cssi/SciSciGPT-SciSciNet huggingface dataset:
E-Selectin Gets HSCs Buzzing.

The bone marrow—the primary site of blood cell production—has a set hierarchy that can be compared with a beehive. Indeed, all circulating cells (the workers and the drones) are derived from a rare population called hematopoietic stem cells (HSCs), the queen bees. Indeed, under normal conditions most HSCs receive the royal treatment: resting while only a tiny fraction proliferates and differentiates into downstream progenitors. In times of higher demand—for instance, during inflammation or after blood loss—more HSCs proliferate. Yet, the mechanisms that determine which HSCs have to fulfill their proliferate duties are largely a mystery. What we do know is that as with all things, location is everything: There are niches specialized for resting HSCs, called quiescent niches, and others that harbor the minority of HSCs hard at work. These so-called vascular niches are located close to endothelial cells that line the bone marrow sinusoids. Winkler et al. have now made a beeline toward the mechanism that keeps HSCs proliferating. They discovered a new function for the cell adhesion molecule E-selectin, which is expressed by some bone marrow endothelial cells in certain microdomains close to the endosteum. Mice that lacked E-selectin had fewer proliferating HSCs, and adoptive transfer experiments determined that this function is HSC extrinsic; it can be assigned to the bone marrow microenvironment rather than to the stem cells themselves. HSCs that cycled less in E-selectin-deficient mice or in mice treated with a small-molecule inhibitor for E-selectin aged slower and were protected against toxic stressors, including radiation and chemotherapeutic drugs. Indeed, E-selectin inhibition improved mouse survival and recovery after radio and chemotherapy. E-selectin inhibitors are already in clinical trials for sickle cell disease, which may accelerate the translation of these data to the clinic. Treating patients with E-selectin inhibitors before radiation or chemotherapy may protect the quiescent cells from toxic side effects of cancer therapeutics. Moreover, treatment that induces HSC quiescence also reduces leukocyte production, and could therefore elicit anti-inflammatory effects by reducing the systemic supply of leukocytes. By exploring the hive mentality of the blood system and protecting the queens, Winkler et al. may have found a way to protect patients from the side effects of cancer therapy. I. G. Winkler et al. , Vascular niche E-selectin regulates hematopoietic stem cell dormancy, self renewal and chemoresistance. Nat. Med . , published online 21 October 2012 (10.1038/nm.2969). [[Abstract]][1] [1]: http://www.nature.com/doifinder/10.1038/nm.2969
The Grüneisen parameter γ of KBr, RbCl and Bi through high pressure phase transitions

Abstract High pressure values for the adiabatic pressure derivative of temperature ( ∂T ∂P ) s have been obtained by measuring the temperature change caused by a small rapid increase in pressure. Values for KBr and RbCl in phases B1 and B2 and for Bi in phases I, II and III are given for T = 295 K. The Gruneisen parameter γ is given by γ = B s ( ∂T ∂P ) s T where Bs is the adiabatic bulk modulus. Ultrasonic and statk compressibility data are used to estimate the pressure and phase dependence of Bs. Dramatic increases in both γ and (∂T/∂P)s are observed as the pressure increases through a phase transition. Values for the logarithmic derivate q ≡ (∂ ln γ ∂ ln V T are given.
"i read my Twitter the next morning and was astonished": a conversational perspective on Twitter regrets

We present the results of an online survey of 1,221 Twitter users, comparing messages individuals regretted either saying during in-person conversations or posting on Twitter. Participants generally reported similar types of regrets in person and on Twitter. In particular, they often regretted messages that were critical of others. However, regretted messages that were cathartic/expressive or revealed too much information were reported at a higher rate for Twitter. Regretted messages on Twitter also reached broader audiences. In addition, we found that participants who posted on Twitter became aware of, and tried to repair, regret more slowly than those reporting in-person regrets. From this comparison of Twitter and in-person regrets, we provide preliminary ideas for tools to help Twitter users avoid and cope with regret.
Biologic Rhythms in the Immune System

In all of its components, the immune system shows regularly recurring, rhythmic variations in numerous frequencies; the circadian (about 24 h) rhythms are the best explored. The circadian variations in immunocompetent cells circulating in the peripheral blood are of a magnitude to require attention in medical diagnostics. Both the humoral arm and the delayed (cellular) arm of the immune system function in a rhythmic manner. The response of the immune system to introduction of an antigen and to challenge of the sensitized organism varies in extent in the circadian frequency range and also in lower frequencies, for example, of about a week (circaseptan) or seasonally (circannual). The medical application of the biologic rhythms of the immune system extends to diagnostic measures, as well as treatment.
America and the World: Isolationism Resurgent?

Building on an earlier argument that isolationism may well be America's natural state, Schlesinger explains how the apparent rejection of isolationism during the long standoff with the Soviet Union during the Cold War was nothing more than a reaction to what was perceived as a direct and urgent threat to the security of the United States. In the wake of the Cold War's end, the incompatibility between collective international action and conceptions of national interest has highlighted the difficulties of democracies in sending their armies to war, especially those that do not directly threaten national security. While much more can and should be done to enhance the effectiveness of global organizations already in place, what is needed, Schlesinger argues, is both a reexamination of the Wilsonian doctrine of collective security and a greater concentration on preventive diplomacy.
Late Holocene variations in Pacific surface circulation and biogeochemistry inferred from proteinaceous deep-sea corals

δ 15 N and δ 13 C data obtained from samples of proteinaceous deep-sea corals collected from the North Pacific Subtropical Gyre (Hawaiian Archipelago) and the central equatorial Pacific (Line Islands) document multidecadal to century-scale variability in the isotopic composition of surface-produced particulate organic matter exported to the deep sea. Comparison of the δ 13 C data, where Line Islands samples are 0.6‰ more positive than the Hawaiian samples, supports the contention that the North Pacific Subtropical Gyre is more efficient than the tropical upwelling system at trapping and/or recycling nutrients within the mixed layer. δ 15 N values from the Line Islands samples are also more positive than those from the central gyre, and within the Hawaiian samples there is a gradient with more positive δ 15 N values in samples from the main Hawaiian Islands versus the French Frigate Shoals in the Northwestern Hawaiian Islands. The gradient in the Hawaiian samples likely reflects the relative importance of algal acquisition of metabolic N via dissolved seawater nitrate uptake versus nitrogen fixation. The Hawaiian sample set also exhibits a strong decrease in δ 15 N values from the mid-Holocene to present. We hypothesize that this decrease is most likely the result of decreasing trade winds, and possibly a commensurate decrease in entrainment of more positive δ 15 N-NO 3 subthermocline water masses.
Interactive bootstrapped learning for end-user programming

End-user programming raises the possibility that the people who know best what a software system should do will be able to customize, remedy original programming defects and adapt systems as requirements change. As computing increasingly enters the home and workplace, the need for such tools is high, but state of practice approaches offer very limited capability. We describe the Interactive Bootstrapped Learning (iBL) system which allows users to modify code by interactive teaching similar to human instruction. It builds on an earlier system focused on exploring how machine learning can be used to compensate for limited instructional content. iBL provides an end-to-end solution in which user-iBL dialog gradually refines a hypothesis about what transformation to a target code base will best achieve user intent. The approach integrates elements of many AI technologies including machine learning, dialog management, AI planning and automated model construction.
Regulatory Takings in the Wetland Context

Federal regulation of wetlands begins with the U.S. Constitution. To justify the assertion of authority over privately owned wetlands, Congress must rely on an affirmative grant of authority enumerated in the Constitution. As we have seen, the Interstate Commerce Clause provides Congress (and thus the Corps and the EPA) the principal gateway to wetland regulation. The Constitution, however, also supplies a check on this federal authority through the Fifth Amendment’s prohibition on the governmental “taking” of private property without the payment of just compensation.
FPGA-Accelerated Molecular Dynamics

Molecular dynamics simulation (MD) is one of the most important applications in computational science and engineering. Despite its widespread use, there exists a many order-of-magnitude gap between the demand and the performance currently achieved. Acceleration of MD has therefore received much attention. In this chapter, we discuss the progress made in accelerating MD using Field-Programmable Gate Arrays (FPGAs). We first introduce the algorithms and computational methods used in MD and describe the general issues in accelerating MD. In the core of this chapter, we show how to design an efficient force computation pipeline for the range-limited force computation, the most time-consuming part of MD and the most mature topic in FPGA acceleration of MD. We discuss computational techniques and simulation quality and present efficient filtering and mapping schemes. We also discuss overall design, host–accelerator interaction and other board-level issues. We conclude with future challenges and the potential of production FPGA-accelerated MD.
Las novelas morales de Juan Piña Izquierdo

Los criticos "que se han ocupado de la novela colonial mexicana citan unas Novelas morales (1624) de Juan de Pina Izquierdo como uno de los pocos libros de ficcion novohispana del siglo XVII. Se nos dice que Pina vivio en Puebla y que publico ese libro en Madrid. La noticia originalmente viene de Jose Mariano Beristain de Souza, quien en el articulo dedicado a "Izquierdo Pina (D. Juan)" dice: "Natural de Buendia en Castilla. Ejercio en Madrid el oficio de notario de la santa inquisicion; y habiendopasado a la N.E. se avecindo en la ciudad de la Puebla donde fue notario apostolico y escribano real.
Prediction of Patient Activation during Technology Enabled Continuity of Care Intervention

Patients’ skills, knowledge, and motivation to actively engage in their healthcare are assessed with the Patient Activation Measure (PAM) – a metric associated with positive healthcare outcomes. The literature on predicting PAM, when patient counseling is coupled with a telemonitoring intervention, is scant. This proof-of-concept study employs a two-phase framework to (i) posit a causal relationship between a telemonitoring intervention and enhanced patient activation; and (ii) link healthcare providers’ operating decisions and patients’ willingness to change with prediction of PAM. We test the framework using data from a randomized, controlled field experiment and find a causal relationship between telemonitoring and increased PAM. Based on this causal result the PAM levels are predicted as a function of the strength of the information signals using a machine learning methodology. We show that these predictions are subject to under-over-estimation biases, consistent with the behavioral concept of system neglect in signal detection theory.
Integrating Hands-On Design Education and Faculty Research at Washington University

It is generally accepted that hands-on design/build/fly projects are effective tools for training students to be engineers. However, such “real” design classes require significant resources and impose the cost, schedule and complexity challenges common to “real” programs, especially given the constraints of an academic calendar and the limited skill set of the students; instructors are hard-pressed to create design problems that are relevant as well as tractable. Hands-on projects pursued outside of the classroom, such as clubs or contests, tend to attract enthusiastic students from a spectrum of backgrounds but struggle to both train younger students and retain them after the first two years. In either setting, students often ignore good engineering practice until they are “burned” by their own mistakes. If experience is truly the only way for students to accept good practice, then instructors must find ways for them to be “burned” without significantly affecting cost or schedule. This paper presents one approach to solve these three problems through Project Aria, a combined education and research initiative at the School of Engineering and Applied Science at Washington University in St. Louis. Project Aria uses hands-on design projects as teaching and research tools; these projects are intentionally scoped for the student environment, yet they are viable research activities. The history of Project Aria will be reviewed with case studies of several successful and less-than-successful activities. The majority of the paper concerns the Akoya spacecraft project, part of the University Nanosat3 program administered by the Air Force Research Laboratory.
Determining the Thermal Conductivity of W/B4C Multilayer Structures Using Photothermal Deflection Spectroscopy

The thermal conductivities of W/B4C multilayer thin film structures have been determined using a photothermal deflection spectroscopy technique in conjunction with a model-based parameter estimation algorithm. The four samples studied share an overall multilayer thickness of 0.45 μm, while the total number of periods was varied from 75 – 300. The ensemble average thermal conductivity of the samples was found to be 0.97 W/m-K in the cross-plane direction; significantly less than the bulk values of the constituent materials. This difference is believed to be the combined result of confinement effects of electron and phonon energy carriers and the cumulative thermal contact resistance experienced at layer interfaces.
Optimization of carbon dioxide-assisted nanoparticle deposition process with uncertain design space

A sequential design of experiments methodology with adaptive design space has been applied to optimize a nanoparticle deposition process using elevated pressure, elevated temperature carbon dioxide. This methodology is termed Layers of Experiments (LoE) with Adaptive Combined Design (ACD). Optimizing the CO2-assisted nanoparticle deposition system presents significant challenges: uncertainty in the design region, uncertainty in model structure, a lack of information regarding the process from mechanistic considerations and/or empirical studies, significant costs related to materials processing and characterization, and an engineering tolerance requirement on the characteristics of the products. The contribution of the LoE/ACD methodology presented here is that it systematically finds the optimum of a process while robustly managing the aforementioned challenges.
Analysis on epidemiological characteristics of epidemic hemorrhagic fever in Fuzhou City from 2007-2011

[Objective]To analyze the epidemiological characteristics and law of epidemic hemorrhagic fever in Fuzhou City from 2007-2011,provide scientific reference for making the prevention and control measures.[Methods]Using descriptive epidemiological method,the epidemic data of epidemic hemorrhagic fever in Fuzhou City from 2007-2011 were analyzed.[Results]A total of 163 cases of epidemic hemorrhagic fever were reported in Fuzhou City from 2007-2011,the average annual incidence rate was 0.51/lakh,and there was no death case.The peak seasons were March to June and November to next January.The incidence rate in urban area was higher than that in rural area,and the incidence rate in males was higher than that in females.The occupational distribution mainly included housework,unemployed and farmers,which accounted for 38.7%.Most of patients were people aged 20-60 years old,and 115 cases were in 30-35 year-old age group,which accounted for 70.6% of total cases.[Conclusion]The incidence rate of epidemic hemorrhagic fever in Fuzhou City shows a rising tendency in the recent years.It is necessary to carry out the comprehensive prevention and control measures(including deratization and vaccination) combined to the activities of building an advanced clean and civilized city.
Endothelin in the Urinary Bladder. I. Synthesis of Endothelin-1 by Epithelia, Smooth Muscle and Fibroblasts Suggests Autocrine and Paracrine Cellular Regulation

Abstract The synthesis and localization of endothelin-1 were studied in human and rabbit bladder. In addition, the effects of endothelin-1 on smooth muscle tone and cholinergic neurotransmission were investigated in rabbit bladder. Endothelin-like immunoreactivity was localized in the transitional epithelium, serosal mesothelium, and vascular endothelium; smooth muscle of the bladder (non-vascular) and that of blood vessels; and fibroblasts. With in situ hybridization, transcripts of endothelin messenger ribonucleic acid (mRNA) were localized with the same cellular distribution as endothelin-like immunoreactivity, in bladder tissue. Northern blot analysis of bladder RNA confirmed the expression of preproendothelin-1 mRNA. Rabbit bladder strips in organ chambers contracted when exposed to endothelin-1 and this response was partially attenuated by calcium channel blockers or by removal of extracellular calcium. Transmural electrical stimulation of rabbit bladder strips elicited contractions that were greatly reduced by atropine. The remaining atropine resistant component was blocked by α,β-methylene ATP, which desensitizes purinergic receptors. Endothelin-1 caused a small but consistent attenuation of the atropine sensitive component of the neurogenic contraction, while it had no effect on the atropine resistant component. The localization of endothelin synthesis in epithelia, smooth muscle, and fibroblasts suggests that endothelin may act as an autocrine hormone in the regulation of the bladder wall structure and smooth muscle tone. In addition, endothelin-1 may regulate cholinergic neurotransmission by a paracrine mechanism.
Conclusion: “Plenty of Room at the Bottom” for Computational Methods

Google returns over 400,000 references to R. Feynman’s talk “There’s Plenty of Room at the Bottom” [Fey59]. This talk, given on December 29, 1959, at the annual meeting of the American Physical Society, presaged the development of nanoscale science and technology.
Capillarity and Water Potential

Surface tension is a characteristic of a liquid-gas interface. It may be attributed to an imbalance of intermolecular forces of attraction (van der Waals’ forces) as illustrated in Fig. 4.1. Within the body of the liquid the intermolecular forces are essentially in balance while, on the surface, there is no upward component. Therefore, there is a net downward force, normal to the surface, and the surface is apparently in tension. If a line is visualized along the surface of a liquid, the forces on one side are balanced by those on the other and the surface tension at the interface is equal to the magnitude of the total force along one side of the line divided by the length. Surface tension is then expressed as force per unit length.
Performance of a pilot-scale multitube membrane module under coal-derived syngas for hydrogen production and separation

Abstract Pilot-scale tests generate information about the performance of energy systems and thus help in the deployment of new technologies. This work aims at demonstrating the pilot-scale application of palladium-based membrane technology for the purification of H 2 . A multitube membrane module with a total permeable area of 1050 cm 2 was tested under actual coal-derived syngas. The module was composed of seven membranes with a Pd/Au/Pd layered structure supported on PSS tubes. The membranes were arranged with one membrane at the center and six equally distributed around it. The membranes had a composition of 7 µm Pd and 0.4 µm Au and a cumulative He leak of 3 /min/bar before testing. The module was operated at 450 °C, 12.6 bar and 10 lb/h of desulfurized syngas provided by a gasification unit and enriched with H 2 to 34%. The module showed a stable H 2 permeance of 16.2 Nm 3 m −2 h −1 bar −0.5 throughout 840 h. The produced H 2 purity was in the range of 99.87–98%. An H 2 production of 6 lb/day and recovery of 64% were achieved, representing a significant development in the field. The scalability and industrial applicability of this technology was successfully demonstrated. Furthermore, a CFD model illustrated different physical phenomena associated with this multitube configuration.
Surface Microenvironment and Penetration of Bacteria into Meat1

Surface contamination in the form of discrete colony-forming units is the main source of bacteria associated with meat spoilage. The fate of these bacteria is determined by the microenvironment at the meat-atmosphere interface, where the constraints determine the nature of a developing microflora. Nutrients, water availability and nutrient diffusion are prominent factors influencing microbial activity. While surface growth is most commonly recognized through enumeration studies based on removal of microorganisms, the less-studied phenomenon of movement of bacteria may be of considerable significance. In model systems, Serratia marcescens moves rapidly in intact meat as well as in compacted comminuted meat. The invasion process may depend on specific enzymes rather than the general class of collagenases. Need for more knowledge about factors that control surface microenvironment of meat is apparent.
Effects of PGC-1α Overexpression on Glucocorticoid-induced Atrophy Signaling in C2C12 Muscle Cells

Muscle wasting (atrophy) is a debilitating consequence of many catabolic conditions and has been linked to decreased expression of the transcriptional coactivator PGC-1α. In some models of atrophy,...
Maintenance Belatacept-Based Immunosuppression in Lung Transplantation Recipients Who Failed Calcineurin Inhibitors.

BackgroundTraditional immunosuppressive regimens (ISR) used in lung transplantation rely on calcineurin inhibitors (CNI) that occasionally cause severe adverse reactions necessitating discontinuation. Belatacept is a novel costimulation antagonist approved for use in renal transplantation which lack
A dual-axis MEMS vibratory gyroscope ASIC with 0.0061°/s/VHz noise floor over 480 Hz bandwidth

This paper presents a high performance dual-axis (pitch and roll) MEMS vibratory gyroscope readout ASIC which converts angular rate information to digital output. Two signal processing chains surrounding the MEMS sensor are implemented, namely the drive channel and the sense channel. The drive channel drives the sensor to resonate at its resonant frequency, which produces a velocity of the sensor disc to generate the Coriolis force during angular rotation. The sense channel employs a low noise trans-impedance amplifier (TIA) followed by a demodulator which down-converts the angular rate input signal from the resonant frequency to baseband. Two switched-capacitor (SC) 2-1 MASH delta-sigma ADCs convert the input angular rate from the pitch and roll arises to digital output. The reference of the ADC is also demodulated from the sensor output to cancel out supply voltage dependence. The whole ASIC including the high-voltage MEMS sensor driver, digital-filter, on-chip regulator and temperature sensor is fabricated in a 0.18pm CMOS technology with an area of 7.3 mm2. The design achieves a noise floor of 0.0032°/s/VHz and 0.0061°/s/VHz in full-scale input ranges of 500°/s and 2000°/s, respectively, over a 480Hz signal bandwidth. The bias instability is measured as 2.5°/h at input range of 500°/s. The whole ASIC consumes 7mA from a 3V supply.
Stability and Antioxidant Activity of Annatto (Bixa orellana L.) Tocotrienols During Frying and in Fried Tortilla Chips

Annatto tocotrienols (AnT3), which contain approximately 90% d-tocotrienol (d-T3), were added to mid-oleic sunflower oil used for frying tortilla chips over 3 d. The objectives were to evaluate their stability during frying, absorption by the fried food, and activity as antioxidants in frying oil and in tortilla chips during storage. AnT3 did not significantly affect the stability of the oil during frying or the sensory profiles of freshly fried chips. The naturally present a-tocopherol (a-T) in the oil degraded at a lower rate in the presence of AnT3, resulting in significantly higher a-T by the end of the frying study. Levels of tocopherols and tocotrienols in the chips mirrored oil levels. AnT3 did not affect the sensory profile of the chips after 1 wk of storage at 50 °C, but after 3 wk of storage, the control chips had higher levels of painty and rancid flavors compared to chips with AnT3. Headspace hexanal was also significantly higher in the control chips compared to the chips with AnT3 after 3 wk of storage. Annatto tocotrienols, containing primarily delta- and gamma-tocotrienols, were added to mid-oleic sunflower oil used for frying tortilla chips. The tocotrienols were absorbed by the chips along with the oil. They slowed the degradation of a tocopherol during frying, and reduced levels of painty and rancid flavor scores as well as headspace hexanal in chips that were stored for 3 wk at elevated temperatures. The results indicated that fried snack foods such as tortilla chips may be a suitable and convenient vehicle for enriching tocotrienols in the diet, and that tocotrienols may also enhance the shelf-life of fried foods.
Development of Improved Feeding Methods in the Culture of Yellow Tang, Zebrasoma flavescens

Yellow tang, Zebrasoma flavescens, are one of the most heavily traded marine aquarium fish species, with nearly 400,000 individuals collected annually from Hawaii's reefs. Despite recent success culturing this species, significant challenges in the rearing processes remain to be overcome before commercialization is feasible. This study compared two feeding regimens, an original diet treatment, which was initially used to successfully culture yellow tang, and a revised diet, which differed in the timing of the introduction of feed items and weaning periods. Both diet regimens consisted of Parvocalanus crassirostris nauplii, enriched Brachionus rotundiformis rotifers, and Artemia nauplii, followed by a transition to dry and frozen feed items. The revised feeding regimen aimed to considerably reduce the amount of copepods and rotifers needed in the rearing process. Eggs were stocked at 40/L into replicate (n = 3) 200‐L tanks for the feeding regimen trial. A follow‐up rearing study, in which eggs were stocked at 19/L in a single 1000‐L tank, tested the revised feeding method at pilot scale. Fish reared on the revised feeding regimen were observed to grow faster in body length and body depth after 2 wk in culture and transitioned more quickly to juveniles as 41% had completed their transition to juvenile coloration by 70 d after hatch. None of the fish reared under the original feeding regimen attained full juvenile coloration during the study period. Survival was not significantly different between treatments and was 0.13% ± 0.13 and 0.29% ± 0.17 in the original and revised feeding regimens, respectively. In the pilot‐scale study, growth was comparable to that of both treatments in the 200‐L scale trial, but survival was much better at 1.9%. This study successfully shortened the copepod and rotifer feeding periods for yellow tang, while not jeopardizing growth or survival. This outcome enhances the commercialization potential for this and likely other Acanthuridae species.
Normative Nominalism: The Paradox of Egalitarian Law in Inegalitarian Cultures - Some Lessons from Recent Latin American Historiography

This essay is a contribution to the discussion of the conflict that often exists between legal norms and legal practice in Latin America. It examines the conflict between equality under the law as a legal and constitutional norm in Latin America and the persistence of strong inequality as a social reality in Latin America. The essay examines this tension through a look at recent Latin American legal historiography. Essays include issues of race, class and the law in the nineteenth century Brazilian Empire, race and the law in early 20th century Cuba and Brazilian labor law in the middle and latter part of the 20th century.
Human Mononuclear Phagocyte Nitric Oxide Production and Inducible Nitric Oxide Synthase Expression

Despite lingering controversy,it is evident from a detailed review of the literature that human mononuclear phagocytes can be stimulated by various means both in vitro and in vivo to express NOS2 and produce NO.It is difficult to quantitatively compare levels of NO production and NOS2 expression by human and murine mononuclear phagocytes.However,based on several studies in which both murine and human cells have been examined in parallel under identical conditions,human cells appear to produce less NO and express lower levels of NOS2 than do murine cells.This might help to explain the innate resistance of mice to certain human pathogens (e.g.,Mycobacterium tuberculosis).Despite the apparent species differences,it is very likely that human mononuclear phagocyte-generated NO is important in certain pathological states (e.g.,in resistance to infection and mediation of inflammation),and possibly under normal physiological conditions as well.Pharmacological modulation of mononuclear phagocyte NO production should prove to be a useful therapeutic option in some disease states.
The Role of Nucleic Acid Sensing in Controlling Microbial and Autoimmune Disorders

Innate immunity, the first line of defense against invading pathogens, is an ancient form of host defense found in all animals, from sponges to humans. During infection, innate immune receptors recognize conserved molecular patterns, such as microbial surface molecules, metabolites produces during infection, or nucleic acids of the microbe's genome. When initiated, the innate immune response activates a host defense program that leads to the synthesis proteins capable of pathogen killing. In mammals, the induction of cytokines during the innate immune response leads to the recruitment of professional immune cells to the site of infection, leading to an adaptive immune response. While a fully functional innate immune response is crucial for a proper host response and curbing microbial infection, if the innate immune response is dysfunctional and is activated in the absence of infection, autoinflammation and autoimmune disorders can develop. Therefore, it follows that the innate immune response must be tightly controlled to avoid an autoimmune response from host-derived molecules, yet still unencumbered to respond to infection. In this review, we will focus on the innate immune response activated from cytosolic nucleic acids, derived from the microbe or host itself. We will depict how viruses and bacteria activate these nucleic acid sensing pathways and their mechanisms to inhibit the pathways. We will also describe the autoinflammatory and autoimmune disorders that develop when these pathways are hyperactive. Finally, we will discuss gaps in knowledge with regard to innate immune response failure and identify where further research is needed.
Surface functionalization of silica nanoparticles to enhance aging resistance of asphalt binder

Abstract Oxidation aging of asphalt pavement is among most prevalent factors causing pavement distresses. Introduction of silica nanoparticles (SNPs) has been found promising to reduce oxidation aging of asphalt binder. However, the effectiveness of SNPs is limited by their poor dispersion caused mainly by SNP agglomeration requiring significant mechanical energy in processing to ensure dispersion. This paper examined merits of surface functionalization of SNPs with (3-aminopropyl) triethoxysilane (APTES) to improve its dispersion in asphalt binder using conventional processing techniques at relatively high loading of SNPs with low mechanical energy input. The morphology, size, amount of amine functional groups of APTES surface-modified SNPs (APTES-SNPs) were characterized and optimized by scanning electron microscope (SEM), dynamic light scattering (DLS), Fourier-transform infrared spectroscopy (FTIR) and fluorescence measurement. The comparison between the surface-modified and pristine SNPs on the anti-aging and rheological properties of asphalt binder was conducted. The asphalt binders which contained APTES-SNPs demonstrated much better resistance to oxidative aging as evidenced by enhanced rheological properties compared to those containing pristine SNPs. The findings from this research provides insights as to the effect of APTES-SNPs on aging resistance of asphalt binder.
A new approach to ship repair using CONWIP and parts kits

The Constant Work in Process (CONWIP) system uses elements of push, pull, and parts kitting to reduce overall process times and minimize variability. The research presented in this paper introduces the CONWIP concept to ship repair through the completion of a discrete event simulation. The research demonstrates that a CONWIP approach to ship repair can improve drydock turnover for large classes of ships requiring similar repairs, such as the US Coast Guards Mission Effectiveness Project.
The isometric embedding problem for length metric spaces

We prove that every proper n-dimensional length metric space admits an “approximate isometric embedding” into Lorentzian space ℝ3n+6,1. By an “approximate isometric embedding” we mean an embedding ...
Geographic and demographic features of neuroendocrine tumors in the United States of America: A population‐based study

BACKGROUND The incidence of neuroendocrine tumors (NETs) is rapidly rising. There are very few studies investigating the role of sociodemographic factors in NETs. This study was aimed at examining how geographic and sociodemographic characteristics shape outcomes in the NET population. METHODS A retrospective analysis using the Surveillance, Epidemiology, and End Results database was performed, and the NET patient population from 1973 to 2015 was studied. Univariate and multivariable analyses were performed to evaluate patients' disease-specific survival (DSS) and overall survival (OS). Geographic and sociodemographic factors, including the location of residence (urban area [UA] vs rural area [RA]), sex, race, insurance status, and marital status, were included in the analysis. RESULTS A total of 53,034 patients (5517 in RAs and 47,517 in UAs) were included in the analysis. The incidence of NETs was found to be rising in both RAs and UAs but more rapidly in RAs (with the highest incidence in 2006-2015: 5.93 per 100,000 in RAs vs 4.10 per 100,000 in UAs). Patients from RAs presented at advanced stages in comparison with patients from UAs (regional, 18% vs 16%; distant, 15% vs 13%; P < .01). In the multivariable model, RA patients had a trend toward poorer OS (hazard ratio, 1.05; P = .053) in comparison with UA patients. The multivariable analysis showed significantly worse DSS and OS for uninsured, single, and male patients in comparison with insured, married, and female patients, respectively. CONCLUSIONS This study has identified sociodemographic disparities in NET outcomes. Access to health care could be a potential contributing factor, although differences in environmental exposure, health behavior, and tumor biology could also be responsible.
Senile Systemic Amyloidosis Presenting as Hematuria: A Rare Presentation and Review of Literature.

Introduction. Senile systemic amyloidosis is a multisystem disease where wild-type insoluble transthyretin (ATTRwt) protein gets deposited in the tissues leading to organ dysfunction. Methodology. We present the case of a patient who presented with hematuria and bladder involvement by ATTRwt amyloidosis who ultimately died of multiorgan failure. Results. The patient was an 82-year-old white male with a history of ischemic cardiomyopathy (ejection fraction (EF): 20–25%), chronic atrial fibrillation, chronic kidney disease (CKD), and carpal tunnel syndrome who presented with acute hematuria, urinary retention, and progressive fatigue. He underwent cystoscopy and bladder biopsy which was positive on congo-red stain diagnostic for amyloidosis. Echocardiogram demonstrated worsening of EF to 10–15% and concentric left ventricle hypertrophy. MRI was not performed due to underlying CKD. His condition deteriorated during the hospital stay, and he developed cardiogenic shock and progressive liver dysfunction. Infectious workup was negative. Meanwhile, the biochemical investigations (serum protein electrophoresis, immunofixation, and urine kappa/lambda chains) ruled out plasma cell dyscrasias. Mass spectrometry analysis of the bladder biopsy specimen confirmed wild-type transthyretin (ATTRwt) amyloidosis consistent with senile systemic amyloidosis. Due to patients’ extremely poor prognosis, his family wished to focus on patient’s comfort-oriented measures only, and patient passed away shortly thereafter. Conclusion. Senile systemic amyloidosis can rarely present in an atypical fashion such as hematuria. The treatment options are limited in this disease process. Novel therapies are in the early phases of development. Concern also exists that in patients with multiple comorbidities, this entity is under recognized until the more advanced stages.
The relationship of COVID-19 severity with cardiovascular disease and its traditional risk factors: A systematic review and meta-analysis

Abstract Background Whether cardiovascular disease (CVD) and its traditional risk factors predict severe coronavirus disease 2019 (COVID-19) is uncertain, in part, because of potential confounding by age and sex. Methods We performed a systematic review of studies that explored pre-existing CVD and its traditional risk factors as risk factors of severe COVID-19 (defined as death, acute respiratory distress syndrome, mechanical ventilation, or intensive care unit admission). We searched PubMed and Embase for papers in English with original data (≥10 cases of severe COVID-19). Using random-effects models, we pooled relative risk (RR) estimates and conducted meta-regression analyses. Results Of the 661 publications identified in our search, 25 papers met our inclusion criteria, with 76,638 COVID-19 patients including 11,766 severe cases. Older age was consistently associated with severe COVID-19 in all eight eligible studies, with RR >∼5 in >60-65 vs. Conclusions Despite the potential for confounding, these results suggest that hypertension, diabetes, and CVD are independently associated with severe COVID-19 and, together with age and male sex, can be used to inform objective decisions on COVID-19 testing, clinical management, and workforce planning.
Prospective evaluation of the impact of stress, anxiety, and depression on household income among young women with early breast cancer from the Young and Strong trial.

Young women with breast cancer tend to report lower quality of life and higher levels of stress than older women with breast cancer, and this may have implications for other psychosocial factors including finances. We sought to determine if stress, anxiety, and depression at diagnosis were associated with changes in household income over 12-months in young women with breast cancer in the United States. This study was a prospective, longitudinal cohort study comprised of women enrolled in the Young and Strong trial. Of the 467 women aged 18–45 newly diagnosed with early-stage breast cancer enrolled in the Young and Strong trial from 2012 to 2013, 356 (76%) answered income questions. Change in household income from baseline to 12 months was assessed and women were categorized as having lost, gained, maintained the same household income <$100,000, or maintained household income ≥$100,000. Patient-reported stress, anxiety, and depression were assessed close to diagnosis at trial enrollment. Adjusted multinomial logistic regression models were used to compare women who lost, gained, or maintained household income ≥$100,000 to women who maintained the same household income <$100,000. Although most women maintained household income ≥$100,000 (37.1%) or the same household income <$100,000 (32.3%), 15.4% lost household income and 15.2% gained household income. Stress, anxiety, and depression were not associated with gaining or losing household income compared to women maintaining household incomes <$100,000. Women with household incomes <$50,000 had a higher risk of losing household income compared to women with household incomes ≥$50,000. Women who maintained household incomes ≥$100,000 were less likely to report financial or insurance problems. Among women who lost household income, 56% reported financial problems and 20% reported insurance problems at 12 months. Baseline stress, anxiety, and depression were not associated with household income changes for young women with breast cancer. However, lower baseline household income was associated with losing household income. Some young survivors encounter financial and insurance problems in the first year after diagnosis, and further support for these women should be considered. Clinicaltrials.gov , NCT01647607 ; date registered: July 23, 2012.
Pre-Service Teachers' Collaborative Learning Experiences in a Science Content Course.

Developing an in-depth understanding, skills, and level of comfort to teach through inquiry requires that pre-service teachers themselves learn through an inquiry-based approach that would allow them to explore various dimensions of such an approach. Productive discourse and collaboration, involving extensive interactions among students, constant and mutual exchange of ideas, and higher-order thinking are critical components of inquiry-based learning. Further research is needed to understand the dynamics of collaborative experiences and the process by which science is learned in collaborative team contexts, particularly with teacher candidates who will be responsible for implementing such approaches in their future classrooms. This qualitative study aimed to explore the dynamics of inquiry-based learning experiences of two teams of elementary pre-service teachers in an introductory science content course. Analysis of observation data indicated that although the team engaged in a less structured activity engaged in slightly more productive communication, both teams experienced inequitable levels of involvement by different team members. Team members assumed different roles and varying degrees of participation and engagement in discourse. Our research indicated possible challenges of collaborative interaction and discourse which are critical to consider as teacher educators and researchers. It is imperative that science content and methods courses offer pre-service teachers opportunities for direct experience and explicit instruction on effective means of productive interactions and discourse.
Phosphorylation of cytosolic proteins by resting and activated human neutrophils

A study was conducted on the phosphorylation of proteins in the neutrophil cytosol in response to phorbol myristate acetate (PMA) and N-formyl-methionyl-leucyl-phenylalanine (fMLP). Autoradiography of gel electrophoretograms prepared from neutrophils incubated with 32Pi in the presence and absence of the activators showed nine proteins whose state of phosphorylation was affected by neutrophil activation. 32P was gained by eight of these proteins and was lost by the ninth. For all but one of these proteins, the change in the extent of labeling appeared to reach completion by one to two minutes. It was possible to quantitate the changes in 32P content of three of the nine proteins. One of these was the 20-kD protein that lost label when the neutrophils were activated. Quantitation showed that over half the 32P present in this protein in the resting state was gone within 0.2 minutes after activation. The other two were proteins weighing 11 and 69 kD. The phosphorylation characteristics of these two proteins differed, depending on whether activation had been carried out with PMA or fMLP. These differences in protein phosphorylation support other evidence suggesting that PMA and fMLP do not activate neutrophils by identical biochemical pathways. Differences in phosphorylation between resting and activated cells were not affected by dibutyryl cyclic guanosine monophosphate (cGMP), dibutyryl cyclic adenosine monophosphate (cAMP), theophylline, aspirin, hydrocortisone, or colchicine. The differences were abolished, however, by 30 mumol/L trifluoperazine. This finding is consistent with the hypothesis that the calcium/calmodulin system plays a biochemical role in the activation of neutrophils.
Purification and N-terminal characterization of Chinchilla villidera α-1-antitrypsin

Abstract 1. 1. Chinchilla, Chinchilla villidera, α-1-antitrypsin has been purified to homogeneity and partially characterized according to mol. wt, amino acid and carbohydrate composition and N- terminal amino acid sequence (30 residues). 2. 2. The mol. wt is between 52,000 and 55,000 as determined by PAGE or sedimentation equilibrium. 3. 3. The best alignment between chinchilla, human and baboon α-1-antitrypsin amino acid sequences offsets the chinchilla sequence 6 positions vs the primate structures. 4. 4. This alignment suggests potential importance of the sequence His-Glu-Gln-Glu-His at positions 11–15. 5. 5. Additionally, the segment Leu-Ala-Glu-Phe-Ala, positions 25–29, is strictly conserved. 6. 6. Shorter N- terminal sequences available for rat and rabbit α-1-antitrypsin appear to follow the offset alignment vs the primate structures.
Hierarchical modeling of mode-switching systems

This paper introduces a set of input-output blocks to build intuitive models of dynamic systems with mode switching due to changes in operating conditions, sensor failure, model reconfiguration, and model-order reduction. These blocks make it possible to construct hierarchical component models of mode-switching systems. An application to an automotive steer-by-wire example and Simulink simulation results are presented.
Mesenteric infarction: Diagnostic and therapeutic enigmas*

Summary The syndrome of massive intestinal infarction has posed difficult diagnostic and therapeutic problems. An awareness of this entity and a better understanding of the factors which predispose to poor tissue perfusion have not changed the high mortality. Emergency angiography has been helpful in establishing the presence of vascular obstruction in patients in whom the diagnosis is suspected, but vascular operation has produced a low survival rate. Our experience with thirty-eight patients in a ten year period has demonstrated the protean manifestations of this syndrome and has emphasized the importance of arteriosclerosis as a major cause. Advanced valvular or arteriosclerotic heart disease with congestive heart failure was seen commonly. Nine patients had primary occlusive disease of the mesenteric arteries, and seven others having nonocclusive intestinal infarction also had some degree of major arterial obstruction. Venous thrombosis and polyarteritis were also causal factors. The only patients who survived were those with limited bowel infarction and early adequate resection. These data suggest that arteriosclerosis is a common factor in patients in whom intestinal infarction develops and that early surgical resection offers the only effective form of therapy.