cssi/SciSciGPT-SciSciNet huggingface dataset:
HGF-induced invasion by prostate tumor cells requires anterograde lysosome trafficking and activity of Na+-H+ exchangers

Hepatocyte growth factor (HGF) is found in tumor microenvironments, and interaction with its tyrosine kinase receptor Met triggers cell invasion and metastasis. It was previously shown that acidic extracellular pH stimulated peripheral lysosome trafficking, resulting in increased cathepsin B secretion and tumor cell invasion, which was dependent upon sodium-proton exchanger (NHE) activity. We now demonstrate that HGF induced the trafficking of lysosomes to the cell periphery, independent of HGF-induced epithelial-mesenchymal transition. HGF-induced anterograde lysosome trafficking depended upon the PI3K pathway, microtubules and RhoA, resulting in increased cathepsin B secretion and invasion by the cells. HGF-induced NHE activity via increased net acid production, and inhibition of NHE activity with 5-(N-ethyl-N-isopropyl)-amiloride (EIPA), or a combination of the NHE1-specific drug cariporide and the NHE3-specific drug s3226 prevented HGF-induced anterograde trafficking and induced retrograde trafficking in HGF-overexpressing cells. EIPA treatment reduced cathepsin B secretion and HGF-induced invasion by the tumor cells. Lysosomes were located more peripherally in Rab7-shRNA-expressing cells and these cells were more invasive than control cells. Overexpression of the Rab7 effector protein, RILP, resulted in a juxtanuclear location of lysosomes and reduced HGF-induced invasion. Together, these results suggest that the location of lysosomes is an inherently important aspect of invasion by tumor cells.
Population Genetics of the Invasive Fire Ant Solenopsis invicta (Hymenoptera: Formicidae) in the United States

Analyses of population genetic variation in invasive species can provide information on the history of the invasions, breeding systems, and gene flow patterns. We surveyed genetic variation in both social forms of the red imported fire ant, Solenopsis invicta Buren (Hymenoptera: Formicidae), throughout the species' introduced range in the United States, to learn how the unique breeding biology of each form shapes genetic structure at various scales, to discern genetic footprints of the invasion process, and to reconstruct the origin and spread of each form. Consistent with more limited earlier studies, our analyses revealed significant local mitochondrial DNA (mtDNA) differentiation in the polygyne (multiple colony queens) but not in the monogyne (single colony queen) social form as well as pronounced mtDNA differentiation coupled with weaker nuclear differentiation between sympatric populations of the two forms. At a larger scale, we found no mtDNA but significant nuclear regional differentiation. In general, populations were most similar to other populations of the same social form at their mtDNA genomes. These higher level patterns of structure are consistent with the spread of the ant by long-distance, human-mediated dispersal, with subfounder populations of each form typically established by queens of the same form. Bayesian analyses showed that study populations most distant from the claimed site of entry, Mobile, AL, have diverged most from the hypothetical founder population, consistent with an invasion scenario in which the ants spread outward from Mobile through repeated subfounder events. Several lines of evidence raise the possibility of secondary introductions of S. invicta into the United States.
Definitional Test of Complex Systems

Created for the current study, the Definitional Test of Complex Systems (DTCS) is our attempt at an exhaustive tool for determining the extent to which a complex system’s definition fits a topic. The DTCS is not, however, a standardized instrument. As such, we have not normed or validated it. Instead, it is a conceptual tool meant to move scholars toward empirically-driven, synthetic definitions of complex systems.
Wound Dressings and Skin Replacement

Wounds to the skin are encountered every day. Minor skin wounds cause some pain, but these wounds will heal by themselves in time. Even though many minor wounds heal effectively without scarring in the absence of treatment, they heal more rapidly if they are kept clean and moist. Devices such as Band-Aids are used to assist in wound healing. For deeper wounds, a variety of wound dressings have been developed including cell cultured artificial skin. These materials are intended to promote healing of skin damaged or removed as a result of skin grafting, ulceration, burns, cancer excision or mechanical trauma.
Isolation and Characterization of Lymphocytes from Mature Mouse Liver

Publisher Summary This chapter discusses isolation and characterization of lymphocytes from mature mouse liver. Lymphoid cells in the gastrointestinal tract include several important subpopulations of cells that are strategically located for interactions of antigens encountered at these mucosal surfaces. A study described in the chapter was used to examine the composition and characteristics of lymphocytes obtained from adult liver because the liver serves as an important clearance depot for circulating antigens, because substances absorbed from the gastrointestinal tract must pass through the liver before being allowed to enter other organs, because there are histologically apparent lymphocytes in association with the portal triads in the adult liver, and because the fetal liver is an important site for the genesis of lymphocyte precursors. The purest fractions of lymphocytes were pooled, washed free of Percoll, and resuspended in RPMI 1640 with FCS prior to immunologic characterization. Differential cell counts of Wright–Giemsa-stained preparations demonstrated that the pooled fractions contained lymphocytes, hepatocytes, Kupffer cells, and monocytes. Liver lymphocytes were prepared and were stained by resuspension inpredetermined optimal dilution of the desired reagent and incubated in ice. This histochemically demonstrable pattern of esterase is characteristic of a subpopulation of T cells.
Excess dividend smoothing

I find that dividends are a strong predictor of forced executive turnover, which suggests that managerial career concerns can be an important force behind observed dividend smoothness. I study the effect of this channel by developing a dynamic agency model in which dividends signal the firm's persistent earnings. In equilibrium, dividends and earnings are informational substitutes. Stock prices react to both earnings announcements and dividend changes, and this price reaction has a first-order effect on executive turnover. Managers, therefore, smooth dividends relative to earnings to withhold negative news and lower their turnover risk. Empirical estimates of the model parameters imply that 38% of observed dividend smoothness is turnover-induced. Having a turnover risk leads managers to smooth dividends excessively, compared to the level that maximizes the shareholders' wealth. This excess dividend smoothing destroys firm value by 2.84%.
Screening for Homelessness in the Veterans Health Administration: Monitoring Housing Stability through Repeat Screening.

Objective.This study examined veterans' responses to the Veterans Health Administration's (VHA's) universal screen for homelessness and risk of homelessness during the first 12 months of implementa...
Formation of Serotonin by Rat Kidneys in Vivo

Renal formation of serotonin by decarboxylation of its amino acid precursor L-5-hydroxytryptophan (L-5-HTP) has been demonstrated with renal tissue homogenates and isolated perfused rat kidneys. Our objective in the present study was to determine whether the conversion of L-5-HTP to serotonin was associated with functional changes by kidneys in vivo. Renal clearance studies were conducted in anesthetized, volume-expanded male Sprague-Dawley rats receiving either saline (n = 9) or L-5-HTP (15 and 75 micrograms/min iv, n = 9). No change in mean arterial pressure was measured during infusions of L-5-HTP at either dose, whereas glomerular filtration rate (GFR), as measured by the clearance of inulin, and effective renal plasma flow (CPAH) decreased by 34 +/- 5% (mean +/- SE, P less than 0.001) and 26 +/- 7% (P greater than 0.07), respectively. Urine flow and sodium excretion decreased by 41 +/- 9% (P less than 0.01). Serotonin and 5-HTP were determined in urine and plasma using HPLC. High levels of 5-HTP were present in plasma, but not urine. Urinary serotonin increased in the rats receiving L-5-HTP without concomitant increases in plasma serotonin. More than 20% of the infused L-5-HTP was recovered in the urine as serotonin. The decarboxylase inhibitor carbidopa (20 micrograms/min) markedly reduced urinary serotonin excretion in the rats which received L-5-HTP and reversed the changes in GFR, CPAH, urine flow, and sodium excretion. Infusions of the amino acid precursor of L-5-HTP, L-tryptophan (n = 7), did not alter kidney function or increase plasma or urinary 5-HTP or serotonin levels. These results are consistent with the intrarenal formation of serotonin by renal decarboxylase with attendant alterations in renal hemodynamics and salt and water excretion.
Nonlinear response surface in the study of interaction analysis of three combination drugs

Few articles have been written on analyzing three-way interactions between drugs. It may seem to be quite straightforward to extend a statistical method from two-drugs to three-drugs. However, there may exist more complex nonlinear response surface of the interaction index (II) with more complex local synergy and/or local antagonism interspersed in different regions of drug combinations in a three-drug study, compared in a two-drug study. In addition, it is not possible to obtain a four-dimensional (4D) response surface plot for a three-drug study. We propose an analysis procedure to construct the dose combination regions of interest (say, the synergistic areas with II≤0.9). First, use the model robust regression method (MRR), a semiparametric method, to fit the entire response surface of the II, which allows to fit a complex response surface with local synergy/antagonism. Second, we run a modified genetic algorithm (MGA), a stochastic optimization method, many times with different random seeds, to allow to collect as many feasible points as possible that satisfy the estimated values of II≤0.9. Last, all these feasible points are used to construct the approximate dose regions of interest in a 3D. A case study with three anti-cancer drugs in an in vitro experiment is employed to illustrate how to find the dose regions of interest.
Development of an instrument for endoscopic nasal surgery.

A newly developed instrument specifically designed for endoscopic nasal procedures has been used clinically in the treatment of the septum and nasal dorsum with success. Dissection and resection of bone and cartilage is performed with precision, and the magnified image is of extreme value as an educational tool.
Time Dependent Radiation Exposures Surrounding Technetium-99m MDP Patients

Radiation surveys of technetium-99m (99mTc) MDP bone scan patients were performed at 5 min, 4 hr, and 24 hr post administration. The measurement distances chosen were surface, 1 ft (30.5 cm) and 3 ft (100 cm) resulting in variable radiation exposures as a function of time and bony pathology. As expected the highest exposures were immediately after tracer administration. Thereafter, urinary excretion and biologic redistribution dominated, resulting in significantly lower exposures at 4 hr and 24 hr for the negative bone scan group. Patients with bony metastases retained more of the injected dose than those with negative scintigrams. This was reflected with the 4 hr and 24 hr surveys.
The dynamics of income distribution: total wages and their shares

In our dynamic framework we shall now introduce the behavior of the distributive variables. The analysis undertaken in Chapter V on unit wage, profit rate and rent will now be further developed in a dynamic context. The following sections will study how distribution changes during the process of growth in the case of maximum accumulation.
Imaging surfactant concentration distributions at the air/water interface

Surfactant concentrations at the peaks and troughs of a standing capillary wave field were measured using a reflected second harmonic generation (SHG) imaging technique. The results revealed behaviour that is consistent with a compaction of the insoluble monolayer at the crests of the capillary waves and a dilation of the monolayer in the troughs. Each measurement was obtained using a single 3 nanosecond laser pulse, providing essentially instantaneous measurements of surfactant concentrations.
The impact of reactive surface area on brine-rock-carbon dioxide reactions in CO2 sequestration

Abstract Injection of carbon dioxide into saline aquifers is one the most promising methods for mitigating the increase in atmospheric CO2 concentrations. Reactions of CO2 with brine and formation rocks are important in determining the ultimate fate of CO2. Rates of reactions of the different relevant minerals are dependent on rate constants and mineral surface area. It is important to quantify the effect of surface area on reaction rates when different types of rock samples are employed in experiments. Batch experiments with different forms of the Berea sandstone were set up and performed at high pressure (2000 psi) and reservoir temperature (60 °C) for two-week under reservoir CO2 sequestration conditions. Experiments were performed with markedly different samples (cores, rock chips, and powdered) with progressively increased surface areas. Experiments with the different forms of sandstones showed similar trends in major minerals dissolution with increase in cation concentrations of iron, magnesium, and calcium in the effluent brine. Under realistic aquifer pressure and temperature conditions, iron chemistry plays an important role in the dissolution reactions in the Berea sandstone. Reactivities increased leading to larger cationic concentrations in brine (as determined using ICP-MS) as the surface areas increased. Morphology of the reacted volume was viewed using QEMSCAN and Micro-CT for core plug samples. These experiments helped quantity the effect of surface area (higher surface area leading to more dissolution) and revealed that reactions appear to be limited more to the surface in Berea sandstone. It was shown that the factor used to obtain geometric surface area from a core decreased when samples with higher surface areas were used. This indicated that some internal surface area became available for fragmented (fractured), and powdered samples. Mineral dissolution caused the growth and expansion of pores in Berea sandstone and surface area measurements (BET) showed that the new porosity generated was characterized by a smaller pore size distribution in comparison to the unreacted one.
An Integrated Sensor for Detecting Moisture Ingress in Printed Circuit Board Assemblies

Abstract Numerous applications exist where electronics must operate reliably in moist environments, and often for long periods of time. In these environments, the circuit board assemblies may experience moisture ingress, which can deleteriously affect the operation and life span of these systems. Detecting moisture ingress is therefore useful for improving system design, assembly techniques, packaging technologies and maintenance scheduling. Capacitive fringing field sensors are useful for measuring the moisture content of materials. Therefore, a capacitive fringing field sensor, implemented in printed circuit board technology with a CMOS relaxation oscillator interface circuit, is proposed for detecting moisture ingress into the printed circuit board assembly. A set of instrumented sensors was designed, fabricated and tested. The results demonstrated that when the test articles experienced prolonged exposure to moisture, the instrumented sensors experienced an 18.42% change in output value, indicating a ...
Potential of bisbenzimidazole-analogs toward metronidazole-resistant Trichomonas vaginalis isolates.

A bisoxyphenylene-bisbenzimidazole series with increasing aliphatic chain length (CH2 to C10H20) containing a meta (m) or para (p) benzimidazole linkage to the phenylene ring was tested for ability to inhibit the growth of metronidazole susceptible (C1) and refractory (085) Trichomonas vaginalis isolates under aerobic and anaerobic conditions. Compound 3m, 2,2’-[α,ω-propadiylbis(oxy-1,3-phenylene)]bis-1H-benzimidazole, displayed a 5.5-fold lower minimum inhibitory concentration (MIC) towards T. vaginalis isolate 085 than metronidazole under aerobic growth conditions, (26 μM compared to 145 μM). A dose of 25 mg/kg per day for four days of compound 3m cured a subcutaneous mouse model infection using T. vaginalis isolates 286 (metronidazole-susceptible) and 085 (metronidazole refractory). Compound 3m was weakly reduced by pyruvate:ferredoxin oxidoreductase, but unlike metronidazole was not dependent upon added ferredoxin. It is concluded from structure-activity relationships that there was no obvious trend based on the length of the central aliphatic chain, or the steric position of the bisbenzimidazole enabling prediction of biological activity. The compounds generally fulfill Lipinski's rile of five, indicating their potential as drug leads. This article is protected by copyright. All rights reserved.
Smart Automated Water Sprinkler (SAWS): Residential irrigation by boundary mapping and variable water pressure control

The Smart Automated Water Sprinkler (SAWS) System is an innovative approach to lawn irrigation that allows the watering pattern to match the contours of the yard. It utilizes a mapping technology to deliver water to only the marked grassy area of the property, avoiding water delivery to driveways, homes, fences, and other unintended landscape fixtures. Consequently, the SAWS system helps homeowners save water, money, inconvenience, and time, and ultimately benefits the environment by reducing countless gallons of water wasted every year when people water their lawn. Currently, other lawn watering solutions, such as permanently installed irrigation systems or standard hose-attached sprinklers, are expensive, wasteful, inconvenient, and/or has limited range of distance/orientation to be a good choice for unusually shaped lawns. The SAWS system, with its components for mapping and water delivering mechanism, is designed to be housed in a PVC tube with wheels mounted on either end for ease of operation. In mapping mode, the unit is rolled around the perimeter of a desired area. It utilizes inertial mapping with an Inertial Measurement Unit (IMU) to map the boundaries of any terrain of an arbitrary shape and size assuming that its interior contains no objects or obstacles. The data for these mapped areas are stored indefinitely allowing for one-time mapping. In usage mode, the unit is rolled into the interior of a previously mapped area with a standard garden hose attached. The unit then detects its location within the specified boundary of the map and, with a water flow valve controlled by a stepper motor and an infrared beam sensor, starts directing water with a spray nozzle in such a manner not to substantially overflow the marked boundaries. In testing, the SAWS system was able to produce a perimeter map as specified by the user. Once placed and water provided, the SAWS system was able to adjust to the proper spray distance as the spray nozzle was rotated, and thus avoid watering unintended area and objects.
Singularity Formation on Vortex Sheets: The Rayleigh-Taylor Problem

Evidence is now quite strong that vortex sheets with mean vorticity density develop a finite time curvature singularity when viscosity and surface tension are neglected. This singularity is due to a global Kelvin-Helmholtz instability, which in turn results from the presence of a mean sheet vorticity. We examine the possibility of singularity formation in the related Rayleigh-Taylor problem. In this problem density stratification causes vorticity to be barotropically generated on the sheet, although there is no mean sheet vorticity. A simple approximate theory is developed as a generalization of Moore’s approximation for vortex sheets in the Kelvin-Helmholtz problem. For the approximate theory, a family of exact solutions is found in the form of traveling waves in the complex plane for which singularities develop on the interface. These exact solutions eliminate the need for a second asymptotic analysis like that employed by Moore. The resulting predictions for the time, type and location of singularity formation are directly verified by numerical computation for the full Rayleigh-Taylor problem. Excellent agreement between the theoretical predicitons and the numerical results is exhibited over a wide range of Atwood numbers. For A near 1, however, some aspects of the agreement break down. An additional traveling wave solution to the approximate equations is found which exhibits a new and stronger singularity.
An investigation of coastal groundwater discharge and associated nutrient inputs using electrical resistivity, temperature, and geochemical tracers in Pescadero Lagoon, California

Pescadero Lagoon is a complex lagoon system located on the central California coast in San Mateo County. Over the last decade, external stressors such as degraded water quality, restricted circulation, heightened groundwater withdrawals, changes in the fluvial geomorphology that affect surface water runoff, and widespread agriculture in the watershed have impacted the lagoon. The lagoon system is bounded on the marine side by an ephemeral sand berm that is seasonally closed and so hinders open exchange with the ocean. This berm and the Mediterranean-type climate play an important role in the lagoon's circulation and water quality. The most high-profile and deleterious effect of reduced ocean-lagoon exchange and restricted water circulation is the occurrence of bottom-water low oxygen events that can trigger seasonal fish kills. This project employed a suite of geophysical and geochemical techniques to better understand the role of groundwater on lagoon water and constituent balances. The main objective of this research was to quantify groundwater seepage rates into Pescadero Lagoon across broad spatial and temporal scales using electrical resistivity, temperature, and Radon-222 (222Rn) as tracers of groundwater movement. Resulting seepage rate estimates were then used to derive associated nutrient flux estimates, which can be compared to atmospheric and riverine nutrient load estimates to yield more comprehensive nutrient budgets.
The Evolution of Low Mass Binary Systems

The generally accepted model for Type II X-ray sources, of which the galactic bulge sources are a subset, consists of a close binary system in which matter from a low mass star is transferred to its neutron star companion. As a class, these sources are characterized by a level of X-ray emission ranging from about 103 6 to 103 8 ergs s-1 (corresponding to mass accretion rates onto the neutron star of about 10-10 to 10-8 M⊙ yr-1). For a detailed review of the observational data of these objects, see Lewin and Joss (1983). Although the fundamental nature of these sources is understood, their origin and evolution remain obscure. Among the many questions raised by the existence of these sources is the one related to their evolution to their present state. Based upon the number of such systems (~60) and their theoretically expected lifetimes (~108 – 109 years), their formation must have been extremely rare (see van den Heuvel, 1983). If they have formed from primoridal binaries, then it is likely that the system lost substantial mass and angular momentum in a common envelope phase (van den Heuvel, 1981). On the other hand, it is also possible that if the systems did not evolve from primordial binaries, then exchange processes (Hills, 1975) or inelastic tidal capture processes (Fabian et al., 1975) may have played an important role in their evolution. The evolution of stellar systems to the X-ray stage is of great intrinsic interest and has been reviewed by van den Heuvel (1981, 1983), Taam (1984), and Iben and Tutukov (1984).
An algorithm for probabilistic least-commitment planning

We define the probabilistic planning problem in terms of a probability distribution over initial world states, a boolean combination of goal propositions, a probability threshold, and actions whose effects depend on the execution-time state of the world and on random chance. Adopting a probabilistic model complicates the definition of plan success: instead of demanding a plan that provably achieves the goal, we seek plans whose probability of success exceeds the threshold. This paper describes a probabilistic semantics for planning under uncertainty, and presents a fully implemented algorithm that generates plans that succeed with probability no less than a user-supplied probability threshold. The algorithm is sound (if it terminates then the generated plan is sufficiently likely to achieve the goal) and complete (the algorithm will generate a solution if one exists).
Blood Vessel Formation

Primitive blood vessels in vertebrate embryos form by a process called vasculogenesis, during which mesodermal cells differentiate into endothelial precursor cells called angioblasts. These angioblasts then differentiate into endothelial cells (ECs) and coalesce to form the earliest vessels. The subsequent growth and remodeling of the vasculature occurs by angiogenesis, during which new blood vessels sprout from pre-existing vessels. The vascular endothelial growth factor (VEGF) signaling pathway has been shown to be important for the migration, proliferation, maintenance, and survival of ECs and is critical during both vasculogenesis and angiogenesis. In addition to its important function during embryonic development, VEGF is thought to play a major role in tumor-induced neovascularization. Angiopoietin–Tie signaling is thought to be critical for the maturation and stabilization of the nascent vascular network. One of the most fundamental steps in the differentiation of the vasculature is the specification of the arterial and venous endothelium. Recent work has highlighted the role of Notch, VEGF and Hedgehog signaling in the specification of arterial identity. Classically, differences between arteries and veins were attributed to physiological factors such as the direction and pressure of blood flow. However, recent work has shown that molecular distinctions between arterial and venous endothelium can appear before the onset of blood flow. Vertebrates possess a second, blind-ended vascular system, the lymphatic system, that is responsible for clearing and draining fluids and macromolecules that leak from blood vessels into the interstitial spaces of tissues and organs. Evidence suggests that the first lymphatic endothelial cells (LECs) emerge by transdifferentiation from primitive veins. The transcription factor Prox1 is a critical regulator of LEC specification, whereas the VEGF family members VEGF-C and VEGF-D are important for LEC migration and lymphangiogenesis. During early development, newly formed vessels follow a highly stereotypic and evolutionarily well-conserved pattern of network assembly that is reminiscent of that followed by the nervous system and axon tracts. A variety of recent studies have shown that many well-known molecular pathways used for the guidance of migrating axons play an important role in the guidance and patterning of developing blood vessels.
Hepatitis mutants of mouse hepatitis virus strain A59

MHV-A59 causes acute meningoencephalitis and hepatitis in susceptible mice, and a persistent productive, but nonlytic, infection of cultured glial cells. We have shown previously that viruses isolated from persistently infected glial cell cultures have a fusion-defective phenotype and were impaired in their abilities to cause hepatitis compared to wild-type MHV-A59. Two mutants chosen for detailed study, B11 and C12, display two distinct hepatitis phenotypes. The ability of B11 to replicate in the liver was dependent on infectious dose and route of inoculation, while C12 consistently displayed decreased liver titers regardless of dose and route of inoculation. Sequence analysis of wild-type, mutant and revertant S proteins indicates that 1) a mutation in the N terminal subunit of S, resulting in a glutamine to leucine amino acid substitution (Q159L), may affect ability to cause hepatitis and 2) a cleavage site mutation (H716D) which determines fusogenicity is not responsible for the altered hepatitis phenotype. Sequence analysis indicated that hepatitis-producing revertants did not revert at mutation Q159L, although it is possible that a mutation in the heptad repeat domain of S2 may compensate for the mutation in S1. Since B11, C12 and a nonattenuated fusion mutant (B12) have identical S protein sequences, there must be additional mutations outside of S which influence both virulence and ability to replicate in the liver.
Particulate matter, nitrogen oxides, ozone, and select volatile organic compounds during a winter sampling period in Logan, Utah, USA.

ABSTRACTParticulate matter mass (PM), trace gaseous pollutants, and select volatile organic compounds (VOCs) with meteorological variables were measured in Logan, Utah (Cache Valley), for >4 weeks during winter 2017 as part of the Utah Winter Fine Particle Study (UWFPS). Higher PM levels for short time periods and lower ozone (O3) levels were present due to meteorological and mountain valley conditions. Nitrogenous pollutants were relatively strongly correlated with PM variables. Diurnal cycles of NOx, O3, and fine PM(PM 2.5) (aerodynamic diameter <2.5 μm [PM2.5]) suggested formation from NOx. O3 levels increased from early morning into midafternoon, and NOx and PM2.5 increased throughout the morning, followed by sharp decreases. Toluene/benzene and xylenes/benzene ratios and VOC correlations with nitrogenous and PM species were indicative of local traffic sources. Wind sector comparisons suggested that pollutant levels were lower when winds were from nearby mountains to the east versus winds from norther...
Effects of percentage Brahman and Angus breeding, age-season of feeding and slaughter end point on feedlot performance and carcass characteristics.

Steers (n = 165) of known percentage Brahman (B) and Angus (A) breeding were used to study effects of breed group (A, 3/4A:1/4B, 1/2A:1/2B, 1/4A:3/4B), age-season of feeding (calves fed during the cool season vs yearlings fed during the warm season) and slaughter end point (less than .90, 1.0 to 1.15, 1.27 to 1.40, greater than or equal to 1.5 cm of adjusted fat over the ribeye) on feedlot performance and carcass characteristics. The 1/2B and 3/4B steers had heavier (P less than .05) initial and final feedlot weights than the A and 1/4B steers and higher (P less than .05) unshrunk ADG than the A steers did. Breed types did not differ for feed efficiency. Yearling steers fed in the warm season had higher (P less than .05) unshrunk ADG than calves fed in the cool season, but ADG calculated on an empty-rumen basis did not differ between the two age-seasons of feeding. Calves fed in the cool season were more efficient (P less than .05) than yearlings fed in the warm season when efficiency was expressed on an empty-rumen basis; however, on a live weight basis there was no difference in feed efficiency. No breed group by age-season of feeding interactions on performance were detected. Slaughter end point did not significantly affect feed efficiency on an empty-rumen basis. The 1/2B and 3/4B steers had smaller ribeye areas (REA) per 100 kg hot carcass and lower marbling scores than the 1/4B and A steers. Yearlings fed in the warm season produced heavier carcasses (P less than .05) than calves fed in the cool season. As s.c. fat thickness at slaughter increased, hot carcass weight and numerical yield grade increased, whereas REA per 100 kg of hot carcass decreased. Marbling also increased as fatness increased up to about 1.5 cm subcutaneous fat.
Molecular prognosis in liver cirrhosis

Abstract Liver cirrhosis is the terminal stage of chronic inflammatory and fibrotic liver diseases caused by viral hepatitis and metabolic disorders. Natural history of cirrhosis varies across the patients, therefore prognostic prediction in each individual is crucial for cost-effective patient management. Several clinical prognostic indicators have been developed, although their performance is generally limited. Molecular prognostic biomarkers are expected to refine the prognostication to enable personalized clinical care according to estimated risk of poor prognosis. Some of the biomarkers may also serve as clue to chemopreventive intervention. Non-invasive technologies based on body fluid-derived biospecimens will enable more flexible application of such biomarkers compared to liver biopsy-based methods. However, given the limitations in sensitivity and specificity of the currently available circulating biomolecule-based assays, acquisition of liver tissues will be necessary at least during the process of developing such biomarkers.
A Brief Tour of Logic and Optimization

This paper is an informal survey of some of the deep connections between logic and optimization. It covers George Boole's probability logic, decision diagrams, logic and cutting planes, first order predicate logic, default and nonmonotonic logics, logic and duality, and finite-domain constraint programming. There is particular emphasis on practical optimization methods that stem from these connections, including decision-diagram based methods, logic-based Benders decomposition, and integration of CP and optimization technologies. The paper is a slight revision of an invited article for the INFORMS Optimization Society Newsletter in observance of the 2018 Khachian Award.
Progressive Multifocal Leukoencephalopathy Associated with Rituximab Treatment of B-Cell Lymphoproliferative Disorders: A Report of 29 Cases from the RADAR Project.

Background- Progressive multifocal leukoencephalopathy (PML) is a demyelinating disorder of the brain caused by the reactivation of latent JC polyoma virus. Rituximab (Rituxan, Mabthera) is a B-cell depleting, monoclonal antibody which has been linked to reactivation of the hepatitis B virus. HIV infection, purine analog therapy, hematopoietic transplant and lymphoma have previously been associated with PML. We evaluated the characteristics of patients with B-cell lymphoproliferative disorders who developed PML after exposure to rituximab, and the quality of case reports available in the medical literature and at the FDA. Methods- Data sources included 1 observation at Northwestern Memorial Hospital, 14 reports obtained from the FDA MedWatch database, 9 case reports from the medical literature, and 21 reports from the manufacturer, Genentech, that were submitted to the FDA. Reports that did not confirm the diagnosis of PML, were associated with HIV infection, or rituximab use for a rheumatologic indication were excluded. Results- Of 47 unique case reports screened, 3 were excluded for rituximab use in rheumatologic disease, 2 for pre-existing HIV, and 13 for inadequate confirmation of the PML diagnosis. In the 29 remaining cases, survival of PML was reported in only one patient. Diagnosis was made by brain biopsy (n=6), autopsy (n=6), or MRI of brain AND positive JC virus by PCR (n=17). Five cases were seen in hematopoietic transplant recipients, 4 autologous and 1 allogeneic. Of the 24 patients who were not transplanted, 10 had purine analog exposure. Thirteen of the 14 patients that did not receive transplant or a purine analog received an alkylating agent, with 7 receiving standard R-CHOP. The median age of the 29 patients was 63.5 years (range 32–89), 15 were female and 14 male. Indications for rituximab were: large B-cell lymphoma (n=6), follicular lymphoma (n=6), CLL (n=5), Waldenstrom (n=2) and other non-Hodgkin lymphomas (n=10). Median time to diagnosis of PML from first and last rituximab doses was 10 and 5 months respectively. The median number of rituximab doses was 6. Quality comparison of source data is contained in table 1. Overall completeness ratio for literature and observed reports vs. FDA and manufacturer reports was 1.48. Conclusions: We have found 29 cases of rituximab-associated PML, of which 14 were not associated with transplantation or purine analog exposure, suggesting an association of rituximab therapy independent of these other treatment related risk factors. FDA and manufacturer reports are inferior to those available in published case reports or through active surveillance. Further examination of the relationship of rituximab to PML, using an active surveillance strategy, is warranted.
Nephrotoxicity Risk and Clinical Effectiveness of Continuous versus Intermittent Infusion Vancomycin Among Patients in an Outpatient Parenteral Antimicrobial Therapy Program

Study objective To compare rates of nephrotoxicity, time to nephrotoxicity onset, and clinical failure among patients who received continuous infusion (C-I) or intermittent infusion (I-I) vancomycin in an outpatient parenteral antimicrobial therapy (OPAT) program. Nephrotoxicity was defined as an increase in serum creatinine greater than 0.5 mg/dl or a 50% increase from baseline for two consecutive measurements while receiving vancomycin during OPAT. Clinical failure was defined as unplanned readmission, extension of therapy, or change in antibiotics. Design Single-center propensity score-matched retrospective cohort study. Setting OPAT clinic affiliated with two nearby hospitals. Patients We identified 300 patients who received C-I or I-I vancomycin for at least 1 week in the OPAT program between October 1, 2017, and March 31, 2019. Propensity score matching based on age, sex, and infection was performed to minimize differences in patient characteristics between groups. Measurements and main results After propensity score matching and exclusion criteria, 74 patients were included in each cohort. Continuous infusion vancomycin was associated with a 3.22-fold decrease in nephrotoxicity risk (C-I 6.8% [5/74 patients] vs I-I 18.9% [14/74 patients]; odds ratio 3.22, 95% confidence interval 1.10-9.46, p=0.027) and a significantly slower onset to nephrotoxicity compared with I-I (p=0.035). No statistically significant difference in clinical failure rates was observed between the C-I and I-I groups (13.5% [10/74 patients] vs 23.0% [17/74 patients], p=0.147). Conclusion In an OPAT setting, C-I vancomycin was associated with a lower risk of and slower onset to nephrotoxicity than I-I vancomycin; however, no statistically significant difference in clinical failure rates was observed with C-I versus I-I vancomycin.
Rational Design of a Uranyl Metal-Organic Framework for the Capture and Colorimetric Detection of Organic Dyes.

A new uranyl containing metal-organic framework, RPL-1: [(UO2)2(C28H18O8)] . H2O (RPL for Radiochemical Processing Laboratory), was prepared, structurally characterized, and the solid-state photoluminescence properties explored. Single crystal X-ray diffraction data reveals the structure of RPL-1 consists of two crystallographically unique three dimensional, interpenetrating nets with a 4,3-connected tbo topology. Each net contains large pores with an average width of 22.8 A and is formed from monomeric, hexagonal bipyramidal uranyl nodes that are linked via 1,2,4,5-tetrakis(4-carboxyphenyl)benzene (TCPB) ligands. The thermal and photophysical properties of RPL-1 were investigated using thermogravimetric analysis and absorbance, fluorescence, and lifetime spectroscopies. The material displays excellent thermal stability and temperature dependent uranyl and TCPB luminescence. The framework is stable in aqueous media and due to the large void space (constituting 76 % of the unit cell by volume) can sequester organic dyes, the uptake of which induces a visible change to the color of the material.
Amplicon contamination in labs masquerades as COVID19 in surveillance tests

Abstract A cohort of laboratorians with positive SARS-CoV2 test results were uncovered during asymptomatic COVID-19 screening programs at six universities. Follow-up PCR and antibody tests showed that most of these cases were not true COVID-19 infection but instead arose from reverse-transcribed and amplified viral sequences (amplicons) that are generated during research. Environmental testing showed widespread contamination of amplicons in lab spaces including notebooks, keyboards, glasses, and doorknobs. Minimizing instances of amplicon contamination and developing protocols for handling suspected cases are critical to propel research efforts and to avoid diverting university and healthcare resources from patients with COVID-19. Removal of these individuals from the standard testing protocol, per CDC guidelines for positive cases, risks the spread of true infection. We discuss potential prevention and mitigation strategies.
Change in or of global governance

Michael Zurn's Theory of Global Governance is an original, bold, and compelling argument regarding the causes of change in global governance. A core argument is that legitimation problems trigger changes in global governance. This contribution addresses two core features of the argument. Although I am persuaded that legitimacy matters, there are times when: legitimacy appears to be given too much credit to the relative neglect of other factors; other times when the lack of legitimacy has little discernible impact on the working of global governance; and unanswered questions about how the legitimacy of global governance relates to the legitimacy of the international order of which it is a part. The second feature is what counts as change in global governance. Zurn reduces change to either deepening or decline, overlooking the possible how of global governance. In contrast to Zurn's map of global governance that is dominated by hierarchies in the form of international organizations, an alternative map locates multiple modes of governance: hierarchies, markets, and networks. The kinds of legitimation problems that Zurn identifies, I argue, can help explain some of the movement from hierarchical to other modes of global governance.
Using an Electrocardiogram as a Component of Athlete Screening

Debate and discussion surround the issue as to whether an electrocardiogram (ECG) should universally be included in pre-participation screening examinations of asymptomatic athletes. Leading medical organizations have advanced powerful arguments both for and against the standard inclusion of an ECG in athlete screening based on review of data generated by large-scale epidemiological studies of athlete sudden cardiac death (SCD) events both with and without ECG screening and through analyses of the pros and pitfalls of the ECG to accurately identify underlying cardiac disease. A significant challenge associated with the use of the ECG in athlete screening involves balancing the power of an ECG to increase the yield of detection for cardiac disorders associated with SCD in athletes with potential adverse consequences to both individual athletes and healthcare systems in the events of false-positive ECGs. To help improve the accuracy of ECG interpretation and lower false-positive rates, athlete-specific ECG interpretation criteria have been developed and refined in recent years, culminating in the 2017 International Recommendations. Healthcare providers and institutions that choose to incorporate an ECG into the screening process of asymptomatic athletes should be familiar with the current standards for proper athlete ECG interpretation as well as the inherent potential benefits and risks to the athlete.
Demographic and clinical factors associated with variations in opioid administration using conscious sedation during HDR brachytherapy for cervical cancer.

PURPOSE/OBJECTIVES To examine patient characteristics that predispose to higher opioid administration during tandem and ovoid (T&O) high-dose rate (HDR) brachytherapy. METHODS A single-institution retrospective review was performed on patients who underwent brachytherapy for cervical cancer. Patients were included if they received at least one fraction of HDR T&O brachytherapy with analgesia administration recorded in the Medication Administration Record. Fentanyl dose was dichotomized as "low" (mean <125 μg per fraction), or "high" (mean ≥ 125 μg per fraction). Descriptive statistics and multiple logistic regression analysis were performed comparing mean opioid dose per fraction with demographic and clinical information. RESULTS From July 2014 through May 2020, 113 patients underwent 531 T&O HDR brachytherapy fractions with oral benzodiazepine and intravenous opioid fentanyl for conscious sedation. The median opioid dose per fraction was 100 μg fentanyl (range 0-250 μg). Using multiple logistic regression analysis, younger age (OR 1.071, p = 0.002) and higher BMI (OR 1.091, p = 0.019) were associated with increased opioid administration during brachytherapy. Black women received less opioid during brachytherapy when compared to White women (OR 0.296, p = 0.047). FIGO stage, ECOG score, smoking status, prior narcotic use, prior illicit drug use, parity, prior cervical procedure, Smit sleeve placement, and distance to treatment center were not associated with high opioid dose. CONCLUSION Cervical cancer patients who are younger or have higher BMI receive more narcotic analgesia during HDR brachytherapy whereas Black women received less narcotic analgesia, irrespective of age and BMI. This underscores the immediate need to address how pain is assessed and managed during brachytherapy.
An African Slaving Port and the Atlantic World: Benguela and its Hinterland

This book traces the history and development of the port of Benguela, the third largest port of slave embarkation on the coast of Africa, from the early seventeenth to the mid-nineteenth century. Benguela, located on the central coast of present-day Angola, was founded by the Portuguese in the early seventeenth century. In discussing the impact of the transatlantic slave trade on African societies, Mariana P. Candido explores the formation of new elites, the collapse of old states and the emergence of new states. Placing Benguela in an Atlantic perspective, this study shows how events in the Caribbean and Brazil affected social and political changes on the African coast. This book emphasizes the importance of the South Atlantic as a space for the circulation of people, ideas and crops.
α-Synuclein Shares Physical and Functional Homology with 14-3-3 Proteins

alpha-Synuclein has been implicated in the pathophysiology of many neurodegenerative diseases, including Parkinson's disease (PD) and Alzheimer's disease. Mutations in alpha-synuclein cause some cases of familial PD (Polymeropoulos et al., 1997; Kruger et al., 1998). In addition, many neurodegenerative diseases show accumulation of alpha-synuclein in dystrophic neurites and in Lewy bodies (Spillantini et al., 1998). Here, we show that alpha-synuclein shares physical and functional homology with 14-3-3 proteins, which are a family of ubiquitous cytoplasmic chaperones. Regions of alpha-synuclein and 14-3-3 proteins share over 40% homology. In addition, alpha-synuclein binds to 14-3-3 proteins, as well as some proteins known to associate with 14-3-3, including protein kinase C, BAD, and extracellular regulated kinase, but not Raf-1. We also show that overexpression of alpha-synuclein inhibits protein kinase C activity. The association of alpha-synuclein with BAD and inhibition of protein kinase C suggests that increased expression of alpha-synuclein could be harmful. Consistent with this hypothesis, we observed that overexpression of wild-type alpha-synuclein is toxic, and overexpression of alpha-synuclein containing the A53T or A30P mutations exhibits even greater toxicity. The activity and binding profile of alpha-synuclein suggests that it might act as a protein chaperone and that accumulation of alpha-synuclein could contribute to cell death in neurodegenerative diseases.