cssi/SciSciGPT-SciSciNet huggingface dataset:
Normal Aging Involves Modulation of Specific Inflammatory Markers in the Rat Retina and Choroid

Recent work has suggested that inflammation is a common component of a number of age-related diseases. The hypothesis of the present study was that normal aging of the retina and choroid would increase levels of inducible nitric oxide synthase (iNOS), prostaglandin E2 (PGE2), and tumor necrosis factor alpha (TNF-α). To investigate this hypothesis, gene expression and protein analyses were completed on retinal and choroidal samples from Fischer 344 × Brown Norway F1 hybrid rats at 8, 22, and 32 months of age. Aging of the choroid produced significant increases in PGE2, with decreased TNF-α protein. Protein levels and messenger RNA of iNOS and TNF-α protein levels were significantly decreased in the aging retina in contrast to PGE2 protein activity, which was increased with age in the retina. These results suggest that PGE2 is likely involved in the aging process in both the retina and choroid, whereas iNOS plays a role predominantly in the retina.
Good advice for type-directed programming aspect-oriented programming and extensible generic functions

Type-directed programming is an important idiom for software design. In type-directed programming the behavior of programs is guided by the type structure of data. It makes it possible to implement many sorts of operations, such as serialization,traversals, and queries,only once and without needing to continually revise their implementations as new data types are defined.Type-directed programming is the basis for recent research into "scrapping" tedious boilerplate code that arises in functional programming with algebraic data types. This research has primarily focused on writing type-directed functions that are closed to extension. However, Lammel and Peyton Jones recently developed a technique for writing openly extensible type-directed functions in Haskell by making clever use of type classes. Unfortunately, this technique has a number of limitations such as the inability to write specialized cases for existential or nested data types and function types becoming too constrained to be used as first-class functions.We present an alternate approach to writing openly extensible type-directed functions by using the aspect-oriented programming features provided by the language AspectML. Our solution not only avoids the limitations present in Lammel and Peyton Jones's technique, but also allows type-directed functions to be extended at any time with cases for types that were not even known at compiletime. This capability is critical to writing programs that make use of dynamic loading or runtime type generativity.
The Horizon Model: Human Process Improvement Model from 30,000 Feet to Below Sea Level

Incorporating macro- to micro-levels of an organization, the horizon model is introduced in this article as a practical tool for organizational performance and process improvement. The horizon model is based on existing theories and models in the human performance technology and the human performance improvement industries. Application of this model is demonstrated by a real-life example with the City Club of Boise and illustrates when, where, and how the horizon model can be used to improve performance.
Fluorous base-pairing effects in a DNA polymerase active site.

We describe selective "fluorous" effects in the active site of a DNA polymerase, by using nucleotide analogues whose pairing edges are perfluorinated. The 5'-triphosphate deoxynucleotide derivatives of DNA base analogues 2,3,4,5-tetrafluorobenzene ( F B) and 4,5,6,7-tetrafluoroindole ( F I), as well as hydrocarbon controls benzene (B) and indole (I), were synthesized and studied as substrates for the DNA Polymerase I Klenow fragment (KF exo-). Modified nucleotides were present in the DNA template or were supplied as nucleoside triphosphates in studies of the steady-state kinetics of single nucleotide insertion. When supplied opposite the non-natural bases in the template strand, the hydrophobic nucleoside triphosphates were incorporated by up to two orders of magnitude more efficiently than the natural deoxynucleoside triphosphates. The purine-like fluorinated indole nucleotide ( F I) was the most efficiently inserted of the four hydrophobic analogues, with the most effective incorporation occurring opposite the pyrimidine-like tetrafluorobenzene ( F B). In all cases, the poly-fluorinated base pairs were more efficiently processed than the analogous hydrocarbon pairs. A preliminary test of polymerase extension beyond these pairs showed that only the F B base is appreciably extended; the inefficient extension is consistent with recently published data regarding other nonpolar base pairs. These results suggest the importance of hydrophobicity, stacking, and steric interactions in the polymerase-mediated replication of DNA base pairs that lack hydrogen bonds. These findings further suggest that the enhanced hydrophobicity of polyfluoroaromatic bases could be employed in the design of new, selective base pairs that are orthogonal to the natural Watson-Crick pairs used in replication.
Forests in climate policy: technical, institutional and economic issues in measurement and monitoring

Despite the economic and environmental significance of the world’s forests, we have limited data about them. Estimates of deforestation in tropical countries and rates of reforestation or afforestation in boreal and temperate countries are inconsistent. Accordingly, estimates of emissions released in deforestation vary widely and range from 7% to 17% of all sources of greenhouse gas (GHG) emissions. The lack of good data severely hampers efforts to shape climate policy because it is difficult to model the role of forests both in the physical global carbon (C) cycle and in cost-effective regimes to abate GHG. Data limits strain the capacity of even the best models to estimate marginal cost functions for forest carbon (C) sequestration. It is technically possible to obtain better information, but for institutional and economic reasons these technologies have not yet been fully deployed. The emergence of carbon (C) trading or tax policy in which forest carbon (C) storage becomes valued would strengthen incentives to supply better data, as would nonmarket regulation if it elicited a shadow value of forest carbon (C) in substituting for reductions in greenhouse gas emissions. “Geo-wiki” may provide a short-term solution to at least part of the data problem. The ultimate solution is the development of a comprehensive forest monitoring system involving remote sensing and on-the-ground truthing. This paper briefly discusses the role of forests in climate policy and then describes data gaps, the capability of technology to fill them, the limits of institutions and budgets in realizing this capability, and possible near-term solutions.
Religion, Historical Contingencies, and Institutional Conditions of Criminal Punishment: The German Case and Beyond

Religion and historical contingencies help explain cross-national and historic variation of criminal law and punishment. Case studies from German history suggest: First, the Calvinist affiliation of early Prussian monarchs advanced the centralization of power, rationalization of government bureaucracy, and elements of the welfare state, factors that are likely to affect punishment. Second, the dominant position of Lutheranism in the German population advanced the institutionalization of a separation of forgiveness in the private sphere versus punishment of “outer behavior” by the state. Third, these principles became secularized in philosophy, jurisprudence, and nineteenth-century criminal codes. Fourth, partly due to historical contingencies, these codes remained in effect into post–World War II Germany. Fifth, the experience of the Nazi regime motivated major changes in criminal law, legal thought, public opinion, and religious ideas about punishment in the Federal Republic of Germany. Religion thus directly and indirectly affects criminal law and punishment, in interaction with historical contingencies, institutional conditions of the state, and other structural factors.
Fibulin-5 null mice with decreased arterial compliance maintain normal systolic left ventricular function, but not diastolic function during maturation

The large arteries serve as compliant vessels that store energy during systole and return it during diastole. This function is made possible by the elastic fibers in the arterial wall that are assembled during late embryonic and early postnatal development from various proteins, including fibulin-5. Mice and humans with insufficient amounts of fibulin-5 have reduced arterial compliance as adults. Reduced compliance of the large arteries is correlated with hypertension, reduced cardiac function, and an increased risk of death from cardiac and cardiovascular disease. The goal of this study was to quantify arterial compliance, blood pressure, and left ventricular (LV) function from early postnatal development to young adulthood in fibulin-5 null (Fbln5/) mice to determine the effects of reduced arterial compliance during this critical period of elastic fiber assembly. We find that ascending aorta compliance is reduced as early as postnatal day (P) 7 and carotid artery compliance is reduced by P21 in Fbln5/ mice. We did not find significant increases in systolic blood pressure by P60, but pulse pressures are increased by P21 in Fbln5/ mice. LV systolic function, as measured by ejection fraction and fractional shortening, is unaffected in Fbln5/ mice. However, LV diastolic function, as measured by tissue Doppler imaging, is compromised at all ages in Fbln5/ mice. We propose that Fbln5/ mice represent a suitable model for further studies to determine mechanistic relationships between arterial compliance and LV diastolic function.
Time-domain optical sampling of switched-mode microwave amplifiers and multipliers

Time-domain measurements of the output waveforms of two 8-GHz high-efficiency power amplifiers, a 1-GHz frequency doubler, and a 5-GHz frequency doubler are presented in this paper. A new photoconductive probe has enabled nonintrusive time-domain voltage measurements, which confirm switched-mode class-E and class-F amplifier operation. In order to analyze nonlinear amplifiers designed to deliver a sinusoidal wave to the load, voltages at characteristic points inside the circuit need to be known. In multipliers, waveform measurements track harmonic leakage, expediting the design cycle. The high-impedance probe used here is an optoelectronic sampler, which can sense the charge on an exposed interconnect or the field associated with a buried interconnect. These electric-field data are then converted into voltage.
Analytical and Experimental Investigation of Self-Loosening of Preloaded Cap Screw Fasteners

In an effort to establish a theoretical outline of a criterion for preventing the vibration-induced loosening of preloaded threaded fasteners, this paper provides an experimental and analytical insight into the effect of the initial bolt preload and the excitation amplitude on the self-loosening performance of a cap screw fastener. A nonlinear model is used for predicting the clamp load loss caused by the vibration-induced loosening of cap screw fasteners under cyclic transverse loading. Experimental verification was conducted on the twisting torque variation and the effect of the preload level and transverse displacement amplitude. Comparison of the experimental and analytical results on the clamp load loss with the number of cycles verifies that the proposed model accurately predicts self-loosening performance.
Kidney Function of Single Comb White Leghorn Pullets Following Acute Renal Portal Infusion of the Mycotoxin Citrinin

Abstract Poultry consuming diets contaminated with citrinin excrete copious quantities of urine and exhibit increased water consumption. The present study was conducted to determine if citrinin acts directly on the kidneys and, if so, to provide a detailed physiological evaluation of the nephrotoxic effects of citrinin. Single Comb White Leghorn pullets were anesthetized and prepared for renal function studies. Ureteral urine was collected during a pre-infusion period (30 min), during unilateral renal portal infusion of 200 ppm citrinin (30 min), and during a recovery period following citrinin infusion (90 min). Pilot studies had shown that 200 ppm citrinin is the lowest dose capable of causing consistent unilateral responses when infused at a rate of .2 ml/kg body weight (BW)·min. The responses of the portal-infused kidneys were compared with the responses of the contralateral (uninfused) kidneys to determine the direct effects of citrinin. Citrinin had no acute direct (unilateral) effect on glomerular filtration rate, renal plasma flow rate, urine pH, or fractional calcium or magnesium excretion. Citrinin caused rapid unilateral increases in urine flow rates, free water clearance, and in fractional sodium, potassium, and inorganic phosphate excretion. Increased solute excretion did not compensate for increased free water clearance, as reflected by a significant decrease in urine osmolality. Recovery from the effects of citrinin occurred within 30 min after cessation of unilateral renal portal infusion. No histopathological damage was seen when citrinin was infused at 200 and 800 ppm, although dose-related increases in urine flow and decreases in urine osmolality were observed. These results indicate that citrinin acts directly on the kidneys to alter several tubular transport processes, and that the effects of citrinin are reversible.
Asynchronous, irregular automata nets: the path not taken.

This is a prelude to, and an extension of the original paper Artificial tissue models (Stark, R., 1994. The topology and analysis of asynchronous processes. http://www.math.usf.edu/ approximately stark/documents). However, this exposition is designed for a broader audience - anyone working in biological information processing. A primary objective is to demonstrate that irregular asynchronous automata nets, as opposed to cellular automata, are a realistic approach to modeling biological information processing. Also, new material is presented. Sections 1 and 2 review the early history of von Neumann's attempt explore biological information processing and finally the emergence of cellular automata. The history is guided by the question of why John von Neumann knowingly (we believe) compromised his investigation of biological information processing by falling back to the model we now know as cellular automata. Section 3 defines and explores examples of cellular automata and artificial tissue. Sections 4 and 5 contain philosophical observations which unify our paper, and propose an answer to the original question. A new model for Turing's leopards' spot problem is presented. The asynchronous models are defined by a cell program and a local commumications protocol only. Computational freedom comes from asynchronous activity, while global organization emerges from the entropy reducing nature of the cell programs.
Prolonged Cell Cycle Response of HeLa Cells to Low-Level Alkylation Exposure

Alkylation chemotherapy has been a long-standing treatment protocol for human neoplasia. N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) is a direct-acting monofunctional alkylator. Temozolomide is a clinical chemotherapeutic equivalent requiring metabolic breakdown to the alkylating agent. Both chemicals have similar mechanistic efficacy against DNA mismatch repair-proficient tumor cells that lack expression of methylguanine methyltransferase. Clinically relevant concentrations of both agents affect replicating cells only after the first cell cycle. This phenomenon has been attributed to replication fork arrest at unrepaired O(6)-methyldeoxyguanine lesions mispaired with thymine during the first replication cycle. Here, we show, by several different approaches, that MNNG-treated tumor cells do not arrest within the second cell cycle. Instead, the population slowly traverses through mitosis without cytokinesis into a third cell cycle. The peak of both ssDNA and dsDNA breaks occurs at the height of the long mitotic phase. The majority of the population emerges from mitosis as multinucleated cells that subsequently undergo cell death. However, a very small proportion of cells, <1:45,000, survive to form new colonies. Taken together, these results indicate that multinucleation within the third cell cycle, rather than replication fork arrest within the second cell cycle, is the primary trigger for cell death. Importantly, multinucleation and cell death are consistently avoided by a small percentage of the population that continues to divide. This information should prove clinically relevant for the future design of enhanced cancer chemotherapeutics.
The Economic Losers from Smoking Bans

Proponents of smoking bans frequently claim that the bans do not have detrimental economic effects on businesses in the hospitality industry. In making this claim, the proponents typically cite aggregate hospitality industry data indicating there is little change in gross receipts or tax receipts following the implementation of a ban. Such analysis does not detect the economic effect of bans on specific businesses or types of business - for instance, economic harm to bars from such a ban may be offset by gains by restaurants. This paper attempts to determine which types of hospitality businesses are “winners” and which are “losers” under the ban. The paper examines noncompliance violations in Ohio, where a ban was recently implemented, under the theory that businesses that repeatedly violate the ban believe it is in their economic interest to do so. The research finds that Ohio restaurants rarely violate the ban, but bars and fraternal organizations often do.
Cloning and Functional Characterization of Two BTB Genes in the Predatory Mite Metaseiulus occidentalis

Proteins containing the BTB (Bric-a-brac, tramtrack, and Broad Complex) domain typically share low sequence similarities and are involved in a wide range of cellular functions. We previously identified two putative and closely related BTB genes, BTB1 and BTB2, in the genome of the predatory mite Metaseiulus occidentalis. In the current study, full-length BTB1 and BTB2 cDNAs were cloned and sequenced. BTB1 and BTB2 encode proteins of 380 and 401 amino acids, respectively. BTB1 and BTB2 proteins each contain an N-terminal BTB domain and no other identifiable domains. Thus, they belong to a large category of BTB-domain proteins that are widely distributed in eukaryotes, yet with largely unknown function(s). BTB1 and BTB2 gene knockdowns in M. occidentalis females using RNAi reduced their fecundity by approximately 40% and 73%, respectively, whereas knockdown had no impact on their survival or the development of their offspring. These findings suggest these two proteins may be involved in processes related to egg production in this predatory mite, expanding the list of functions attributed to these diverse proteins.
Lung Cancer Risk from Radon in Marcellus Shale Gas in Northeast U.S. Homes

The amount of radon in natural gas varies with its source. Little has been published about the radon from shale gas to date, making estimates of its impact on radon-induced lung cancer speculative. We measured radon in natural gas pipelines carrying gas from the Marcellus Shale in Pennsylvania and West Virginia. Radon concentrations ranged from 1,520 to 2,750 Bq/m3 (41-74 pCi/L), and the throughput-weighted average was 1,983 Bq/m3 (54 pCi/L). Potential radon exposure due to the use of Marcellus Shale gas for cooking and space heating using vent-free heaters or gas ranges in northeastern U.S. homes and apartments was assessed. Though the measured radon concentrations are higher than what has been previously reported, it is unlikely that exposure from natural gas cooking would exceed 1.2 Bq/m3 (<1% of the U.S. Environmental Protection Agency's action level). Using worst-case assumptions, we estimate the excess lifetime (70 years) lung cancer risk associated with cooking to be 1.8×10-4 (interval spanning 95% of simulation results: 8.5×10-5 , 3.4×10-4 ). The risk profile for supplemental heating with unvented gas appliances is similar. Individuals using unvented gas appliances to provide primary heating may face lifetime risks as high as 3.9×10-3 . Under current housing stock and gas consumption assumptions, expected levels of residential radon exposure due to unvented combustion of Marcellus Shale natural gas in the Northeast United States do not result in a detectable change in the lung cancer death rates.
Solanum watneyi, a new bush tomato species from the Northern Territory, Australia named for Mark Watney of the book and film “The Martian”

A new species of andromonoecious Solanum from the Australian "bush tomato clade" of Solanum subgenus Leptostemonum is described. Solanum watneyi Martine & Frawley, sp. nov. is closely allied with Solanum eburneum, and is sympatric with it in parts of its range in the Northern Territory. The new species has been recognized as a variant of Solanum eburneum for decades, at times being referred to by local botanists as Solanum sp. "Bullita" because of its relative abundance in the vicinity of the Bullita Station area of Judbarra/Gregory National Park. Morphometric analyses show that Solanum watneyi differs statistically from Solanum eburneum in several key reproductive and vegetative characters and field observations suggest that the two sister species may represent a case of edaphic speciation. We provide morphometric evidence for the novelty of Solanum watneyi, a complete description, and cite specimens for both species.
New Cryogenic Controls for the Tevatron Low Temperature Upgrade

Fermilab’s Tevatron accelerator is undergoing a major cryogenic system upgrade. This upgrade project is necessary to lower coil temperature of the accelerator’s magnets by approximately 1K. The new system configuration utilizes a new valve box containing a 130 liter subcooling dewar and a Cold Compressor at each of the 24 satellite refrigerators. Each Cold Compressor pumps on a dewar to maintain the two-phase pressure at 50.7 kPa (0.5 atm) producing 3.56K helium in the dewar and magnet strings.
Minimal periods of discrete and smooth orbits

(1989). Minimal Periods of Discrete and Smooth Orbits. The American Mathematical Monthly: Vol. 96, No. 1, pp. 5-17.
Investigation of plant resources in Lanshan National Forest Parkof Hunan Province

The out-door investigation of plant resources in Lanshan National Park of Hunan in 2007 to 2008 in different season and time period in eight times.The plant resources in Lanshan National Forest Park are rich plant resources and luxuriant vegetation,rare and endangered plants enrichment.complex geographical elements and transitional,and a typical characteristic of Nanling Mountain Range.Lanshan National Forest Park as the zonal vegetation in typical subtropical evergreen broadleaved forest,vegetation types,characteristics of community many simple stability;and the area of Castanopsis eyrei forest is the biggest one in Hunan.The suggestion of monitor and protect the rare and endangered plant species and preserve the forest vegetation were pointed out,establish the botanical garden,protect the forest vegetation of the strategic target of sustainable development also measured.
Registries of Birth Defects and Genetic Diseases

Birth defects and genetic disease are the leading causes of infant mortality in the United States and in most developed countries. They are a major contributor to developmental disabilities, representing the fifth leading cause of disability years. About 25% of birth defects and genetic diseases can be prevented by using existing technology. Registries provide investigators with basic information to identify the causes of birth defects and develop prevention strategies.
Definition and evaluation of a synthesis-oriented, user-centered task analysis technique: the task mapping model

Analytic evaluation is a term describing a class of techniques for examining a representation of a user interface design and discovering design flaws and/or predicting user task performance. In our work with analytic evaluation, we have observed limitations on the effectiveness and efficiency of analytic techniques for formative evaluation supporting the iterative design and re-design cycle. In our search for an alternative, we have developed the Task Mapping Model, a substantively different approach to analysis for supporting the user interface design. This body of work defines the task mapping model. This definition includes a task description framework and analysis methodology for using the task mapping model in the iterative user interface development process. An evaluation experiment was performed to illustrate the usefulness of the task mapping model in comparison to using design guidelines. The evaluation experiment compared both methods ability and utility for synthesizing new user interface design requirements. As is often the case with first-time users of complex but effective techniques, quality measures of the resulting analyses were more positive than perceived complexity. The study showed that the task mapping model was more difficult to use and learn than design guidelines; however, the task mapping model was shown to produce higher quality UIDRs than DGL. This study serves as a stepping stone for future studies involving the task mapping model and real world user interface developers.
Analyzing Math-to-Mastery through Brief Experimental Analysis.

The current study evaluated the effectiveness of individualized math-to-mastery (MTM) interventions, selected though brief experimental analysis (BEA), at increasing math fluency skills for three elementary-aged females. As MTM has only been investigated as a multicomponent intervention, the present study utilized BEA to identify those specific components that led to math skills gains in the most efficient manner possible. BEA results indicated that for two of three participants only a partial MTM intervention was necessary to prompt fluency gains, while the entire intervention was the most effective for the third. During extended analysis all three participants displayed math skills gains above those seen during repeated baseline assessments. Results are discussed in terms of further refining MTM through BEA procedures so as to individually target math skill deficits by considering both intervention effectiveness and efficiency.
How grain size controls friction and wear in nanocrystalline metals

Using molecular simulations we investigated the dependence of friction and wear on grain size in nanocrystalline copper. We found that effects of grain size are coupled to the effects of contact size, resulting in a transition from grain size--sensitive regime to grain size--insensitive regime in friction. This transition occurs because for small tips, friction-induced easy-shear planes can be entirely accommodated in a single grain, rendering grain boundaries less relevant to sliding resistance. Trends in friction do not follow trends in hardness, which is sensitive to grain diameter in the entire grain size regime considered in this study. We have also discovered that coupling of the effects of grain diameter and contact size leads to an optimum grain size that minimizes formation of wear chips on the surface.
Topochemically Controlled Polymerization of a Smectic Liquid Crystalline Diacrylate Monomer

In the past two decades, the field of polymerization in the mesomorphic phase has drawn the attention of an increasing number of both chemists and physicists due to the possibility of using a liquid crystalline matrix to control both the polymerization kinetics and the structure of resulting polymers (topochemical control). Macromolecules possessing unique chemical and physical characteristics can be obtained this way. The combination of local molecular orientation and molecular mobility exhibited by mesophases is considered to be of prime importance in achieving both kinds of control. Most of the systems studied so far concern only thermally initiated polymerization of mono-functional monomers in the nematic phase; both in bulk and in nematic media (or solvents). Generally no real enhancement of polymerization rate and no substantial structural difference of the resulting polymers were observed when compared with polymerization in isotropic state.1, 2, 3 This is probably due to the fact that there is no marked structural difference between the isotropic liquid and nematic liquid crystal schematically illustrated in Figure 1. Both of them lack long range and even medium range positional correlation between the molecules, which in our view is necessary to attain both kinetic and structural control during polymerization.
Ortstein and Placic Horizons

Ortstein horizons are relatively common in the USA, but placic horizons are less common. Soils bearing ortstein and placic horizons are used for cranberry and blueberry culture, truck crops, and forestry operations but have many limitations for other kinds of land use. The factors influencing the distribution and formation of these cemented horizons are poorly understood. According to Soil Taxonomy (ST), ortstein consists of spodic materials and occurs in a layer that is ≥25 mm thick and ≥50 % cemented (Soil Survey Staff 2010) (Fig. 18.1). In ST, ortstein is both a diagnostic subsurface horizon and the only rupture-resistance class recognized in the system. In contrast, a placic horizon does not require spodic materials and ranges between 1 and 25 mm in thickness (Fig. 18.2). Unlike the ortstein horizon, the placic horizon is not penetrated by roots except in fractures.
Enhancing Corn Yield in a Winter Cereal Rye Cover Crop System in Southwest Iowa

Water quality impairment related to nitrogen (N) is a concern in Iowa, including meeting nitrate (NO3) drinking water standards and reducing the amount of N lost to the Gulf of Mexico. The Iowa Nutrient Reduction Strategy science assessment identified a rye cover crop as an important in-field management practice for reducing N and phosphorus (P) loss from fields (31% NO3-N and 29% P), and for reducing soil erosion. However, the science assessment identified a corn yield reduction of 6 percent when grown following a rye cover crop. Lower corn yield with use of a cover crop is unacceptable to farmers, so it is important to identify practices that minimize impact on corn establishment, early-season growth, and yield. The objective of this project was to study production practices that might enhance corn yield when grown in a winter cereal rye cover cropping system.
Facility Location Planning with Qualitative Location Factors

In the literature concerning facility location planning quantitative as well as qualitative methods can be found. Since empirical studies mention the importance of qualitative location factors beside quantitative criteria, this paper deals with corresponding planning methods in particular. The methods known from the literature are to criticize, because the given quantitative and qualitative information is not represented adequately. To face this criticism, approaches resulting by the application of multivariate methods of data analysis are presented.
Does the Surgical Correction of Tibial Torsion with Genu Varum Produce Outcomes Similar to Those in Varus Correction Alone

The aim of this article is to study the relationship between tibia vara and external tibial torsion in adults. The following questions were asked: (1) what is the incidence of rotational deformity in patients with genu varum and (2) do patients who undergo correction of tibial torsion with genu varum have similar outcomes to those who undergo simple tibia vara correction? In this study, 69 patients (138 limbs) underwent bilateral proximal tibial osteotomy for the correction of genu varum. Patients with simple coronal plane deformity (varus alone) were treated with either a monolateral external fixator or a hexapod frame. Those with concomitant external tibial torsion were treated with circular external fixation. The primary outcome was the ability to achieve the desired correction of alignment in the coronal, sagittal, and axial planes. Secondary outcomes included a postoperative Knee Injury and Osteoarthritis Outcome Score (KOOS) and a routine patient satisfaction questionnaire. The incidence of tibial torsion among the entire group of patients with bilateral tibia vara was 46% and overwhelmingly external in direction. The two groups had some significant differences in demographics with torsion patients tending to be younger and thinner. The final mechanical axis deviation and medial proximal tibial angle values for both groups did not differ significantly (p = 0.956). The postcorrection thigh–foot axis was not significantly different between the two groups (p = 0.666). Time to union was not significant (p > 0.999). KOOS was not different between the two groups in symptoms, pain, activities of daily living, and return to sport. There was a difference in the quality of life score between the two groups (p = 0.044). There was no difference between the two groups regarding the patient questionnaire. Based on the finding of this analysis, the incidence of rotational malalignment with genu varum is close to 50%. The recognition of this close association with external tibial torsion deformity may allow for further insights into the role of rotation in varus deformity-related knee pathology and treatment. Patients can expect nearly identical outcomes from this surgery.
The Council of Emergency Medicine Residency Directors Speaker Evaluation Form for Medical Conference Planners.

Introduction No summative speaker evaluation form with validity and reliability evidence currently exists in the English medical education literature specifically to help conference planners make future decisions on speakers. We seek to perform a proof of concept evaluation of a concise, effective evaluation form to be filled out by audience members to aid conference planners. Methods We created the CORD-EM form, a novel, 3-question speaker evaluation form for the Council of Emergency Medicine Residency Directors (CORD-EM) national conference and evaluated it for proof of concept. The CORD-EM form was analyzed with three evaluators and randomized to select only 2 evaluators’ ratings to make results more generalizable to a generic audience evaluating the speaker. Results 46 total evaluations ranged from 6 to 9, mean ± standard deviation 8.1 ± 1.2. The form demonstrated excellent internal consistency (Cronbach's alpha .923) with good inter-rater reliability (ICC .617) in the conference context. Conclusions The CORD-EM speaker evaluation form is, to our knowledge, the first evaluation form with early reliability and validity evidence specifically designed to help conference planners. Our results suggest that a short speaker evaluation form can be an effective instrument in the toolbox for conference planners. This article is protected by copyright. All rights reserved.
Monitoring Hydrogen Exchange During Protein Folding by Fast Pressure Jump NMR Spectroscopy

A method is introduced that permits direct observation of the rates at which backbone amide hydrogens become protected from solvent exchange after rapidly dropping the hydrostatic pressure inside the NMR sample cell from denaturing (2.5 kbar) to native (1 bar) conditions. The method is demonstrated for a pressure-sensitized ubiquitin variant that contains two Val to Ala mutations. Increased protection against hydrogen exchange with solvent is monitored as a function of time during the folding process. Results for 53 backbone amides show narrow clustering with protection occurring with a time constant of ca. 85 ms, but slower protection is observed around a reverse turn near the C-terminus of the protein. Remarkably, the native NMR spectrum returns with this slower time constant of ca. 150 ms, indicating that the almost fully folded protein retains molten globule characteristics with severe NMR line broadening until the final hydrogen bonds are formed. Prior to crossing the transition state barrier, hydrog...
State of the Art of Health Care: The Cubism Period

The aim of this chapter is to provide to the reader a quick view of the current “Digital Health” market, including concepts and definitions. In addition, some considerations are done regarding the new imperatives and challenges the system has, and will have, to take care about.
Optimizing Protein-Excipient Interactions for the Development of Aggregation-Reducing Lyophilized Formulations

Abstract As protein drugs become increasing popular therapeutic approaches, formulations must be developed to ensure stability of the final drug product. Lyophilization, or freeze - drying, is an approach commonly used to produce stable protein drugs, yet protein aggregation may still occur in lyophilized formulations. Excipients in the formulation may be selected to reduce the propensity of a protein to aggregate through interaction with aggregation prone regions. In the following work, molecular docking simulations were used to predict the regions on a protein where different excipients were most likely to interact. Simulation results compared variably with experimental hydrogen/deuterium exchange experiments used to determine regions of protein-excipient interactions. The results were used to design formulations for lyophilized calmodulin (PID #1CLL). Sugar and surfactant pairs were selected that would maximize protection of different aggregation prone regions through direct interactions.
Epigenetic Regulations in the Pathogenesis of HCC and the Clinical Application

Hepatocellular carcinoma (HCC) arises from hepatocytes, which constitute 70–80% of all liver cells, and is the most frequent liver malignancy, causing more than 80% of liver cancer cases globally. HCC is rarely associated with the inheritance of familial genetic mutations [70, 129]; this explains in part why pediatric HCC cases are so rare. In fact most HCC cases are diagnosed later in life and are caused by prolonged exposure to environmental factors known to damage the liver progressively over time. Two of the major risk factors associated with the development of HCC include chronic infection with hepatitis B virus (HBV) and chronic infection with hepatitis C virus (HCV); these viruses are detectable in approximately 80% of all HCC cases [108, 123, 132]. Another contributing factor driving the development of viral HCC is the accidental consumption of aflatoxin B1 (AFB1). The toxin is found in contaminated food stores containing Aspergillus fungal species. Heavy chronic cigarette smoking has also recently emerged as a contributory factor [21]. Apart from the hepatitis viruses, the other major independent risk factor for the development of HCC is chronic over consumption of alcohol [36, 90]. Another emerging risk factor is overnutrition. Consumption of excess calories routinely can lead to nonalcoholic fatty liver disease (NAFLD). NAFLD can progress to nonalcoholic steatohepatitis (NASH) which may then further develop into HCC. HCC caused by overnutrition is also linked to obesity and diabetes [120].
Does trade liberalization narrow the gender wage gap? The role of sectoral mobility

Abstract This paper analyzes the impact of import competition and dynamic labor adjustment on gender outcomes in wages and welfare in the U.S.. I consider a dynamic model of sectoral choice and structurally estimate mobility costs using data from the Current Population Survey and O*NET. A measure of intersectoral distance in task characteristics facilitates the structural estimation of switching costs that vary by gender and across sectors. In a set of trade shock simulations, an import competition shock in the manufacturing sector disproportionately affects male employment and wages. Since manufacturing is male labor intensive and men face higher exit costs from manufacturing, wage and welfare gains from trade are higher for women than men.
Near κ - K mass degeneracy and the Kl3 form factors

Abstract We show how the soft pion theorems on the Kl3 and Kl4 matrix elements can be made consistent with the negative values of ξ obtained by the polarization experiments by assuming the existence of a κ-meson with a mass nearly equal to that of the kaon.
Society, Time, and Religious Imagination

We have always known, it seems, that man is a social being. And yet it is evident that we have not discovered how to build a fully satsfying and lasting social order. The difficulty we have in constructing a social order suggests that even though we know that man is a social being we do not understand effectively what it means to be social. This lack of effective understanding is not unique to our time, of course. The problem, in fact, may be as old as our knowledge that man is social. The ancient Confucian philosopher Mencius noted the problem and, in fact, suggested one possible reason for it. He said that when men cultivate the nobility of man and neglect the nobility of heaven they deceive themselves and will end by losing the nobility of man as well as that of heaven.1
THE SYNTHESIS OF PEPTIDES AND PROTEINS BY THE SOLID PHASE METHOD

It is now feasible to study proteins by the synthetic approach. The chemical synthesis of proteins, especially of enzymes, has developed along three general lines; by classical fragment condensations, by the N-carboxyanhydride method, and by the solid phase method. The latter technique was applied to the total synthesis of bovine pancreatic ribonuclease A in this laboratory. The enzyme was synthesized by the stepwise, automated solid phase procedure and was purified by digestion of impurities with trypsin, followed by gel filtration, ion exchange chromatography and ammonium sulfate fractionation. The product had a specific activity of 78% and possessed the expected chemical and physical properties and substrate specificity of natural RNase A. This constitutes a new kind of evidence that the primary structure of an enzyme determines its tertiary structure. Synthetic des (21-25) S-protein was used to demonstrate that residues 21 through 25 are not necessary for the recombination of S-protein with S-peptide to give an active enzyme. The C-terminal tetradecapeptide, RNase 111–124, was synthesized and found to combine with inactive RNase 1–118 to regenerate nearly full activity. A minimum of 9 residues was found to be required for efficient binding. Amino acid replacements in the tetradecapeptide have shown that Phe 120 is important for the binding of the peptide to the protein, but not for the binding of substrate to the enzyme.
Abstract 1707: Tumor treating fields exert cellular and immunologic effects

While there is clear clinical evidence to support the therapeutic efficacy of low dose alternating electric fields (TTFields) in treating glioblastoma, their intracellular targets and mechanism of action remains poorly defined. Historically, TTFields have been thought to operate by inducing extensive plasma membrane blebbing during the entry into anaphase resulting in aberrant mitotic exit and cell death. However, we have found that cells exposed to TTFields exhibited increased granularity and evidence of endoplasmic reticulum stress and genotoxic stress suggesting other mechanisms to explain their clinical efficacy. Cells exposed to TTFields exhibited reductions in levels of culture media acidification and analysis of intracellular metabolism showed evidence for an increase in mitochondrial respiration and glutaminolysis pathway. Our previous analysis of data from the pivotal phase III EF-11 clinical trial showed that increased corticosteroid use was strongly correlated with poor outcomes in TTFields-treated patients, possibly by suppressing immune effector function required for to drive tumor regression. TTFields drives the cell surface expression of immune stimulatory stress marker proteins calreticulin, and the secretion of the Alarmin/DAMP protein, HMGB1 which are together suggest that TTFields can stimulate immunogenic cell death. Co-culture of bone marrow derived macrophages with TTFields-treated CT26 cells resulted in the up-regulation of cell surface activation markers in the macrophage population that was blocked by a monoclonal antibody directed against HMGB1. Further, supernatants from these co-cultures contained increased levels of pro-inflammatory cytokines and chemokines and a reduction of anti-inflammatory cytokines associated with the presence of the TTFields-treated cells relative to co-cultures containing naive tumor cells. Further, in vivo, engrafted Lewis lung carcinoma tumors exhibited increased levels of granzyme positive cells following TTFields treatment. Together, these data suggest that TTFields affect cancer cells during interphase and this insult leads to alterations in cancer cell metabolism and increased tumor cell immunogenicity and thus act to drive increased immune recognition and tumor rejection. In patients, these effects are likely to be opposed by the immune suppressive functions within the tumor microenvironment and corticosteroid use. Therefore, this model of TTFields action may provide a therapeutically rational base to devise improved TTFields treatment strategies from. Citation Format: Eric T. Wong, Joshua Timmons, Kenneth D. Swanson. Tumor treating fields exert cellular and immunologic effects [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1707.
A new cell culture exposure system for studying the toxicity of volatile chemicals at the air–liquid interface

AbstractA cell culture exposure system (CCES) was developed to expose cells established at an air–liquid interface (ALI) to volatile chemicals. We characterized the CCES by exposing indigo dye-impregnated filter inserts inside culture wells to 125 ppb ozone (O3) for 1 h at flow rates of 5 and 25 mL/min/well; the reaction of O3 with an indigo dye produces a fluorescent product. A 5-fold increase in fluorescence at 25 mL/min/well versus 5 mL/min/well was observed, suggesting higher flows were more effective. We then exposed primary human bronchial epithelial cells (HBECs) to 0.3 ppm acrolein for 2 h at 3, 5, and 25 mL/min/well and compared our results against well-established in vitro exposure chambers at the U.S. EPA’s Human Studies Facility (HSF Chambers). We measured transcript changes of heme oxygenase-1 (HMOX1) and interleukin-8 (IL-8), as well as lactate dehydrogenase (LDH) release, at 0, 1, and 24 h post-exposure. Comparing responses from HSF Chambers to the CCES, differences were only observed at 1 ...
Identification of N-terminal protein processing sites by chemical labeling mass spectrometry.

RATIONALE Proteins undergo post-translational modifications and proteolytic processing that can affect their biological function. Processing often involves the loss of single residues. Cleavage of signal peptides from the N-terminus is commonly associated with translocation. Recent reports have suggested that other processing sites also exist. METHODS The secreted proteins from S. aureus N315 were precipitated with trichloroacetic acid (TCA) and amidinated with S-methyl thioacetimidate (SMTA). Amidinated proteins were digested with trypsin and analyzed with a high-resolution orbitrap mass spectrometer. RESULTS Sixteen examples of Staphylococcus aureus secretory proteins that lose an N-terminal signal peptide during their export were identified using this amidination approach. The N-termini of proteins with and without methionine were identified. Unanticipated protein cleavages due to sortase and an unknown protease were also uncovered. CONCLUSIONS A simple N-terminal amidination based mass spectrometry approach is described that facilitates identification of the N-terminus of a mature protein and the discovery of unexpected processing sites.