cssi/SciSciGPT-SciSciNet huggingface dataset:
Transtracheal delivery of gas decreases the oxygen cost of breathing.

Transtracheally administered gases decrease inspired minute ventilation in both dogs and humans. To test if this is associated with a decrease in the oxygen cost of breathing and to evaluate subsequent changes in the breathing pattern, we studied five patients with chronic respiratory diseases while they spontaneously breathed air and different flows of tracheally administered gases. In a blinded crossover design, the gas consisted of either oxygen or air at 2, 4, and 6 L/min. Oxygen cost of breathing was estimated by the calculation of pleural pressure-time index (PPTI). The pattern of breathing was evaluated utilizing the tension time index for the diaphragm (TTdi). There were significant decreases in PPTI when the patients received 2, 4, and 6 L/min of transtracheal oxygen or air. TTdi also decreased as gas flow increased. This drop was significant at 6 L/min flow for both gases. We conclude that transtracheally administered gas reduces the oxygen cost of breathing. It also changes the respiratory patt...
The enhancement of acausal effects by multiple scattering

Abstract The theory of finite electrodynamics due to Lee and Wick predicts small acausal effects. In elementary scattering processes, these effects are too small, by many orders of magnitude, to be detected. We apply a simplified version of this theory, due to Lee and Wick, to multiple coherent scattering processes. The target particles are arranged in various ways - two-particle target; very small, very dense target; many random scatterers; periodic monolayer; three-dimensional periodic array - and the change in the wave packet on passing through the target is calculated. It is found that, in principle, significant enhancement of the acausal effects may be achieved. Unfortunately, the requirements on the target parameters are quite severe and probably met only in dense stars, if anywhere.
The Kalman filter in analytical chemistry

Abstract During the past ten years, the means by which more information can be extracted from experimental data have become an important area of research in analytical chemistry. Digital filters have been demonstrated to have a number of applications to analytical problems. These techniques typically involve a least-squares fit of experimental data to some model of the process being filtered. One method for filtering experimental data is based on the Kalman filter, a recursive, linear digital filter first developed for use in navigation, but now used in many fields. This paper discusses the implementation of Kalman filters in analytical chemistry. The principles of state-space digital filtering are reviewed, and the development of state/space models is discussed. Discussion is focused on the discrete Kalman algorithms. Two examples are provided to demonstrate the operation of the discrete Kalman filtering algorithm. Similarities between Kalman filtering and weighted least-squares methods are considered, and the specific advantages and disadvantages of linear and nonlinear Kalman filtering approaches are evaluated. To illustrate the range of problems which benefit from use of the filter, a comprehensive literature survey of the application of Kalman filtering to chemical problems is provided.
Why Wait? Modeling Factors that Influence the Decision of When to Learn a New Use of Technology

This study examines the decision of when potential system users choose to learn new uses of technology. To explain the outcome of this decision, we construct a model based on deferral option pricing theory and operationalize its parameters through constructs consisting of anticipated emotions regarding failure costs, waiting costs, and potential rewards. Additionally we operationalize and test alternative explanations defining the outcome of when a new use of technology is learned and these consist of perceived usefulness of the technology, time pressure, and subjective norms. These decision determinants are examined across two experiments; each experiment using a vignette‐based methodology that evokes a different level of external motivation. In the case of a powerful external referent, subjective norms appear to crowd out intrinsic responses and they dominate the decision to learn a new use of technology. However, when an external referent does not dominate the decision setting, anticipated emotions in ...
A comparative study of the maturation of NaK-ATPase activity in different nephron segments

In the kidney the development of deep nephrons preceeds the development of superficial (sf) nephrons and the structural maturation of proximal tubular (PT) segments preceeds the structural maturation of distal tubular segments. NaKATPase is present in all nephron segments. The comparison between the development of NaKATPase activity in PT and thick ascending limbs of Henle (TAL) in deep and sf nephrons can therefore yield information about the relative importance of genetic and environmental factors for enzymatic differentiation. NaKATPase activity was determined in isolated rat tubular segments with Doucet's method (AJP 1979). NaKATPase activity increased in both PT and TAL till the age of 40 days. In PT development was linear while in TAL development was accelerated between 16 and 20 days. The developmental pattern for NaKATPase was the same in cortical and medullary TAL and the same in sf and deep PT. Serum corticosterone was determined with RIA. It was low till 16 days, then increased rapidly to reach adult values at 20 days. Adrenalectomy inhibited the development of NaKATPase. Treatment with betamethasone (up to 60 μg/100 g) precociously induced NaKATPase in TAL at 16 days of age and in PT at 10 to 20 days of age. PT concentration of cytosolic glucocorticoid receptors determined with isoelectric focusing was significantly higher in 20- than in 40-day-old rats. Conclusion: The enzymatic differentiation is typical for each cell type. In a given cell type extracellular factors appear to influence the enzymatic differentiation simultaneously and irrespective of embryonic age.
Metabolic adaptations to early life protein restriction differ by offspring sex and post-weaning diet in the mouse

Abstract Background and aims Low birth weight affects 1 in every 7 babies born globally and can predict a lifetime of increased risk for adverse health outcomes, including cardiovascular disease, hypertension, obesity, diabetes, and metabolic syndrome. Maternal low protein diet during pregnancy and lactation is a well-characterized rat model for low birth weight and the subsequent increase in chronic disease risk. However, mice have been relatively understudied in this paradigm and represent a critical resource for investigating the underlying molecular mechanisms that link adverse early life experience and the development of chronic disease. Methods and results The present manuscript describes a mouse model of low birth weight (maternal consumption of low protein diet (8% protein) through pregnancy and lactation) and characterizes metabolic adaptations (food intake, locomotor activity, oxygen consumption, and glucose tolerance) in male and female offspring. At weaning, mice were maintained either on the control diet or a high fat diet. Notable sex differences were observed, with male mice from the low protein pregnancies showing increased food intake, hyperactivity and increased metabolic rate only when weaned to the high fat diet, while female mice consistently showed increased food intake and were hypometabolic, regardless of post-weaning diet. Conclusion These data identify offspring sex and post-weaning diet as critical variables in the metabolic adaptations to early life protein deficiency, and suggest that females may be more vulnerable to the adverse long-term health consequences of low birth weight
Cardiac glycoside effects on rat skeletal muscle potentials and electrolytes.

SummaryThe effect of cardiac glycosides on rat skeletal muscle intracellular action potenials was studied and correlated with changes in serum and muscle electrolytes and water. In the early minutes after subcutaneous administration of ouabain, 25-200 μg, there was a significant shortening of depolarization and repolarization times. After 15-min repolarization lengthened and after 50 min depolarization also becomes prolonged. The early phase of shortening is more easily demonstrated with 25-50 μg doses, and the latter prolongation of the action potential is more marked and consistent with the larger doses.There is also a biphasic action on muscle water content. This is apparently an increase in intracellular water as no change was seen in inulin space. The time relationship to this effect is unrelated to the time of changes in action potentials. Muscle water was increased for the first hour after injection of ouabain, returned to normal 1 to 2 hr after huge doses of ouabain, 400-600 μg, and was decreased ...
Effect of europium(III) on the thermal denaturation and cleavage of transfer ribonucleic acids

The interaction of tRNA with Eu(III) has been studied by optical and gel electrophoretic tecfhniques. At low levels (less than six metals per tRNA), Eu(III) stabilizes yeast tRNAPhe against thermal denaturation; however, at higher levels (about eight to ten Eu/tRNA) the tRNA is destabilized by Eu(III). This may have important implications regarding recent attempts to grow crystals of tRNA from solutions containing europium. Comparative studies of the effects of Mg(II) and Eu(III) on tRNA structure confirm that the first four Eu(III) ions are more strongly bound than Mg(II). At slightly elevated temperatures (50°C, pH 7) the binding of Eu(III) catalyzes the hydrolysis of the tRNA backbone. From an analysis of the fragments produced by the hydrolysis and of the variation in the rate of cleavage as a function of the metal per tRNA ratio, we conclude that (i) the addition of Eu(III) to the tRNA is sequential, (ii) the first Eu(III) is bound in close proximity to the two dihydrouridine residues, and (iii) the rate of hydrolysis depends on the number of Eu(III) free in solution. Metals bound at sites 2–4 are relatively much less active in promoting the cleavage but the metal bound at site 5 is again active. The initial cleavage products are shown to be identical with those obtained using magnesium, zinc, or lead.
Episodic dike swarms inferred from near‐bottom magnetic anomaly maps at the southern East Pacific Rise

fissure eruption at 1728 0 S. Similar lows are observed at three other drained lava lake troughs, including one which is at least 1800 years old, residing 400 m away from the present-day axis. We attribute these lows to the presence of shallow dike swarms. The degree to which other geologic features may contribute to the lows is constrained using geologic, geophysical, and geochemical observations and forward modeling. Compositional analyses of Alvin samples at 1728 0 S do not support Fe or Ti variations as a primary source. Hypotheses requiring hydrothermal alteration and porosity variations are both inconsistent with geologic observations and near-bottom gravity data analysis from similar areas. Previous mappings between paleointensity variations and the observed magnetic field over distances of several kilometers from the axis suggest that such variations do not create the field low. The dominant source of the magnetization low is most likely the presence of a 100–200 m wide region of shallow dikes which are poorly magnetized relative to extrusives, or a region heated above magnetic blocking or Curie temperatures by intrusions during the most recent eruption (though the latter interpretation cannot explain the low at the fossil trough). In the first case, this extrusive thinning implies a change in eruptive behavior over the last 750–1500 years given the local spreading rate. For the latter case, thermal models suggest the anomaly had to have been created by a dike swarms totaling at least 45 m width during the most recent eruption(s), corresponding to � 300 years of plate spreading. Models indicate that the source of the low is centered slightly east of the axial trough. This offset suggests that the axis has been progressively migrating westward over the past millennium, consistent with other studies covering greater length and timescales. Westward migration provides an explanation for the preferential emplacement of recent lavas flows west of the axis, evident in ABE bathymetry and submersible observations. INDEX TERMS: 3035 Marine Geology and Geophysics: Midocean ridge processes; 1517 Geomagnetism and Paleomagnetism: Magnetic anomaly modeling; 8499 Volcanology: General or miscellaneous; 3045 Marine Geology and Geophysics: Seafloor morphology and bottom photography; 3005 Marine Geology and Geophysics: Geomagnetism (1550);
Battery state-of-charge estimation

This paper discusses the problem of lead acid battery state-of-charge estimation for (hybrid) electric vehicles. The problem is to accurately estimate the remaining battery capacity for both driver notification and automated energy management. The article presents a review of the problem, existing solution methods, presentation of a new solution method, and experimental analysis of the performance of that method.
Complete single-channel solutions to hidden terminal problems in wireless LANs

We specify and analyze two variants of floor acquisition multiple access protocols for CSMA single-channel wireless LANs (WLANs) with hidden terminals. One variant assumes that all stations have the same functionality, and the other assumes base station control. These are the first protocols that solve the hidden-terminal problems of single-channel WLANS. Stations use carrier sensing and a three way handshake, just as advocated in MACA, IEEE 802.11 and FAMA-NTR introduced in the past. However, the clear to send (CTS) from a receiver lasts long enough to be able to jam any hidden sender that did not hear the request to send (RTS) being acknowledged and who started sending its RTS after the receiver started sending the CTS. We verify that this jamming of the "offending senders" by the receivers permits floor acquisition to be enforced correctly, i.e., that no data packet sent by a sender will ever collide at the intended receiver with any packet sent by any other station hidden or exposed from the sender. The performance of these protocols is compared by simulation with the performance of MACAW reported in the past.
On the Rough Number Computation and the Ada Language

This paper examines a numerical computation problem from a theoretical viewpoint. It concludes that computer systems are not capable of computing real numbers correctly due to the differences between the algebraic structures of real numbers and model numbers. These two classes of numbers are not isomorphic. This paper proposes using the concept of computer model numbers to approximate rough numbers for computation and selecting the Ada language for computation. The Ada language allows a user to declare variables with designated number of digits or to specify a suitable size "small" for computation. This way, the user can preset the desired accuracy for all variables
Project FAMOUS: Operational techniques and American submersible operations

The diving operations associated with Project FAMOUS utilized an advanced deep-diving submersible with many capabilities, including a highly accurate positioning system. As the capabilities and mode of operation of this submersible in the context of a major research project are not well known, the operational techniques are described in some detail. Project FAMOUS dive operations relied upon extensive regional and intermediate-scale surface-ship studies prior to and during the dive period. These provided the basic geological and geophysical context in which the studies by the submersible Alvin were placed. The detailed bathymetric charts provided by the U.S. Navy on the basis of multi–narrow-beam echo-sounding, precision submersible navigation, advanced submersible data logging, and post-cruise processing systems furnished an accurate frame of reference for the dive operations as well as for the subsequent studies of the tectonic and volcanic processes within the rift on a scale not hitherto possible. The integration of the dive data with this and other surface ship information was subject to various difficulties which are discussed. Dive tracks adjusted to the basic frame of reference of the Navy bathymetry, a revised bathymetric chart for the dive area, and sample locations and particulars are provided. The FAMOUS operations furnished, in addition to the scientific results, a much better understanding of the best mode of operation for detailed deep – sea-floor studies that utilize a combination of surface-ship and submersible techniques. The lessons learned during this project are discussed in some detail.
Global cPILOT analysis of the APP/PS-1 mouse liver proteome

Purpose A quantitative proteomics strategy called combined precursor isotopic labeling and isobaric tagging (cPILOT) was designed to discover alterations in the amyloid precursor protein/presenilin-1 (APP/PS-1) mouse liver proteome. The multiplexing strategy allows simultaneous quantitation of 12 samples in a single experiment. Experimental design For cPILOT samples, six APP/PS-1 and six heterozygous mouse livers were modified using precursor dimethylation (pH 2.5) followed by isobaric tagging (pH 8.0). Samples were pooled, fractioned with strong cation exchange, and analyzed using RPLC-MS3 for protein identification and relative quantitation. In order to increase proteome coverage, a two-tiered data collection strategy was employed. Six duplex precursor dimethylation experiments were also performed to verify cPILOT protein quantitation. Results The combination of cPILOT with precursor dimethylation data resulted in 2437 total liver proteins identified and 77 differentially expressed proteins in APP/PS-1 liver. Differentially expressed proteins are involved in metabolic processes such as B-oxidation, pyruvate metabolism, and glucose regulation. Conclusions and clinical relevance cPILOT expands protein quantitation using isobaric tags and can be applied to any clinical laboratory interested in enhanced multiplexing strategies. Differentially expressed proteins in APP/PS-1 mouse liver suggest the potential use of ketone bodies to alleviate metabolic dysregulation in Alzheimer's disease brain. Our work also suggests alterations in the alanine cycle potentially leading to hyperammonia production, may contribute to Alzheimer's disease pathogenesis.
Second Life®: A New Strategy in Educating Nursing Students

Abstract The purpose of this article is to discuss how the University of Michigan School of Nursing designed and implemented a virtual hospital unit in Second Life® to run virtual simulations. Three scenarios were developed about topics that represent areas that contribute to patient safety, as well as key student learning challenges. Fifteen students completed a 6-question survey evaluating their experience. Comments indicated students did identify the potential benefits of the Second Life® simulation. The Second Life® platform may also provide avenues for learning in the clinical arena for a multitude of health care professionals. The opportunity to simulate emergent, complex situations in a nonthreatening, safe environment allows all members of the team to develop critical communication skills necessary to provide safe patient care.
Effects of temperature on disease progression and swimming stamina in Ichthyophonus-infected rainbow trout, Oncorhynchus mykiss (Walbaum).

Rainbow trout, Oncorhynchus mykiss, were infected with Ichthyophonus sp. and held at 10 � C, 15 � C and 20 � C for 28 days to monitor mortality and disease progression. Infected fish demonstrated more rapid onset of disease, higher parasite load, more severe host tissue reaction and reduced meanday-to-death at higher temperature. In a second experiment, Ichthyophonus-infected fish were reared at 15 � C for 16 weeks then subjected to forced swimming at 10 � C, 15 � C and 20 � C. Stamina improved significantly with increased temperature in uninfected fish; however, this was not observed for infected fish. The difference in performance between infected and uninfected fish became significant at 15 � C( P = 0.02) and highly significant at 20 � C( P = 0.005). These results have implications for changes in the ecology of fish diseases in the face of global warming and demonstrate the effects of higher temperature on the progression and severity of ichthyophoniasis as well as on swimming stamina, a critical fitness trait of salmonids. This study helps explain field observations showing the recent emergence of clinical ichthyophoniasis in Yukon River Chinook salmon later in their spawning migration when water temperatures were high, as well as the apparent failure of a substantial percentage of infected fish to successfully reach their natal spawning areas.
Performance evaluation of production of IT capital goods across OECD countries: A stochastic frontier approach to Malmquist index

As integrated supply chains, ubiquitous computing, and mobile applications have become the backbone for conducting business nowadays, the economic significance of information technology (IT) is self-evident. In this paper, we study IT value from an unconventional perspective: the production of IT capital goods. Using the true fixed-effects model of translog stochastic production frontier, we evaluate the performance of IT industries for 19 Organization of Economic Cooperation and Development (OECD) countries over the period of 2000 to 2009. We examine the productivity growth of these IT industries based on the Malmquist index and further analyze these productivity patterns through technological change and efficiency change. Overall, these IT industries are found to enjoy greater productivity growth than other industries when compared with previous findings. Our results show that technological progress is the main driver of productivity growth for the IT industry, efficiency change has a negligible effect, and each country's IT industry exhibits a distinctive performance profile. Policy implications are drawn from our results and related issues are identified for future research. We also highlight the advance of research methodology used in the study that can account for measurement errors, random fluctuations, and unobserved heterogeneity commonly encountered in empirical information systems research.
Implementation and performance of Munin

Munin is a distributed shared memory (DSM) system that allows shared memory parallel programs to be executed efficiently on distributed memory multiprocessors. Munin is unique among existing DSM systems in its use of multiple consistency protocols and in its use of release consistency. In Munin, shared program variables are annotated with their expected access pattern, and these annotations are then used by the runtime system to choose a consistency protocol best suited to that access pattern. Release consistency allows Munin to mask network latency and reduce the number of messages required to keep memory consistent. Munin's multiprotocol release consistency is implemented in software using a delayed update queue that buffers and merges pending outgoing writes. A sixteen-processor prototype of Munin is currently operational. We evaluate its implementation and describe the execution of two Munin programs that achieve performance within ten percent of message passing implementations of the same programs. Munin achieves this level of performance with only minor annotations to the shared memory programs.
Mate guarding and frequent in-pair copulation in humans

Cuckoldry is an adaptive problem faced by parentally investing males of socially monogamous species (e.g., humans and many avian species). Mate guarding and frequent in-pair copulation (IPC) may have evolved as anti-cuckoldry tactics in avian species and in humans. In some avian species, the tactics are used concurrently, with the result that mate guarding behaviors and IPC frequency are correlated positively. In other avian species, the tactics are compensatory, with the result that mate guarding behaviors and IPC frequency are correlated negatively. The relationship between mate guarding and IPC frequency in humans is unknown. Avian males that use these tactics concurrently share with human males an inability to guard a female partner continuously during her peak fertile period. We hypothesized, therefore, that men’s mate guarding and IPC frequency function as concurrent anti-cuckoldry tactics, resulting in a positive correlation between them. Study 1 (n=305) secured men’s self-reports of mate guarding and IPC frequency. Study 2 (n+367) secured women’s reports of their partners’ mate guarding and IPC frequency. The concurrent tactics hypothesis was supported in both studies: Men’s mate guarding and IPC frequency are correlated positively, and this association is not attributable to male age, female age, relationship satisfaction, relationship length, or time that the couple spends together. The Discussion section addresses potential limitations of this research and future research directions.
Tuning Guidelines of a Dynamic Matrix Controller for Integrating (Non-Self-Regulating) Processes

Designing a multivariable dynamic matrix conrtoller (DMC) controller for integrating processes is challenging because of the number of tuning parameters that affect the closed-loop performance. These tuning parameters required to implement DMC include the sample time; the prediction, model, and control horizons; the controlled variable weights; and the move suppression coefficients. The move suppression coefficients are used as the key tuning parameters to obtain a desirable DMC performance. This paper derives and demonstrates expressions for computing the complete set of tuning parameters for integrating processes. A novel contribution of this work is the derivation of an analytical expression for computing the move suppression coefficients based on the process model and the other DMC design parameters. The tuning rules are demonstrated on simulated processes including a constrained multivariable process simulation that displays integrating characteristics.
Aluminium content of foods and diets.

Literature data on the aluminium content of individual foods have been compiled, summarized and presented by food groups. The contribution of aluminium from food preparation and cooking utensils and from food additives is discussed. Literature data on the daily intake of aluminium are summarized, and the contribution of food groups to daily aluminium intake is estimated. The major sources of dietary aluminium include several with aluminium additives (grain products, processed cheese and salt) and several that are naturally high in aluminium (tea, herbs and spices). The aluminium that may migrate from aluminium utensils is probably not a major or consistent source of this element. Daily intakes of aluminium, as reported prior to 1980, were 18–36 mg per day. More recent data, which are probably more accurate, indicate intakes of 9 mg per day for teenage and adult females and 12–14 mg per day for teenage and adult males.
Recognition of RNA branch point sequences by the KH domain of splicing factor 1 (mammalian branch point binding protein) in a splicing factor complex.

Mammalian splicing factor 1 (SF1; also mammalian branch point binding protein [mBBP]; hereafter SF1/mBBP) specifically recognizes the seven-nucleotide branch point sequence (BPS) located at 3* splice sites and participates in the assembly of early spliceosomal complexes. SF1/mBBP utilizes a “maxi-K homology” (maxi-KH) domain for recognition of the single-stranded BPS and requires a cooperative interaction with splicing factor U2AF65 bound to an adjacent polypyrimidine tract (PPT) for high-affinity binding. To investigate how the KH domain of SF1/mBBP recognizes the BPS in conjunction with U2AF and possibly other proteins, we constructed a transcriptional reporter system utilizing human immunodeficiency virus type 1 Tat fusion proteins and examined the RNA-binding specificity of the complex using KH domain and RNA-binding site mutants. We first established that SF1/mBBP and U2AF cooperatively assemble in our reporter system at RNA sites composed of the BPS, PPT, and AG dinucleotide found at 3* splice sites, with endogenous proteins assembled along with the Tat fusions. We next found that the activities of the Tat fusion proteins on different BPS variants correlated well with the known splicing efficiencies of the variants, supporting a model in which the SF1/mBBP-BPS interaction helps determine splicing efficiency prior to the U2 snRNP-BPS interaction. Finally, the likely RNA-binding surface of the maxi-KH domain was identified by mutagenesis and appears similar to that used by “simple” KH domains, involving residues from two putative a helices, a highly conserved loop, and parts of a b sheet. Using a homology model constructed from the cocrystal structure of a Nova KH domain-RNA complex (Lewis et al., Cell 100:323‐332, 2000), we propose a plausible arrangement for SF1/mBBP-U2AF complexes assembled at 3* splice sites.
Exploring Why People Love Their Jobs: A Multi-Industry Case Study

Unfortunately, many businesses discuss that rather than valuing people as their most important asset, firms are focusing their efforts on downsizing, outsourcing and taking other actions in order to reduce their labor costs. Instead, developing employee loyalty through inspiring leadership, knockout facilities, and a sense of purpose, management strategically leverages the three most popular traits that employees love about their companies. By questioning HR representatives, managers, and fellow co-workers, the authors were able to determine our own version of the most common traits that employees develop loyalty at Mellon Financial Corporation, the Abreon Group, and the Pine-Richland School District . A number of interesting trends from surveying both administrator and employees of these three diverse settings in Pittsburgh, PA were found. Toxic worry was minimized and loyalty maximized when employees are encouraged to professionally and personally enjoy the people they work with, since this is extremely important to tactical on-time issues with minimum conflict.
Undercover Investigations, Ethics of

Undercover investigations are a common, although not dominant feature of law enforcement in the United States. A popular cartoon nicely illustrates the central features of one type of investigation. Next to a sign reading ‘Do not feed the bears,’ a park ranger wearing a bear’s costume gives a ticket to a couple who have just fed the ‘bear,’ not realizing that it was a trick. This is a facilitative operation in which authorities provide the opportunity for the rule to be broken. This contrasts with intelligence operations in which the goal is to find out information about a crime that has already occurred. An example of the latter is an officer in plainclothes who befriends a suspect in a bar in an effort to learn about a particular crime. These in turn contrast with preventive operations in which authorities believe that a crime is to be committed and then take actions to stop it, for example, posing as clerks in a targeted jewelry store. Arguments supportive of and in opposition to covert police means are discussed.
Management of early stage non-small cell lung cancer

It is a great honor to serve as Guest Editor for this special issue of Translational Lung Cancer Research devoted to early stage lung cancer. While lung cancer remains a leading cause of cancer death for both men and women globally, rapid advances in our understanding of the disease has led to significant improvements in recent years. In this issue we have brought together a truly multidisciplinary group of experts to discuss the challenges and advances that have been made in diagnosis and treatment of patients with potentially curable disease.
Proximity Optimization for Adaptive Circuit Design

The performance growth of conventional VLSI circuits is seriously hampered by various variation effects and the fundamental limit of chip power density. Adaptive circuit design is recognized as a power-efficient approach to tackling the variation challenge. However, it tends to entail large area overhead if not carefully designed. This work studies how to reduce the overhead by forming adaptivity blocks considering both timing and spatial proximity among logic cells. The proximity optimization consists of timing and location aware cell clustering and incremental placement enforcing the clusters. Experiments are performed on the ICCAD 2014 benchmark circuits, which include case of near one million cells. Compared to alternative methods, our approach achieves 1/4 to 3/4 area overhead reduction with an average of 0.6% wirelength overhead, while retains about the same timing yield and power.
The Industrial Revolution and the Advent of Modern Surgery

In the early nineteenth century, surgery was a much less refined and respected profession than it is today. Due to the very slow progression of the practice, surgery was risky and often ineffective. Furthermore, the applications of surgery were very limited at that time. It is widely accepted that the advent of anesthesia and aseptic technique are largely responsible for the modernization of surgery—they produced changes that would revolutionize the profession. Before the introduction of these surgical principles, very little surgical progress was seen. Although we know that these technologies played an important role in the advancement of surgery, we still have yet to fully understand what led to the establishment of these technologies. The goal of this paper is to understand how the societal trends of the Industrial Revolution are directly linked to these innovations and ultimately, the introduction of modern surgery.
Austrian Economics, Market Process, and the EVA(R) Framework

In this paper I present a financial framework, known as Economic Value Added or EVA®, used to value firms and apply it to topics highlighted in the Austrian literature. In particular I contrast the market process emphasize in the Austrian literature with the neoclassical firm profit maximization and the role of Kirzner’s entrepreneurial alertness. Then I show how these micro topics can be aggregated into macro issues such as the Cantillon Effect, an aggregate average period of production, and the impact of country risk into value creation.
Introduction to Part One

Linear series have long stood at the center of algebraic geometry. Systems of divisors were employed classically to study and define invariants of projective varieties, and it was recognized that varieties share many properties with their hyperplane sections. The classical picture was greatly clarified by the revolutionary new ideas that entered the field starting in the 1950s. To begin with, Serre’s great paper [530], along with the work of Kodaira (e.g. [353]), brought into focus the importance of amplitude for line bundles. By the mid 1960s a very beautiful theory was in place, showing that one could recognize positivity geometrically, cohomologically, or numerically. During the same years, Zariski and others began to investigate the more complicated behavior of linear series defined by line bundles that may not be ample. This led to particularly profound insights in the case of surfaces [623]. In yet another direction, the classical theorems of Lefschetz comparing the topology of a variety with that of a hyperplane section were understood from new points of view, and developed in surprising ways in [258] and [30].
Design and early evaluation of the RUBI-5 sociable robots

The RUBI project [2,3,4,5,6,7,8,9] started in 2004 with the goal of designing sociable robots for early childhood education. The project relies on an immersive, iterative approach to robot development and scientific progress. From the beginning of the project scientists and engineers immersed themselves at the Early Childhood Education Center at UC San Diego, designed robot prototypes to interact and teach toddlers in close collaboration with teachers, toddlers, and parents. As part of this process we learned many lessons on how to develop hardware and software components, that are safe, reliable, and that can withstand the rigors of daily interactions with toddlers. Here we present our last robot platforms: RUBI-5. The robot components are off-the-shelf and the 3D-CAD files are being made available for free to the research community to ease replication and adaptation by other groups. One of the goals of the new platform is to greatly accelerate the design, data-gathering, and statistical analysis of early education experiments.
A 43-mW MASH 2-2 CT $\Sigma \Delta$ Modulator Attaining 74.4/75.8/76.8 dB of SNDR/SNR/DR and 50 MHz of BW in 40-nm CMOS

This paper proposes a multistage noise-shaping continuous-time sigma-delta modulator (CT $\Sigma \Delta \text{M}$ ) with on-chip RC time constant calibration circuits, multiple feedforward interstage paths, and a fully integrated noise-cancellation filter (NCF). The core modulator architecture is a cascade of two single-loop second-order CT $\Sigma \Delta \text{M}$ stages, each of which consists of an integrator-based active- RC loop filter, current-steering feedback digital-to-analog converters, and a 4-b flash quantizer. On-chip RC time constant calibration circuits and high-gain multistage operational amplifiers are realized to mitigate quantization noise leakage due to process variation. Multiple feedforward interstage paths are introduced to: 1) synthesize a fourth-order noise transfer function with dc zeros; 2) simplify the design of NCF; and 3) reduce signal swings at the second-stage integrator outputs. Fully integrated in 40-nm CMOS, the prototype chip achieves 74.4 dB of signal-to-noise-and-distortion ratio (SNDR), 75.8 dB of signal-to-noise ratio, and 76.8 dB of dynamic range in 50.3 MHz of bandwidth (BW) at 1 GHz of sampling frequency with 43 mW of power consumption (P) from 1.1/1.15/2.5-V power supplies. It does not require external software calibration and possesses minimal out-of-band signal transfer function peaking. The figure-of-merit (FOM), defined as $\text {FOM}=\text {SNDR}+10\times \log _{10}(\text {BW}/\text {P})$ , is 165.1 dB.
Historical Reflections: Sosa’s Perspective on the Epistemological Tradition

Ernest Sosa’s work in epistemology has frequently progressed through careful examination of key moments in the history of philosophy. Here I examine some of the most important cases in which this is so, including his introduction of virtues into epistemology and his reason for adding the subject’s perspective to externalism. I especially focus on the way Sosa adapts the structure of Descartes’s epistemology for his own externalist, virtue theoretic answer to skepticism.
Perspectives on Manufacturing of High-Quality Cell Therapies

Cell therapies are taking center stage in medicine spanning cancer immunotherapy, stem cell engineering, and regenerative medicine. Recently, the first ex vivo hematopoietic stem cell (HSC) gene therapy for the treatment of adenosine deaminase deficiency-severe combined immunodeficiency (ADA-SCID) received marketing approval.1 By now, the majority of the 150 plus patients who have received HSC gene therapy to treat monogenic diseases have demonstrated clinical benefits.2 Promising clinical outcomes in phase I/II trials based on T cells engineered to express T cell chimeric antigen receptors (CARs)3 against hematological malignancies have also spurred unprecedented interest from pharmaceutical and biotechnology companies.
Keynote speakers: Nature's gift: How the discovery of structural principles in a microbial protein helped illuminate the pathophysiology of psychiatry

Karl Deisseroth is the D.H. Chen Professor of Bioengineering and of Psychiatry and Behavioral Sciences at Stanford University, and Investigator of the Howard Hughes Medical Institute. He received his undergraduate degree from Harvard, his PhD from Stanford, and his MD from Stanford; he also completed postdoctoral training, medical internship, and adult psychiatry residency at Stanford, and he is board-certified by the American Board of Psychiatry and Neurology. He continues as a practicing psychiatrist at Stanford with specialization in affective disorders and autism-spectrum disease, employing medications along with neural stimulation. In the engineering school he developed and launched the undergraduate degree in Bioengineering at Stanford, and continues to serve as Director of Undergraduate Education in Bioengineering, while also teaching yearly medical physiology and optics courses. National-scale service has included the NIH BRAIN Initiative Working Group and nonprofit disease foundations including the Brain and Behavior Research Foundation (NARSAD) and the Michael J. Fox Foundation for Parkinsons Research. He was selected a Howard Hughes Medical Institute Investigator in 2013, began serving as a foreign adjunct professor at the Karolinska Institute in 2013, and was elected to the US National Academy of Medicine in 2010, to the US National Academy of Sciences in 2012, and to the German National Academy of Sciences (Leopoldina) in 2014.
Clinical and clinicopathologic changes in cows with endotoxin-induced mastitis treated with small volumes of isotonic or hypertonic sodium chloride administered intravenously

We characterized the clinicopathologic manifestations of experimentally induced endotoxin-induced mastitis. Responses to hypertonic fluid therapy also were assessed. Eight cows received 1 mg of endotoxin by intramammary infusion in the left forequarter. Four hours after endotoxin administration, cows received 0.9% NaCl, 5 ml/kg of body weight (n = 4) or 7.5% NaCl, 5 ml/kg (n = 4) IV. Endotoxin-infused cows had expanded plasma volume, hyponatremia, transient hyperchloremia and hypophosphatemia, increased serum glucose concentration, and decreased serum activities of liver- and muscle-specific enzymes. Calculated plasma volume increased at 6 hours in cows receiving hypertonic NaCl, and at 12, 24, and 48 hours after endotoxin infusion in both groups. Concurrent observations of decreased serum protein concentration, erythrocyte count, and hematocrit supported observations of increased plasma volume. Relative plasma volume was greater in cows receiving hypertonic NaCl (124.3%) than in cows receiving isotonic NaCl (106.6%) at 6 hours after endotoxin infusion. Cattle receiving hypertonic NaCl had increased voluntary water intake after IV fluid administration. Increased water consumption was not accompanied by increased body weight, indicating probable occurrence of offsetting body water loss. Serum sodium concentration in cows receiving hypertonic NaCl was increased 2 hours after fluid administration, but the magnitude of the change was minimal (< 4 mmol/L) and transient, indicating rapid equilibration with either interstitial or intracellular spaces. Serum sodium concentration was decreased in cows receiving isotonic NaCl at 12, 24, and 48 hours after endotoxin administration, compared with concentration prior to endotoxin administration, indicating selective loss of sodium.
TCT-736 Characteristics, Clinical Presentation, and Outcomes of Patients with Recurrent In-stent Restenosis of Drug-Eluting Stents Compared to Patients with Single Episode of In-stent Restenosis

Drug-eluting stents (DES) have significantly improved the rate of in-stent restenosis (ISR) following percutaneous coronary intervention (PCI). However, ISR remains a therapeutic challenge, often leading to recurrent ISR. The aim of this study was to compare patients with a single DES ISR event to
The acute action of ammonia on rat brain metabolism in vivo

1. Acute NH4+ toxicity was studied by using a new apparatus that removes and freezes the brains of conscious rats within 1s. 2. Brains were removed and frozen 5min after intraperitoneal injection of ammonium acetate (2–3min before the onset of convulsions). Arterial [NH4+] rose from less than 0.01 to 1.74mm at 4–5min. The concentrations of all glycolytic intermediates measured, except glucose 6-phosphate, were increased by the indicated percentage above the control value as follows: glucose (by 41%), fructose 1,6-diphosphate (by 133%), dihydroxyacetone phosphate (by 164%), α-glycerophosphate (by 45%), phosphoenolpyruvate (by 67%) and pyruvate (by 26%). 4. Citrate and α-oxoglutarate concentrations were unchanged and that of malate was increased (by 17%). 5. Adenine nucleotides and Pi concentrations were unchanged but the concentration of creatine phosphate decreased slightly (by 6%). 6. Brain [NH4+] increased from 0.2 to 1.53mm. Net glutamine synthesis occurred at an average rate of 0.33μmol/min per g. 7. The rate of brain glucose utilization was measured in vivo as 0.62μmol/min per g in controls and 0.81μmol/min per g after NH4+ injection. 8. The arteriovenous difference of glucose and O2 increased by 35%. 9. No significant arteriovenous differences of glutamate or glutamine were detected. Thus, although much NH4+ was incorporated into glutamine the latter was not rapidly released from the brain to the circulation. 10. Plasma [K+] increased from 3.3 to 5.4mm. 11. The results indicate that NH4+ stimulates oxidative metabolism but does not interfere with brain energy balance. The increased rate of oxidative metabolism could not be accounted for only on the basis of glutamine synthesis. We suggest that increased extracellular [NH4+] and [K+] decreased the resting transmembrane potential and stimulated Na+,K+-stimulated adenosine triphosphatase activity thus accounting for the increased metabolic rate.
Constitutive Modelling for Interfaces Under Cyclic Loading

SUMMARY Importance of appropriate modelling and laboratory testing for constitutive behavior of interfaces in dynamic soil-structure is identified. A brief description of the constitutive models developed by the authors and co-workers is presented here. The models are verified with respect to typical results from special laboratory tests.
Ethics of cutting-edge device research.

A physician comments on the ethical issues that arise when a patient participates in a research study for a new medical device where there is a certain degree of risk involved with experimental treatments. Virtual Mentor is a monthly bioethics journal published by the American Medical Association.
Tycho, Longomontanus, and Kepler on Ptolemy’s Solar Observations and Theory, Precession of the Equinoxes, and Obliquity of the Ecliptic

It is well known that there are errors in Ptolemy’s observations of the Sun with consequences for his own astronomy and for later astronomy up to some time in the seventeenth century. The principal problems and their consequences in Ptolemy’s astronomy are the following:
The Effect of the Relationship of APOE Polymorphisms and Cerebral Vasospasm on Functional Outcomes in Children With Traumatic Brain Injury

Background:Pediatric traumatic brain injury (TBI) is a leading cause of death and disability. Polymorphisms in the apolipoprotein E (APOE) gene have been linked to cerebral vasospasm (CV) and poor ...