cssi/SciSciGPT-SciSciNet huggingface dataset:
Insights into the molecular determinants of EF-G catalyzed translocation.

Translocation, the directional movement of transfer RNA (tRNA) and messenger RNA (mRNA) substrates on the ribosome during protein synthesis, is regulated by dynamic processes intrinsic to the translating particle. Using single-molecule fluorescence resonance energy transfer (smFRET) imaging, in combination with site-directed mutagenesis of the ribosome and tRNA substrates, we show that peptidyl-tRNA within the aminoacyl site of the bacterial pretranslocation complex can adopt distinct hybrid tRNA configurations resulting from uncoupled motions of the 3′-CCA terminus and the tRNA body. As expected for an on-path translocation intermediate, the hybrid configuration where both the 3′-CCA end and body of peptidyl-tRNA have moved in the direction of translocation exhibits dramatically enhanced puromycin reactivity, an increase in the rate at which EF-G engages the ribosome, and accelerated rates of translocation. These findings provide compelling evidence that the substrate for EF-G catalyzed translocation is an intermediate wherein the bodies of both tRNA substrates adopt hybrid positions within the translating ribosome.
Evolving Applications for Patient-Centered Health Status Measures

Patient-centered health status measures-assessments of patients' symptoms, function, and quality of life-have matured substantially over the past 2 decades. Currently, valid, reliable, and sensitive disease-specific measures are available for quantifying the health status of patients with cardiovascular disease. This article briefly reviews the concept of health status measures, with a focus on their interpretation. It then discusses both the rationale and potential applications of health status measures in clinical care. Health status measures are not surrogate measures of outcome but rather highly meaningful outcomes of care. As such, they have important emerging roles as outcomes in clinical trials, as tools for monitoring patients in routine clinical care, as a mechanism for operationalizing and evaluating disease management programs, and as tools for quality assessment/improvement. Over time, it is expected that health status measures will also have an increasingly important role in patient-centered medical decision making. By becoming aware of the evolving roles of health status measures, clinicians can help to accelerate the realization of the Institute of Medicine's vision for a more transparent, evidence-based, patient-centered healthcare system.
A maximum entropy approach to the analysis of loss systems

The maximum entropy principle allows us to obtain an estimate of the state probability distribution when our knowledge about the system is only the expected value of some functions of the system state. In this paper we explore the maximum entropy approach to evaluate the state probability distribution of loss systems where the call arrival processes are unknown or not specified. We present some numerical results for a simple loss system and compare them with the well-known Erlang loss model. We also generalize the formulation to the case of multiclass traffic, which will have practical applications in the performance analysis of B-ISDN, all-optical networks, and other networks which can be modeled as loss systems.
Nkx2.2 homeodomain transcription factor is required for the development of serotonin-producing cells in the gut

CONCLUSIONS: This is the first study to demonstrate 1) GATA-5 activation of the SGLT1 promoter and 2) synergistic activation of the SGLT1 promoter by HNF1alpha and GATA-5. This complex interplay of GATA-5, expressed in the villi, and HNF1-alpha, preferentially expressed in crypts, may facilitate control of the differential expression of SGLT1 along the crypt-villus axis. Identifying therapeutic targets in this regulatory pathway may allow modulation of intestinal absorption.
Plant physiological and environmental controls over the exchange of acetaldehyde between forest canopies and the atmosphere

Abstract. We quantified fine scale sources and sinks of gas phase acetaldehyde in two forested ecosystems in the US. During the daytime, the upper canopy behaved as a net source while at lower heights, reduced emission rates or net uptake were observed. At night, uptake generally predominated throughout the canopies. Net ecosystem emission rates were inversely related to foliar density due to the extinction of light in the canopy and a respective decrease of the acetaldehyde compensation point. This is supported by branch level studies revealing much higher compensation points in the light than in the dark for poplar (Populus deltoides) and holly oak (Quercus ilex) implying a higher light/temperature sensitivity for acetaldehyde production relative to consumption. The view of stomata as the major pathway for acetaldehyde exchange is supported by strong linear correlations between branch transpiration rates and acetaldehyde exchange velocities for both species. In addition, natural abundance carbon isotope analysis of gas-phase acetaldehyde during poplar branch fumigation experiments revealed a significant kinetic isotope effect of 5.1±0.3‰ associated with the uptake of acetaldehyde. Similar experiments with dry dead poplar leaves showed no fractionation or uptake of acetaldehyde, confirming that this is only a property of living leaves. We suggest that acetaldehyde belongs to a potentially large list of plant metabolites where stomatal resistance can exert long term control over both emission and uptake rates due to the presence of both source(s) and sink(s) within the leaf which strongly buffer large changes in concentrations in the substomatal airspace due to changes in stomatal resistance. We conclude that the exchange of acetaldehyde between plant canopies and the atmosphere is fundamentally controlled by ambient acetaldehyde concentrations, stomatal resistance, and the compensation point which is a function of light/temperature.
DNA-induced dimerization of the single-stranded DNA binding telomeric protein Pot1 from Schizosaccharomyces pombe

Eukaryotic chromosome ends are protected from illicit DNA joining by protein–DNA complexes called telomeres. In most studied organisms, telomeric DNA is composed of multiple short G-rich repeats that end in a single-stranded tail that is protected by the protein POT1. Mammalian POT1 binds two telomeric repeats as a monomer in a sequence-specific manner, and discriminates against RNA of telomeric sequence. While addressing the RNA discrimination properties of SpPot1, the POT1 homolog in Schizosaccharomyces pombe, we found an unanticipated ssDNA-binding mode in which two SpPot1 molecules bind an oligonucleotide containing two telomeric repeats. DNA binding seems to be achieved via binding of the most N-terminal OB domain of each monomer to each telomeric repeat. The SpPot1 dimer may have evolved to accommodate the heterogeneous spacers that occur between S. pombe telomeric repeats, and it also has implications for telomere architecture. We further show that the S. pombe telomeric protein Tpz1, like its mammalian homolog TPP1, increases the affinity of Pot1 for telomeric single-stranded DNA and enhances the discrimination of Pot1 against RNA.
Post-operative apnoea in the former preterm infant: a review

Summary Former preterm infants are known to be at increased risk for apnoea, periodic breathing, and bradycardia. When surgery cannot be postponed until respiratory function is more mature, speical peri-operative considerations and measures are essential. In this article, the literature concerning this subject is reviewed, summarizing prospective and retrospective studies of risks associated with surgery in former preterm infants during the first year of life. This work is placed within the context of our ongoing studies of peri-operative risk in former preterm infants undergoing surgery at the Children's National Medical Center (CNMC), which have focused on three particular areas: (1) the effects of spinal versus general anaesthesia on the incidence of post-operative apnoea and bradycardia; (2) the possible contribution of anaemia of prematurity to surgical risk; and (3) the effect of peri-operative caffeine in preventing post-operative apnoea. Recommendations are made concerning surgical and anaesthetic management of infants who undergo surgery at < 44 weeks' post-conceptual age.
The Unique Position of the Degenerating Macronucleus in Tetrahymena tropicalis

In contrast to the situation in 13 other species of the Tetrahymena pyriformis complex, in which the condensed degenerating old macronucleus lies in the posterior end of the cell during the late stages of conjugation, in Tetrahymena tropicalis that nucleus is found in the anterior portion. This developmental characteristic may be useful for taxonomic purposes as well as being of value in investigations on nucleocytoplasmic interaction.
Molecular Approaches to Microbiological Monitoring: Fecal Source Detection

Molecular methods are useful both to monitor natural communities of bacteria, and to track specific bacterial markers in complex environments. Length-heterogeneity polymerase chain reaction (LH-PCR) and terminal restriction fragment length polymorphism (T-RFLP) of 16S rDNAs discriminate among 16S rRNA genes based on length polymorphisms of their PCR products. With these methods, we developed an alternative indicator that distinguishes the source of fecal pollution in water. We amplify 16S rRNA gene fragments from the fecal anaerobic genus Bacteroides with specific primers. Because Bacteroides normally resides in gut habitats, its presence in water indicates fecal pollution. Molecular detection circumvents the complexities of growing anaerobic bacteria. We identified Bacteroides LH-PCR and T-RFLP ribosomal DNA markers unique to either ruminant or human feces. The same unique fecal markers were recovered from polluted natural waters. We cloned and sequenced the unique markers; marker sequences were used to design specific PCR primers that reliably distinguish human from ruminant sources of fecal contamination. Primers for more species are under development. This approach is more sensitive than fecal coliform assays, is comparable in complexity to standard food safety and public health diagnostic tests, and lends itself to automation and high-throughput. Thus molecular genetic markers for fecal anaerobic bacteria hold promise for monitoring bacterial pollution and water quality.
Post-translational regulation of the 54K cellular tumor antigen in normal and transformed cells.

Abstract The 54K cellular tumor antigen has been translated in vitro, using messenger ribonucleic acids from simian virus 40 (SV40)-transformed cells or 3T3 cells. The in vitro 54K product could be immunoprecipitated with SV40 tumor serum and had a peptide map that was similar, but not identical, to the in vivo product. The levels of this 54K protein in SV3T3 cells were significantly higher than those detected in 3T3 cells (D. I. H. Linzer, W. Maltzman, and A. J. Levine, Virology 98:308-318, 1979). In spite of this, the levels of translatable 54K messenger ribonucleic acid from 3T3 and SV3T3 cells were roughly equivalent or often greater in 3T3 cells. Pulse-chase experiments with the 54K protein from 3T3 or SV3T3 cells demonstrated that this protein, once synthesized, was rapidly degraded in 3T3 cells but was extremely stable in SV3T3 cells. Similarly, in an SV40 tsA-transformed cell line, temperature sensitive for the SV40 T-antigen, the 54K protein was rapidly turned over at the nonpermissive temperature and stable at the permissive temperature, whereas the levels of translatable 54K messenger ribonucleic acid at each temperature were roughly equal. These results demonstrate a post-translational regulation of the 54K cellular tumor antigen and suggest that this control is mediated by the SV40 large T-antigen.
Daily nest survival rates of Gunnison Sage-Grouse (Centrocercus minimus): assessing local- and landscape-scale drivers

The Gunnison Sage-Grouse (Centrocercus minimus) is a species of conservation concern and is a candidate for listing under the U.S. Endangered Species Act because of substantial declines in populations from historic levels. It is thought that loss, fragmentation, and deterioration of sagebrush (Artemisia spp.) habitat have contributed to the decline and isolation of this species into seven geographically distinct subpopulations. Nest survival is known to be a primary driver of demography of Greater Sage-Grouse (C. urophasianus), but no unbiased estimates of daily nest survival rates (hereafter nest survival) exist for Gunnison Sage-Grouse or published studies identifying factors that influence nest survival. We estimated nest survival of Gunnison Sage-Grouse for the western portion of Colorado's Gunnison Basin subpopulation, and assessed the effects and relative importance of local- and landscape-scale habitat characteristics on nest survival. Our top performing model was one that allowed variation in nest survival among areas, suggesting a larger landscape-area effect. Overall nest success during a 38-day nesting period (egg-laying plus incubation) was 50% (daily survival rate; SE 5 0.982 (0.003)), which is higher than previous estimates for Gunnison Sage-Grouse and generally higher than published for the closely related Greater Sage-Grouse. We did not find strong evidence that local-scale habitat variables were better predictors of nest survival than landscape-scale predictors, nor did we find strong evidence that any of the habitat variables we measured were good predictors of nest survival. Nest success of Gunnison Sage-Grouse in the western portion of the Gunnison Basin was higher than previously believed. Received 9 January 2014. Accepted 13 August 2014.
Teaching With Data In The Principles Of Macroeconomics Course

Economic data play an important role in the study of macroeconomics. Teaching with data through interactive classes can engage students more fully in the learning process. Although the pedagogy of teaching with data has been widely applied in the undergraduate science classroom, its extension to the economics classroom is rarely discussed. This paper attempts to fill in this paucity in the literature by discussing two examples of integrating economic data in a principles of macroeconomics course.
New discretization procedure for the breakage equation

A new discretization method, applicable for both batch and continuous systems, is developed for the breakage equation. The problem of intrainterval interactions due to discretization is accounted for by matching the zeroth and first moments of the continuous population balance equation with the corresponding moments of the discretized equation, thereby guaranteeing conservation of mass and total number of particles. Without loss of generality, the use of this method is demonstrated with a power law form of the specific rate of breakage, and with both theoretical and empirical breakage functions. The systematic method requires minimum computational efforts by allowing the user to choose either geometric size intervals with any geometric ratio or equal-size intervals for the particle size range. Simulation results show that the new method significantly improves predictions of the particle size distribution over the discretization method currently in use.
Factors predicting complication rates following total knee replacement.

Background: The purpose of this investigation was to expand on previous studies by more fully examining the role of a variety of patient and hospital characteristics in determining adverse outcomes following total knee replacement. Methods: With use of data from all hospital admissions in California from 1991 through 2001, multiple logistic regression was performed on the information regarding patients treated with total knee replacement. Rates of mortality and readmission due to infection and pulmonary embolism during the first ninety days after discharge were regressed against a variety of independent variables, including demographic factors (age, gender, race, ethnicity, and insurance type), burden of comorbid disease (Charlson comorbidity index), and provider variables (hospital size, teaching status, and surgical volume). A separate baseline probability analysis was then performed to compare the relative importance of all predictor variables. Results: The sample size for this analysis was 222,684. A total of 1176 deaths (rate, 0.53%), 1586 infections (0.71%), and 914 pulmonary emboli (0.41%) occurred within the first ninety days after discharge. The average age of the patients at the time of surgery was sixty-nine years. Sixty-two percent of the patients were women, and 32% had a Charlson comorbidity index of >0. The significant predictors for complications (p < 0.05) included age, gender, race/ethnicity, Charlson comorbidity index, insurance type, and hospital volume. A baseline probability analysis was performed with the base case considered to be a white woman who was over the age of sixty-five years, had a Charlson comorbidity index of 0, had Medicare insurance, and was treated at a high-volume, non-teaching hospital. For a patient with the baseline case characteristics, the probability of death was 31/10,000, the probability of infection was 59/10,000, and the probability of pulmonary embolism was 41/10,000 in the first ninety days after discharge. Altering the base case by assuming that care was received at a low-volume hospital increased the expected mortality rate by a factor of 26%. Increasing the Charlson comorbidity index to 1 increased the mortality rate by 170%, whereas decreasing the age to younger than sixty-five years lowered the mortality rate by 73%. Hospital volume, comorbidity, and age had similar effects on the expected rates of readmission due to infection and pulmonary embolism. Conclusions: The effects of age and the Charlson comorbidity index on the baseline probability of adverse outcomes following total knee replacement were shown to be similar to or greater than the effect of hospital volume. This study elucidates and compares the relative importance of the effects of several different factors on outcome. This information is important when considering the conclusions and implications of this type of policy-relevant outcomes research. Level of Evidence: Prognostic Level II. See Instructions to Authors for a complete description of levels of evidence.
Using neutral models to identify constraints on low-severity fire regimes*

Climate, topography, fuel loadings, and human activities all affect spatial and temporal patterns of fire occurrence. Because fire is modeled as a stochastic process, for which each fire history is only one realization, a simulation approach is necessary to understand baseline variability, thereby identifying constraints, or forcing functions, that affect fire regimes. With a suitable neutral model, characteristics of natural fire regimes estimated from fire history data can be compared to a “null hypothesis”. We generated random landscapes of fire-scarred trees via a point process with sequential spatial inhibition. Random ignition points, fire sizes, and fire years were drawn from uniform and exponential family probability distributions. We compared two characteristics of neutral fire regimes to those from five watersheds in eastern Washington that have experienced low-severity fire. Composite fire intervals (CFIs) at multiple spatial scales displayed similar monotonic decreases with increasing sample area in neutral vs. real landscapes, although patterns of residuals from statistical models differed. In contrast, parameters of the Weibull distribution associated with temporal trends in fire hazard exhibited different forms of scale dependence in real vs. simulated data. Clear patterns in neutral landscapes suggest that deviations from them in empirical data represent real constraints on fire regimes (e.g., topography, fuels). As with any null model, however, neutral fire-regime models need to be carefully tuned to avoid confounding these constraints with artifacts of modeling. Neutral models show promise for investigating low-severity fire regimes to separate intrinsic properties of stochastic processes from the effects of climate, fuel loadings, topography, and management.
Novel function of the flap endonuclease 1 complex in processing stalled DNA replication forks

Restarting stalled replication forks partly depends on the break-induced recombination pathway, in which a DNA double-stranded break (DSB) is created on the stalled replication fork to initiate the downstream recombination cascades. Single-stranded DNA gaps accumulating on stalled replication forks are potential targets for endonucleases to generate DSBs. However, it is unclear how this process is executed and which nucleases are involved in eukaryotic cells. Here, we identify a novel gap endonuclease (GEN) activity of human flap endonuclease 1 (FEN-1), critical in resolving stalled replication fork. In response to replication arrest, FEN-1 interacts specifically with Werner syndrome protein for efficient fork cleavage. Replication protein A facilitates FEN-1 interaction with DNA bubble structures. Human FEN-1, but not the GEN-deficient mutant, E178A, was shown to rescue the defect in resistance to UV and camptothecin in a yeast FEN-1 null mutant.
Three-Dimensional Shape Analysis Using Local Shape Descriptors

The three-dimensional shape analysis problem is a very demanding test of shape analysis algorithms. Previous approaches to the problem have employed global features such as moments and Fourier descriptors. Global features lack the capacity for solving the partial shape recognition problem, in which only part of the unknown shape is available. Previous approaches to local shape analysis have employed structural (syntactic) methods, but these methods have so far failed to solve the three-dimensional problem. This paper describes a hybrid structural/statistical local shape analysis algorithm which is applied to the three-dimensional problem.
A two-way interactive nesting procedure with variable terrain resolution

Abstract A two-way interactive, nested-grid system tested with The Pennsylvania Slate University/INCAR three-dimensional mesoscale model is described. A mesh structure, designed to minimize numerical noise, together with a procedure for obtaining compatible coarse grid mesh (COM) and fine grid mesh (FOM) terrain conditions, is presented. Also, a method to initialize the nested-grid meshes is proposed. The nested-grid system has been tested with real data and raw terrain under different severe conditions. A 12-h simulation of a propagating jet streak over complex terrain is presented; the results indicate relatively noise-free solutions on both the OGM and FGM domains.
Efficient deployment of mobile detectors for security applications

We present a real-world problem that arises in security threat detection applications. The problem consists of deploying mobile detectors on moving units that follow predefined routes. Examples of such units are buses, coaches, and trolleys. Due to a limited budget not all available units can be equipped with a detector. The goal is to equip a subset of units such that the utility of the resulting coverage is maximized. Existing methods for detector deployment are designed to place detectors in fixed locations and are therefore not applicable to the problem considered here. We formulate the planning problem as a binary linear program and present a coverage heuristic for generating effective deployments in short CPU time. The heuristic has theoretical performance guarantees for important special cases of the problem. The effectiveness of the coverage heuristic is demonstrated in a computational analysis based on 28 instances that we derived from real-world data.
Reprogramming eukaryotic translation with ligand-responsive synthetic RNA switches

Protein synthesis in eukaryotes is regulated by diverse reprogramming mechanisms that expand the coding capacity of individual genes. Here, we exploit one such mechanism, termed -1 programmed ribosomal frameshifting (-1 PRF), to engineer ligand-responsive RNA switches that regulate protein expression. First, efficient -1 PRF stimulatory RNA elements were discovered by in vitro selection; then, ligand-responsive switches were constructed by coupling -1 PRF stimulatory elements to RNA aptamers using rational design and directed evolution in Saccharomyces cerevisiae. We demonstrate that -1 PRF switches tightly control the relative stoichiometry of two distinct protein outputs from a single mRNA, exhibiting consistent ligand response across whole populations of cells. Furthermore, -1 PRF switches were applied to build single-mRNA logic gates and an apoptosis module in yeast. Together, these results showcase the potential for harnessing translation-reprogramming mechanisms for synthetic biology, and they establish -1 PRF switches as powerful RNA tools for controlling protein synthesis in eukaryotes.
Heavy residue formation in 20 MeV/nucleon {sup 197}Au-{sup 12}C and {sup 197}Au-{sup 27}Al collisions

The yields and velocity distributions of heavy residues and fission fragments from the reaction of 20 MeV/nucleon {sup 197}Au with {sup 12}C and {sup 27}Al have been measured using the MSU A1200 fragment separator. The mass and isotopic distributions of the reaction products are generally consistent with previously measured radiochemical data. One observes, especially for the Au+Al reaction, the production of very neutron deficient nuclides, possibly including {open_quotes}new{close_quotes} nuclei. The heavy-residue velocity distributions can be resolved into components due to fusionlike collisions (incomplete fusion, v{sub res}/v{sub cn}{approx_equal}0.8) along with components due to more peripheral interactions. Fusionlike events were observed that lead to near- and trans-gold species. The observed mass and charge distributions of the fusionlike products, sorted by velocity, are compared with the results of simulations using PACE2 and GEMINI of the decay of the excited incomplete fusion products. The simulations, while reproducing the general features of the data, predict residue distributions that are too neutron deficient relative to the observed distributions. The observed yields of the trans-gold species are not predicted in the simulations. {copyright} {ital 1998} {ital The American Physical Society}
When the Left Ventricle Rocks: Its Causes and Relevance.

To rock: to move back and forth in or as if in a cradle; to rouse to excitement—Merriam Webster Dictionary [(1)][1] The left ventricle (LV), when imaged in horizontal plane, may exhibit 3 types of motion: inward (reflective of muscle thickening); along the long axis (reflecting piston-like
Effects of Peritoneal Ventilation with Perfluorocarbon after Acute Lung Injury in Rabbits

Objective:To investigate the effects of peritoneal ventilation with perfluorocarbon after acute lung injury(ALI) in rabbits.Methods:Twenty four rabbits with ALI induced by centre intravenous injection of oleic acid and saline suspension were randomly assigned to four groups,control group,conventional mechanical ventilation(CMV) group,peritoneal ventilation with perfluorocarbon(PFC-PV) group and CMV+PFC-PV group.All of the rabbits were ventilated for two hours.The blood gas index,oxygenation index and respiratory system dynamic compliance(Cdyn) were measured and analyzed at 0,30,60,and 120 min after ALI.Results:Compared with control group,p(O2)level was significantly elevated among PFC-PV,CMV and CMV+PFC-PV groups,with the highest level in CMV+PFC-PV group.The level of PaO2/FiO2 was also improved in PFC-PV,CMV and CMV +PFC -PV groups,best in CMV +PFC -PV group.The respiratory system dynamic compliance remained unchanged in CMV group,while improved in CMV+PFC-PV group(P 0.05).The Cdyn level was elevated from 0.78 to 0.90 after 60min of ALI.Conclusion:The treatment of CMV+PFC-PV could induce a significant improvement on gas exchange and Cdyn in rabbits with ALI,thus providing a new treatment method for serious anoxia in reversible lung injury.
Case 1: African-American Infant and Family

A 3-year-old African-American infant is brought to the Emergency Department by her 19-year-old mother and her 55-year-old grandmother. The infant is febrile to 104.2 °F and is inconsolable, pulling on her left ear and clinging to her mother. The infant is wrapped in several blankets and dressed in flannel long-sleeved pajamas. In the patient treatment area, the resident, a young white man, undresses the infant to examine her. The exam is remarkable for a dull left tympanic membrane with decreased movement on pneumatoscopy: the rest of the physical exam is unremarkable. The doctor, believing the child to be overdressed, prevents the mother from replacing all of the layers of clothing and blankets. The infant’s grandmother becomes so hostile that she has to be removed by security.
Los Alamos Advanced FEL

Many industrial and research applications can benefit from the availability of a compact, turn-key laser that puts out 100 W or more of tunable light. Free-electron lasers are inherently capable of generating many wavelengths of light with high average powers but they are typically large and complex machines. Over tire past three years, Los Alamos has sponsored an engineering effort to design, build and test a compact and versatile free-electron laser called the Advanced FEL.
Insulin-Like Growth Factors: Natural Regulators of the Cell Cycle

Publisher Summary This chapter discusses a family of substances that is called somatomedins. The somatomedins are like insulin in structure and, therefore referred to as insulin-like growth factors (IGFs). It describes the mechanism of action of the IGFs. The somatomedin peptides resemble insulin in both structure and metabolic activity. Insulin's bioactivity—such as stimulation of glucose influx in rat adipose tissue or diaphragm—is not coincident with its immunoreactivity. Antibodies raised against insulin obliterate only about 10% of its effect. The left -over material that is still able to act in insulin's place is termed as nonsuppressible insulin-like activity (NSILA). A spectrum of effects similar to those for somatomedins and IGFs has also been reported for multiplication stimulating activity (MSA). This factor has insulin-like activity and shares with IGFs and somatomedins the ability to support fibroblast proliferation in vitro.
Imaging Instability in the Contact Athlete: What to Look For

Intra-articular pathology that occurs from glenohumeral instability events, including labral tears, glenoid bone loss, and Hill-Sachs lesions, may contribute to increased risk of recurrent instability and persistent pain and disability following initial treatment. Careful analysis of radiographic and advanced imaging studies can assist in the recognition of clinically significant pathology. This article provides guidance on the appropriate use of diagnostic imaging for the evaluation of glenohumeral instability and describes radiographic and advanced imaging findings that can affect treatment outcomes in the contact athlete.
427. 3D Modeling of Lung Adenocarcinoma With a Hydrogel Scaffold

The contribution of the microenvironment to tumorigenesis is now widely recognized and encompasses both the 3D architectural structure and the interaction between malignant and normal stromal cells. This interactivity cannot be reproduced by conventional 2D cell culture systems. We have developed a fibrin-based hydrogel 3D lung cancer model that allows in vitro and in vivo modeling of tumor-stromal interaction under reproducible and tunable conditions. We engineered the model by culturing tumor cells (A549 or H1299), alone or in combination with fibroblasts (MRC5) and/or endothelial cells (HUVECs), within a PEG-fibrin hydrogel which is readily produced, biocompatible and stable (for up to 40 days). The hydrogel 3D culture can be monitored through microscopy and enables cells to acquire a more physiological ‘tumor-like’ morphology compared to 2D cultures. An enzymatic system (Nattokinase) enables efficient cell retrieval of almost 100% of the cells, which are >95% viable and retain their surface markers. Using this model we showed that A549 lung adenocarcinoma tumor cells organized into glandular clusters whose HE p<0.0001).Having shown the feasibility of 3D-modeling a lung adenocarcinoma, we compared the response of these 3D tumors to the oncolytic adenovirus (OncAd) ICOVIR15 with the effects on 2D culture and compared both with the activity of the OncAd in vivo in a SCID-beige mice xenograft model by monitoring tumor bioluminescence. The 3D model more closely replicated the kinetics of tumor growth control in vivo than did the 2D model. Control required 14 days in vivo and in the3D model whereas in the 2D culture complete eradication was obtained by day 7 (fold increase in signal in untreated and treated groups respectively at day 14: in vivo, 14.56±7.81 and 6.50±5.24 vs 3D, 7.41±4.02 and 2.75±0.72 vs 2D, 328.3±72.71 and 0.01±0.01).To test the system in vivo, we injected the hydrogels (A549, A549 + MRC5 or A549+MRC5+HUVECs) i.p. into SCID-beige mice and let them grow for 2 weeks before retrieving and analyzing them. The tumor grew as islands and H&E confirmed a more aggressive phenotype, with larger tumor size and higher vascularization in the presence of MRC5 and HUVECs.In conclusion, we developed a 3D lung adenocarcinoma model with morphological and biological features of in vivo tumors. This model offers the opportunity to study, in vitro and in vivo, the role of human stroma in cancer progression and to more realistically predict tumor response to biological and other therapies including Onc Ad.
37 – The Insight Toolkit: An Open-Source Initiative in Data Segmentation and Registration

Insight Toolkit (ITK) is an open-source library of software components for data segmentation and registration, supported by federal funding through the National Library of Medicine and National Institutes of Health, and is available in the public domain. ITK is designed to complement visualization and user interface systems to provide advanced algorithms for filtering, segmentation, and registration of volumetric data. Created originally to provide preprocessing and analysis tools for medical data, ITK is being used for image processing in a wide range of applications from handwriting recognition to robotic computer vision. This chapter begins with an overview and introduction to ITK, its history, its design principles, and the resulting architecture of the collection image processing software components. The chapter also provides sources for obtaining additional information and locations for downloading ITK source code.
Advances in Absorbable Biomaterials and Nasal Packing

Nasal biomaterials have been developed to improve postoperative outcomes after functional endoscopic sinus surgery (FESS). These products have been designed to overcome certain common complications in FESS, and to maximize patient comfort. This article evaluates the performance of nonabsorbable and absorbable packing with respect to these outcomes. The collected trials suggest superior performance of bioabsorbable packs compared with absorbable packs with respect to patient comfort. For hemostasis and wound healing, variation in performance metrics makes interstudy comparison difficult. Before further trials are conducted, consensus must be reached among rhinologists as to the proper method of evaluating these products.
Characteristics of Pediatric Emergency Revisits After an Asthma-Related Hospitalization.

Study objective We identify and characterize factors related to subsequent emergency revisits among children hospitalized for asthma. Methods This population-based, prospective, observational cohort included children aged 2 to 16 years, hospitalized for asthma at an urban pediatric facility and followed for greater than or equal to 12 months. The primary outcome was asthma-related emergency revisit within 12 months of discharge. Revisits were identified by billing codes, respiratory chief complaints, and medications administered (eg, albuterol, systemic corticosteroids), dispensed, or prescribed. Predictors and covariates include demographic, socioeconomic, access, and environmental exposure variables collected during index admission. Multivariable logistic regression was used to evaluate the association between predictors and odds of asthma-related revisit. Results A total of 671 children were enrolled; the majority were boys (65%), aged 4 to 11 years (59%), black (59%), and publicly insured (73%). There were 274 patients (41%) who were treated for asthma-related emergency revisits within 12 months of the index admission. In adjusted models, younger children, black children, children with excellent reported access to primary care, and children with a history of inhaled steroids were more likely to experience emergency revisits. Low income, detectable cotinine levels, and traffic exposure did not independently predict revisit. Conclusion Asthma-related emergency revisit is common after hospitalization, with more than 40% of children returning within 12 months. Socioeconomic and exposure-related risk factors typically predictive of asthma morbidity were not independently associated with emergency revisit among children in this cohort.
Access To Obstetric Services In Rural Counties Still Declining, With 9 Percent Losing Services, 2004–14

Recent closures of rural obstetric units and entire hospitals have exacerbated concerns about access to care for more than eighteen million women of reproductive age living in rural America. Yet th...
DNA polymerase β: A missing link of the base excision repair machinery in mammalian mitochondria.

Abstract Mitochondrial genome integrity is fundamental to mammalian cell viability. Since mitochondrial DNA is constantly under attack from oxygen radicals released during ATP production, DNA repair is vital in removing oxidatively generated lesions in mitochondrial DNA, but the presence of a strong base excision repair system has not been demonstrated. Here, we addressed the presence of such a system in mammalian mitochondria involving the primary base lesion repair enzyme DNA polymerase (pol) β. Pol β was localized to mammalian mitochondria by electron microscopic-immunogold staining, immunofluorescence co-localization and biochemical experiments. Extracts from purified mitochondria exhibited base excision repair activity that was dependent on pol β. Mitochondria from pol β-deficient mouse fibroblasts had compromised DNA repair and showed elevated levels of superoxide radicals after hydrogen peroxide treatment. Mitochondria in pol β-deficient fibroblasts displayed altered morphology by electron microscopy. These results indicate that mammalian mitochondria contain an efficient base lesion repair system mediated in part by pol β and thus pol β plays a role in preserving mitochondrial genome stability.
Structural Emergence in Particle Dispersions

Particle dispersions, such as pigment-based inks, comprise weakly bound, milled nanoparticles. The properties of these pigments depend on both their chemical composition and a rather complex structural hierarchy which emerges from these dispersions. The emergence of structure under semidilute conditions is related to the structure of the dilute particles, the particle spacing (mesh size), processing history, and the interaction potential. Kinetic simulations could predict such emergence using these input parameters. In this paper, organic pigments are studied as an example of the importance of emergent structure to predict properties such as brilliance and opacity. Organic pigments are used to impart color to commercial inks, plastics, coatings, and cosmetics. In many cases, dilute pigments are mass fractal structures consisting of aggregated nanoparticles held together by weak van der Waals forces. In water, surfactant is added to create a pigment dispersion (an ink). The final properties of a pigment em...
Altered homeostasis and development of regulatory T cell subsets represent an IL-2R-dependent risk for diabetes in NOD mice.

The cytokine interleukin-2 (IL-2) is critical for the functions of regulatory T cells (T regs ). The contribution of polymorphisms in the gene encoding the IL-2 receptor α subunit ( IL2RA ), which are associated with type 1 diabetes, is difficult to determine because autoimmunity depends on variations in multiple genes, where the contribution of any one gene product is small. We investigated the mechanisms whereby a modest reduction in IL-2R signaling selectively in T lymphocytes influenced the development of diabetes in the NOD mouse model. The sensitivity of IL-2R signaling was reduced by about two- to threefold in T regs from mice that coexpressed wild-type IL-2Rβ and a mutant subunit (IL-2Rβ Y3 ) with reduced signaling (designated NOD-Y3). Male and female NOD-Y3 mice exhibited accelerated diabetes onset due to intrinsic effects on multiple activities in T regs . Bone marrow chimera and adoptive transfer experiments demonstrated that IL-2Rβ Y3 T regs resulted in impaired homeostasis of lymphoid-residing central T regs and inefficient development of highly activated effector T regs and that they were less suppressive. Pancreatic IL-2Rβ Y3 T regs showed impaired development into IL-10–secreting effector T regs . The pancreatic lymph nodes and pancreases of NOD-Y3 mice had increased numbers of antigen-experienced CD4 + effector T cells, which was largely due to impaired T regs , because adoptively transferred pancreatic autoantigen–specific CD4 + Foxp3 − T cells from NOD-Y3 mice did not accelerate diabetes in NOD.SCID recipients. Our study indicates that the primary defect associated with chronic, mildly reduced IL-2R signaling is due to impaired T regs that cannot effectively produce and maintain highly functional tissue-seeking effector T reg subsets.
Increased Incidence of Nocardial Infections in an Era of Atovaquone Prophylaxis in Allogeneic Hematopoietic Stem Cell Transplant Recipients

Abstract Nocardial infections have been rare after allogeneic hematopoietic stem cell transplantation (HSCT). We report 10 recent cases of late-onset nocardiosis (median time of onset of 508 days after transplantation) primarily in patients on high doses of corticosteroids for graft-versus-host disease. All 10 patients had pulmonary infection caused by Nocardia species susceptible to trimethoprim-sulfamethoxazole (TMP-SMX). At time of diagnosis 8 of 10 patients were not receiving TMP-SMX for prophylaxis of Pneumocystis jiroveci pneumonia (PJP; 7 on atovaquone, 1 on i.v. pentamidine). After the initiation of atovaquone prophylaxis for PJP in place of TMP-SMX for many UCLA allogeneic HSCT patients in 2012, 9 cases of nocardiosis occurred in 411 patients (2.2%) over the next 6 years (2012 to 2017) compared with only 1 case in 575 patients (0.17%) during the previous 12 years (2000 to 2011). Although there were no deaths directly related to nocardial infection treated primarily with TMP-SMX, overall mortality in this group of patients was 40%. Based on this experience, the use of atovaquone for PJP prophylaxis in place of TMP-SMX may be associated with an increased risk for previously rare nocardial infections after allogeneic HSCT.
Frailty in a racially and socioeconomically diverse sample of middle-aged Americans in Baltimore.

Frailty is a risk factor for disability and mortality, and is more prevalent among African American (AA) elderly than whites. We examine frailty in middle-aged racially and economically diverse adults, and investigate how race, poverty and frailty are associated with mortality. Data were from 2541 participants in the Healthy Aging in Neighborhoods of Diversity across the Life Span study in Baltimore, Maryland; 35–64 years old at initial assessment (56% women; 58% AA). Frailty was assessed using a modified FRAIL scale of fatigue, resistance, ambulation, illness and weight loss, and compared with difficulties in physical functioning and daily activities. Frailty prevalence was calculated across race and age groups, and associations with survival were assessed by Cox Regression. 278 participants were frail (11%); 924 pre-frail (36%); 1339 not frail (53%). For those aged 45–54, a higher proportion of whites (13%) than AAs (8%) were frail; while the proportions were similar for those 55–64 (14%,16%). Frailty was associated with overall survival with an average follow-up of 6.6 years, independent of race, sex and poverty status (HR = 2.30; 95%CI 1.67–3.18). In this sample of economically and racially diverse older adults, the known association of frailty prevalence and age differed across race with whites having higher prevalence at younger ages. Frailty was associated with survival beyond the risk factors of race and poverty status in this middle-aged group. Early recognition of frailty at these younger ages may provide an effective method for preventing or delaying disabilities.
Examining Hepatitis, A and B Vaccination, and HBV Reactivation Monitoring During Direct-Acting Antiviral Therapy for Hepatitis C

The objective of this study was to examine Hepatitis A (HAV) and Hepatitis B (HBV) screening, and the risk of HBV reactivation during Hepatitis C (HCV) therapy with direct-acting antivirals (DAAs). A retrospective chart review was performed of patients treated with second generation DAA therapy from January 2014 to September 2016 at the Iowa City VA Healthcare System. In total 409 patients initiated HCV treatment, 308 (75%) and 241 (59%) were HAV and HBV vaccine eligible, respectively. Among those, 24 (8%) received a HAV vaccine, while only 20 (8%) received a HBV vaccine. Of these, 7 patients initiating an immunization in the clinic had record of completing the series. Further, 101 patients had a reactive Hepatitis B core Antibody indicating previous HBV infection, and 3 of these were tested for HBV reactivation during HCV therapy. Overall, the assessment found low rates of HAV and HBV vaccine administration, indicating missed opportunities for preventative care during HCV therapy. With the known risk of HBV reactivation with DAAs, the need for HAV and HBV screening is essential.
Standardization of Featureless Variables for Machine Learning Models Using Natural Language Processing

AI and machine learning are mathematical modeling methods for learning from data and producing intelligent models based on this learning. The data these models need to deal with, is normally a mixed of data type where both numerical (continuous) variables and categorical (non-numerical) data types. Most models in AI and machine learning accept only numerical data as their input and thus, standardization of mixed data into numerical data is a critical step when applying machine learning models. Having data in the standard shape and format that models require often a time consuming, nevertheless very significant step of the process.
Thrombotic Microangiopathy (TTP/ HUS)

In this chapter thrombotic microangiopathies are discussed—TTP, HUS, and atypical HUS—including diagnosis and treatment. Pregnancy and drug-induced TM are also discussed. The thrombotic microangiopathies (TMs) are a group of diseases which share the traits of microvascular occlusion, thrombocytopenia, and microangiopathic hemolytic anemia. Common to these diseases are a dramatic presentation and often fulminant illness. Although these diseases share some common characteristics, course and prognosis may vary.
A Question Important to Investors (Whether They Realize It or Not): Is Realization a Constitutional Requirement for Income Taxation?

This article considers whether realization continues to be a constitutional requirement for an accession to wealth to be included in the base of the federal income tax. Most commentators had thought that the Supreme Court’s 1920 decision in Eisner v. Macomber, which treated realization as central to the meaning of “taxes on incomes” in the Sixteenth Amendment, was deadwood, or close to it. In 2012, however, in his controlling opinion in National Federation of Independent Business v. Sebelius, Chief Justice Roberts cited Macomber favorably on a point critical to the resolution of that case. If realization still has constitutional legs, a number of provisions in the Internal Revenue Code, including those that rely on mark-to-market concepts, are constitutionally suspect.