cssi/SciSciGPT-SciSciNet huggingface dataset:
Evolution in Saccharomyces cerevisiae : Identification of Mutations Increasing Fitness in Laboratory Populations

Since the publication of the complete sequence of the genome of Saccharomyces cerevisiae, a number of comprehensive investigations have been initiated to gain insight into cellular function. The focus of these studies has been to identify genes essential for survival in specific environments or those that when mutated cause gross phenotypic defects in growth. Here we describe Ty1-based mutational approaches designed to identify genes, which when mutated generate evolutionarily significant phenotypes causing small but positive increments on fitness. As expected, Ty1 mutations with a positive fitness effect were in the minority. However, mutations in two loci, one inactivating FAR3 and one upstream of CYR1, identified in evolving populations, were shown to have small but significantly positive fitness effects.
Minimising the adverse effects of ketorolac.

Gastrointestinal bleeding and perforation, platelet inhibition with altered haemostasis, and renal impairment are among the list of adverse effects associated with the administration of ketorolac. The incidence of serious adverse events has declined since dosage guidelines were revised. Most of the published literature suggests that the overall risk of gastrointestinal or operative site bleeding related to ketorolac therapy is only slightly higher than with opioids. The risk for adverse events, however, increases with high doses, with prolonged therapy (>5 days) or in vulnerable patients (e.g. the elderly). Acute renal failure has been reported after ketorolac treatment but is usually reversible after discontinuation of the drug. As with other nonsteroidal anti-inflammatory drugs (NSAIDs), ketorolac may trigger allergic or hypersensitivity reactions. Careful patient selection is essential if use of ketorolac is considered. Contraindications to ketorolac use include a history of, or current risk of, gastrointestinal bleeding, risk of renal failure, compromised haemostasis, hypersensitivity to aspirin (acetylsalicylic acid) or other NSAIDs, labour, delivery and nursing. Ketorolac should be prescribed at the lowest dosage necessary to control pain; the duration of therapy should also be limited to as few days as possible. Practitioners should be familiar with, and follow, label warnings and dosage guidelines.
Determination of elasticity parameters in lumped element (mass-spring) models of deformable objects

Lumped element models, also known as, mass-spring-damper models, are widely used to simulate deformable objects because of their simplicity and computational efficiency. However, the parameters of lumped element models are typically determined in an ad hoc fashion through trial-and-error, as these models are not directly based on continuum mechanics of deformable objects. In this paper, an alternative method to determine the elasticity parameters of lumped element models of deformable objects is presented. The elasticity parameters are determined using an optimization that minimizes the matrix norm of the error between the stiffness matrices of the linear lumped element model and the linear finite element model of the same object. The method has been developed for two-dimensions and for three-dimensional volumetric objects with tetrahedral and hexahedral (brick) elements. The method has been validated by comparing deformation results of the lumped element models with the deformation results given by finite element models, under various tension, and compression loading conditions.
Using Individualized Learning Plans to Facilitate Learner-Centered Teaching

Individualized learning plans (ILPs) are helpful tools that can facilitate learner-centered education and can be used with all levels of learners. We introduce the concept of ILPs, the rationale for their use in pediatric and adolescent gynecology education, and review the challenges that learners might face in creating ILPs, and describes how educators can support learners during this process.
A Practical Approach for Expanding the Review of Commercial Arbitration Awards: Using an Appellate Arbitrator

Arbitration is supposed to be a quick efficient way to resolve a dispute. One of the main benefits is finality. The Federal Arbitration Act does not allow for a merit based appeal from an arbitral award. If an arbitrator makes an error interpreting or apply law, courts are not empowered to intervene. Hall v. Mattel, 552 U.S. 576 (2008). The only review possible is pursuant to the vacatur provisions of Section 10 of the FAA. For this reason, many lawyers and their clients avoid arbitration. Recently some have recognized that nothing in the FAA prohibits a merit based appeal to another arbitrator. Practitioners aware of this possibility now have a tool for addressing the possibility of mistakes in the interpretation or application of law. This article discusses this procedure examining the rules for appeals adopted by the AAA, CPR and JAMS. The chapter updates a previous version published in 2010.
Regional and Racial Variation in Hospitalization Costs in Patients with Duchenne Muscular Dystrophy

Advances in management for Duchenne muscular dystrophy (DMD) have improved survival. The purpose of this study was to describe hospital outcomes and costs for DMD patients and to identify regional and racial variation. Retrospective review of University Health System Consortium Clinical Data Base/Resource Manager, a …
AIDS-Related Knowledge Among High School Students in Changle County Prevention and Control

Objective To understand the Changle County high school students in AIDS prevention and control knowledge, attitudes, behaviors known cases.Methods A cluster sampling method,Changle County,two high schools(one in Changle,Changle II) of all high school sophomores were 648, its questionnaires and health education.Results The survey was way to high awareness of AIDS infection, but do not know much of the non-transmission routes; substantial proportion of students considered unsafe intercourse with HIV-infected persons; most students are willing to learn more about AIDS prevention and control knowledge. Conclusion Already sexually active high school students are also the focus of AIDS education, schools should strengthen AIDS prevention education, improve the acceptance and level of interest in adolescent patients and HIV AIDS.
Translation Quality Assessment in Health Research: A Functionalist Alternative to Back-Translation:

As international research studies become more commonplace, the importance of developing multilingual research instruments continues to increase and with it that of translated materials. It is therefore not unexpected that assessing the quality of translated materials (e.g., research instruments, questionnaires, etc.) has become essential to cross-cultural research, given that the reliability and validity of the research findings crucially depend on the translated instruments. In some fields (e.g., public health and medicine), the quality of translated instruments can also impact the effectiveness and success of interventions and public campaigns. Back-translation (BT) is a commonly used quality assessment tool in cross-cultural research. This quality assurance technique consists of (a) translation (target text [TT1]) of the source text (ST), (b) translation (TT2) of TT1 back into the source language, and (c) comparison of TT2 with ST to make sure there are no discrepancies. The accuracy of the BT with respect to the source is supposed to reflect equivalence/accuracy of the TT. This article shows how the use of BT as a translation quality assessment method can have a detrimental effect on a research study and proposes alternatives to BT. One alternative is illustrated on the basis of the translation and quality assessment methods used in a research study on hearing loss carried out in a border community in the southwest of the United States.
Mechanisms regulating airway nucleotides.

In the respiratory system, extracellular nucleotides and nucleosides serve as signaling molecules for a wide spectrum of biological functions regulating airway defenses against infection and toxic material. Their concentrations are controlled by a complex network of cell surface enzymes named ectonucleotidases. This highly integrated metabolic network combines the activities of three dephosphorylating ectonucleotidases, namely nucleoside triphosphate diphosphohydrolases (NTPDases), nucleotide pyrophosphatase/phosphodiesterases (NPPs) and alkaline phosphatases (APs). Extracellular nucleotides are also inter-converted by the transphosphorylating activities of ecto adenylate kinase (ectoAK) and nucleoside diphosphokinase (NDPK). Different cell types use specific combinations of ectonucleotidases to regulate local concentrations of P2 receptor agonists (ATP, UTP, ADP and UDP). In addition, they provide AMP for the activity of ecto 5′-nucleotidase (ecto 5′-NT; CD73), which produces the P1 receptor agonist: adenosine (ADO). Finally, mechanisms are in place to prevent the accumulation of airway ADO, namely adenosine deaminases and nucleoside transporters. This chapter reviews the properties of each enzyme and transporter, and the current knowledge on their distribution and regulation in the airways.
In Memoriam: Robert E. Rodes, Jr.

This short piece was composed in honor, appreciation, and memory of Prof. Robert E. Rodes, Jr., who died on November 25, 2014 after serving on the faculty of the Notre Dame Law School for nearly six decades.
A Whole-Body Approach to Point of Care Ultrasound

Ultrasonography is an essential imaging modality in the ICU used to diagnose and guide the treatment of cardiopulmonary failure. Critical care ultrasonography requires that all image acquisition, image interpretation, and clinical applications of ultrasonography are personally performed by the critical care clinician at the point of care and that the information obtained is combined with the history, physical, and laboratory information. Point-of-care ultrasonography is often compartmentalized such that the clinician will focus on one body system while performing the critical care ultrasonography examination. We suggest a change from this compartmentalized approach to a systematic whole-body ultrasonography approach. The standard whole-body ultrasonography examination includes thoracic, cardiac, limited abdominal, and an evaluation for DVT. Other elements of ultrasonography are used when clinically indicated. Each of these elements is reviewed in this article and are accompanied by a link to pertinent cases from the Ultrasound Corner section of CHEST.
A Provisional Thermodynamic Property Formulation for air for States From the Freezing Liquid Line to 873 K With Pressures to 70 Mpa

A provisional thermodynamic property formulation for air based upon new experimental data is presented. The new formulation is valid for temperatures from 65 K to 873 K at pressures to 70 MPa and is based upon new measurements of the density and isochoric heat capacity of liquid air recently completed at the National Institute of Standards and Technology in Boulder, Colorado. This formulation represents a significant improvement over previous formulations, particularly for calculation of properties of liquid air. Separate equations for the calculation of dew and bubble point properties of air from prior work were incorporated in the development of a new fundamental equation of state explicit in Helmholtz energy. The equation of state was developed using a least-squares fitting procedure which has recently been adapted for application to air. The accuracy of properties calculated using the new thermodynamic property formulation is established by comparison to selected experimental data for air.
Prioritization, clustering and functional annotation of MicroRNAs using latent semantic indexing of MEDLINE abstracts.

The amount of scientific information about MicroRNAs (miRNAs) is growing exponentially, making it difficult for researchers to interpret experimental results. In this study, we present an automated text mining approach using Latent Semantic Indexing (LSI) for prioritization, clustering and functional annotation of miRNAs. For approximately 900 human miRNAs indexed in miRBase, text documents were created by concatenating titles and abstracts of MEDLINE citations which refer to the miRNAs. The documents were parsed and a weighted term-by-miRNA frequency matrix was created, which was subsequently factorized via singular value decomposition to extract pair-wise cosine values between the term (keyword) and miRNA vectors in reduced rank semantic space. LSI enables derivation of both explicit and implicit associations between entities based on word usage patterns. Using miR2Disease as a gold standard, we found that LSI identified keyword-to-miRNA relationships with high accuracy. In addition, we demonstrate that pair-wise associations between miRNAs can be used to group them into categories which are functionally aligned. Finally, term ranking by querying the LSI space with a group of miRNAs enabled annotation of the clusters with functionally related terms. LSI modeling of MEDLINE abstracts provides a robust and automated method for miRNA related knowledge discovery. The latest collection of miRNA abstracts and LSI model can be accessed through the web tool miRNA Literature Network (miRLiN) at http://bioinfo.memphis.edu/mirlin .
Religion in the Emergence of Civilization: Çatalhöyük as a Case Study

Few archaeological sites are more iconic than Catalhoyuk. Long seen as an exemplar of the Neolithic transition, it is large in size (about 14 hectares) and housed an ample population (3500–8000 peo...
Abstract 3770: The spindle assembly checkpoint requires phosphatase activity

The spindle assembly checkpoint (SAC) prevents activation of the anaphase-promoting complex (APC/C) until all chromosomes are correctly attached to the mitotic spindle. A defective SAC contributes to errors in chromosome segregation, which promotes aneuploidy and may eventually lead to cancer. Early in mitosis, the mitotic checkpoint complex (MCC) inactivates the APC/C by binding the APC/C activating protein cdc20 until the chromosomes are properly aligned, at which point the MCC dissociates and releases cdc20 to activate the APC/C. Once the APC/C is activated, it targets many substrates for degradation, including cyclin B and securin, and the cell progresses into anaphase. The precise molecular mechanisms regulating SAC inactivation are still poorly understood. We sought to determine the role of mitotic phosphatases in the SAC. To address this question, we treated mitotic cells with various phosphatase inhibitors to examine their effect on APC/C activation. Using this approach we identified two inhibitors, calyculin A and okadaic acid (1uM), that cause MCC dissociation and APC/C activation leading to cyclin A and cyclin B degradation in nocodazole-arrested cells. Although the cells are able to degrade cyclin B, they do not exit mitosis as evidenced by high levels of cdk1 substrate phosphorylation and chromosome condensation. Our results demonstrate that a calyculin A and okadaic acid (1uM) sensitive phosphatase is required for SAC activation. Citation Format: Kristen Foss, Liguo Zhang, Alexander C. Robeson, Sally Kornbluth. The spindle assembly checkpoint requires phosphatase activity. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3770. doi:10.1158/1538-7445.AM2015-3770
Determinants of the increase in ketone concentration during SGLT2 inhibition in NGT, IFG and T2DM patients

Aim To examine metabolic factors that influence ketone production after sodium-glucose cotransport inhibitor (SGLT2) administration Research Design and Methods Fasting plasma glucose, insulin, glucagon, free fatty acid and ketone concentrations were measured in 15 type 2 diabetes mellitus (T2DM) and 16 non-diabetic subjects before and at 1 and 14 days after treatment with empagliflozin. Results Empagliflozin caused 38 mg/dl reduction in the fasting plasma glucose (FPG) concentration in T2DM patients. However, it caused only small but significant (7 mg/dl) reduction in the FPG concentration in impaired fasting glucose (IFG) subjects and did not affect the FPG concentration in normal glucose tolerant (NGT) subjects. Empagliflozin caused a significant increase in the mean plasma glucagon, free fatty acid (FFA) and ketone concentrations in T2DM subjects. However, empagliflozin did not cause a significant change in the mean plasma insulin, glucagon or ketone concentrations in non-diabetic subjects. An index which integrates the change in plasma glucose, insulin and FFA concentration at day 1 strongly correlates with plasma ketone concentration at day 1 (r = 0.85, p < 0.001) and day 14 (r = 0.63, r = 0.01) and predicts with 86% sensitivity and 83% specificity subjects at the top tertile for plasma ketone concentration after empagliflozin treatment. Conclusion The results of the present study demonstrate that SGLT2 inhibition exert different metabolic effects in non-diabetic individuals compared diabetic patients.
Triple oxygen isotope composition of leaf waters in Mpala, central Kenya

Abstract Variations in triple oxygen isotopes have been used in studies of atmospheric photochemistry, global productivity and increasingly in studies of hydroclimate. Understanding the distribution of triple oxygen isotopes in plant waters is critical to studying the fluxes of oxygen isotopes between the atmosphere and hydrosphere, in which plants play an important role. In this paper we report triple oxygen isotope data for stem and leaf waters from Mpala, Kenya and explore how Δ 17 O , the deviation from an expected relationship between O 17 / O 16 and O 18 / O 16 ratios, in plant waters vary with respect to relative humidity and deuterium excess (d-excess). We observe significant variation in Δ 17 O among waters in leaves and stems from a single plant (up to 0.16‰ range in Δ 17 O in leaf water in a plant over the course of a signal day), which correlates to changes in relative humidity. A steady state model for evaporation in leaf water reproduces the majority of variation in Δ 17 O and d-excess we observed in leaf waters, except for samples that were collected in the morning, when relative humidity is high and the degree of fractionation in the system is minimal. The data and the steady state model indicate that the slope, λ transp , that links δ 17 O and δ 18 O values of stem and leaf waters and characterizes the fractionation during transpiration, is strongly influenced by the isotopic composition of ambient vapor when relative humidity is high. We observe a strong, positive relationship between d-excess and Δ 17 O , with a slope 2.2 ± 0.2 per meg ‰ − 1 , which is consistent with the observed relationship in tropical rainfall and in water in an evaporating open pan. The strong linear relationship between d-excess and Δ 17 O should be typical for any process involving evaporation or any other fractionation that is governed by kinetic effects.
High Early Major Complication Rate After Revision for Mechanically Assisted Crevice Corrosion in Metal-on-Polyethylene Total Hip Arthroplasty.

Abstract Background Failed total hip arthroplasty caused by mechanically assisted crevice corrosion (MACC) has serious consequences such as adverse local tissue reaction. Revision is currently indicated for significant hip pain, stiffness, and dysfunction; hip instability; progressive bone loss; and soft tissue destruction. Outcomes of this revision surgery are not yet completely understood. Methods We examined the surgical outcomes at a minimum of 6 months (average, 25; range, 7-68 months) in a cohort of 27 consecutive patients who underwent revision total hip arthroplasty for MACC associated with a single implant vendor and taper type. Results Major orthopedic complications occurred in 7 of 27 patients (25.9%), each after the original revision surgery. Five additional major complications occurred in subsequent surgeries. Postoperative hip dislocation occurred in 6 of 27 (22.2%), deep infection occurred in 3 of 27 (11.1%), and aseptic acetabular loosening, seroma requiring irrigation and debridement, pulmonary embolism, periprosthetic fracture, and reintubation each occurred in 1 of 27 (3.7%). Harris hip scores improved significantly with surgery ( P = .0002), but overall, scores were lower for those who had major complications (70.9 vs 89.2), and only 20 of 27 patients (74.1%) had good or excellent outcomes. Conclusion Symptomatic MACC is a potentially devastating diagnosis, because of decreased soft tissue and bone viability associated with adverse local tissue reaction. This leads to a high early major complication rate.
Powder metallurgy of titanium – past, present, and future

Powder metallurgy (PM) of titanium is a potentially cost-effective alternative to conventional wrought titanium. This article examines both traditional and emerging technologies, including the prod...
Refactoring gene sequences for broad assembly standards compatibility

Four cloning standards in synthetic biology are BioBrick, BglBrick, MoClo and GoldenBraid, with each requiring their constitutive parts be compatible with the associated restriction enzymes. To standardize parts for the broadest usage, it would be useful to synthesize genes that are simultaneously compatible with all 4 popular assembly strategies. Here it is shown that using a defined set of rules, implemented in a computational program, any protein coding sequence can be made compatible with all four standards by silent mutations. Using a coding sequence as an input, all BioBrick, BglBrick, MoClo, and GoldenBraid restriction sites and chi recombination hot spots can be destroyed with silent mutations that approximate the codon usage of the organism. As an application, all open reading frames in the model organisms Escherichia Coli and Bacillus Subtilis are computationally refactored, showing the feasibility of implementing this umbrella strategy for synthesizing genes with the broadest compatibility.
Interpreting Clinical Trial Data

Effective interpretation of clinical trial data allows for the integration of high-quality clinical research into clinical practice. Evidence from clinical trials directly impacts clinical decision making, which ultimately guides patient management (Page, Int J Sports Phys Ther 9: 726, 2014). The purpose of this chapter is to provide an overview of fundamental aspects of clinical trials, such as study designs, analyses, and methods of handling missing data along with potential sources of bias and uncertainty. Subject withdrawal can make statistical analysis difficult as studies are aimed to determine the impact of an intervention from beginning to end. The different approaches to account for missing data are presented: last observation carried forward (LOCF), nonresponder imputation (NRI), as-observed data analysis, and anytime analysis (Langley and Reich, Br J Dermatol 169:1198–1206, 2013). Identifying sources of error and understanding limitations of these methods helps clinicians evaluate the validity of clinical data, ultimately enhancing clinical decision making and patient care.
The Cube Duplication and Angle Trisection by Abū Sahl al-Qūhī

The text of the tract on cube duplication and angle trisection by Abū Sahl al-Qūhī (here denoted as E) is taken from the Cairo ms. 40m, f. 226v–227r (copied in the 18th century). Through the courtesy of J.P. Hogendijk, I have had access to another copy, the Istanbul ms. Aya Sofya 4832/28, f. 147v (copied in the 11th century; cf. Sezgin, p. 318, no. 4). The portion of this latter ms. dealing with the angle trisection has already been edited in Arabic, with Turkish and English translations, by A. Sayili (Belleten, 1962, 26:693–700), and I have found his text especially helpful in deciphering the ms. readings. After the notes to text E below I list variants from the Istanbul ms. (denoted E*).
Integrated Electronics for Acoustic Imaging Arrays

Within the past five years acoustic imaging systems based on the use of arrays of transducer elements rather than a single element have undergone a rapid stage of development. Primary performance objectives of these systems in medical applications include high resolution, large field of view, long range and rapid frame rate. Various approaches to array systems can be classified according to transducer geometry, scanning technique and method of focus. Analysis of the salient electronic device and circuit requirements of these systems indicates well matched circuit arrays of 1) high voltage transmitters, 2) low noise, wide dynamic range preamplifiers and logarithmic compressors, 3) high voltage multiplex switches and 4) electronically variable analog delay lines are needed, with variable delay lines representing perhaps the most acute requirement. Custom silicon monolithic integrated circuits offer a promising means for fulfilling these needs, particularly in the case of charge coupled device (CCD) delay lines. Array imaging systems offer promise of extraordinary future progress.
Multisensory Integration Predicts Balance and Falls in Older Adults.

BACKGROUND Effective integration of concurrent sensory information is crucial for successful locomotion. This study aimed to determine the association of multisensory integration with mobility outcomes in aging. METHODS A total of 289 healthy older adults (mean age 76.67 ± 6.37 years; 53% female participants) participated in a visual-somatosensory simple reaction time task. Magnitude of multisensory effects was assessed using probability models, and then categorized into four multisensory integration classifications (superior, good, poor, or deficient). Associations of multisensory integration with falls and balance (unipedal stance) were tested at cross-section and longitudinally using Cox proportional hazards models. RESULTS At baseline, the prevalence of falls in the previous year was 24%, and 52% reported an incident fall over a mean follow-up period of 24 ± 17 months. Mean unipedal stance time was 15 ± 11 seconds. Magnitude of multisensory integration was a strong predictor of balance performance at cross-section (β = 0.11; p < .05). Of the cohort, 31% had superior, 26% had good, 28% had poor, and 15% had deficient multisensory effects. Older adults with superior multisensory integration abilities were significantly less likely to report a fall in the past year (17%), compared to the rest of the cohort (28%; χ2 = 4.01; p = .04). Magnitude of multisensory integration was an incremental predictor of incident falls (adjusted hazard ratio = 0.24; p = .01), over and above balance and other known fall risk factors. CONCLUSIONS Our study highlights the clinical relevance of multisensory integration in aging; worse visual-somatosensory integration is associated with worse balance and increased risk of incident falls.
Aufzeichnung des Druck-Volumendiagramms

Fur die Berechnung des Kurbeltriebes und des Schwungrades wird das pv-Diagramm verlangt. Zu seiner Aufzeichnung kann in einfachster Weise die geradlinige Adiabate des Entropiediagramms benutzt werden. Das Verfahren ist weitaus genauer als die bekannte Konstruktion nach Brauer, bei der sich eine kleine anfangliche Ungenauigkeit mit dem Fortschreiten der Punktbestimmung stets vergrosert.
Dynamic Contrast Optical Coherence Tomography reveals laminar microvascular hemodynamics in the mouse neocortex in vivo.

Abstract Studies of flow-metabolism coupling often presume that microvessel architecture is a surrogate for blood flow. To test this assumption, we introduce an in vivo Dynamic Contrast Optical Coherence Tomography (DyC-OCT) method to quantify layer-resolved microvascular blood flow and volume across the full depth of the mouse neocortex, where the angioarchitecture has been previously described. First, we cross-validate average DyC-OCT cortical flow against conventional Doppler OCT flow. Next, with laminar DyC-OCT, we discover that layer 4 consistently exhibits the highest microvascular blood flow, approximately two-fold higher than the outer cortical layers. While flow differences between layers are well-explained by microvascular volume and density, flow differences between subjects are better explained by transit time. Finally, from layer-resolved tracer enhancement, we also infer that microvascular hematocrit increases in deep cortical layers, consistent with predictions of plasma skimming. Altogether, our results show that while the cortical blood supply derives mainly from the pial surface, laminar hemodynamics ensure that the energetic needs of individual cortical layers are met. The laminar trends reported here provide data that links predictions based on the cortical angioarchitecture to cerebrovascular physiology in vivo.
Predicting Friendship Pairs from BLE Beacons Using Dining Hall Visits

The age of the Internet of things has brought about the field of smartphone sensing, which has found numerous uses for the growing population of smartphones throughout the world. Among these uses are longitudinal studies that have studied social networks, health behaviors, productivity, and other topics with large participant bases and detailed data. In this paper we demonstrate another way to study social behavior during one of these longitudinal studies, the NetHealth study, by predicting whether a pair of students are friends or not through visit data patterns of a social hub of any college campus - the dining hall. We use Bluetooth Low Energy (BLE) beacons deployed throughout the dining hall to detect when students enter and leave, and create features from this visit data that can cope with varying amounts of data among study participants. We then demonstrate the predictive power of these features, calculated over a semester of data, against ground truth friendship labels given by the participants themselves, obtaining an AUROC of 0.716.
Complete Charge Regulation by a Redox Enzyme Upon Single Electron Transfer.

The degree by which metalloproteins partially regulate net charge (Z) upon electron transfer (ET) was recently measured for the first time using "protein charge ladders" of azurin, cytochrome c, and myoglobin [Angew. Chem. Int. Ed. 2018, 57(19), 5364-5368; Angew. Chem. 2018, 130, 5462-5466]. Here, we show that Cu, Zn superoxide dismutase (SOD1) is unique among proteins in its ability to resist changes in net charge upon single ET (e.g., ΔZET(SOD1) =0.05±0.08 per electron, compared to ΔZET(Cyt-c) =1.19±0.02). This total regulation of net charge by SOD1 is attributed to the protonation of the bridging histidine upon copper reduction, yielding redox centers that are isoelectric at both copper oxidation states. Charge regulation by SOD1 would prevent long range coulombic perturbations to residue pKa 's upon ET at copper, allowing SOD1's "electrostatic loop" to attract superoxide with equal affinity (at both redox states of copper) during diffusion-limited reduction and oxidation of superoxide.
Abstract IA13: An mTOR/eIF4E-independent translation mechanism promotes breast cancer metastasis

While translation initiation of most mammalian mRNAs is mediated by a 59 cap structure that binds eIF4E, inactivation/silencing of eIF4E, or quantitative sequestration of eIF4E by 4E-BPs through mTORC1 inhibition, does not impair translation of many capped mRNAs. This suggests an alternate mechanism may exist for cap-dependent but eIF4E/mTORC1-independent translation. DAP5 (NAT1, eIF4G2, p97) is an eIF4G family member that lacks the N-terminal binding domains for eIF4E and PABP. DAP5 was shown to mediate translation initiation through internal ribosome entry sites (IRES elements). We recently showed that DAP5 utilizes the cap binding activity of eIF3d to facilitate cap-dependent translation of a large number of capped mRNAs, making it a previous unknown major mechanism of cap-dependent but eIF4E/mTORC1-independent mRNA translation. Genome-wide transcriptomic and translatomic analyses indicate that DAP5 is required for translation of many transcription factor and cell receptor capped mRNAs and their mRNA targets involved in cell survival, motility, DNA repair, oncogenesis, translation initiation, and cancer cell metastasis. Up to 20% of cellular mRNAs utilize DAP5-eIF3d for cap-dependent mRNA translation. Mass spectrometry and in vivo cross-linking studies found that eIF3d is a direct binding partner of DAP5 but does not bind strongly to eIF4GI or II family members that bind eIF4E. In vitro translation and ribosome complex studies demonstrate that DAP5 and eIF3d are both essential for eIF4E and mTORC1-independent capped-mRNA translation. Given the prevalence of oncogenic and survival mRNAs directed in translation by DAP5-eIF3d, we analyzed the NCI human tissue genome cancer atlas (TCGA) and found that high expression of DAP5 mRNA is strongly associated with estrogen receptor-negative (ER-) breast cancer metastasis and poor survival. We therefore investigated the role of DAP5 in preclinical mouse models of highly metastatic ER- breast cancer. Reduction of DAP5 expression by ~70% almost eliminated metastasis to the lung and significantly increased survival with no impact on primary tumor growth. These and other studies indicate that the DAP5-eIF3d complex is a significant alternate mechanism for cap-dependent, eIF4E/mTORC1-independent mRNA translation despite lacking eIF4E and PABP binding, that DAP5 directs translation of many capped mRNAs that are involved in cell stress and survival pathways, is essential for promoting breast cancer metastasis, and that most mRNAs translated by DAP5 do not utilize an IRES. Citation Format: Columba de la Parra, Amanda Ernlund, Amandine Alard, Kelly Ruggles, Beatrix Ueberheide, Olga Katsara, Robert J. Schneider. An mTOR/eIF4E-independent translation mechanism promotes breast cancer metastasis [abstract]. In: Proceedings of the AACR Special Conference on Targeting PI3K/mTOR Signaling; 2018 Nov 30-Dec 8; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Res 2020;18(10_Suppl):Abstract nr IA13.
Demographic, Socioeconomic, Health Systems, and Geographic Factors Associated with Vaginal Birth After Cesarean: An Analysis of 2017 U.S. Birth Certificate Data

In order to better understand the current rates of vaginal birth after cesarean (VBAC) in the United States, 2017 U.S. birth certificate data were used to examine sociodemographic and geographic factors associated with the outcome of a VBAC. The 2017 Natality Limited Geography Dataset and block sequential logistic regression were used to examine sociodemographic and geographic factors associated with subsequent births in 2017 in the United States to women with a history of 1 or 2 cesareans (N = 540,711). The adjusted odds of VBAC were 6% higher for Black women (1.06; 95% CI: 1.04, 1.08) and 18% higher for American Indian/Alaska Native women (aOR 1.18; 95% CI: 1.10, 1.27) relative to white women. Asian/Pacific Islander women were 9% less likely to have a VBAC (aOR 0.91; 95% CI: 0.88, 0.94) than similar white women with a history of cesarean delivery. Latina women had a 10% less likelihood of a VBAC (aOR 0.90; 95% CI: 0.88, 0.92) when compared with non-Latina women. Women with a high school education (aOR 0.85; 95% CI: 0.83, 0.88) or some college (aOR 0.85; 95% CI: 0.84, 0.87) were less likely to have a VBAC than women educated at a baccalaureate level or higher. Women whose births were paid for by Medicaid had a 5% increased likelihood of VBAC over women with private insurance (aOR 1.05, 95% CI: 1.03, 1.07). Women who self-pay have twice the likelihood of VBAC (aOR 1.99; 95% CI: 1.92, 2.07) compared to women with private insurance. The adjusted odds of VBAC were lowest for women giving birth in Southern states (aOR 0.72; 95% CI: 0.71, 0.74) and highest for women giving birth in the Midwest (aOR 1.19; 95% CI: 1.16, 1.22) relative to women in the Northeastern U.S. Thirteen percent (13%) of women who had a VBAC had a certified nurse-midwife (CNM) birth attendant, which is 44% higher than the national CNM-attended birth rate. Significant variation exists in VBAC rates based on a number of sociodemographic and geographic factors, likely reflecting disparities in access to vaginal birth after cesarean and differences in preference regarding mode of birth after cesarean. Further research is recommended to better understand and address these disparities to improve maternity care.
Exclusion and exploitation: The incarceration of Black Americans from slavery to the present.

Understanding long-run patterns in the incarceration of Black Americans requires integrating the study of racial inequality with the study of political economy. I offer a parsimonious framework des...
4He on Grafoil: The Melting Transition

Recent measurements of both the heat capacity and vapor pressure of helium adsorbed on Grafoil have been of sufficient accuracy, reproducibility, and completeness to allow characterization of all the static thermodynamic properties of the two-dimensional film above 2 K. Interactions between the film and the bulk gas have been accurately modeled, showing that the first layer of the film behaves even more like the bulk solid than was previously apparent. The only major difference is that the transition from crystal to fluid is no longer of first order. Two recent theories of melting are discussed. It is suggested that the growth of dislocations may be the cause of melting in both two and three dimensions and the true basis for the empirical Lindemann formula.
Incidence of Salmonella in fish and seafood.

Field laboratories of the U.S. Food and Drug Administration collected and tested 11,312 import and 768 domestic seafood samples over a 9-year period (1990 to 1998) for the presence of Salmonella. The overall incidence of Salmonella was 7.2% for import and 1.3% for domestic seafood. Nearly 10% of import and 2.8% of domestic raw seafood were positive for Salmonella. The overall incidence of Salmonella in ready-to-eat seafood and shellfish eaten raw was 0.47% for domestic--one shucked oyster and one shark cartilage powder. The incidence in the 2,734 ready-to-eat import seafood was 2.6%--cooked shrimp, shellfish or fish paste, smoked fish, salted/dried fish, and caviar. The incidence in import shellfish consumed raw was 1% in oyster, 3.4% in clams, and 0% in mussels. The incidence in raw, import fish was 12.2%. Distribution of Salmonella in seafood on a regional basis indicated the incidence to be highest in central Pacific and Africa and lowest in Europe/Russia and North America (12% versus 1.6%). Data on a country basis indicated Vietnam to have the highest (30%) and Republic of Korea the lowest (0.7%). While the most frequent serotypes in import seafood were Salmonella Weltevreden (1st), Salmonella Senftenberg (2nd), Salmonella Lexington, and Salmonella Paratyphi-B (3rd, equal numbers for each serotype), the top 20 list included Salmonella enteritidis (5th), Salmonella Newport (6th), Salmonella Thompson (7th), Salmonella typhimurium (12th), and Salmonella anatum (13th), commonly involved in foodborne illness in the United States. Because the incidence in the present study is based on only a small fraction of the seafood imported into the United States, efforts should be directed toward implementation of hazard analysis and critical control points to reduce the incidence of Salmonella in seafood without relying on testing for Salmonella.
Assessing the intersection of cardiovascular disease, venous thromboembolism, and polycystic ovary syndrome

Introduction No study has examined how the relationship between polycystic ovary syndrome (PCOS) and atherosclerotic cardiovascular diseases (aCVD), of ischemic stroke (ISCH), acute myocardial infarction (AMI), and peripheral vascular disease (PAD), differ in the presence of venous thromboembolism (VTE).
Desmoid Tumor: Prognostic Factors and Outcome After Surgery, Radiation Therapy, or Combined Surgery and Radiation Therapy

PURPOSE: To evaluate the therapeutic value of resection and the potential benefits of and indications for adjuvant and definitive radiation therapy for desmoid tumors. MATERIALS AND METHODS: We performed a retrospective review of 189 consecutive cases of desmoid tumor treated with surgical resection, resection and radiation therapy, or radiation therapy alone. Treatment was surgery alone in 122 cases, surgery and radiation therapy in 46, and radiation therapy alone in 21. Median follow-up was 9.4 years. RESULTS: Overall, 5- and 10-year actuarial relapse rates were 30% and 33%, respectively. Uncorrected survival rates were 96%, 92%, and 87% at 5, 10, and 15 years, respectively. For the patients treated with surgery, the actuarial relapse rates were 34% and 38% at 5 and 10 years, respectively. Among 78 patients with negative margins, the 10-year recurrence rate was 27%, whereas 40 margin-positive patients had a 10-year relapse rate of 54% (P = .003). Tumors located in an extremity also had a poorer prognosi...
Glucose Oxidase Method for Continuous Automated Blood Glucose Determination

A glucose oxidase-peroxidase method for continuous automated monitoring of blood glucose has been developed. The response is linear over the range 0-800 mg/100 ml. Sensitivity can be maintained for 24 hr or longer and can be restored by rinsing the analytic system with sulfuric acid to permit studies of longer than 48 hr in duration. A precision of ± 1% can be maintained between rinses for samples containing 100-600 mg of glucose per 100 ml. This method is satisfactorily specific for glucose: The response with other sugars is less than 1% of the response obtained with the same concentration of glucose. Ascorbic acid causes no significant inhibition of the response to glucose. The inhibition by uric acid has been reduced fifty-fold compared to that in other methods. Transit through the sampling catheter and analytic system requires 15 min. Timed from the first detectable response to a change in concentration, 25% of total response is achieved in 30 sec and 90% in 80 sec. Fifty percent of an oscillation with a half-period of 45 sec can be detected; no oscillations this short were observed in records of human blood glucose. Applicability and feasibility of this method have been demonstrated in over 2000 hr of repeated blood glucose recordings in 12 diabetic and 6 normal subjects.
'Replica-extraction-transfer' nanostructure-initiator mass spectrometry imaging of acoustically printed bacteria

Traditionally, microbes are studied under controlled laboratory conditions as isolates in planktonic culture. However, this is a vast extrapolation from their natural state; development of new techniques is required to decipher the largely unknown world of microbial chemical interactions in more realistic environments. The field of mass spectrometry imaging has made significant progress in localizing metabolites in and around bacterial colonies, primarily by using MALDI and ESI-based techniques that interrogate the top surface of the sample. Unfortunately, surface-based laser-desorption techniques, such as nanostructure-initiator mass spectrometry (NIMS), which has advantages in detection of small metabolite compounds and low background, has not been suitable for direct microbe imaging because desorption/ionization occurs on the bottom of the sample. Here, we describe a “replica-extraction-transfer” (REX) technique that overcomes this barrier by transferring biomolecules from agar cultures of spatially ar...
Group Process and Success in Meeting the Joint Commission on Accreditation of Healthcare Organizations review

Attention to and use of group process with hospital staff can contribute significantly to success in preparing for and passing a review by the Joint Commission on Accreditation of Healthcare Organizations. Group format, key elements, stages of group development, factors to facilitate group work, and the role of the leader are addressed.
Benign partial epilepsy in infancy: myth or reality?

Summary: Purpose: Benign partial epilepsy in infancy (BPEI) was first described by Watanabe in 1987. The aim of this study is to describe a series of infants from the United States to characterize this entity further. Methods: Among patients with the diagnosis of epilepsy followed up at our institution between 2002 and 2004, those satisfying the criteria for BPEI were included in a retrospective study. Results: Sixteen (10.2%) of 150 patients with new onset of epilepsy younger than 2 years were identified. The mean age at seizure onset was 8 months. Four (25%) infants had a family history of benign seizures. All infants were neurologically and developmentally normal at the onset of seizures. The seizures occurred in clusters in 75% of patients, predominantly in wakefulness. The initial manifestation was behavioral arrest with staring (69%) and apnea with cyanosis or pallor (37.5%). These symptoms were followed by deviation of eyes or head or both (56%), mild clonic movements (31%), or increased limb tone (35%). Secondary generalization was noticed in 37.5% of patients. All infants had normal interictal EEGs and brain MRIs. Ictal EEGs disclosed electrographic seizures in 50% of patients (temporal origin in 62% and central in 38%). Fifteen (94%) patients were treated with AEDs with good response. The mean duration of treatment was 12.4 months. The final developmental assessment of all patients was normal. Conclusions: We believe that BPEI exists as a unique entity and should be included in the differential diagnosis of epilepsies in infancy with partial origin.
Muscarinic receptors of rabbit irides.

After occlusion of a fraction of the receptors with the irreversible blocker dibenamine, dissociation constants (K A) of several muscarinic stimulants like carbachol, muscarine, bethanechol and oxotremorine are determined in four types of irides (presence or absence of pigment and/or plasma atropinesterase). Thus, the pharmacological activity of many muscarinic stimulants like carbachol, oxotremorine, bethanechol and muscarine in irides is not influenced by the presence or absence of plasma atropinesterase or the melanin pigment. The dissociation constants obtained from the pharmacological (K A) and biochemical (K D) studies indicates that unequal effects of certain drugs in irides may be largely related to the drug binding to the pigment. Hence, the contribution of the atypical muscarinic receptor, if any, to explain the unequal pharmacological effects in different types of irides must be small.