cssi/SciSciGPT-SciSciNet huggingface dataset:
Insight from TonB Hybrid Proteins into the Mechanism of Iron Transport through the Outer Membrane

We created hybrid proteins to study the functions of TonB. We first fused the portion of Escherichia coli tonB that encodes the C-terminal 69 amino acids (amino acids 170 to 239) of TonB downstream from E. coli malE (MalE-TonB69C). Production of MalE-TonB69C in tonB+ bacteria inhibited siderophore transport. After overexpression and purification of the fusion protein on an amylose column, we proteolytically released the TonB C terminus and characterized it. Fluorescence spectra positioned its sole tryptophan (W213) in a weakly polar site in the protein interior, shielded from quenchers. Affinity chromatography showed the binding of the TonB C-domain to other proteins: immobilized TonB-dependent (FepA and colicin B) and TonB-independent (FepAΔ3-17, OmpA, and lysozyme) proteins adsorbed MalE-TonB69C, revealing a general affinity of the C terminus for other proteins. Additional constructions fused full-length TonB upstream or downstream of green fluorescent protein (GFP). TonB-GFP constructs had partial functionality but no fluorescence; GFP-TonB fusion proteins were functional and fluorescent. The activity of the latter constructs, which localized GFP in the cytoplasm and TonB in the cell envelope, indicate that the TonB N terminus remains in the inner membrane during its biological function. Finally, sequence analyses revealed homology in the TonB C terminus to E. coli YcfS, a proline-rich protein that contains the lysin (LysM) peptidoglycan-binding motif. LysM structural mimicry occurs in two positions of the dimeric TonB C-domain, and experiments confirmed that it physically binds to the murein sacculus. Together, these findings infer that the TonB N terminus remains associated with the inner membrane, while the downstream region bridges the cell envelope from the affinity of the C terminus for peptidoglycan. This architecture suggests a membrane surveillance model of action, in which TonB finds occupied receptor proteins by surveying the underside of peptidoglycan-associated outer membrane proteins.
Coupling photoisomerization of retinal to directional transport in bacteriorhodopsin.

In order to understand how isomerization of the retinal drives uni- directional transmembrane ion transport in bacteriorhodopsin, we deter- mined the atomic structures of the BR state and M photointermediate of the E204Q mutant, to 1.7 and 1.8 Aresolution, respectively. Comparison of this M, in which proton release to the extracellular surface is blocked, with the previously determined M in the D96N mutant indicates that the changes in the extracellular region are initiated by changes in the electro- static interactions of the retinal Schiff base with Asp85 and Asp212, but those on the cytoplasmic side originate from steric conflict of the 13-methyl retinal group with Trp182 and distortion of the p-bulge of helix G. The structural changes suggest that protonation of Asp85 initiates a cascade of atomic displacements in the extracellular region that cause release of a proton to the surface. The progressive relaxation of the strained 13-cis retinal chain with deprotonated Schiff base, in turn, initiates atomic displacements in the cytoplasmic region that cause the intercalation of a hydrogen-bonded water molecule between Thr46 and Asp96. This accounts for the lowering of the pK a of Asp96, which then reprotonates the Schiff base via a newly formed chain of water molecules that is extending toward the Schiff base. # 2000 Academic Press
Compressive properties of yttrium oxide

Compressive properties of polycrystalline yttrium oxide (Y{sub 2}O{sub 3}) were studied by slow-strain-rate experiments ({dot {var_epsilon}} = 5.7 {times} 10{sup {minus}6} s{sup {minus}1}) between room temperature and 1,600 C. It was shown that Y{sub 2}O{sub 3} fails in a brittle manner up to 1,000 C, and at 1,200 C and above plastic deformation becomes dominant. Plastic deformation of Y{sub 2}O{sub 3} takes place exclusively by dislocation motion. Maximum stress, yield stress, and elastic modulus decrease with increasing temperature, although the decrease at temperatures above 1,000 C is much more pronounced.
IN MEMORIAM: EBERHARD GWINNER, 1938–2004

Eberhard Gwinner, founding director of tbe Max-Planck-lnstitut (MPI) fiir Ornitbologie (Max Planck Research Center for Ornithology) and Corresponding Fellow of the AOU since 1975, passed away suddenly on 7 September 2004, after a brief battle with cancer. His pivotal studies provided the foundation on which our understanding of biological clocks and their role in organizing migration, breeding, and other life-history events are based. His energy, wit, and charming smile, along witb his expansive warmth and generosity, will be deeply missed. He is survived by his wife, Helga, their three children, and four grandchildren.
Pearson Type III Distribution

The Pearson type (PT) III distribution is the generalized gamma distribution and is one of the most popular distributions for hydrologic frequency analysis. Bobee and Robitaille (1977) compared PT III and log PT III distributions using several long-term records of annual flood flows and found PT III distribution to be preferable, especially when the method of moments (MOM) was applied to observed sample data. Bobee (1973), Chang and Moore (1983), among others, used it for flood frequency analysis. Markovic found practically no difference in fitting of Pearson and lognormal distributions to annual precipitation and runoff data. Matalas (1963) found PT III distribution to be representative of low flows. Obeyesekera and Yevjevich (1985) presented a procedure for generation of samples of an autoregressive scheme that has an exact Pearson type III distribution with given mean, variance and skewness. Harter (1958) prepared tables for percentage points of the PT III distribution. Wilk et al. (1962) described a procedure for preparing probability plots for randon samples from an assumed PT III distribution Haktanir (1991) developed a practical method for computation of PT III frequency factors. Shaligram and Lele (1978) analyzed hydrologic data using PT III distribution and showed that the confidence intervals for this distribution were larger than for the Gumbel distribution.
Supplemental folic acid therapy in pernicious anemia: the effect on erythropoiesis and serum vitamin B12 concentrations in selected cases.

Abstract 1.1. Administration of 30 μg of vitamin B 12 intramuscularly every two weeks increased the hemoglobin levels of only five of a group of twenty-two patients previously receiving 15 μg of crystalline vitamin B 12 every four weeks. None of eleven patients who received 20 μg of vitamin B 12 in the form of Liver Injection U.S.P. every two weeks was so benefited. 2.2. Supplemental folic acid did not alter hemoglobin levels; therefore folic acid deficiency as a limiting factor in hematopoiesis was shown not to exist in twenty-nine patients given adequate therapy with vitamin B 12 . 3.3. The serum vitamin B 12 level in twenty of thirty-five patients receiving 15 μg of vitamin B 12 once every four weeks was less than 100 μg per milliliter, which is characteristic of patients with pernicious anemia in relapse. It is greater than 100 μμg per milliliter in most patients receiving 30 μg of vitamin B 12 once every four weeks. Inasmuch as the serum vitamin B 12 concentration probably reflects tissue saturation, treatment with the larger dose of vitamin B 12 appears to be more nearly adequate. 4.4. Administration of folic acid adversely affected the serum vitamin B 12 level of eighteen of twenty-seven patients receiving 20 or 30 μg of vitamin B 12 intramuscularly every two weeks, possibly by accelerating the utilization of vitamin B 12 . Therefore, supplementation of inadequate intramuscular vitamin B 12 therapy with folic acid, in addition to being unnecessary for nearly all patients, may actually be inadvisable unless larger doses of vitamin B 12 are given.
Fungal peritonitis in children treated with peritoneal dialysis and gastrostomy feeding.

Feeding gastrostomies were placed in three children treated with chronic peritoneal dialysis at our center because of persistent, severe malnutrition and inadequate growth. Two had frequent fungal infections of the gastrostomy site and all three developedCandida peritonitis which occurred at 1 month, 2 months and 2 years after insertion of gastrostomy. Complications included multiple intra-abdominal adhesions, abscess formation and loss of peritoneal function necessitating transfer to hemodialysis. The presence of a gastrostomy may predispose to the development of fungal peritonitis with its high morbidity and should be avoided in children on chronic peritoneal dialysis.
Effect of exogenous triiodothyronine on weight and composition of the heart in rats.

SummaryUnder the conditions of our experiment two doses of T3 resulted in cardiac hypertrophy which, relatively, was more pronounced in the right ventricle. The changes in heart weight were predominantly a reflection of substances not containing hydroxyproline.
Effect of parenteral acetazolamide on intestinal absorption of salt and water in man.

SummaryAcetazolamide was administered intravenously during jejunal perfusion of isotonic saline in six subjects. Bicarbonate was present in very low concentration intraluminally and there was net bicarbonate secretion during control and acetazolamide perfusions. Acetazolamide significantly inhibited sodium chloride, and water absorption. As this occurred in the absence of an effect on net bicarbonate secretion, it may have been due to an action other than carbonic anhydrase inhibition.This research was supported by the National Foundation for Ileitis and Colitis, Inc., and by Grant RR-71 to the Clinical Research Center of The Mount Sinai Hospital. Lederle Laboratories kindly donated the acetazolamide.
Challenges of Identifying Clinically Actionable Genetic Variants for Precision Medicine

Advances in genomic medicine have the potential to change the way we treat human disease, but translating these advances into reality for improving healthcare outcomes depends essentially on our ability to discover disease- and/or drug-associated clinically actionable genetic mutations. Integration and manipulation of diverse genomic data and comprehensive electronic health records (EHRs) on a big data infrastructure can provide an efficient and effective way to identify clinically actionable genetic variants for personalized treatments and reduce healthcare costs. We review bioinformatics processing of next-generation sequencing (NGS) data, bioinformatics infrastructures for implementing precision medicine, and bioinformatics approaches for identifying clinically actionable genetic variants using high-throughput NGS data and EHRs.
Effect of oral or caecal administration of protein supplements on equine plasma amino acids.

SUMMARY Plasma amino acid and ammonia concentrations were determined for oral and caecal administration of three different proteins to four mature ponies fitted with permanent caecal cannulae and fed a diet low in digestible protein. Caecal administration of fishmeal, linseed meal or soybean meal increased the ratio of plasma non-essential to essential amino acids, the ratio of plasma ammonia plus non-essential amino acids to essential amino acids and the ratio of plasma ammonia to essential amino acids when compared to the conventional method of feeding. Elevated levels of plasma ammonia were observed when fishmeal, linseed meal or soybean meal were administered via the caecum, suggesting deamination of the infused protein or its digestion products by caecal micro-organisms. It appeared that an appreciable amount of the nitrogen released from caecally infused protein supplements was absorbed as ammonia. Although it has been shown that amino acids from microbial protein introduced into the caecum can be absorbed intact the present experiment did not indicate that any major proportion of caecally infused protein nitrogen appeared in the blood as essential amino acids.
Marijuana use and viral suppression in persons receiving medical care for HIV-infection

ABSTRACTBackground: Marijuana use is common among persons living with HIV (PLWH), but studies on its effect on HIV clinical outcomes are limited. Objectives: We determined the association between marijuana use and HIV viral suppression among PLWH. Methods: Data came from five repeated cross-sections (2009–2013) of the Florida Medical Monitoring Project, a population-based sample of PLWH in Florida. Data were obtained via interview and medical record abstraction (MRA). Weighted logistic regression models were used to determine the association between marijuana use (past 12 months) and durable viral suppression (HIV-1 RNA value of ≤ 200 copies/milliliter in all measurements within the past 12 months). Results: Of the 1,902 PLWH receiving antiretroviral therapy, completed an interview, and had a linked MRA, 20% reported marijuana use (13% less than daily and 7% daily use) and 73% achieved durable viral suppression. In multivariable analysis, marijuana use was not significantly associated with durable viral s...
Vitamin D Gene Regulation

Publisher Summary Vitamin D is a principal factor required for the development and maintenance of bone as well as for maintaining normal calcium and phosphorus homeostasis. In addition, evidence has indicated the involvement of vitamin D in a number of diverse cellular processes, including effects on differentiation and cell proliferation, on hormone secretion, and on the immune system. Vitamin D, which is taken in the diet or is synthesized in the skin from 7-dehydrocholesterol in a reaction catalyzed by ultraviolet irradiation, is transported in the blood by the vitamin D-binding protein to the liver. In the liver, vitamin D is hydroxylated at C-25, resulting in the formation of 25-hydroxyvitamin D3 [25(OH)D3]. This chapter describes the vitamin D gene regulation. It begins with an explanation of the role of 1,25(OH)2D3 in classical target tissues, including bone, intestine, kidney, and parathyroid glands. Following this, it considers the nonclassical actions of 1,25(OH)2D. These include the effects of 1,25(OH)2D3 on differentiation and proliferation, on hormone secretion, and on the immune system. Subsequently, it provides an understanding of the transcriptional regulation by 1,25(OH)2D3, elucidating the factors involved in vitamin D mediated transcriptional regulation.
Big Data Essentials

The main objective of this chapter is to organize the big data essentials that contribute to the analytics of big data systematically. It includes their presentations in a simple form that can help readers conceptualize and summarize the classification objectives easily. The topics are organized into three sections: big data analytics, big data classification, and big data scalability. In the big data analytics section, the big data controllers that play major roles in data representation and knowledge extraction will be presented and discussed in detail. These controllers, the problems and challenges that they bring to big data analytics, and the solutions to address these problems and challenges will also be discussed. In the big data classification section, the machine learning processes, the classification modeling that is characterized by the big data controllers, and the classification algorithms that can manage the effect of big data controllers will be discussed. In the big data scalability section, the importance of the low-dimensional structures that can be extracted from a high-dimensional system for addressing scalability issues will be discussed as well.
Fluence-compensated down-scattered neutron imaging using the neutron imaging system at the National Ignition Facility

The Neutron Imaging System at the National Ignition Facility is used to observe the primary ∼14 MeV neutrons from the hotspot and down-scattered neutrons (6-12 MeV) from the assembled shell. Due to the strong spatial dependence of the primary neutron fluence through the dense shell, the down-scattered image is convolved with the primary-neutron fluence much like a backlighter profile. Using a characteristic scattering angle assumption, we estimate the primary neutron fluence and compensate the down-scattered image, which reveals information about asymmetry that is otherwise difficult to extract without invoking complicated models.
Roles of deep and shallow convection and microphysics in the MJO simulated by the Model for Prediction Across Scales

The November event of the Madden-Julian Oscillation (MJO) during the DYNAMO field campaign was simulated using the global compressible nonhydrostatic Model for Prediction Across Scales (MPAS) with global coarse (60 and 15 km) and regional (the Indian Ocean) cloud-permitting (3 km) meshes. The purpose of this study is to compare roles of parameterized deep and shallow cumulus and microphysics in MJO simulations. Two cumulus schemes were used: Tiedtke and Grell-Freitas. The deep and shallow components of Tiedtke scheme can be turned on and off individually. The results reveal that microphysics alone (without cumulus parameterization) is able to produce strong signals of the MJO in precipitation with 3 km mesh and weak MJO signals with 15 km mesh. A shallow scheme (Tiedtke) along with microphysics strengthens the MJO signals but makes them less well organized on large scales. A deep cumulus scheme can either improve the large-scale organization of MJO precipitation produced by microphysics and shallow convection (Tiedtke) or impair them (Grell-Freitas). The deep scheme of Tiedtke cannot reproduce the MJO well without its shallow counterpart. The main role of shallow convection in the model is to transport moisture upward to the lower-mid troposphere. By doing so, it removes dry biases in the lower-mid troposphere, a distinct feature in simulations with weak or no MJO signals, and enhances total precipitation and diabatic heating produced by microphysics and deep cumulus schemes. Changing model grid spacing from 60 to 15 km makes a little difference in the model fidelity of reproducing the MJO. All roles of shallow convection in 15 km simulations with parameterized deep convection cannot be reproduced in 3 km simulations without parameterized deep convection. Results from this study suggest that we should pay more attention to the treatment of shallow convection and its connection to other parameterized processes for improving MJO simulations. In other words, a holistic approach should be taken that consider parameterization of shallow cumulus, microphysics, boundary layer, as well as deep cumulus as a whole for model improvement.
How a Mutation that Slows Aging Can Also Disproportionately Extend End-of-Life Decrepitude

The goal of aging research is to extend healthy, active life. For decades, C. elegans daf-2 insulin/insulin-like growth factor 1 (IGF-1) receptor mutants have served as a model for extended lifespan and youthfulness. However, a recent report suggested that their longevity is associated with an undesirable phenotype: a disproportionately long period of decrepitude at the end of life. In the human population, such an outcome would be a burden to society, bringing into question the relevance of daf-2 mutants as a model for life extension. However, here we report that, following an extended period of movement, daf-2 mutants survive longer in a decrepit state because of a beneficial trait: they are resistant to colonization of the digestive tract by dietary bacteria, a condition that leads to premature death in the wild-type and prevents their manifestation of decrepitude. If bacterial colonization is prevented, then daf-2 mutants lead both chronologically and proportionately healthier lives relative to the wild-type.
The Use of Molecular Modelling to Delineate B-Cell and T-Cell Epitopes of Human Sperm-Specific LDH-C4

Publisher Summary This chapter discusses the use of molecular modeling to delineate B-cell and T-cell epitopes of human sperm-specific LDH-C4. The sperm-specific isozyme of lactate dehydrogenase (LDH-C4) has been purified from mouse testes, and has been shown to suppress fertility in female mice, rabbits, and baboons. The results of a study described in the chapter have suggested that LDH-C4 might form the basis of an immunocontraceptive vaccine that would not rely on disrupting the endocrine milieu of the recipient. A combination of immunoaffinity purification of tryptic peptides and epitope mapping using synthetic peptides has identified several peptides that can elicit LDH-C4 reactive antibodies. Molecular modeling has been used to localize these peptides within the crystal structure of the protein. This study used computer-assisted secondary structure analyses together with experience with mouse LDH-C4 to predict an immunodominant B-cell epitope of human LDH-C4. This peptide, when conjugated to diphtheria toxoid (DT-hC9-20), was highly immunogenic in rabbits. In addition, similar analyses enabled to identify a T-cell epitope of human LDH-C4 that could substitute for the normally required carrier molecule in eliciting an immune response to hC9-20.
Raman spectroscopy: Enhanced by organic surfaces

Nanostructured films of organic semiconductors are now shown to enhance the Raman signal of probe molecules, paving the way to the realization of substrates for Raman spectroscopy with molecular selectivity.
Extracting polarizability of complementary metamaterial elements using equivalence principles

A novel Metamaterial Dipole Model (MDM) has been proposed as a powerful tool for modeling and designing metasurface antennas for numerous applications such as beamforming arrays, holograms, and flat lenses among others. In this technique, a metasurface antenna is described as a collection of effective magnetic dipoles characterized by their polarizability. The utility of this modeling technique relies on polarizability extraction, i.e. the proper characterization of each individual metamaterial element when it is embedded in a waveguide. In this presentation, we employ a volumetric equivalence principle in a comprehensive procedure for retrieving the polarizability of complementary metamaterial elements, when these are embedded in rectangular waveguides, planar waveguides, and periodic metascreens. We demonstrate that the extracted polarizability changes for each supporting waveguide structure, highlighting the importance of proper characterization of metamaterial elements in different environments.
Determining live prey preferences of larval ornamental marine fish utilizing fluorescent microspheres

Abstract As the popularity of marine aquaria grows, the potential exists for increased harvest of marine ornamental fishes and invertebrates from the oceans around the world. Aquaculture may be an alternative source to wild capture fisheries if commercial production protocols can be developed for species of interest, however numerous impediments must be overcome. Experiments were conducted on the reef butterflyfish (Chaetodon sedentarius), Pacific blue tang (Paracanthurus hepatus), African moony (Monodactylus sebae) and golden trevally (Gnathanodon speciosus) to evaluate and define prey preferences at first feeding among the rotifer, Brachionus plicatiilis, the copepod, Parvocalanus crassirostris, and the ciliate Euplotes sp., by marking each prey with a different colored fluorescent microsphere. Prey preferences observed at the larval first feeding stage were species specific. Pacific blue tang larvae preferred rotifers above ciliates, and ciliates above copepod nauplii. African moony larvae preferred ciliates and nauplii equally over rotifers. Reef butterflyfish larvae preferred ciliates over rotifers and rotifers over nauplii. Golden trevally larvae preferred nauplii over ciliates, and ciliates over rotifers. Take together these data provide critical information which may aid in development of feeding protocols for marine ornamental species.
Thermal acclimation of fast-growing quail exhibit decreased oxidative stress and increased muscle fiber diameters after acute heat challenges.

Many predict dire consequences of increasing temperatures; however, high temperatures in early life may aid animals during extreme thermal events later in life. The underlying physiological mechani...
SnO2−In2O3 Nanocomposites as Semiconductor Gas Sensors for CO and NOx Detection

Gas sensors based upon semiconductor metal oxides provide for the safe detection of toxic gases, such as carbon monoxide in households, natural gas in coal mines, and ethanol in fermentation processes. However, they still suffer from several limitations, such as long-term response reproducibility and gas sensitivity and selectivity. The need for thermally stable gas sensor materials that possess ultrahigh sensitivity and selectivity, often in the presence of other adsorbing gases, presents a major challenge. In this work, we have synthesized tin−indium oxide (SnO2−In2O3) nanocomposites that exhibited superior thermal stability against grain growth. Through the introduction of metal clusters and oxide surface coatings, the SnO2−In2O3 nanocomposites achieved superb sensitivity for both reducing and oxidizing gases. Our synthesis method provided an inexpensive and flexible wet-chemical route toward tailoring semiconductor metal oxide nanocomposites for the selective and reproducible detection of toxic or com...
Femtochemistry and Max Bodenstein’s Impact

This article gives a summary of the presentation made in tribute to Max Bodenstein at the conference entitled “Gas Phase Chemical Reaction Systems: Experiments and Models 100 Years after Max Bodenstein”, in Heidelberg, during the period July 25 to 28, 1995.
Overview of Integrative Therapies and Healing Practices

Growth in the use of integrative therapies has been stimulated by consumer interest in a more comprehensive, holistic approach to care that includes both conventional medical practices and complementary or integrative therapies. Increased utilization has also been fueled by the growing evidence base that has documented safety and efficacy for many of these unconventional practices. Increasingly, health professional students are exposed to integrative therapies within their curriculum and within clinical sites where they practice. Students, faculty teaching in health professional schools, and practitioners recognize the importance of educating students about integrative health and offering services that provide patients choice and the opportunity to integrate the best of conventional and CAM approaches. The policy issues surrounding integrative health/medicine are complex and include education and workforce development, care delivery, and economics and financing issues. For patients facing chronic health issues such as pulmonary disease and sleep disorders, integrative health approaches may offer improved symptom management and quality of life.
k-Means Clustering

As we learned in Chaps. 7, 8, and 9, classification could help us make predictions on new observations. However, classification requires (human supervised) predefined label classes. What if we are in the early phases of a study and/or don’t have the required resources to manually define, derive, or generate these class labels? Clustering can help us explore the dataset and separate cases into groups representing similar traits or characteristics. Each group could be a potential candidate for a class. Clustering is used for exploratory data analytics, i.e., as unsupervised learning, rather than for confirmatory analytics, or for predicting specific outcomes.
Chemical-Free Recovery of Elemental Selenium from Selenate-Contaminated Water by a System Combining a Biological Reactor, a Bacterium–Nanoparticle Separator, and a Tangential Flow Filter

Biological selenate (SeO42–) reduction to elemental selenium nanoparticles (SeNPs) has been intensively studied but little practiced because of the additional cost associated with separation of SeN...
Work, Love, and Learning in Utopia: Equality Reimagined

Work, Love, and Learning in Utopia breathes new life into the age-old human preoccupation with how to create a happier society. With a fascinating mix of research from cross-cultural psychology, macro history, and evolutionary biology, the book gives new credibility to the advocacy of radical equality. The author, a psychological anthropologist, argues that the negative emotions of sadness, anger, and fear evolved in tandem with hierarchy, while happiness evolved separately and in connection to prosociality and compassion. The book covers a wide range of human concerns, from economics and education, to media and communication, to gender and sexuality. It breaks new boundaries with its scope, arguing that equality of love is as important and possible as is economic equality. Its argument is provocative yet practical, and each chapter ends with concrete proposals that invite dialogue with any student of policy. Written in an easily accessible style, this book will appeal to anyone who has ever puzzled over how our social world could be remade. In particular, it will be very useful to students and scholars of anthropology, sociology, and psychology.
Part III Primer: The Elements of Document Algorithms

In Chaps. 14 through 21, we find our math touchstone in the world of software engineering, where flowcharted algorithms made of symbols, functions, arrows, and labels provide software designers with a top-level view of how a program moves through its operations—start to finish, input to output. A document algorithm is analogous. It defines how the operative flow of a human language message develops; how and when the message’s language stream articulates descriptions, claims, and evidence; and how these elements aggregate and synthesize into a coherent, cohesive, and convincing message output.
Review article: the management of heartburn during pregnancy and lactation.

Background Gestational reflux is common, affecting up to 80% of pregnant women. Most symptoms will abate during lactation. During both of these periods, interventions used to relieve symptoms focus on a "step-up" methodology with progressive intensification of treatment. This begins with lifestyle modifications. Aim To provide guidance in the treatment of reflux in pregnancy and lactation, as well as briefly summarising the pathogenesis, clinical presentation and diagnostic workup. Methods A comprehensive search, using online databases PubMed and MEDLINE, along with relevant manuscripts published in English between 1966 and 2019 was used. All abstracts were screened, potentially relevant articles were researched, and bibliographies were reviewed. Results Only a small percentage of relevant drugs are contraindicated for use in pregnancy or while breastfeeding. However, not all drug agents have been extensively evaluated in pregnant women or during the breastfeeding period. Antacids, alginates, and sucralfate are the first-line therapeutic agents. If symptoms persist, any of the H2 RAs can be used except for nizatidine (due to foetal teratogenicity or harm in animal studies). PPIs are reserved for women with intractable symptoms or complicated GERD; all are FDA category B drugs, except for omeprazole, which is a category C drug. Conclusions The management of heartburn during pregnancy and lactation begins with lifestyle modifications. In situations where disease severity increases, medical providers must discuss risks and benefits of these medicines with the patient in detail.
Identification of pAKT as a pharmacodynamic marker for MER kinase in human melanoma G361 cells

The MER signaling pathway represents an attractive therapeutic target for human cancers. Growth arrest–specific protein 6 (GAS6)–induced MER phosphorylation is often unstable and difficult to detect without pervanadate pretreatment in human cancer cells, posing a challenge for the development of selective MER kinase inhibitors. Here, we identified phosphorylated AKT (pAKT) as a specific pharmacodynamic marker for MER kinase inhibitors in human melanoma G361 cells. The expression of MER, TYRO3, and AXL were profiled among multiple human cancer cells. To determine whether they play a role in the activation of pAKT, MER and TYRO3 were selectively depleted by small, interfering RNA knockdown. In addition, using AKT phosphorylation as a readout, a high-throughput cell-based assay was established in G361 cells for evaluation of the potency of potential inhibitors of MER pathway activation. We demonstrated that high levels of MER and TYRO3, but not AXL, were expressed in G361 cells. In these cells, pAKT was induced by GAS6 treatment, which could be reversed by AXL/MER inhibitors. We showed that GAS6-induced pAKT is only dependent on MER kinase, but not TYRO3, in G361 cells. Furthermore, we observed a correlation in potency between inhibition of pAKT in G361 cells and pMER in MER-overexpressing Ba/F3 cells by these inhibitors. In summary, we have demonstrated that GAS6-induced pAKT is a possible pharmacodynamic marker for the inhibition of MER kinase, and we have successfully developed a cell-based functional assay for screening small-molecule inhibitors of MER kinase for potential therapeutic utility in treating GAS6/MER-deregulated human cancers.
Prioritizing community environmental concerns with a hybrid approach to multi-criteria decision-making – a case study of Newport News, Virginia, USA

Local communities can play a very important role in evaluating their environmental conditions and in developing innovative, practical, and effective solutions to improve community environmental hea...
Arene dearomatization through a catalytic N-centered radical cascade reaction.

Arene dearomatization reactions are an important class of synthetic technologies for the rapid assembly of unique chemical architectures. Herein, we report a catalytic protocol to initiate a carboamination/dearomatization cascade that proceeds through transient sulfonamidyl radical intermediates formed from native sulfonamide N–H bonds leading to 1,4-cyclohexadiene-fused sultams. Importantly, this work demonstrates a facile approach to employ two-dimensional aromatic compounds as modular building blocks to generate richly substituted, three-dimensional compounds. These reactions occur at room temperature under visible light irradiation and are catalyzed by the combination of an iridium(III) photocatalyst and a dialkyl phosphate base. Reaction optimization, substrate scope, mechanistic features, and synthetic applications of this transformation are presented. Arene dearomatization reactions allow chemists to rapidly build unique chemical architectures from largely available starting materials. Here, the authors show a photocatalytic carboamination/dearomatization cascade process leading to 1,4-cyclohexadiene-fused sultams via N-centered radicals.
Single-cell RNA transcriptomics identifies Hivep3 as essential in regulating the development of innate-like T lymphocytes

Most T lymphocytes leave the thymus as naive cells with limited functionality. However, unique populations of T cells, commonly known as innate-like T cells, differentiate into functionally distinct effector subsets during thymic development under the influence of the transcription factor PLZF. Here, we profiled >10,000 differentiating thymic iNKT cells using single-cell RNA sequencing to provide a comprehensive transcriptional landscape of their maturation, function, and fate decision in steady state. We identified Hivep3, a zinc finger transcription factor and adaptor protein, as a key factor that is expressed in early precursors and regulates the post-selection proliferative burst, differentiation and functions of iNKT cells. Importantly, we extended these results to other PLZF+ innate-like T cell populations, highlighting the unique and common requirement of Hivep3 to the development of all innate-like T cells.
Heavy ion space radiation triggers ongoing DNA base damage by downregulating DNA repair pathways

Abstract Long-duration space missions outside low earth orbit will expose astronauts to a cumulative dose of high-energy particle radiation especially to highly damaging heavy ion radiation, which poses considerable risk to astronauts’ health. The purpose of the current study was to quantitatively identify oxidatively induced DNA base modifications and assess status of the repair pathways involved in removing the modified bases in mouse intestinal cells after exposure to γ-rays and iron radiation. Mice (C57BL/6J; 6 to 8 weeks; female) were exposed to 0.5 Gy of either γ-rays or iron radiation and control mice were sham-irradiated. Intestinal tissues were collected 2 months after radiation. DNA base lesions were measured using gas chromatography-tandem mass spectrometry with isotope‑dilution. Base excision repair (BER) and nucleotide excision repair (NER) pathways were assessed using PCR and immunoblotting. Effects of iron radiation were compared to γ-rays and sham-irradiated controls. Exposure to iron radiation resulted in significantly higher levels of several DNA base lesions relative to control animals and those exposed to γ radiation. Assessment of BER and NER showed downregulation of pathway factors both at the RNA as well as at the protein levels. Our results not only provide important insight into DNA damage pattern in intestinal cells in response to iron radiation, but they also confirm our previous immunohistochemistry data on oxidatively induced DNA damage. We suggest that downregulation of the BER and NER pathways is contributing to ongoing DNA base damages long time after radiation exposure and has implications for chronic diseases including gastrointestinal diseases after heavy ion radiation exposure during space travel.
Relationship between initial management strategy and survival in patients with gastric outlet obstruction due to gastric cancer.

Background The optimal management of gastric outlet obstruction (GOO) due to gastric cancer (GC) is unclear. We examined the relationships between clinical and management variables and outcomes in patients with GC having GOO. Methods The GOO management and clinical course were reviewed in patients with GC and GOO. Cox regression and Kaplan-Meier analyses were used to identify variables predictive of overall survival (OS). Results The study included 59 patients. Eleven had imaging evidence of metastasis and 35 had pathologically confirmed peritoneal disease. Initial management included resection in 23 patients, feeding jejunostomy ± decompressive gastrostomy (JT/GT) in 25, surgical gastrojejunostomy in five, and endoscopic intervention in six. Seven patients with initial JT/GT underwent resection after neoadjuvant therapy. Median OS (95% confidence interval [CI]) was 21.4 (0.0-45.1) months in the upfront resection group (median follow-up, 14.7 months) and not reached in those with initial JT/GT, neoadjuvant therapy, and later resection (median follow-up, 26.5 months) (P = .18). On multivariable analysis, clinically positive nodes (hazard ratio [HR]: 3.76; 95% CI, 1.17-12.12; P = .03), metastasis on CT (HR: 3.97; 95% CI: 1.53-10.26;P = .01), and resection (HR: 0.37; 95% CI: 0.17-0.79;P = .01) independently predicted OS. Conclusion In GOO due to GC, OS is similar after treatment with upfront resection compared with JT/GT, neoadjuvant therapy, and later resection. Upfront JT/GT may allow patients to tolerate chemotherapy and improve selection for gastrectomy.
A Comparative Study on the Predictability of Two Models for Ecologically Conscious Consumer Behavior

A survey of 357 homeowners found the respondent's opm10ns about the nation's more serious environmental issues (EI), specific lawn care issues (LCC), and conscious environmental initiatives (EC), using two different models, were significant but weak predictors of ecologically conscious consumer behavior (EA). The general model was superior to the specific model regarding its ability to predict the contribution of attitudes on ecological behavior. An assessment of significant ecological responses are examined and future research implications are suggested.
Using the Penn State Worry Questionnaire in the Peripartum.

Purpose: Pathological worry is a major feature of anxiety in the peripartum, and we sought to examine the factor structure, validity, and reliability in the peripartum of a scale used to measure wo...
Risk factors for laminitis and nonsurvival in acute colitis: Retrospective study of 85 hospitalized horses (2011-2019).

BACKGROUND Acute colitis is a serious cause of morbidity and death in horses. Recent studies have compared clinical features of coronavirus and salmonellosis, but no study has compared clinical features of enteric salmonellosis, coronavirus, and neorickettsiosis. HYPOTHESIS/OBJECTIVES To identify risk factors for laminitis and nonsurvival to discharge in horses with enteric salmonellosis, coronavirus, or neorickettsiosis. ANIMALS Eighty-five horses hospitalized for acute colitis from 2011 to 2019. METHODS Retrospective case series. Medical record review (2011-2019) of adult (≥2 years) horses with colitis. Primary outcomes were laminitis and survival to discharge. Multivariable logistic regression was performed to assess association between variables and the development of laminitis. Stepwise Cox regression was performed to assess association between variables and survival. RESULTS Seventeen of 85 (20%) horses developed laminitis during hospitalization. Neorickettsiosis cases (11/26, 42%) were more likely to develop laminitis than coronavirus (0/16, 0%) cases (odds ratio [OR] 24.48; 95% confidence interval [CI]: 1.33-451.74, P = .03). There was no significant difference in laminitis between salmonellosis and neorickettsiosis cases (OR 0.27; 95% CI: 0.07-1.07, P = .06). Admission heart rate (OR 1.08; 95% CI: 1.02-1.15, P = .01), total solids (OR 0.17; 95% CI: 0.06-0.54, P = .003), band neutrophils (OR 1248.47; 95% CI: 6.62-235 540, P = .008), and bicarbonate concentration (OR 0.68; 95% CI: 0.5-0.92, P = .01) were predictive of development of laminitis during hospitalization. Sixty-three of 85 (74%) horses survived to discharge: 16/16 (100%) coronavirus cases, 17/26 (65%) neorickettsiosis cases, 14/20 (70%) salmonellosis cases, and 16/23 (70%) unknown cases. Packed cell volume (hazard ratio [HR] 1.17; 95% CI: 1.09-1.26, P < .001), L-lactate concentration (HR 1.33; 95% CI: 1.14-1.55, P < .001), and development of laminitis (HR 7.07; 95% CI: 1.67-29.95, P = .008) were retained in the final multivariable model for prediction of nonsurvival to discharge. CONCLUSION AND CLINICAL IMPORTANCE Nonsurvival and laminitis rates were high, likely related to the presence of neorickettsiosis in the region.
Remote Concurrent Engineering: A-Team Studies in the Virtual World

NASA Jet Propulsion Laboratory's (JPL's) Architecture Team (A-Team) has nearly a decade of experience in maturing early formulation mission and technology concepts by combining innovative collaborative engineering methods with cutting-edge subject matter expertise and advanced analysis tools in an in-person environment. When COVID-19 forced JPL's workforce to work remotely in March 2020, A-Team had to quickly pivot from an in-person collaborative environment to a remote working environment. Through introspection, careful planning, and considerable practice, A-Team was able to develop new operating procedures to effectively continue early formulation studies in a virtual environment. A-Team has held over 57 remote studies in the 10 months since the start of mandatory telework at JPL in March 2020. In the remote setting, A-Team conducts studies in half-day sessions with clients and subject matter experts (SMEs) via videoconferencing, shared computer screens, and digital collaborative tools. The key lesson is that increased staffing and planning is needed to prepare and successfully run remote A-Team studies. Remote A-Team studies require careful selection of the appropriate tools for security, accessibility, and usability within the NASA/JPL environment. Knowledge capture methods and templates need to be thought out and agreed upon in advance as there is less room for improvising in a remote format. Various communication channels have to be monitored to allow for team coordination while maintaining fruitful participant engagement during a session. In addition, technical backup for all roles within the A-Team have to be identified to allow the study to continue even if a team member's connectivity is temporarily interrupted. Finally, careful thought has to be put into methods and processes to create a collaborative environment in a virtual space such that a group of experts who are only connected via the internet can experience the creative spark and flow of a great collaborative and innovative study.
Statesman of the Old Republic

New on the bookshelf is R. Kent Newmyer’s splendid Supreme Court Justice Joseph Story: Statesman of the Old Republic (1986). This exemplary biography is the first thoroughgoing study of Story’s intellectual life. It succeeds brilliantly in conveying both the main influences on Story’s thought and the principal themes in his work. Along the way, however, Newmyer manages also to provide a fascinating portrait of Story’s world. This is Story’s biography, yes; but it is a biography of his age as well. Name a leading figure or vital issue of early nineteenth century America and, virtually without exception, he, she, or it will appear in these pages. Each is deftly summarized and sketched; all are accorded scrupulously fair treatment by a master historian. This volume is the product of painstaking and unprecedented research. It is carefully conceived, illuminating, rich in detail, and entertainingly written. It is absolutely first-rate. Story’s accomplishments in his many legal roles beyond judging – as a publicist, legislative draftsman, codifier, and Harvard law professor, for example – all receive detailed treatment. In each of his roles, Story’s purpose was constant: to bring consistent, carefully conceived legal principles to bear in resolving the great political and economic problems of his own generation, and so to safeguard the precious inheritance bequeathed to it by those who had made the Revolution. For much of Story’s career, his purpose and style suited perfectly the needs of his age. Toward the end, however, he saw much cause for gloom. John Marshall, Story’s colleague and steadfast friend during nearly a quarter century on the Supreme Court, was dead. Jacksonian Democracy, which Story greatly feared, ran rampant. And slavery, the original sin that the founding generation could not absolve, was tearing asunder the nation they had created. Yet Story’s vision, idealism, and elemental decency remained intact to the end. Upon his death in 1845, even his sometime adversary, the Jacksonian Chief Justice Roger B. Taney, was moved to mourn the nation’s loss as “irreparable, utterly irreparable in this generation, for there is nobody equal to him.” Kent Newmyer now has demonstrated the utter accuracy of Taney’s judgment.
Implementation of a High-Speed FPGA and DSP Based FFT Processor for Improving Strain Demodulation Performance in a Fiber-Optic-Based Sensing System

NASA's Aviation Safety and Security Program is pursuing research in on-board Structural Health Management (SHM) technologies for purposes of reducing or eliminating aircraft accidents due to system and component failures. Under this program, NASA Langley Research Center (LaRC) is developing a strain-based structural health-monitoring concept that incorporates a fiber optic-based measuring system for acquiring strain values. This fiber optic-based measuring system provides for the distribution of thousands of strain sensors embedded in a network of fiber optic cables. The resolution of strain value at each discrete sensor point requires a computationally demanding data reduction software process that, when hosted on a conventional processor, is not suitable for near real-time measurement. This report describes the development and integration of an alternative computing environment using dedicated computing hardware for performing the data reduction. Performance comparison between the existing and the hardware-based system is presented.