outcomes After Discharge.

Objective Vital signs are critical markers of illness severity in the emergency department (ED). Providers need to understand the abnormal vital signs in older adults that are problematic. We hypothesized that in patients age > 65 years discharged from the ED, there are abnormal vital signs that are associated with an admission to an inpatient bed within 7 days of discharge. Methods We conducted a retrospective cohort study using data from a regional integrated health system of members age > 65 years during the years 2009 to 2010. We used univariate contingency tables to assess the relationship between hospital admission within 7 days of discharge and vital sign (including systolic blood pressure [sBP], heart rate [HR], body temperature, and pulse oximetry [SpO2] values measured closest to discharge) using standard thresholds for abnormal and thresholds derived from the study data. Results Of 104,025 ED discharges, 4,638 (4.5%) were followed by inpatient admission within 7 days. Vital signs had a greater odds of admission beyond a single cutoff. The vital signs with at least twice the odds of admission were sBP 101 beats/min (OR = 2.00 95% CI = 1.75–2.29), body temperature > 37.3°C (OR = 2.14, 95% CI = 1.90–2.41), and pulse oximetry < 92 SpO2 (OR = 2.04, 95% CI = 1.55–2.68). Patients with two vital sign abnormalities per the analysis had the highest odds of admission. A majority of patients discharged with abnormal vital signs per the analysis were not admitted within 7 days of ED discharge. Conclusion While we found a majority of patients discharged with abnormal vital signs as defined by the analysis, not to be admitted after discharge, we identified vital signs associated with at least twice the odds of admission.
A general model for salmon run reconstruction that accounts for interception and differences in availability to harvest

Understanding population-specific spawner–recruit relationships is necessary for sustainable salmon management. Where multiple populations are harvested together, run reconstruction methods partiti...
Perspectives on “Control of Ca release from within the cardiac sarcoplasmic reticulum”

Every time the heart beats, increases and decreases in cytosolic free Ca2+ ([Ca2+]cyto) switch on and off the mechanochemical reaction that produces movement and force. These [Ca2+]cyto transients are generated by the interplay of several different mechanisms, including (1) Ca2+ entry into the cell
Topological Edge Floppy Modes in Disordered Fiber Networks.

Presented at the Workshop on Topological Protection in Messy Matter on May 14, 2018 at 2:20 p.m.-3:00 p.m. in the Marcus Nanotechnology Building, Rooms 1116-1118, Georgia Tech.
Sirolimus and mirabegron interaction in a hematopoietic cell transplant patient.

PurposeHematopoietic cell transplant patients are exposed to numerous classes of medications. Transplant practitioners must vigilantly monitor for drug interactions especially involving immunosuppressants. We report a hematopoietic cell transplant patient receiving sirolimus who developed supratherapeutic serum concentrations after initiating mirabegron.SummaryA 31-year-old, 98 kg female received a second umbilical cord blood transplant four years after the first transplant for relapsed acute myeloid leukemia. Mycophenolate mofetil and sirolimus were utilized for graft versus host disease prophylaxis. The patient was receiving sirolimus 2 mg daily and the serum concentration on day 26 post-transplant (day + 26) was within therapeutic range (6.7 μg/L, goal range 3–12 μg/L). Her post-transplant course was complicated by BK viruria-associated cystitis for which she was started on mirabegron. Six days after starting the new medication (day + 33), the sirolimus serum concentration increased to 19.2 μg/L. Thus ...
Linking lowermost mantle structure, core-mantle boundary heat flux and mantle plume formation

Abstract The dynamics of Earth’s lowermost mantle exert significant control on the formation of mantle plumes and the core-mantle boundary (CMB) heat flux. However, it is not clear if and how the variation of CMB heat flux and mantle plume activity are related. Here, we perform geodynamic model experiments that show how temporal variations in CMB heat flux and pulses of mantle plumes are related to morphologic changes of the thermochemical piles of large-scale compositional heterogeneities in Earth’s lowermost mantle, represented by the large low shear velocity provinces (LLSVPs). We find good correlation between the morphologic changes of the thermochemical piles and the time variation of CMB heat flux. The morphology of the thermochemical piles is significantly altered during the initiation and ascent of strong mantle plumes, and the changes in pile morphology cause variations in the local and the total CMB heat flux. Our modeling results indicate that plume-induced episodic variations of CMB heat flux link geomagnetic superchrons to pulses of surface volcanism, although the relative timing of these two phenomena remains problematic. We also find that the density distribution in thermochemical piles is heterogeneous, and that the piles are denser on average than the surrounding mantle when both thermal and chemical effects are included.
Psychological Impact of Genetic Testing

News reports about how our genes affect many aspects of our life and health are increasing in both frequency and complexity. The last several years have seen amazing progress in our understanding of human genetics. The completion of the Human Genome Project in 2003 brought this issue into the mainstream more than any other single event (Collins et al 2003). Perhaps contrary to expectations, this milestone created more questions than it answered. Certainly, knowledge of the human genome sequence has increased the pace of genetic discovery for many diseases, but translating discoveries into patient care applications is not always straightforward.
The Pain of the Seer in the Civilization of the Blind: Faulkner and Salinger

In Seymour, An Introduction, J. D. Salinger’s character Buddy Glass juxtaposes words of a literary artist (Kafka) and a philosopher (Kierkegaard) in Buddy’s agonized attempt to understand the suicide of his brother Seymour, a suicide that echoes in many ways that of William Faulkner’s character Quentin Compson. Both of Salinger’s quotations depict an author’s inability to fully realize his or her vision of characters, depiciting this failure as the defiance of the characters against the author. Buddy says that the ideas reflect danger to the eyes, a reference that calls to mind Jacques Derrida’s interpretation of Rousseau—that civilization advances at the price of blindness to its inhabitants. Interestingly, Faulkner’s Quentin also fears for his eyes at one point. Both the Quentin section of William Faulkner’s The Sound and the Fury and J.D. Salinger’s “A Perfect Day for Bananafish” lead up to a suicide which shocks the reader, and then each author wrote other works to reveal the back-story as if to help explain the suicide. Both story and novel-section have parallels in action (the main character spends time before the suicide with a little girl), image (fish), and character (both are aspiring authors and “seers”). Both Quentin and Seymour regret the idea that girls must grow into women, and both see flaws in their respective societies too well to live comfortably in them. Quentin sees the heritage of slavery and racial hatred that has formed the South of his day, and Seymour sees the aspects of society that are hostile to the imagination. While not fully explaining Seymour’s suicide, the similarities of “Bananafish” to the Quentin section of The Sound and the Fury provide a suggestive background that makes Seymour’s suicide more comprehensible, and especially why Seymour chose to shoot himself in the head over the sleeping form of his wife Muriel, rather than to slip quietly into deep water as Faulkner’s Quentin did.
Emotion and Satisficing Engineering

Emotion has been considered to be noises in our traditional engineering because it is situation-dependent and fluctuates very much. But today situations come to change very often and extensively so that it is very difficult to make decisions on a rational basis. If we remember that global optimization is achieved utilizing fluctuations and if we note that AI programs such as the one described by Prolog manages the processing sequence based on verbs, and that verbs are very closely related with our motions, which relates to emotions as etymology indicates. Thus, emotion plays a very important role in our decision making. Although our world is expanding very quickly, the distance and width we can see or what we can experience are limited. Thus Simon’s idea of “satisficing” or “satisfied enough” becomes very important. “Satisfied enough” is nothing other than emotion. Therefore, tomorrow’s engineering must consider emotion as a very important factor in our product development, because everybody has his or her own perspective of the Open Word, or “My World”. He or she makes decisions from the standpoint of My World. Thus, products must be designed and developed to meet expectations which originate from My World.
Echocardiographic assessment of right ventricular systolic function in Boxers with arrhythmogenic right ventricular cardiomyopathy.

Abstract Objectives To determine whether there are differences in measures of longitudinal right ventricular (RV) systolic function among Boxers with arrhythmogenic right ventricular cardiomyopathy (ARVC) compared with healthy control Boxer dogs. To explore relationships between markers of RV systolic function and age, body weight, gender, arrhythmia frequency, and markers of left ventricular (LV) systolic function in Boxer dogs. Animals The study included 50 client-owned Boxer dogs. Methods This is a retrospective echocardiographic study. Tricuspid annular plane systolic excursion (TAPSE) and pulsed wave tissue Doppler imaging–derived systolic myocardial velocity of the lateral tricuspid annulus (S') were measured in healthy control Boxers (n = 18), Boxers with ARVC and normal LV systolic function (n = 19), and Boxers with ARVC and reduced LV systolic function (n = 13). Results Tricuspid annular plane systolic excursion (p=0.002) and S' (p=0.001) were significantly different between affected and control groups. Significant correlations were found between measures of left heart size and function and both TAPSE and S'. No correlations were found between RV function parameters and age, gender, or body weight in this fairly homogeneous, single-breed population. Receiver operating characteristic curve analysis revealed that both TAPSE and S' had an area under the curve of 0.77 in distinguishing healthy Boxers from those with ARVC. Conclusions Tricuspid annular plane systolic excursion and S' are reduced in Boxers with ARVC. In contrast to prior studies evaluating these parameters in dogs of different breeds and body types, no correlation was found between markers of RV function and body weight in this population of Boxer dogs.