cssi/SciSciGPT-SciSciNet huggingface dataset:
Asymmetric Usage of Antagonist Charged Residues Drives Interleukin-5 Receptor Recruitment but is Insufficient for Receptor Activation

The cyclic peptide AF17121 (VDECWRIIASHTWFCAEE) is a library-derived antagonist for human Interleukin-5 receptor alpha (IL5Ralpha). We have previously demonstrated that AF17121 mimics Interleukin-5 (IL5) by binding in a region of IL5Ralpha that overlaps the IL5 binding epitope. In the present study, to explore the functional importance of the amino acid residues of AF17121 required for effective binding to, and antagonism of, IL5Ralpha, each charged residue was subjected to site-directed mutagenesis and examined for IL5Ralpha interaction by using a surface plasmon resonance biosensor. One residue, Arg(6), was found to be essential for receptor antagonism; its replacement with either alanine or lysine completely abolished the interaction between AF17121 and IL5Ralpha. Other charged residues play modulatory roles. One class consists of the N-terminal acidic cluster (Asp(2) and Glu(3)) for which alanine replacement decreased the association rate. A second class consists of His(11) and the C-terminal acidic cluster (Glu(17) and Glu(18)) for which alanine replacement increased the dissociation rate. Binding model analysis of the mutants of the latter class of residues indicated the existence of conformational rearrangement during the interaction. On the basis of these results, we propose a model in which Arg(6) and N-terminal acidic residues drive the encounter complex, while Arg(6), His(11), and C-terminal acidic residues are involved in stabilizing the final complex. These data argue that the charged residues of AF17121 are utilized asymmetrically in the pathway of inhibitor-receptor complex formation to deactivate the receptor function. The results also help focus emerging models for the mechanism by which IL5 activates the IL5Ralpha-betac receptor system.
Calcium drives fusion of SNARE-apposed bilayers

N-ethylmalemide-sensitive factor attachment protein receptor (SNARE) has been proposed to play a critical role in the membrane fusion process. The SNARE complex was suggested to be the minimal fusion machinery. However, there is mounting evidence for a major role of calcium in membrane fusion. Hence, the role of calcium in SNARE-induced membrane fusion was the focus of this study. It revealed that recombinant v-SNARE and t-SNARE, reconstituted into separate liposomes, interact to bring lipid vesicles into close proximity, enabling calcium to drive fusion of opposing bilayers. Exposure to calcium triggered vesicle fusion at both, high potency and efficacy. The half-time for calcium-induced fusion of SNARE-reconstituted vesicles was determined to be ∼10 s, which is two orders of magnitude faster than in its absence. Calcium acts downstream of SNAREs, since the presence of SNAREs in bilayers increases the potency of calcium-induced vesicle fusion, without significantly influencing its efficacy. Hence, this study suggests that in the physiological state in cells, both SNAREs and calcium operate as the minimal fusion machinery.
Operant discrimination as a function of rate of stimulus alternation

Three groups of rats were given operant discrimination training in which Sd-SΔ alternation occurred 3, 6, or 12 times per min. Only the 3/min. group learned to inhibit SΔ responses. The nonlearning of the 6/min. and 12/min. groups was discussed in terms of adventitious reinforcement of SΔ responses.
Intraspecific phylogenetic congruence among multiple symbiont genomes

Eukaryotes often form intimate endosymbioses with prokaryotic organisms. Cases in which these symbionts are transmitted cytoplasmically to host progeny create the potential for cospeciation or cong...
Urbach's rule in Er3+ activated silicate glass

Abstract Urbach's rule is observed for a particular Er 3+ optical transition in a silicate glass. Results for this system differ from that previously observed in other solids, and a possible explanation of this behaviour is given.
A Perspective on Progress and Gaps in HIV Prevention Science

In the past few years, the transdisciplinary field of HIV prevention has reached several milestones. Topically applied tenofovir gel provided significant protection from sexual transmission of HIV in a large-scale clinical trial and oral Truvada (emtricitabine/tenofovir disoproxil fumarate) was recently approved for preexposure prophylaxis (PrEP) following two successful clinical trials in men and women. These achievements are tempered by the disappointing results of other clinical trials, which highlight the complexities of prevention research. In this perspective, we discuss scientific and developmental gaps for topical chemoprophylaxis of the sexual transmission of HIV, which depends on the complex interactions between the pharmacokinetics and pharmacodynamics of drugs, formulation and delivery systems, anatomic site of transmission, and host mucosal immune defenses. Despite the considerable time and resources devoted to unraveling the initial steps in sexual transmission of HIV, current knowledge is based on animal models and human explanted tissue, which may not fully recapitulate what happens clinically. Understanding these events, including the role that sex hormones, semen, and mucosal secretions play in transmission, and the interplay between innate immunity, the mucosal environment, and drug efficacy is paramount. This drives some of the most pressing questions in the field.
Formin-induced actin cables are required for polarized recruitment of the Ste5 scaffold and high level activation of MAPK Fus3

Little is known about how a mitogen-activated protein kinase (MAPK) cascade is targeted to specific sites at the plasma membrane during receptor stimulation. In budding yeast, the Ste5 scaffold is recruited to a receptor-coupled G protein during mating pheromone stimulation, allowing the tethered MAPK cascade to be activated by Ste20, a Cdc42-anchored kinase. Here we show that stable recruitment of Ste5 at cortical sites requires the formin Bni1, Bni1-induced actin cables, Rho1 and Myo2. Rho1 directs recruitment of Bni1 via the Rho-binding domain, and Bni1 mediates localization of Ste5 through actin cables and Myo2, which co-immunoprecipitates with Ste5 during receptor stimulation. Bni1 is also required for polarized recruitment and full activation of MAPK Fus3, which must bind Ste5 to be activated, and polarized recruitment of Cdc24, the guanine exchange factor that binds Ste5 and promotes its recruitment to the G protein. In contrast, Bni1 is not important for activation of MAPK Kss1, which can be activated while not bound to Ste5 and does not accumulate at cortical sites. These findings reveal that Bni1 mediates the formation of a Ste5 scaffold/Fus3 MAPK signaling complex at polarized sites, and suggests that a pool of Ste5 may translocate along formin-induced actin cables to the cell cortex.
D.F.T. computation by fast polynomial transform algorithms

A new method is introduced for the fast computation of multidimensional discrete Fourier transforms (d.f.t.). We show that some multidimensional d.f.t.s are mapped efficiently into one-dimensional d.f.t.s by using a single polynomial transform and some auxiliary calculations. Since polynomial transforms can be computed without multiplications, this approach reduces significantly the number of operations over the conventional fast Fourier transform (f.f.t.) and is therefore attractive for image-processing applications.
PlexC: a policy language for exposure control

With the widespread use of online social networks and mobile devices, it is not uncommon for people to continuously broadcast contextual information such as their current location or activity. These technologies present both new opportunities for social engagement and new risks to privacy, and traditional static "write once" disclosure policies are not well suited for controlling aggregate exposure risks in the current technological landscape.Therefore, we present PlexC, a new policy language designed for exposure control. We take advantage of several recent user studies to identify a set of language requirements and features, providing the expressive power to accommodate information sharing in dynamic environments. In our evaluation we show that PlexC can concisely express common policy idioms drawn from survey responses, in addition to more complex information sharing scenarios.
Measuring the Willingness to Pay for Cave Diving

AbstractFresh water springs are unique natural resources that are contained within public lands across the United States. Natural resource management on public lands generates many interesting policy issues as the competing goals of conservation, recreational opportunity provision, and revenue generation often clash. As demand for recreational cave diving sites increases, this article provides natural resource site managers with the first statistical estimate of divers’ willingness to pay (WTP) to dive cave and cavern systems. Using a contingent valuation model (CVM) and correcting for hypothetical bias, we find that divers’ median WTP for cave diving opportunities at the site of interest is between $52 and $83 per dive. Model results also provide weak evidence of diver sensitivity with respect to scope, as individuals are willing to pay more for dives that are judged to be higher in quality.
SERUM SICKNESS IN RABBITS II. PRECIPITINOGEN AND PRECIPITINS IN RELATION TO APPEARANCE OF THE REACTION

1. It has not been possible to demonstrate in rabbits affected with serum sickness any constant temporal relationship between precipitin and precipitinogen in the blood on one hand and of occurrence of serum sickness on the other hand. 2. It has not been possible to demonstrate any differences between the precipitin and precipitinogen curves in injected rabbits which develop serum sickness compared with injected rabbits which did not develop serum sickness. 3. There is therefore no evidence that we can directly associate the occurrence of serum sickness with the production or appearance of precipitins.
p(⁷⁰S⁶K¹) in the TORC1 pathway is essential for the differentiation of Th17 Cells, but not Th1, Th2, or Treg cells in mice

The TORC1 pathway is necessary for ribosomal biogenesis and initiation of protein translation. Furthermore, the differentiation of Th1 and Th17 cells requires TORC1 activity. To investigate the role of the TORC1 pathway in the differentiation of Th1 and/or Th17 cells in more detail, we compared the differentiation capacity of naive T cells from wild type and p70(S6K1) knockout mice. Expression of many of the genes associated with Th17-cell differentiation, such as IL17a, IL17f, and IL-23R, were reduced in p70(S6K1) knockout mice. In contrast, the development of Th1, Th2, and Treg cells was unaffected in the absence of p70(S6K1) . Furthermore, expression of the major transcription factor in Th17-cell differentiation, retinoic acid receptor-related orphan receptor gamma T, remained unchanged. However, the acetylation of histone 3 at the promoters of IL17a and IL17f was reduced in the absence of p70(S6K1) . In accordance with the in vitro data, the kinetics, but not the development, of EAE was affected with the loss of p70(S6K1) expression. Collectively, our findings suggested that both in vitro and in vivo differentiation of Th17 cells were positively regulated by p70(S6K1) .
P3L-1 Elastic Moduli, and their Temperature Coefficients, of Piezoelectric and Nonpiezoelectric Polycrystalline Aggregates

Classical procedures for computing average isotropic elastic moduli of polycrystalline aggregates are associated with the names of Voigt, Reuss, and Hill. The Voigt-Reuss-Hill (VRH) procedures apply to averaging moduli subject solely to mechanical boundary conditions. Piezoelectrics in general, are required to be characterized by both mechanical and electrical boundary conditions. This paper describes proper averaging for piezoelectrics, along with an advanced averaging method. Numerical values are provided for examples using materials with strong piezocoupling values. The examples demonstrate that the piezoelectric effect must be taken into account in the averaging process. Associated temperature coefficients of the elastic moduli are also supplied for some technologically important piezoelectric and nonpiezoelectric substances
Comparison of Experimental Models for Predicting Laser Tissue Interaction from 3.8-Micron Lasers

The purpose of this study was to evaluate the laser-tissue interactions of engineered human skin and in-vivo pig skin following exposure to a single 3.8 micron laser light pulse. The goal of the study was to determine if these tissues shared common histologic features following laser exposure that might prove useful in developing in-vitro and in-vivo experimental models to predict the bioeffects of human laser exposure. The minimum exposure required to produce gross morphologic changes following a four microsecond, pulsed skin exposure for both models was determined. Histology was used to compare the cellular responses of the experimental models following laser exposure. Eighteen engineered skin equivalents ( in-vitro model), were exposed to 3.8 micron laser light and the tissue responses compared to equivalent exposures made on five Yorkshire pigs ( in-vivo model). Representative biopsies of pig skin were taken for histologic evaluation from various body locations immediately, one hour, and 24 hours following exposure. The pattern of epithelial changes seen following in-vitro laser exposure of the engineered human skin and in-vivo exposure of pig skin indicated a common histologic response for this particular combination of laser parameters.
Application of potent potential functions in eye/head movement control

In this paper we study the human eye movement and the head movement system as a simple mechanical control system. Most of the time, eye movements obey Listing's constraint, which states that the allowed orientations of the eye are obtained by rotating a fixed ‘primary gaze direction’ by a subclass of rotation matrices. These rotation matrices have their axes of rotation restricted to a fixed plane perpendicular to the primary gaze direction. Likewise, a spontaneous head movement satisfy Donder's constraint which is similar to the Listing's constraint except that the axes of rotation of the head away from a primary head position is restricted to a fixed surface, which is not necessarily a plane. When head is restrained to remain fixed, eye movement satisfies the Listing's constraint throughout its entire trajectory. On the other hand, when the head is allowed to move (satisfying the Donder's constraint), the eye satisfies the Listing's constraint only at the beginning and at the end of a trajectory. Intermediate points of the trajectory, partially guided by the vestibulo-ocular reflex, do not apparently satisfy the Listing's constraint. In this paper we introduce control strategy that would regulate the eye from an initial to a final gaze position with or without satisfaction of the Listing's constraint during all the intermediate points of the eye movement trajectory. We study the head movement problem under the assumption that the head always satisfies the Donder's constraint. The control signals are generated by choosing a suitable potential function and adding to it a suitable damping term. The overall dynamical system is constructed using the well known Euler Lagrange's equation. The main result of this paper is to compare, using simulations, the total distance and the total time it takes to regulate the eye and the head between two orientations.
UNEXPECTED PRESENCE OF SOLUTE-FREE ZONES AT METAL-WATER INTERFACES

Solute-free zones, termed "exclusion zones" are routinely seen next to hydrophilic surfaces in aqueous solution. Here we report similar zones next to various metals. The largest, approximately 200 µm in width, was found adjacent to zinc. Other reactive metals, including aluminum, tin, lead, and tungsten exhibited distinct but smaller exclusion zones, while precious metals such as platinum and gold did not produce any. Electrical potential measurements showed positive potentials within the exclusion zones, while pH measurements revealed an abundance of OH- groups in the aqueous regions beyond the exclusion zones. A correspondence was found between exclusion-zone size and the respective metal's position within the galvanic series. The presence of these interfacial exclusion zones is unexpected, and may shed new light on electrochemical processes taking place at metal interfaces.
Falling into Freedom: Searching for New Interpretations of Sin in a Secular Society

‘Whatever became of sin?’ – the title of American psychiatrist Kark Menninger's book – encapsulates the problem with which I begin. That there is appalling suffering today, organized crime on a scale which almost defies analysis – and certainly detection! – moral evil in a variety of repugnant forms and so-called ‘natural’ catastrophes which threaten the very continuation of human life on our planet, is beyond dispute. But ‘sin’? Is sinfulness still an accepted category in our society for eidier religious believer or nonbeliever? It is hard to accept that when Professor Kerkhofs (from the University of Leuven, Belgium), surveyed the attitudes on sin and guilt of European Christians in 1985, 40% of those interviewed admitted that they had never experienced any feelings of regret about their actions! There is a double tendency prevailing with regard to responsibility for acknowledged wrongdoing: increasing sense of diminished responsibility for crime seeks either to scapegoat a certain sector of the populace as blameworthy, or attempts are made to cope with criminal damage – for example, injuries sustained by drink-driving – by assessing it in exclusively (reductive) monetary terms.
A framework for coded computation

Error-correcting codes have been very successful in protecting against errors in data transmission. Computing on encoded data, however, has proved more difficult. In this paper we extend a framework introduced by Spielman [14] for computing on encoded data. This new formulation offers significantly more design flexibility, reduced overhead, and simplicity. It allows for a larger variety of codes to be used in computation and makes explicit conditions on codes that are compatible with computation. We also provide a lower bound on the overhead required for a single step of coded computation.
Spectrophotometric determination of the second dissociation constants of the aminoquinolines

The second dissociation constants representing the transition from monocation to dication for all of the isomeric aminoquinolines have been determined as pKa' values. The analogous values for 2- and 4-aminopyridine have been recalculated using a revised HO scale. The accurate determination of the second pKa values follows from measurement, for the first time, of the ultraviolet spectra of all the mono- and dications of the aminoquinolines.
A Green's Function Method For Detection OfA Cavity From One Boundary Measurement

A cavity, or a flux on the boundary of a cavity inside of a planar domain is to be determined from electrostatic or thermostatic measurements taken on the domain boundary. This inverse problem is solved by an optimization method, along with the Green's function modification of a boundary integral formulation of an elliptic partial differential equation which models voltage or heat conduction inside of the domain.
Aging and stress-induced changes in complement activation and neutrophil mobilization

We measured the extent of complement activation and neutrophil mobilization after eccentric exercise to determine whether these responses were age dependent and whether they were associated with ch...
Release of atrial natriuretic factor in hypophysectomized rats

The purpose of these studies was to examine the effect of hypophysectomy (HYPOX) on the secretion of atrial natriuretic factor (ANF) and related changes in renal function. Pentobarbital sodium-anesthetized rats received a 20% intravenous blood volume expansion. In intact rats (n = 7), plasma ANF was 39 +/- 3 pg/ml before volume expansion and increased to 71 +/- 10 and 77 +/- 7 pg/ml after volume expansion (P less than 0.01). Volume expansion in HYPOX rats (n = 8) also resulted in an increase in plasma ANF concentration that was significantly less than in the intact group. With volume expansion, sodium excretion rate increased from 0.19 +/- 0.06 to 1.43 +/- 0.43 microM. min-1.100 g body wt-1 (P less than 0.01) in intact rats and from 0.24 +/- 0.08 to 0.74 +/- 0.14 microM.min-1.100 g body wt-1 (P less than 0.05) in HYPOX rats (HYPOX less than intact; P less than 0.05). In an isolated heart-lung preparation, HYPOX rats secreted significantly less ANF than intact rats during two 30-min perfusion periods (P less than 0.02). Atrial ANF concentration was also significantly less in HYPOX rats (P less than 0.05). These results show that hypophysectomy leads to an attenuation of the ANF response to atrial distention and attenuated natriuretic response to blood volume expansion and suggest that the pituitary is required to maintain normal cardiac endocrine function.
Constructing anarchist sexuality: Queer identity, culture, and politics in the anarchist movement

This article explores the articulation of queer sexuality with anarchist identity. Drawing on interviews and participant observation in the contemporary North American anarchist movement, I show th...
Finite Element Analysis on Modal of Movable Arm of Coal Multifunction Vehicle

Based on the frequency analysis flat on Solidworks,the three-dimensional model and finite model of the movable arm are built.The first ten frequencies and the corresponding mode shapes are obtained through the modal analysis.Combining the external hard oscillation,the mode parameters of the movable arm are researched.The vibration condition of the movable arm is known as well as the modification,and the feasibility of the modification is proved.The weakness of the movable arm is found,which provides some references for improving the movable arm further.
Progressive autologous graft-versus-host disease induced by cyclosporin A

The development of graft-versus-host disease (GVHD) in patients undergoing allogeneic bone marrow transplantation for leukemias and lymphomas has been associated with a lower incidence of relapse. This phenomenon is thought to be secondary to the anti-tumor effect of adoptively transferred cells. Cyclosporin A (CsA) therapy is known to cause autologous and syngeneic GVHD in experimental models and humans, and has been used in patients undergoing autologous bone marrow transplantation. It has been the consensus to date that CsA-induced autologous GVHD is generally mild, confined to the skin, self-limiting and non-life-threatening. We report by case of severe and progressive GVHD induced by CsA in a child following autologous bone marrow transplantation for acute lymphoblastic leukemia in second remission.
Estimated Cost-Effectiveness of Intensive Interdisciplinary Behavioral Treatment for Increasing Oral Intake in Children With Feeding Difficulties

OBJECTIVE : To examine the cost-effectiveness of intensive interdisciplinary behavioral treatment (IIBT) to address severe pediatric feeding difficulties and lead to the removal or prevention of gastrostomy tubes (G tubes) from the perspective of the insurance company. METHODS : Costs associated with G tubes and IIBT were compiled from the available literature and national databases. Costs were updated to price at the start of 2015 to allow data from different years to be analyzed on the same scale. RESULTS : One-way sensitivity and two-way threshold analyses demonstrated that IIBT may be a cost-effective treatment for prevention and removal of G tubes over 5 and 10 years. DISCUSSION : Data from this study can be used to justify cost of services for IIBT, and programs can use these data to discuss conservative savings of IIBT based on their treatment model and level of effectiveness.
Effect of cytochrome P450 1A induction on oxidative damage in rat brain.

Polycyclic and halogenated aromatic hydrocarbons (PAHs and HAHs) can enhance the generation of reactive oxygen species (ROS) by inducing cytochrome P450 1A (CYP 1A) in vivo and in vitro. While the brain is vulnerable to oxidative injury, whether or not CYP 1A induction in the brain can produce measurable levels of oxidative damage has not been reported. The objective of this study was to investigate the effect of this induction on oxidative damage to the CNS. Time course changes in rat brain CYP 1A activity were determined by measurement of ethoxyresorufin O‐deethylase (EROD) activity in whole brain homogenates. Three days after exposure of rats to five daily injections of 3‐methylcholanthrene (3‐MC) an approximately sevenfold increase in EROD activity was observed. Hepatic levels were increased 60–100 fold. This increase in CYP 1A activity was not accompanied by increased protein or lipid oxidation as measured by tryptophan fluorescence and TBAR formation, or decreased glutamine synthetase (GS) activity. These findings indicate that if increased CYP 1A activity in the brain following 3‐MC treatment leads to increased ROS generation, the increase is insufficient to overwhelm the endogenous antioxidant defense system, produce detectable oxidative damage, and alter glutamate homeostasis.
Complementary roles of open and hybrid approaches to thoracoabdominal aortic aneurysm repair

Objective Thoracoabdominal aortic aneurysm (TAAA) repair remains a significant challenge with considerable perioperative morbidity and mortality. A hybrid approach utilizing visceral debranching with endovascular aneurysm exclusion has been used to treat high-risk patients and therefore allow repair in more patients. Limited data exist regarding long-term outcomes with this procedure as well as comparison to conventional open repair. This study describes our institutional algorithmic approach to TAAA repair using both open and hybrid techniques. Methods Hybrid and open TAAA repairs performed between July 2005 and August 2015 were identified from a prospectively maintained institutional aortic surgery database. Perioperative morbidity and mortality, freedom from reintervention, and long-term and aorta-specific survival were calculated and compared between the two groups. Results During the study period, 165 consecutive TAAA repairs were performed, including 84 open repairs and 81 hybrid repairs. Patients in the hybrid repair group were significantly older, were more frequently female, and had a generally greater comorbid disease burden, including significantly more chronic kidney disease. Despite the older and sicker cohort, there was no difference in in-hospital mortality between the two groups (9.9% hybrid vs 7.1% open; P = .59). Major morbidity rates differed by procedure, with patients undergoing open repair having a significantly higher rate of postoperative stroke (9.5% open vs 0% hybrid; P = .017), whereas patients undergoing hybrid repair had a higher rate of new permanent dialysis (14.8% hybrid vs 3.6% open; P = .043). There was no difference between groups in the rate of postoperative permanent paraplegia/paresis (8.3% open vs 7.4% hybrid; P = .294). There was a significantly increased rate of reintervention in the hybrid repair group (12.3% hybrid vs 1.2% open, P = .004), with all hybrid reinterventions performed because of endoleak. One-year survival was similar between groups at 69% in hybrid repairs vs 77% in open repairs. Long-term survival was worse in the hybrid group (5-year survival, 32% hybrid vs 56% open), although late survival appeared to be influenced mainly by comorbid disease burden, given the similar long-term aorta-specific survival between groups. Conclusions Use of an algorithmic approach whereby higher risk patients with TAAA are treated by a hybrid approach and lower risk patients with conventional open repair yields satisfactory short- and long-term outcomes. The availability of multiple options for TAAA repair within a single center likely allows repair in more patients with consequent decrease in the risk of aorta-related death, at the expense of increased reinterventions for endoleak.
Web Application for Measuring Travel-Based Time Signal Performance

With increasing traffic on arterials and intersections controlled by traffic signals, the problem with delays for road users, specifically during periods of peak hours, escalates. The delays are often a consequence of not efficient operation of the traffic signals on that arterials. Many researchers proposed different analytical and heuristic methods for estimating arterial performance measures. The purpose of the Travel Time Based Signal Performance Measures application is to enable traffic operators to evaluate performance of signalized corridors by exploiting the archived upstream-link measured travel times. The web application applies the concept of Volume-Delay Functions to establish the relationship between traffic demand and measured travel times and signal control performance measures. The available signal performance measures for major through movements include: volume-to-capacity ratio, Level of Service (LOS), and number of cycles waiting. Derived measures can be graphically visualized on Google Maps™ as well as in a table on the user interface. Travel time data acquisition is performed using BlueTOAD devices or Acyclica. In order to calculate the requested performance measures, the web application exploits text files containing free flow travel times and actual travel times. Measures can be calculated on two ways, depending on which of the offered two formulas the user has chosen.
Radiology in the Study of Bone Physiology

Rationale and Objectives In this article, we review the core principles of bone physiology alongside imaging examples that demonstrate such principles. Materials and Methods The core principles of bone physiology are reviewed and further solidified with a corresponding abnormal pathophysiologic example. The key principles of bone physiology to be reviewed include the following: (1) formation and growth, (2) maintenance and repair, (3) metabolism and regulation, and (4) neoplastic disease. Lastly, a collection of secondary bone diseases is presented to demonstrate the skeletal manifestations of numerous systemic diseases. With this integrative method, we hope to emphasize the value of using radiology to teach physiology within a clinical context. This is especially relevant now, as many US medical schools undergo curricular reform with more emphasis on integrative interdisciplinary learning. Ultimately, we intend to provide a paradigm for incorporating radiology into the pre-clinical medical curriculum through a review of basic science physiology that underlies key radiographic findings of the skeletal system. Results Radiology is known for its role in helping make diagnoses and clinical decisions. However, radiology is also well suited to enhance medical education by offering the ability to visualize physiology in action. This is especially true in skeletal radiology, where radiographic osseous changes represent a wide range of physiological processes. Therefore, skeletal radiology can be a useful tool for illustrating concepts of physiology that underlie the normal and abnormal radiologic appearances of bone. Conclusion Radiology is an important but underutilized tool for demonstrating concepts in bone physiology.
Tunable Optical Transparency in Self-Assembled Three-Dimensional Polyhedral Graphene Oxide

The origami-like self-folding process is an intellectually stimulating technique for realizing three-dimensional (3D) polyhedral free-standing graphene oxide (GO) structures. This technique allows for easy control of size, shape, and thickness of GO membranes, which in turn permits fabrication of free-standing 3D microscale polyhedral GO structures. Unlike 2D GO sheets, the 3D polyhedral free-standing GO shows a distinct optical switching behavior, resulting from a combination of the geometrical effect of the 3D hollow structure and the water-permeable multilayered GO membrane that affects the optical paths.
APS Takes a Look in the Mirror

Every so often, individuals and organizations should spend time in self-reflection and analyze what is working and what is not, what the challenges, are and how these can be turned into new opportunities. Last fall, the American Physiological Society (APS) took just such an initiative. APS employed
Respiratory Transport of Carbon Dioxide

As you read about the transport of CO2 in this and the remaining chapters, keep in mind the multiple functions of the respiratory system. Ventilation and circulation must maintain the removal of CO2, the major end product of cellular metabolism, at a rate equal to its production. Simultaneously, the PCO2 of the extracellular fluid compartments must be carefully regulated because of its importance to acid-base status. These two functions are obligately linked by their substrate and this linkage occasionally leads to a conflict between them. To understand this interaction, one must grasp the multiple relationships of CO2 with its chemical partners.
Durable response in a thymic neuroendocrine tumor: A case report and review of the literature

Thymic neuroendocrine tumors are rare, representing less than 5% of all thymic cancers, and are biologically distinct in histology and behavior. Conclusive treatment guidelines are limited due to a lack of randomized clinical trials. Current literature, consisting mainly of case reports and series, suggests that complete surgical resection combined with adjuvant radiation therapy offers the greatest survival benefit for patients with thymic neuroendocrine tumors (NET). Adjuvant chemotherapy may also delay the onset of distant metastasis. Prognosis is generally poor, particularly in high-grade tumors, as these patients are prone to early metastasis. Here we present the case of a 62-year-old woman who achieved a durable response after undergoing an aggressive multimodal treatment approach for a primary thymic NET that initially presented as chronic cough and mild dyspnea on exertion.
Role of ApoE‐ε4 Genotype in Gait and Balance in Older Adults: A Pilot Study

Falls are common and costly in older adults. Risk factors include deficits in gait and postural control, both of which are linked to cognitive impairments. These cognitive impairments may be attributed to a genetic predisposition. A previous study found that a genetic risk factor related to Alzheimer's disease (the ApoE-e4 genetic variant) is also related to gait speed decline in older adults. No research has attempted to assess the impact of this variant on postural control in older adults. The purpose of this pilot study was to replicate the gait findings and extend these to measures of balance in older adults. Forty-six older adults, without a history of neurological disorder, were genotyped and had their gait and postural control assessed. Surprisingly, analyses showed lowered double-stance time for carriers than noncarriers of the e4 isoform. However, no significant differences were observed between carriers and noncarriers for any other comparisons, including postural control scores. Results suggest that the e4 isoform may affect gait, but not postural control.
Concavity of entropy power: Equivalent formulations and generalizations

We show that Costa's entropy power inequality, when appropriately formulated, can be precisely generalized to non-Gaussian additive perturbations. This reveals fundamental links between the Gaussian logarithmic Sobolev inequality and the convolution inequalities for entropy and Fisher information. Various consequences including a reverse entropy power inequality and information-theoretic central limit theorems are also established.
Central nervous system actions of somatostatin-related peptides.

Somatostatin-related peptides act within the central nervous system to influence adrenomedullary epinephrine secretion and thermoregulation. Cysteamine-induced depletion of brain somatostatinrelated peptides or central administration of a somatostatin receptor antagonist alters adrenomedullary epinephrine secretion and thermoregulation in a predictable manner. The actions of cysteamine and the somatostatin receptor antagonist are reversed by administration of somatostatins into the central nervous system, supporting the hypothesis that endogenous brain somatostatin-related peptides are involved in the regulation of adrenomedullary epinephrine secretion and thermoregulation.
Humoral Immunity in Comprehensive Immunology

Humoral immunity generally is regarded as that part of the immunological defense system which is mediated by the immunoglobulins. Although full humoral immunocompetence depends also on the biological amplification system, the complement proteins, the immunoglobulins are the primary mediators of humoral defense. The immunoglobulins are a widely heterogeneous range of chemically related glycoprotein macromolecules which normally possess antibody activity, i.e., the ability to combine specifically with an antigen. The classes of molecules differ from each other in specific structure, biological activities, and distribution in blood and tissue fluids, but all are products of activated lymphocytes or plasma cells, and all have certain common general structural features. The first part of this chapter presents the chemical similarities and differences of the classes of immunoglobulin molecules and discusses the biological role each is known to play in the humoral immune response. After this, the subjects of B-cell activation and immunoglobulin synthesis and immunoglobulin evolution are considered.
MK-STYX Alters the Morphology of Primary Neurons, and Outgrowths in MK-STYX Overexpressing PC-12 Cells Develop a Neuronal Phenotype.

We previously reported that the pseudophosphatase MK-STYX (mitogen activated kinase phosphoserine/threonine/tyrosine binding protein) dramatically increases the number of what appeared to be primary neurites in rat pheochromocytoma (PC-12) cells; however, the question remained whether these MK-STYX-induced outgrowths were bona fide neurites, and formed synapses. Here, we report that microtubules and microfilaments, components of the cytoskeleton that are involved in the formation of neurites, are present in MK-STYX-induced outgrowths. In addition, in response to nerve growth factor (NGF), MK-STYX-expressing cells produced more growth cones than non-MK-STYX-expressing cells, further supporting a model in which MK-STYX has a role in actin signaling. Furthermore, immunoblot analysis demonstrates that MK-STYX modulates actin expression. Transmission electron microscopy confirmed that MK-STYX-induced neurites form synapses. To determine whether these MK-STYX-induced neurites have pre-synaptic or post-synaptic properties, we used classical markers for axons and dendrites, Tau-1 and MAP2 (microtubule associated protein 2), respectively. MK-STYX induced neurites were dopaminergic and expression of both Tau-1 and MAP2 suggests that they have both axonal and dendritic properties. Further studies in rat hippocampal primary neurons demonstrated that MK-STYX altered their morphology. A significant number of primary neurons in the presence of MK-STYX had more than the normal number of primary neurites. Our data illustrate the novel findings that MK-STYX induces outgrowths in PC-12 cells that fit the criteria for neurites, have a greater number of growth cones, form synapses, and have pre-synaptic and post-synaptic properties. It also highlights that the pseudophosphatase MK-STYX significantly alters the morphology of primary neurons. Key Findings 1. MK-STYX significantly increases the number of primary neurites in PC-12 cells. 2. MK-STYX-induced neurites exhibit growth cones and small actin protrusions. 3. MK-STYX modulates actin expression. 4. MK-STYX induced neurites form synapses. 5. MK-STYX-induced neurites form pre-synaptic and post-synaptic processes. 6. MK-STYX alters the morphology of hippocampal primary neurons. 7. MK-STYX increases the number of neurites in primary hippocampal neurons.
Heparin-Like Anticoagulant Associated with Plasma Cell Myeloma

A 54-year-old man with plasma cell myeloma had sustained bleeding develop after prophylactic hip hemiarthroplasty. Routine coagulation studies revealed significant prolongation of the prothrombin time, activated partial thromboplastin time, and thrombin time. Further evaluation showed failure of the activated partial thromboplastin time to correct in a 1:1 mixture with pooled normal plasma, correction of the prolonged thrombin time by addition of protamine, and a normal reptilase time. A purified preparation of the immunoglobulin component of patient plasma produced the same pattern of coagulation abnormalities, suggesting the paraprotein possessed heparin-like anticoagulant activity. This appears to be a rare mechanism of bleeding diathesis in plasma cell myeloma.
Hepatic gene therapy

Recent developments in the understanding of molecular genetics have made possible advances in the treatment of various human disorders with gene therapy. These new techniques are not only of theoretical interest; human trials with gene therapy are well under way, and, although many obstacles remain, the initial results are encouraging.
An epidural steroid injection in the 6 months preceding a lumbar decompression without fusion predisposes patients to post-operative infections.

Background: To determine if the timing of a lumbar epidural steroid injection (LESI) effects rates of post-operative infection in patients receiving a non-fusion lumbar decompression (LDC) due to degenerative disc disease (DDD). Lumbar pain due to DDD can frequently be temporized or definitively treated with epidural injections. While there is ample literature regarding the infection risks associated with corticosteroid injections prior to hip/knee replacements, there are few studies relating to the spine. Methods: A nationwide insurance database was queried to identify those who underwent LDC for DDD without instrumentation [2005–2014]. Lumbar fusion procedures were excluded. From this group those with a history of a LESI were identified and matched to a control group without a history of LESI. Four separate cohorts were examined: (I) LDC and no LESI within 6 months (control); (II) LDC performed within 0–1 month after LESI; (III) LDC between 1 and 3 months after LESI; (IV) LDC performed between 3 and 6 months after LESI. Results: There was an increased odds of a 90-day postoperative infection if the LESI was within the 1–3 months (OR =4.69; P Conclusions: While LESI is helpful for possibly delaying or avoid lumbar surgery, it may predispose patients to higher infection rates following lumbar decompressions without fusion. Surgeons and pain management specialist should counsel patients on these risks and
Abstract WMP106: Clinical Benefit of Thrombolytic Removal of Intraventricular Hemorrhage: Number Needed to Treat in the CLEAR 3 Trial

Introduction: The CLEAR III trial found that removal of intraventricular hemorrhage was not associated with a dichotomized improvement in 6-month outcome measured by the modified Rankin Scale score...
Validation of the JEN frailty index in the National Long-Term Care Survey community population: identifying functionally impaired older adults from claims data

Use of a claims-based index to identify persons with physical function impairment and at risk for long-term institutionalization would facilitate population health and comparative effectiveness research. The JEN Frailty Index [JFI] is comprised of diagnosis domains representing impairments and multimorbid clusters with high long-term institutionalization [LTI] risk. We test the index’s discrimination of activities-of-daily-living [ADL] dependency and 1-year LTI and mortality in a nationally representative sample of over 12,000 Medicare beneficiaries, and compare long-term community survival stratified by ADL and JFI. 2004 U.S. National Long-Term Care Survey data were linked to Medicare, Minimum Data Set, Veterans Health Administration files and vital statistics. ADL dependencies, JFI score, age and sex were measured at baseline survey. ADL and JFI groups were cross-tabulated generating likelihood ratios and classification statistics. Logistic regression compared discrimination (areas under receiver operating characteristic curves), multivariable calibration and accuracy of the JFI and, separately, ADLs, in predicting 1-year outcomes. Hall-Wellner bands facilitated contrasts of JFI- and ADL-stratified 5-year community survival. Likelihood ratios rose evenly across JFI risk categories. Areas under the curves of functional dependency at ≥3 and ≥ 2 for JFI, age and sex models were 0.807 [95% c.i.: 0.795, 0.819] and 0.812 [0.801, 0.822], respectively. The area under the LTI curve for JFI and age (0.781 [0.747, 0.815]) discriminated less well than the ADL-based model (0.829 [0.799, 0.860]). Community survival separated by JFI strata was comparable to ADL strata. The JEN Frailty Index with demographic covariates is a valid claims-based measure of concurrent activities-of-daily-living impairments and future long-term institutionalization risk in older populations lacking functional information.
Scoping Archaeological Projects in Relation to Specific Regulations

This chapter discusses how archeologists decide the appropriate scope for projects – where and how archeologists are able to be creative, and when (if ever) they find a more “standard” approach is better suited to the task at hand. Drawing on their personal experience of undertaking archeological fieldwork across the USA in a variety of professional contexts, the authors consider what constraints they have faced when determining the scope of a project, and also what happens when archeologists make unexpected discoveries in the course of their work. The authors also discuss what latitude each has in changing projects while underway in order to best do the job that needs to be done. Perry discusses this in particular relation to his work for the US Army Corps of Engineers (USACE); Stottman in particular relation to his work for the Kentucky Archaeological Survey (KAS).
The domestic resonance of geopolitical competition in American foreign policy: the rise of China and post-war US–Soviet relations compared

For the first time since the end of the Cold War, the USA faces a geopolitical challenger in the shape of China. According to the National Security Strategy 2017 (NSS 2017), China—alongside Russia—poses a threat to America primacy, a view that reflects a new consensus among national security experts about the need to get tough in relations with Beijing. As of now, however, American public opinion remains ambivalent on the China challenge—opinion polls showing only a modest downturn in views of China recently, despite pronounced anti-China rhetoric in the context of the Trump administration’s trade war. The present paper asks why there is such a disparity between elite and popular opinions, and whether the disparity will last. It does so through a historical comparison between the present and the immediate post-WWII period, before a threat from the Soviet Union resonated widely among the American public. Acceptance of a Soviet threat was a product of a rhetoric of anti-communism used in partisan political debate. In turn, anti-communism drew on a conflation of “communism” meaning US-based labor groups and communism meaning the Soviet Union. By showing the immense effort needed to manufacture the resonance of geopolitical competition in the post-war years, the paper highlights the necessary domestic conditions of geopolitical competition, conditions currently absent.