cssi/SciSciGPT-SciSciNet huggingface dataset:
Tuberous sclerosis and epilepsy: Role of astrocytes

Tuberous sclerosis complex (TSC) is an autosomal dominant disorder that is among the most common genetic causes of epilepsy. Focal brain lesions in TSC, known as cortical tubers, have been implicated in promoting epileptogenesis in TSC. Histological, cellular, and molecular abnormalities in astrocytes are characteristic features of tubers and perituberal cortex, suggesting that astrocyte dysfunction may contribute to the pathophysiology of epilepsy in TSC. Numerous astrocytes can be seen histologically in tubers expressing glial fibrillary acidic and S100 proteins. In some analyses, astrocytes exhibit enhanced activation of the mammalian target of rapamycin suggesting a link between TSC1 and TSC2 mutations and astrocytic proliferation. Astrocytic proliferation in subependymal giant cell astrocytoma is associated with progressive growth and compression of surrounding brain structures by these lesions. Increased numbers of enlarged astrocytes has been observed in several TSC mouse models and may be intimately linked to epileptogenesis. Impairment of astrocytic buffering mechanisms for glutamate and potassium has been identified in TSC animal models and human tuber tissue and likely promotes neuronal excitability and seizures in TSC. Targeting these defects in astrocytes may represent a novel therapeutic strategy for epilepsy in patients with TSC.
The Stress-induced omega phase transformation in Ti-V alloys

The deformation behavior of bcc (β) Ti-V single crystals containing the athermal ω phase was studied using tensile tests, optical and electron microscopy and X-ray and electron diffraction. The stress-strain curves were characterized by a marked yield point and an essentially zero work hardening rate. The deformation structures consisted of wavy slip and stress-induced plates. Both X-ray and electron diffraction showed that the stress-induced plates consist of one variant of the omega phase, with the orientation relation to the parents phase close to (0001)ω ‖(001)ω; (•1120)ω ‖(110)β. The habit plane was of the type 554. A small amount of ά (hcp) phase was present within the ω plate, with orientation relation to the β phase close to the Burgers relationshipi.e. (0001)ά, ‖(110)β; [•1120]ά ‖[•111]β. It is suggested that the ω phase may be an intermediate structure in the stress-induced bcc → hep transformation.
Liver‐primed CD8+ T cells suppress antiviral adaptive immunity through galectin‐9‐independent T‐Cell immunoglobulin and mucin 3 engagement of high‐mobility group box 1 in mice

The liver is a tolerogenic environment exploited by persistent infections, such as hepatitis B (HBV) and C (HCV) viruses. In a murine model of intravenous hepatotropic adenovirus infection, liver-primed antiviral CD8+ T cells fail to produce proinflammatory cytokines and do not display cytolytic activity characteristic of effector CD8+ T cells generated by infection at an extrahepatic, that is, subcutaneous, site. Importantly, liver-generated CD8+ T cells also appear to have a T-regulatory (Treg) cell function exemplified by their ability to limit proliferation of antigen-specific T-effector (Teff) cells in vitro and in vivo via T-cell immunoglobulin and mucin 3 (Tim-3) expressed by the CD8+ Treg cells. Regulatory activity did not require recognition of the canonical Tim-3 ligand, galectin-9, but was dependent on CD8+ Treg cell-surface Tim-3 binding to the alarmin, high-mobility group box 1 (HMGB-1). Conclusion: Virus-specific Tim-3+CD8+ T cells operating through HMGB-1 recognition in the setting of acute and chronic viral infections of the liver may act to dampen hepatic T-cell responses in the liver microenvironment and, as a consequence, limit immune-mediated tissue injury or promote the establishment of persistent infections. (Hepatology 2014;59:1351-1365)
Architectural design for next generation heterogeneous memory systems

New enterprise workloads requiring fast, reliable access to increasing amounts of data have pushed today's memory systems to power and capacity limits while creating bottlenecks as they ensure transactions are persistently tracked for reliability. New storage class memory technologies (such as phase change memory) have the potential to offer high capacity within latency and bandwidth ranges acceptable for a computer memory system and persistence which may help ease the system-level burden of balancing performance and reliability. This paper describes architectural options for addressing the challenges of future, heterogeneous memory systems as well as the attributes required of the next generation memory devices.
A new effective and efficient multi-level partitioning algorithm

This paper describes a new multi-level partitioning algorithm (PART) that combines a blend of iterative improvement and clustering, biasing of node gains, and local uphill climbs. PART is competitive with recent state-of-the-art partitioning algorithms. PART was able to find new lower cuts for a number of benchmark circuits.
Effects of different secretagogues and intracellular messengers on the muscarinic modulation of [3H] acetylcholine release

We have investigated whether muscarinic receptors modulate the release of [3H]ACh elicited by secretagogues that act by different mechanisms in rat cerebral cortical synaptosomes. Oxotremorine (10 μM) reduced the calcium-dependent [3H]ACh release induced by mild K+-depolarization (10 and 15 mM K+), but not that by higher K+ concentrations. The ACh-release induced by A23187 (0.2–5 μg/ml), liposomes laden with 113 mM CaCl2, or 4-aminopyridine (1–10 mM) was not modulated by oxotremorine. Ouabain (100 μM)-induced release of [3H]ACh was reduced by oxotremorine in normal but not calcium-free KR, indicating that extracellular calcium-uptake but not Na+, K+-ATPase activity may be necessary for release-modulation. With respect to possible second messenger systems, dibutyrylcyclic AMP (0.1–2 mM), dibutyrylcyclic GMP (0.1–2 mM), forskolin (100 μM), and phorbol ester (0.3–3 μg/ml) were without effect on release or release-modulation. These results are consistent with an involvement of K+-channels and voltage-sensitive calcium-channels in the muscarinic release-inhibition process. They argue against an involvement of Na+, K+-ATPase, adenylate cyclase, guanylate cyclase, and phosphatidylinositol turnover in the release-modulation process.
Structural damage detection for in-service highway bridge under operational and environmental variability

Structural health monitoring has drawn significant attention in the past decades with numerous methodologies and applications for civil structural systems. Although many researchers have developed analytical and experimental damage detection algorithms through vibration-based methods, these methods are not widely accepted for practical structural systems because of their sensitivity to uncertain environmental and operational conditions. The primary environmental factor that influences the structural modal properties is temperature. The goal of this article is to analyze the natural frequency-temperature relationships and detect structural damage in the presence of operational and environmental variations using modal-based method. For this purpose, correlations between natural frequency and temperature are analyzed to select proper independent variables and inputs for the multiple linear regression model and neural network model. In order to capture the changes of natural frequency, confidence intervals to detect the damages for both models are generated. A long-term structural health monitoring system was installed on an in-service highway bridge located in Meriden, Connecticut to obtain vibration and environmental data. Experimental testing results show that the variability of measured natural frequencies due to temperature is captured, and the temperature-induced changes in natural frequencies have been considered prior to the establishment of the threshold in the damage warning system. This novel approach is applicable for structural health monitoring system and helpful to assess the performance of the structure for bridge management and maintenance.
Study of the reaction of NO clusters with water using a pickup technique

Abstract Mixed NO/H 2 O-clusters are produced by merging a beam of pure NO-clusters, formed by supersonic expansion in a pulsed nozzle, with water vapor in a pickup source. After ionization with 400 nm light from a femtosecond laser system, a mixed NO/H 2 O-cluster series of pure protonated water clusters H + (H 2 O) n (with n up to 20) is observed which shows an obvious intensity maximum for cluster size n = 4. Other experimental findings are reported herein on the metastable decay of ionized mixed NO/H 2 O-clusters. Taken together, the results establish that reactions occurring at degrees of hydration corresponding to n ⩾ 4 lead to the production of the protonated hydrates and the concomitant formation of HNO 2 . In this study special attention is paid to NO + (H 2 O) n ions because these ions are considered to be an important precursor for the production of proton hydrates in the ionosphere.
Relative Potency Estimation in Parallel-Line Assays - Method Comparison and Some Extensions

Relative potency estimations in both multiple parallel-line and slope-ratio assays involve construction of simultaneous confidence intervals for ratios of linear combinations of general linear model parameters. The key problem here is that of determining multiplicity adjusted percentage points of a multivariate t-distribution, the correlation matrix R of which depends on the unknown relative potency parameters. Several methods have been proposed in the literature on how to deal with R . In this article, we introduce a method based on an estimate of R (also called the plug-in approach) and compare it with various methods including conservative procedures based on probability inequalities. Attention is restricted to parallel-line assays though the theory is applicable for any ratios of coefficients in the general linear model. Extension of the plug-in method to linear mixed effect models is also discussed. The methods will be compared with respect to their simultaneous coverage probabilities via Monte Carlo...
Biosocial models of deviant behavior

This article describes biological influences on criminality. It presents illustrative data suggesting a biological sex difference in criminality and heritable differences in this trait among individuals. Next, methods of isolating environmental influences are described, including shared environmental effects, genex environment interactions, and nonshared environmental effects. Using research designs that include just one level of genetic relatedness (e.g., full siblings) is scientifically a poor choice. Using environment-friendly behavior genetic research designs is both proper and would offer many avenues for environmental analysis.
Does selective gene activation direct evolution

Mechanisms may have evolved such that the unique metabolic reaction to a particular environmental stress results in higher mutation rates of those genes most likely to solve the problem. Evidence is presented indicating that the environment in effect directs the evolution of organisms by (1) presenting various kinds of stress resulting in metabolic activities that target particular genes for increased rates of transcription and mutation, and (2) selecting among this specifically enriched mutant population those variants that alleviate the imposed stress. This process should be ongoing and would be expected to accelerate the rate of microbial evolution.
A history of Laura Bridgman--from American notes.

Charles Dickens was born at Portsea, England, and lived from 1812 to 1870. He was the author of many books in which the background to his stories described the social conditions of his times. He first visited the United States in 1842, arriving in Boston in January of that year, and again five years later. Whilst in Boston on his first visit, he went to see The Perkins Institution and Massachusetts Asylum for the Blind, and it was here that he first met Laura Bridgman. He speculated on the faces of the blind and how free they were of all concealment. Dickens continues:
Family Context and Spanish‐Language Use: A Study of Latino Children in the United States*

Objective. This article seeks to explain why Latino children maintain some knowledge of their native language even though past research has consistently supported the view that non-English-language use rarely lasts past the third generation. I argue that family context, in addition to assimilation characteristics, plays an important role in determining their language situation. Method. I use both logistic regression and tobit regression, as well as data from the 1988 National Education Longitudinal Study, to examine the use and proficiency of Spanish among Latino children. Results. The results demonstrate that language and family context strongly influence Spanish usage and proficiency for Latino children, regardless of generational status. Conclusions. These findings reveal a relationship between assimilation, family, and language that can have important implications for the future academic and economic success of Latino children.
How Capacity Limits of Attention Influence Information Visualization Effectiveness

In this paper, we explore how the capacity limits of attention influence the effectiveness of information visualizations. We conducted a series of experiments to test how visual feature type (color vs. motion), layout, and variety of visual elements impacted user performance. The experiments tested users' abilities to (1) determine if a specified target is on the screen, (2) detect an odd-ball, deviant target, different from the other visible objects, and (3) gain a qualitative overview by judging the number of unique categories on the screen. Our results show that the severe capacity limits of attention strongly modulate the effectiveness of information visualizations, particularly the ability to detect unexpected information. Keeping in mind these capacity limits, we conclude with a set of design guidelines which depend on a visualization's intended use.
The role of magnetic topological change in the onset of ablation of cylindrical wire arrays

The formation of a dense Z-pinch from a cylindrical wire array follows a process through which the discrete wires expand, ablate plasma onto a common geometric axis, and then implode, forming the pinch. We numerically investigate the transition from the initial core-corona structure to ablating wires and provide an analytic model which predicts the coronal radius over time and the time for onset of ablation. We find that for ablation to occur, the initially compressive vacuum magnetic field topology around each wire, with global field on the outside of the array and local field on the inside of the array, must undergo a transition to a configuration where the JxB force is due entirely to global field contributions around each wire. This only occurs if current is carried toward the center of the array creating a plasma precursor. In these low magnetic Reynolds number flows, the fast wave is damped and an acoustic-like shock carries this initial current to the array axis. Using resistive MHD simulation, we present results using array parameters which verify our analysis, indicating when ablation occurs and when discrete wire implosion without ablation occurs.
Regulation of male traits by testosterone: implications for the evolution of vertebrate life histories

Summary The negative co-variation of life-history traits such as fecundity and lifespan across species suggests the existence of ubiquitous trade-offs. Mechanistically, trade-offs result from the need to differentially allocate limited resources to traits like reproduction versus selfmaintenance, with selection favoring the evolution of optimal allocation mechanism. Here I discuss the physiological (endocrine) mechanisms that underlie optimal allocation rules and how such rules evolve. The hormone testosteronemaymediatelife-historytrade-offsduetoits pleiotropic actions in male vertebrates. Conservation in the actions of testosterone in vertebrates has prompted the ‘evolutionary constraint hypothesis,’ which assumes that testosterone signaling mechanisms and male traits evolve as a unit. This hypothesis implies that the actions of testosterone are similar across sexes and species, and only the levels of circulating testosterone concentrations change during evolution. In contrast, the ‘evolutionary potential hypothesis’ proposes that testosterone signaling mechanisms and male traits evolve independently. In the latter scenario, the linkage between hormone and traits itself can be shaped by selection, leading to variation in trade-off functions. I will review recent case studies supporting the evolutionary potential hypothesis and suggest micro-evolutionary experiments to unravel the mechanistic basis of lifehistory evolution. BioEssays 29:133–144, 2007. 2007 Wiley Periodicals, Inc.
Obesity does not increase effects of synthetic ghrelin on human gastric motor functions.

Background & Aims: Ghrelin is secreted by the stomach and stimulates food intake. Obese individuals have lower fasting plasma ghrelin levels but increased appetite, suggesting greater responses to endogenous ghrelin in obesity. The aim of this study was to compare effects of exogenous ghrelin (at a dose that stimulates growth hormone [GH] release in the physiologic range) versus placebo on gastric emptying, gastric volume, and postprandial symptoms and determine whether body mass (ranging from normal weight to obesity) influences responses to ghrelin. Methods: After intravenous bolus synthetic human ghrelin (0.33 μg/kg) or saline, we measured plasma GH, gastric volume, and gastric emptying by combined 99mTc–single-photon emission computed tomography and scintigraphy (111In egg meal, 300 kcal) and postprandial symptoms using visual analogue scales. Results: In 25 obese subjects (5 men and 20 women; body mass index [BMI], 36 ± 4 kg/m2) and 13 female normal-weight (BMI, 22 ± 2 kg/m2) subjects of similar ages, ghrelin increased GH levels (15.0 ± 2.4 ng/mL) at 40 minutes postinjection and tended to decrease fasting gastric volumes compared with placebo (P = .059). There were no effects of BMI on treatment response and no differences between ghrelin and saline on postprandial (P = .09) or change in (postprandial minus fasting) gastric volumes, gastric emptying, or aggregate postprandial symptoms. Effects of ghrelin did not differ between obese and normal-weight participants. Conclusions: At doses that stimulate physiologic GH plasma levels, synthetic ghrelin tended to decrease fasting gastric volumes without altering postprandial volumes or gastric emptying in a predominantly female cohort. The data are not consistent with the hypothesis that higher body mass is associated with increased gastric responsiveness to ghrelin.
Technology and human purpose: the problem of solids transport on the Earth's surface

Abstract. Displacement of mass of limited deformability ("solids") on the Earth's surface is opposed by friction and (the analog of) form resistance – impediments relaxed by rotational motion, self-powering of mass units, and transport infrastructure. These features of solids transport first evolved in the biosphere prior to the emergence of technology, allowing slope-independent, diffusion-like motion of discrete objects as massive as several tons, as illustrated by animal foraging and movement along game trails. However, high-energy-consumption technology powered by fossil fuels required a mechanism that could support fast advective transport of solids, i.e., long-distance, high-volume, high-speed, unidirectional, slope-independent transport across the land surface of materials like coal, containerized fluids, minerals, and economic goods. Pre-technology nature was able to sustain regional- and global-scale advection only in the limited form of piggybacking on geophysical flows of water (river sediment) and air (dust). The appearance of a mechanism for sustained advection of solids independent of fluid flows and gravity appeared only upon the emergence of human purpose. Purpose enables solids advection by, in effect, simulating a continuous potential gradient, otherwise lacking, between discrete and widely separated fossil-fuel energy sources and sinks. Invoking purpose as a mechanism in solids advection is an example of the need to import anthropic principles and concepts into the language and methodology of modern Earth system dynamics. As part of the emergence of a generalized solids advection mechanism, several additional transport requirements necessary to the function of modern large-scale technological systems were also satisfied. These include spatially accurate delivery of advected payload, targetability to essentially arbitrarily located destinations (such as cities), and independence of structure of advected payload from transport mechanism. The latter property enables the transport of an onboard power supply and delivery of persistent-memory, high-information-content payload, such as technological artifacts ("parts").
Privation theories of pain

Most modern writers accept that a privation theory of evil should explicitly account for the evil of pain. But pains are quintessentially real. The evil of pain does not seem to lie in an absence of good. Though many directly take on the challenges this raises, the metaphysics and axiology of their answers is often obscure. In this paper I try to straighten things out. By clarifying and categorizing the possible types of privation views, I explore the ways in which privationists about evil are—or should or could be—privationists about pain’s evil.
Relationship of Stimulation Frequency to Automaticity in the Canine Purkinje Fiber during Ouabain Administration

Spontaneously beating Purkinje-papillary preparations stimulated transiently at 60-180 beats/min exhibited typical overdrive suppression of spontaneous rate in normal Tyrode9s solution. When superfused with ouabain (2 x 10 -7 g/ml), the same preparations showed a progressive diminution of overdrive suppression and, ultimately, an acceleration of spontaneous rate in the immediate postoverdrive period. Usual effects of stimulation frequency on electrogenic activity associated with automaticity in the Purkinje fiber were altered significantly during the administration of ouabain. With ouabain, rapid stimulation reduced the maximum diastolic potential and the threshold potential by approximately the same amount and increased the rate of diastolic depolarization. During overdrive, the minimum diastolic potential decreased as a function of maximum diastolic potential, rate of diastolic depolarization, and cycle length. The magnitude of all effects increased directly with the stimulation frequency and the exposure time. At any given time, frequency-induced changes were quickly reversible on return to a lower frequency. However, a single early depolarization during recovery transiently reevoked changes in diastolic depolarization similar to those seen during rapid drive. The increase in the rate of diastolic depolarization appears to be the major change responsible for frequency-dependent enhanced automaticity. The effects observed during transient rapid stimulation resemble the electrophysiological alterations responsible for the final toxic effects of ouabain but occur well before any glycoside-induced change in the spontaneous rate. These effects appear to explain the frequency-dependent acceleration of ventricular pacemakers and the phenomenon of repetitive ventricular response previously described in intact animals during digitalization.
Evaluation of Excess Foundry System Sands for Use as Subbase Material

Earthwork associated with highway construction provides an opportunity for high-volume reuse of excess system sands (ESS) discarded by the foundry industry. California bearing ratio (CBR), unconfined compressive strength, and resilient modulus tests were conducted on 13 ESS, one base sand, and two reference materials. Tests were conducted on specimens prepared dry of optimum, wet of optimum, and at optimum water content with standard and modified Proctor compaction effort. Results of these tests were used to identify characteristic engineering properties of ESS, appropriate compaction conditions for ESS when used as subbase, and empirical equations that can be used to predict the engineering properties of ESS based on index properties. Results of the tests indicate that ESS classify as SP, SM, or SP-SM (A-2-4 or A-3 in AASHTO) and should be compacted dry or at optimum water content and, if possible, with higher compactive effort. The CBR of the ESS ranged from 4 to 40 and averaged 20 when compacted with standard effort at optimum water content. Swell during the soaking portion of the CBR tests was small for all ESS. ESS compacted at optimum water content with standard effort had unconfined compressive strengths ranging from 71 to 190 kPa. Resilient moduli of the ESS were similar to that of a reference subbase material but smaller than a reference base material. A power function model in terms of bulk stress described resilient moduli of the ESS well.
Extracellular SOD Inactivation in High-Volume Hypertension Role of Hydrogen Peroxide

Excessive reactive oxygen species (ROS), especially superoxide anion (O2•−), contribute to the pathogenesis of many cardiovascular diseases, including hypertension. The major antioxidant defense system against O2•− is superoxide dismutases (SODs). In mammals, 3 isoforms of superoxide dismutase exist: the cytoplasmic CuZnSOD (SOD1), the mitochondrial MnSOD (SOD2), and the extracellular Cu/ZnSOD (SOD3, ecSOD). The ecSOD is the major SOD in the vascular extracellular space, and synthesized by vascular smooth muscle cells and fibroblasts. It is secreted and anchored to the extracellular matrix and endothelial cell surface through binding to the heparan sulfate proteoglycan, collagen, and fibulin-5.1–3 Of note, the R213G polymorphism in the ecSOD gene, which reduces binding to endothelial surface and increases serum ecSOD levels, has been linked to an increase in cardiovascular risk.4 See page 470 Nitric oxide (NO•) produced by endothelium stimulates vasodilation of vascular smooth muscle and thus exerts antihypertensive action. Because O2•− reacts with NO• at almost diffusion-limited rates, ecSOD which scavenges O2•− in the vascular extracellular space plays an important role in regulating bioactivity of NO•.1 Indeed, gene transfer of ecSOD reduces O2•− and restores impairment of endothelium dependent relaxation, resulting in the decrease in arterial pressure in a genetic model of hypertension.5 Furthermore, ecSOD has peroxidase activity in which H2O2, the dismutation product of O2•−, can inactivate ecSOD by reacting with the copper center of ecSOD, thereby forming the Cu–OH radical and leading to enzyme inactivation.6 This effect can be prevented by scavenging the …
Formation of Intermediate Transcription Initiation Complexes at pfliD and pflgM by ς28 RNA Polymerase

The ς subunit of prokaryotic RNA polymerase is an important factor in the control of transcription initiation. Primary ς factors are essential for growth, while alternative ς factors are activated in response to various stimuli. Expression of class 3 genes during flagellum biosynthesis in Salmonella enterica serovar Typhimurium is dependent on the alternative ς factor ς28. Previously, a novel mechanism of transcription initiation at the fliC promoter by ς28 holoenzyme was proposed. Here, we have characterized the mechanism of transcription initiation by a holoenzyme carrying ς28 at the fliD and flgM promoters to determine if the mechanism of initiation observed at pfliC is a general phenomenon for all ς28-dependent promoters. Temperature-dependent footprinting demonstrated that promoter binding properties and low-temperature open complex formation are similar for pfliC, pfliD, and pflgM. However, certain aspects of DNA strand separation and complex stability are promoter dependent. Open complexes form in a concerted manner at pflgM, while a sequential pattern of open complex formation occurs at pfliD. Open and initiated complexes formed by holoenzyme carrying ς28 are generally unstable to heparin challenge, with the exception of initiated complexes at pflgM, which are stable in the presence of nucleoside triphosphates.
SURVIVAL TRADE-OFFS BETWEEN TWO PREDATOR-INDUCED PHENOTYPES IN PACIFIC TREEFROGS (PSEUDACRIS REGILLA)

In many organisms, specific predator species induce defensive phenotypes that are qualitatively different from the phenotypes induced by other predator species. This differential induction implies that there is no optimal phenotype that works best against all predators. However, few studies have actually tested the hypothesis that each predator-induced phenotype provides the highest survival rate in encounters with the predator that induced that phenotype. In this experiment, I reared Pacific treefrog (Pseudacris regilla) larvae with chemical cues from two different predators (bluegill sunfish and predaceous diving-beetle larvae), and without predator cues. The Pacific treefrog larvae in the three treatments differed in their morphology and foraging behavior. I then exposed tadpoles from each treatment to free-foraging predaceous diving beetles and bluegill sunfish. Tadpoles survived best when exposed to the predator whose cues they were reared with, and worst when exposed to the other predator. In both predator environments, the tadpoles reared in the nonpredator control treatment had intermediate survival between the two predator-induced groups. Thus, there is no generalized "antipredator" response to these predators; rather, there was a clear trade-off in survival abilities between the predators.
The Effects of Exchange Rate Volatility on Agricultural Trade

I extend Cho, Sheldon, and McCorriston's (2002) analysis of the effect of exchange rate volatility on agricultural trade among the G-10 countries to a broad sample of developed and developing nations. I replicate their original finding that exchange rate volatility has a large negative impact on agricultural trade between G-10 members. After controlling for agricultural export subsidies, which are correlated with exchange rate volatility, I show that the original impact declines by half. Using the extended sample, I find that the effect of exchange rate volatility is much larger for developing country exporters than for developed exporters. Copyright 2008, Oxford University Press.
Engineering of Polymeric Nanoparticles from Medical Applications

A variety of organic and inorganic materials have been utilized to generate nanoparticles for drug delivery applications, including polymeric nanoparticles, dendrimers, nanoshells, liposomes, nucleic acid based nanoparticles, magnetic nanoparticles, and virus nanoparticles. The two most commonly used systems are polymeric nanoparticles and liposomes. Controlled release polymer technology has impacted virtually every branch of medicine, including ophthalmology, pulmonary, pain medicine, endocrinology, cardiology, orthopedics, immunology, neurology and dentistry, with several of these systems in clinical practice today such as Atridox, Lupron Depot, Gliadel, Zoladex, Trelstart Depot, Risperidol Consta and Sandostatin LAR. The annual worldwide market of controlled release polymer systems which extends beyond drug delivery is now estimated at $100 billion and these systems are used by over 100 million people each year. Polymeric nanoparticles can deliver drugs in the optimum dosage over time, thus increasing the efficacy of the drug, maximizing patient compliance and enhancing the ability to use highly toxic, poorly soluble, or relatively unstable drugs. These systems can also be used to co-deliver two or more drugs for combination therapy. The surface engineering of these nanoparticles may yield them “stealth” to prolong their residence in blood and the functionalization of these particles with targeting ligands can differentially target their delivery or uptake by a subset of cells, further increasing their specificity and efficacy. More recently combinatorial approaches have been developed to precisely engineer nanoparticles and screen multiple nanoparticle characteristics simultaneously with the goal of identifying formulations with the desired physical and biochemical properties for each specific application. The goal of this talk is to review our efforts in the design and optimization of polymeric nanoparticles for medical applications, which formed the foundation for the clinical translation of the first-in-human targeted and controlled-release nanoparticles (BIND-014) for cancer therapy.
Respiratory Muscle Strength Training for the Management of Airway Protective Deficits

Respiratory muscle strength training (RMST) has received considerable research and clinical interest. There are several studies to support its use in various populations with known airway protective disorders, including Parkinson's disease (PD), multiple sclerosis (MS), and chronic obstructive pulmonary disease (COPD). The goal of this paper is to briefly describe RMST: when it should be used, how it can be used, populations which may benefit from its use, and highlight the gaps which still remain. This goal is achieved through a review of the available literature and practical tips for incorporating RMST into the clinical care of patients with airway protective disorders.
Income Smoothing and Debt Covenants: Evidence from Technical Default

We examine whether income smoothing affects the frequency of technical default in private loan contracts. We find that income smoothing is associated with a lower frequency of “spurious technical default” when the borrower’s economic performance has not declined, but the loan nevertheless enters technical default. In contrast, we find no association between income smoothing and technical default when the borrower’s creditworthiness declines — “performance technical default.” This evidence is consistent with borrowers smoothing income to reduce noise in earnings, and inconsistent with opportunistic motives. Further, we find evidence that the efficiency-enhancing effect of income smoothing is incorporated into the initial loan terms, as debt contracts to borrowers exhibiting greater income smoothing are more likely to include income statement covenants and have lower interest rates.
Tracing phenolic metabolism in Vitis vinifera berries with 13C6-phenylalanine: implication of an unidentified intermediate reservoir.

Understanding the regulation of phenolic compounds in agricultural products has been a topic of great interest. In V. vinifera berries, phenolics are responsible for important sensory and functional characteristics. To elucidate the ripening profile of phenolic compounds in Cabernet Sauvignon berries, the stable-isotope tracer l-phenyl-13C6-alanine (Phe13) was incorporated in situ, and the development of labeled and unlabeled phenolics was tracked in the vineyard at different stages of maturity over two vintages. Phenolic profiles during ripening were consistent with previous research. However, individual anthocyanins accumulated with different profiles during ripening; malvidin species continually climbed in concentration, whereas other anthocyanins tended to plateau or drop near the end of the growing season. The isotopic label was predominantly incorporated into anthocyanins, presumably because of their dominant accumulation during ripening. Notably, the incorporation of label continued long after leve...
EFFECTS OF INTRAHYPOTHALAMIC IMPLANTS OF RESERPINE ON LACTATION AND PITUITARY PROLACTIN CONTENT IN THE RABBIT.

SummaryDirect implantation of minute amounts of solid reserpine phosphate into the posterior median eminence-basal tuberal area of the hypothalamus initiated milk secretion and depleted the hypophysis of prolactin in the estrogen primed ovariectomized rabbit. Reserpine implantation into the hypophysis had no effect. The results indicate the focus of reserpine influence essential to the release of pituitary prolactin and activation of mammary glands is the posterior median eminence-posterior tuberal region of the hypothalamus.
Effect of Selective Head Mild Hypothermia on Serum Cytokines Levels of Neonatal Hypoxic-Ischemic Ence-phalopathy

Objective To explore the effect of selective head mild hypothermia on interleukin-1β(IL-1β),interleukin-2(IL-2)and tumor necrosis factor alpha(TNF-α)in serum of neonatal hypoxic-ischemic encephalopathy(HIE)and those clinical significance.Methods Fifty neonates with moderate or severe HIE were randomly assigned into treatment group(n=25)and control group(n=25).Selective head mild hypothermia was used within 6 hours after birth to keep nasopharyngeal temperature at(34.0±0.5)℃ and rectal temperature at(35.5±0.5)℃ for 72 hours in treatment group,and control group got routine treatment.The dynamic changes of serum IL-1β,IL-2 and TNF-α within 6,24 and 72 hours respectively after birth were monitored using enzyme-linked immunosorbent assay(ELISA).Results Levels of serum IL-1β,IL-2 and TNF-α decreased more significantly at 24 and 72 hours in moderate HIE treatment group than those in control group(Pa0.05).Levels of serum IL-1β and IBF-α at 72 hours between severe HIE treatment group and control group had a significant difference(P0.05),and the level of serum IL-1 at 24 hours also had significant difference between severe HIE treatment group and control group(P0.05).Conclusion Selective head mild hypothermia has the protective effects on brains by relieving immunity.
Comparison Between Two Kinds of Technique for Rapidly Quenched NdFeB Nanocrystalline Ribbons

Rapidly quenched NdFeB ribbons were prepared by vacuum arc-remelting overflow and vacuum induction remelting,followed by subsquent crystallizing. Comparison was made between the powders made by the two routes on surface morphology,thickness and magnetic properties,etc. Experiment indicated that the property of powder prepared by vacuum arc-remelting overflow is lower than that by vacuum induction melting. Analysis reveased that the lowering of magnetic properties of Nd-Fe-B powder prepared by vacuum arc-remelting overflow attributes to the nonhomogeneity of ribbon,mainly resulterd from the nonhomogeneity of melting pool temperature and unstability of melting surface height. Finally,the directionof improvement on technical process of rapid quenching of vacuum arc-remelting overflow was pointed out.
The sources of sodium in rabbit pancreatic juice (39870).

SummaryUsing an in vivo rabbit pancreas preparation, we have shown that approximately 85-90% of the sodium found in rabbit pancreatic juice comes directly from the circulating blood of the animal as opposed to fluids bathing the peritoneum. This conclusion is reached using data from radi-otracer experiments in which the blood and synthetic peritoneal fluid Na is labeled with 22Na and 24Na, respectively. The appearance of the various isotopes in the pancreatic juice has been used to determine the relative contributions of the two Na sources. The preference of the in vivo pancreas for vascular Na suggests that studies of pancreatic secretory mechanisms done in vitro may not be physiolgoically meaningful.We would like to express our gratitude to Miss Deborah Hart for her devoted technical assistance. This work was supported in part by Research Grant 5 RO1-AM 17843-02 from the National Institute of Arthritis, Metabolism and Digestive Diseases.
Chapter 33 – Ii blood group collection

Publisher Summary This chapter focuses on the Ii blood group system. The history, terminology, and the carrier molecule related to the Ii blood group system are reviewed. The i antigen is produced by the sequential action of multiple glycosyltransferases. The i antigen is on the unbranched carbohydrate chains of repeating N-acetyllactosamine units on lipids and proteins on red blood cells (RBCs) and proteins in plasma. With the action of the branching enzyme, β6GlcNAc-transferase, these I antigen-carrying chains become part of the precursor chain of the I antigen. The disease association of the Ii blood group system is also discussed. Enhanced expression of i antigens is associated with leukemia, Tk polyagglutination, thalassemia, sickle cell disease, HEMPAS, Diamond Blackfan anemia, myeloblastic erythropoiesis, sideroblastic erythropoiesis and any condition that results in stress hematopoiesis. Anti-i is associated with infectious mononucleosis and other lymphoproliferative disorders (Hodgkins disease) and occasionally with CHAD.
Improving Medication Adherence and Health Outcomes in Older Adults: An Evidence-Based Review of Randomized Controlled Trials.

Background Poor medication adherence is a major public health problem in older adults often resulting in negative health outcomes.
In vitro models of the cardiac microenvironment to study myocyte and non‐myocyte crosstalk: bioinspired approaches beyond the polystyrene dish

The heart is a complex pluricellular organ composed of cardiomyocytes and non-myocytes including fibroblasts, endothelial cells and immune cells. Myocytes are responsible for electrical conduction and contractile force generation, while the other cell types are responsible for matrix deposition, vascularization, and injury response. Myocytes and non-myocytes are known to communicate and exert mutual regulatory effects. In concert, they determine the structural, electrical and mechanical characteristics in the healthy and remodelled myocardium. Dynamic crosstalk between myocytes and non-myocytes plays a crucial role in stress/injury-induced hypertrophy and fibrosis development that can ultimately lead to heart failure and arrhythmias. Investigations of heterocellular communication in the myocardium are hampered by the intricate interspersion of the different cell types and the complexity of the tissue architecture. In vitro models have facilitated investigations of cardiac cells in a direct and controllable manner and have provided important functional and mechanistic insights. However, these cultures often lack regulatory input from the other cell types as well as additional topographical, electrical, mechanical and biochemical cues from the cardiac microenvironment that all contribute to modulating cell differentiation, maturation, alignment, function and survival. Advancements in the development of more complex pluricellular physiological platforms that incorporate diverse cues from the myocardial microenvironment are expected to lead to more physiologically relevant cardiac tissue-like in vitro models for mechanistic biological research, disease modelling, therapeutic target identification, drug testing and regeneration.
QTL mapping of potato chip color and tuber traits within an autotetraploid family

Cultivated potato (Solanum tuberosum L.) is a highly heterozygous autotetraploid crop species, and this creates challenges for traditional line development and molecular breeding. Recent availability of a single-nucleotide polymorphism (SNP) array with 8303 features and software packages for linkage and association mapping in autotetraploid species present new opportunities for the identification of genomic regions that contribute to high-value traits in cultivated potato. A biparental tetraploid potato population was evaluated across three field seasons and storage trials in order to identify quantitative trait loci (QTL) for multiple tuber traits including fried chip color after 5.5–7.2 °C storage. Tetra-allelic dosage information was used to construct a genetic linkage map that covered 1041 cM and contained 2095 SNP markers with a median marker interval of 0.4 cM. A total of 41 QTL were identified for flower color, tuber yield, tuber number per plant, tuber weight, tuber size, and chip color after various storage regimes. Moderate effect QTL for chip color at 3 months were identified that co-localized with candidate genes vacuolar invertase (VInv), invertase inhibitor (INH2), and apoplastic invertase (Inv ap -b). A separate QTL for chip color after 6 months of storage was identified in the short arm of chromosome 2, and this locus may contribute to variation in senescent sweetening resistance. QTL for tuber weight, length, and width co-localized with a known QTL for plant maturity on chromosome 5. Genome-wide association mapping using a polyploid model detected the tuber size QTL and identified a number of candidate SNPs, but was unable to detect markers significantly associated with chip color.
Modeling Coupled Processes in Municipal Solid Waste Landfills: An Overview with Key Engineering Challenges

Disposal of municipal solid waste (MSW) in engineered landfills is one of the most widely used waste management practices in the USA and worldwide. During its design life, landfilled MSW undergoes various complex mechanisms controlled by physical (hydraulic and mechanical), chemical, thermal, and biological processes and their interrelated behaviors. A thorough understanding of these coupled MSW interactions is critical in designing a stable, effective and well-operational landfill. However, to date, the current practices associated with mathematical modeling as well as long-term monitoring of landfill performance(s) are mostly empirical and limited to site-specific conditions. Moreover, they fail to substantially quantify the changes in the geotechnical properties of MSW that result from coupled processes, especially the highly uncertain biological processes that result in MSW degradation in landfills. Furthermore, the spatially and temporally varied waste composition, heterogeneous and anisotropic nature of field MSW together with leachate and landfill gas production due to biodegradation results in atypical differential MSW settlement and, therefore, can adversely impact the long-term performance of landfills. Over the years, numerous experimental studies, field studies and mathematical modeling studies that focus on these landfill processes have been performed to optimize MSW landfill performance. In this study, a critical review of the previous research efforts on coupled processes is provided to help landfill engineers understand, design and operate MSW landfills safely and efficiently. Moreover, key research issues and challenges related to numerical modeling of landfilled MSW undergoing coupled processes are presented.
Correlation-aware sensing in active and passive modes for source localization

This paper considers the problem of localizing more correlated sources than sensors using an active antenna array. Two algorithms are proposed for coherent source localization with active sensing. The first algorithm builds upon our earlier work on correlation-aware sparse reconstruction, which constructs a sparse measurement model by discretizing the angle space. It can resolve more correlated sources than sensors by exploiting the difference co-array of a certain sum co-array (DCSC), and has significantly lower complexity than other algorithms that use the DCSC. The second algorithm extends this framework to a grid-less setting, thereby avoiding the need for discretizing the parameter-space.
Infundibulum of the common origin of fourth lumbar arteries and median sacral artery

We describe an infundibulum of a common origin of the fourth lumbar arteries and the median sacral artery. To the best of our knowledge there has been no such published case thus far and its natural course is unknown, in view of its novelty. Infundibular dilatations in intracranial arteries have been described to progress in size and potentially rupture. Therefore, we recommended follow-up imaging, as part of the management, to ensure stability of the infundibulum.