cssi/SciSciGPT-SciSciNet huggingface dataset:
Interactions of eukaryotic translation initiation factor 3 (eIF3) subunit NIP1/c with eIF1 and eIF5 promote preinitiation complex assembly and regulate start codon selection.

The N-terminal domain (NTD) of NIP1/eIF3c interacts directly with eIF1 and eIF5 and indirectly through eIF5 with the eIF2-GTP-Met- ternary complex (TC) to form the multifactor complex (MFC). We investigated the physiological importance of these interactions by mutating 16 segments spanning the NIP1-NTD. Mutations in multiple segments reduced the binding of eIF1 or eIF5 to the NIP1-NTD. Mutating a C-terminal segment of the NIP1-NTD increased utilization of UUG start codons (Sui− phenotype) and was lethal in cells expressing eIF5-G31R that is hyperactive in stimulating GTP hydrolysis by the TC at AUG codons. Both effects of this NIP1 mutation were suppressed by eIF1 overexpression, as was the Sui− phenotype conferred by eIF5-G31R. Mutations in two N-terminal segments of the NIP1-NTD suppressed the Sui− phenotypes produced by the eIF1-D83G and eIF5-G31R mutations. From these and other findings, we propose that the NIP1-NTD coordinates an interaction between eIF1 and eIF5 that inhibits GTP hydrolysis at non-AUG codons. Two NIP1-NTD mutations were found to derepress GCN4 translation in a manner suppressed by overexpressing the TC, indicating that MFC formation stimulates TC recruitment to 40S ribosomes. Thus, the NIP1-NTD is required for efficient assembly of preinitiation complexes and also regulates the selection of AUG start codons in vivo.
Thoracolumbar spinal angiolipoma demonstrating high signal on STIR imaging: a case report and review of the literature.

Abstract Background Angiolipomas are rare benign tumors, accounting for 0.14% to 1.2% of all tumors of the spinal axis with vascular and fatty histological features. Spinal angiolipoma (SAL) is most commonly found in the thoracic region and has high signal on contrast enhanced fat-saturated T1-weighted imaging. Although the international literature is extensive, there are few cases reported in United States. Objective To present a case of SAL located in the thoracolumbar region without high signal on contrast enhanced fat-saturated T1-weighted imaging and to review previously reported cases. Study design/Methods Case report and review the literature. Results Magnetic resonance imaging obtained in a 68-year-old man with a long history of lumbago showed a heterogeneous mass (T10–L1) hyperintense on T1-weighted imaging but not enhancing on suppression fat sequences, suggesting epidural hematoma. Surgical excision of the lesion was performed, and SAL was diagnosed and confirmed by pathology. The patient became asymptomatic. Conclusions The predominance of either vascular or fatty components inside the tumor might alter the expected results on magnetic resonance imaging with suppression fat sequences.
Sensitivity and specificity of the StratusOCT for perimetric glaucoma.

Purpose To determine the sensitivity and specificity of measurements of the retinal nerve fiber layer (RNFL) using the StratusOCT in glaucoma subjects with visual field (VF) defects. Design Prospective cross-sectional study. Participants One hundred nine normal and 63 glaucoma subjects. Testing Fast RNFL scans were performed in one eye of each patient using the StratusOCT. Main outcome measures Sensitivity and specificity of different optical coherence tomography (OCT) criteria for identifying glaucoma subjects with glaucomatous VF defects. Secondary outcome measures Areas under the receiver operating characteristic curves (AROCs) for various OCT parameters. Results Severity of VF defects in the glaucoma group was distributed between mild (18 subjects), moderate (21 subjects), and severe (24 subjects). The average mean deviation of the glaucoma fields was −8.4 decibels (dB), with a standard deviation of 6.0 dB and a range from −0.14 to −28.0 dB. The sensitivity and specificity using a criterion of average RNFL thickness abnormal at the Conclusions The sensitivity and specificity of RNFL measurements using the new StratusOCT for glaucoma with manifest VF defects are excellent. The best parameters seem to be ≥1 quadrants abnormal at the ≤5% level or ≥1 clock hours abnormal at the ≤5% level. Future studies are needed to determine the sensitivity and specificity of this new technology for glaucoma without VF defects.
Brain amino acid metabolism and ketosis.

The relationship between ketosis and brain amino acid metabolism was studied in mice that consumed a ketogenic diet (>90% of calories as lipid). After 3 days on the diet the blood concentration of 3-OH-butyrate was approximately 5 mmol/l (control = 0.06-0.1 mmol/l). In forebrain and cerebellum the concentration of 3-OH-butyrate was approximately 10-fold higher than control. Brain [citrate] and [lactate] were greater in the ketotic animals. The concentration of whole brain free coenzyme A was lower in ketotic mice. Brain [aspartate] was reduced in forebrain and cerebellum, but [glutamate] and [glutamine] were unchanged. When [(15)N]leucine was administered to follow N metabolism, this labeled amino acid accumulated to a greater extent in the blood and brain of ketotic mice. Total brain aspartate ((14)N + (15)N) was reduced in the ketotic group. The [(15)N]aspartate/[(15)N]glutamate ratio was lower in ketotic animals, consistent with a shift in the equilibrium of the aspartate aminotransferase reaction away from aspartate. Label in [(15)N]GABA and total [(15)N]GABA was increased in ketotic animals. When the ketotic animals were injected with glucose, there was a partial blunting of ketoacidemia within 40 min as well as an increase of brain [aspartate], which was similar to control. When [U-(13)C(6)]glucose was injected, the (13)C label appeared rapidly in brain lactate and in amino acids. Label in brain [U-(13)C(3)]lactate was greater in the ketotic group. The ratio of brain (13)C-amino acid/(13)C-lactate, which reflects the fraction of amino acid carbon that is derived from glucose, was much lower in ketosis, indicating that another carbon source, i.e., ketone bodies, were precursor to aspartate, glutamate, glutamine and GABA.
Crystalline poly(triazine imide) based g-CN as an efficient electrocatalyst for counter electrodes of dye-sensitized solar cells using a triiodide/iodide redox electrolyte

We report utilization of graphitic carbon nitride (g-CN) as an electrocatalyst for dye-sensitized solar cells (DSSCs). Crystalline poly(triazine imide) based g-CN was synthesized via a modified ionothermal method, and deposited onto the counter electrodes along with a conductive additive and a sacrificial polymer binder. The resulting DSSCs exhibited a power conversion efficiency (7.8%) comparable to that of conventional Pt catalyst (7.9%), confirming the excellent catalytic activity of poly(triazine imide) g-CN as a non-precious metal electrocatalyst.
Roost characteristics of hoary bats in Arkansas

ABSTRACT We radiotracked nine hoary bats (Lasiurus cinereus) and characterized 12 roosts during late spring and early summer in the Ouachita Mountains of central Arkansas. Hoary bats generally roosted on the easterly sides of tree canopies in the foliage of white oaks (Quercus alba), post oaks (Q. stellata) and shortleaf pines (Pinus echinata). Roost heights averaged 16.5 ± 2.2 m and all roost trees were >21 cm dbh and were taller and greater in diameter than random trees. Roost sites averaged 7.7 m2/ha basal area (BA) of overstory pines, 4.4 m2/ha BA of overstory hardwoods and 80% canopy cover. Roost sites had a greater number of understory stems than random sites. All roosts were located in stands dominated by mature (overstory >50 y old) overstory trees. Seven roosts were in relatively unmanaged mixed pine-hardwood and hardwood stands >50 y old and four roosts were in mature mixed pine-hardwoods stands that recently had been thinned and subjected to prescribed burning; one additional roost was located ...
Liability of Treaters for Injuries to Others: Erosion of Three Immunities

For years treaters of mental patients who harmed other persons were largely protected by three doctrines: the common law rule of nonresponsibility, sovereign immunity, and the “honest error” rule. The present paper examines the erosion of these immunities that has occurred over the last 30 years. As the strength and breadth of these protections have lessened, claims of negligence have expanded. Failure to properly diagnose includes failure to foresee violent acts. Failure to properly treat includes failure to restrain a violent patient. The recently asserted failure to protect others is not necessarily based on failure to diagnose or to treat, or, for that matter, on medical malpractice law.
Mechanism of the Flavoprotein L-Hydroxynicotine Oxidase: Kinetic Mechanism, Substrate Specificity, Reaction Product, and Roles of Active-Site Residues.

The flavoprotein l-hydroxynicotine oxidase (LHNO) catalyzes an early step in the bacterial catabolism of nicotine. Although the structure of the enzyme establishes that it is a member of the monoamine oxidase family, LHNO is generally accepted to oxidize a carbon–carbon bond in the pyrrolidine ring of the substrate and has been proposed to catalyze the subsequent tautomerization and hydrolysis of the initial oxidation product to yield 6-hydroxypseudooxynicotine [Kachalova, G., et al. (2011) Proc. Natl. Acad. Sci. U.S.A. 108, 4800–4805]. Analysis of the product of the enzyme from Arthrobacter nicotinovorans by nuclear magnetic resonance and continuous-flow mass spectrometry establishes that the enzyme catalyzes the oxidation of the pyrrolidine carbon–nitrogen bond, the expected reaction for a monoamine oxidase, and that hydrolysis of the amine to form 6-hydroxypseudooxynicotine is nonenzymatic. On the basis of the kcat/Km and kred values for (S)-hydroxynicotine and several analogues, the methyl group contr...
EPIDEMIOLOGY OF GONORRHEA: CURRENT PERSPECTIVES

Once considered a public nuisance of the developed countries, gonorrhea is now established as a leading worldwide public health problem. The rapid increase in reported disease in many developed countries noted in the 1960s and 1970s has been followed by stable or declining disease rates. This may reflect improved gonorrhea control programs or changes in sexual behavior. The assault on the developed countries by imported antibiotic-resistant strains of N. gonorrhoeae has increased, however, indicating the need for intensive control programs. New methods of identifying strains of gonococci have allowed investigation of the distribution and patterns of transmission of gonorrhea. Future studies using these methods will provide valuable knowledge of the ecology and epidemiology of gonorrhea. Within the developing countries, gonorrhea caused by resistant strains of N. gonorrhoeae has become hyperendemic. The current decreases of gonorrhea incidence in the developed countries may not be maintained unless some success is attained in the control of gonorrhea in developing countries.
The hidden alcoholic.

Hidden alcoholism is the result of an interactional process involving both hiders (alcoholics) and seekers (persons who label and take action against alcoholics). Definitions of alcoholism and sanc...
Interlocking Toy Building Blocks as Hands-On Learning Modules for Blind and Visually Impaired Chemistry Students

Interlocking toy building blocks (e.g., Lego) as chemistry learning modules for blind and visually impaired (BVI) students in high school and undergraduate introductory or general chemistry courses are presented. Building blocks were assembled on a baseplate to depict the relative changes in the periodic properties of elements. Modules depicting the electron configuration of an element and molecular orbital theory were also constructed. Modules were presented as a hands-on learning experience for a group of BVI students followed by a survey. Modules were also presented as classroom demonstration for an undergraduate general chemistry class of sighted students.
Chemical Tests for Malignancy

10 ' 3S we have shown that alterations do occur in the quality of the dehydrogenase activity of the liver and kidney. 9 In a clinical study of various liver functions in patients with and without gastrointestinal cancer, the Memorial Hospital Group found that the presence of malignancy was associated with marked alteration in hepatic function, although no direct metastatic in­ volvement of the liver had occurred. 1 ' 354 6 Further, they observed that these changes appeared to be reversible after resection of the tumor. On the basis of these findings they indicated that hepatic insufficiency is a concomitant phe­ nomenon in the presence of gastrointestinal cancer. A similar study of patients with and without breast carcinoma failed to reveal any significant difference in liver function. 42 An effect upon the carbohydrate metabolism of hepatic tissue is indicated by the observation that the hepatic glycogen of cancer patients is not elevated by the oral or parenteral administration of glucose, although the fasting blood sugar, hepatic glycogen and glucose tolerance curves of such patients are not essentially altered from those of normal controls. It is notable that the defect in glycogen synthesis can be at least partially corrected by the administration of adrenal cortical extract. Evaluation of the enzyme activity of the liver of the tumor-bearing host re­ veals that at least three enzymes undergo a reduction in activity with the devel­ opment of a tumor. This decrease in activity, which tends to vary inversely with the size of the tumor, occurs in catalase, d-amino-acid oxidase and arginase. 20 While similar enzyme alterations are also found to occur in the kidney of the tumor-bearing animal, such changes are not as marked in this organ. Perhaps the most striking change induced in the liver by the tumor is in pro
Chemical and Physical Transformations of Aluminosilicate Clay Minerals Due to Acid Treatment and Consequences for Heterogeneous Ice Nucleation

Mineral dust aerosol is one of the largest contributors to global ice nuclei, but physical and chemical processing of dust during atmospheric transport can alter its ice nucleation activity. In particular, several recent studies have noted that sulfuric and nitric acids inhibit heterogeneous ice nucleation in the regime below liquid water saturation in aluminosilicate clay minerals. We have exposed kaolinite, KGa-1b and KGa-2, and montmorillonite, STx-1b and SWy-2, to aqueous sulfuric and nitric acid to determine the physical and chemical changes that are responsible for the observed deactivation. To characterize the changes to the samples upon acid treatment, we use X-ray diffraction, transmission electron microscopy, and inductively coupled plasma-atomic emission spectroscopy. We find that the reaction of kaolinite and montmorillonite with aqueous sulfuric acid results in the formation of hydrated aluminum sulfate. In addition, sulfuric and nitric acids induce large structural changes in montmorillonite. We additionally report the supersaturation with respect to ice required for the onset of ice nucleation for these acid-treated species. On the basis of lattice spacing arguments, we explain how the chemical and physical changes observed upon acid treatment could lead to the observed reduction in ice nucleation activity.
A Disposable, Constricted Tissue Culture Tube

SummaryThe use of a newly designed, disposable tissue culture tube is described. The new tube contains a circular constriction forming a reservoir at the distal end of the tube. Thus cells may be incubated level rather than at an incline, as in the case of conventional tubes. Cells incubated level in these constricted tubes form a monolayer more rapidly than in standard tubes incubated at an angle, and fewer cells are needed as seed for cultures. Other advantages are the uniformity of the cellular monolayer in the entire culture and the prevention of cellular sloughing. A striking safety feature of the disposable tube is the virtual elimination of tube breakage during stoppering.
Application of the complex adaptive system theory in the stock market simulation

The capital market is a financial product provider(such as a listing Corporation),system of exchange and investors.With the continuous development of the economy,the stock market has become the most active,the most rapid development of the market of our country capital market,so it has become the focus of many scholars to study.The traditional financial theories to the stock market in many common characteristic facts,such as fat tails,volatility clustering phenomenon is difficult to explain.At the same time,the linear mathematical analysis method of traditional also fell into a hitherto unknown difficulties.In the environmental requirements,application of complex adaptive system theory in finance has the advantage gradually revealed.
Silicon wafers with optically specular surfaces formed by chemical polishing

This letter investigates chemical polishing with a hydrofluoric acid, nitric acid, and acetic acid (HNA) mixture as an alternative to chemical mechanical polishing (CMP) to produce smooth surfaces on both slurry- and diamond-cut silicon solar wafers. With 30 µm of silicon etched from each side, as-cut wafers appear mirror-like to the naked eye. A quantitative analysis of the specularity of HNA-polished wafers indicates that 97 % of light reflected from slurry-cut wafers falls within ±10 mrad of the specular beam and is isotropically distributed. Conversely, HNA-polished diamond-cut wafers retain a history of the wafer-sawing process: the reflected light is anisotropic with 99.4 % of light within ±10 mrad of the specular beam in the sawing direction but only 89.1 % within ±10 mrad in the perpendicular direction. Topographical characterization by optical profilometry and atomic force microscopy measurements reveals that HNA-polished slurry-cut wafers are spatially uniform with a surface roughness of 45 nm. Diamond-cut wafers have a roughness of only 18 nm but also have residual sawing grooves tens of micrometers across—these are responsible for the anisotropic scattering of light. The HNA-polished wafers are appropriate alternatives to CMP wafers for high-efficiency solar cells, including interdigitated-back-contact and tandem cells that require single-side polished wafers, as well as for other optical applications such as process monitoring with characterization techniques that require planar substrates.
Rent, distribution, prices

The analysis carried out until now started with the choice of an exogenous distributive variable and determined the order of efficiency (Chapter III), and the level of activity of the economy (Chapter IV).
Small molecule stabilization of the KSR inactive state antagonizes oncogenic Ras signalling

Deregulation of the Ras-mitogen activated protein kinase (MAPK) pathway is an early event in many different cancers and a key driver of resistance to targeted therapies. Sustained signalling through this pathway is caused most often by mutations in K-Ras, which biochemically favours the stabilization of active RAF signalling complexes. Kinase suppressor of Ras (KSR) is a MAPK scaffold that is subject to allosteric regulation through dimerization with RAF. Direct targeting of KSR could have important therapeutic implications for cancer; however, testing this hypothesis has been difficult owing to a lack of small-molecule antagonists of KSR function. Guided by KSR mutations that selectively suppress oncogenic, but not wild-type, Ras signalling, we developed a class of compounds that stabilize a previously unrecognized inactive state of KSR. These compounds, exemplified by APS-2-79, modulate KSR-dependent MAPK signalling by antagonizing RAF heterodimerization as well as the conformational changes required for phosphorylation and activation of KSR-bound MEK (mitogen-activated protein kinase kinase). Furthermore, APS-2-79 increased the potency of several MEK inhibitors specifically within Ras-mutant cell lines by antagonizing release of negative feedback signalling, demonstrating the potential of targeting KSR to improve the efficacy of current MAPK inhibitors. These results reveal conformational switching in KSR as a druggable regulator of oncogenic Ras, and further suggest co-targeting of enzymatic and scaffolding activities within Ras-MAPK signalling complexes as a therapeutic strategy for overcoming Ras-driven cancers.
Protein interactions and the spatial organization of cellular functions

P interactions have been extensively studied at the structural, functional, network and evolutionary levels. Yet one of their properties is so elementary as to be occasionally overlooked: they result in the spatial co-localization of their component proteins. We have recently explored the potential impact of such co-localization on metabolism and cellular organization. It has long been believed that cells are organized to allow metabolic channeling between sequential enzymes. I will discuss how indirect protein interactions between enzymes and non-enzymatic mediator proteins may help achieve such channeling in a modular fashion. I will also illustrate how the potential metabolic role of these interactions is supported by genome-scale flux and gene essentiality data. Extending on this idea of spatial organization, I will discuss a new approach for modeling the protein organization of the cellular interior that is based on a discrete lattice. Using this model, I will present evidence that the set of know binary protein interactions from yeast give rise to emergent structures, such as micro-clusters of related enzymes and robustness to over expression. I suggest that this lattice model, while clearly incomplete, indicates that some degree of the complex organization of the cell may be derived from simple rules of aggregation and interaction. Finally, I will present evolutionary evidence for the ancient character of most human protein-protein interactions, again suggesting that they may play important functional roles.
Adhesion modulation using glue droplet spreading in spider capture silk

Orb web spiders use sticky capture spiral silk to retain prey in webs. Capture spiral silk is composed of an axial fibre of flagelliform silk covered with glue droplets that are arranged in a beads-on-a-string morphology that allows multiple droplets to simultaneously extend and resist pull off. Previous studies showed that the adhesion of capture silk is responsive to environmental humidity, increasing up to an optimum humidity that varied among different spider species. The maximum adhesion was hypothesized to occur when the viscoelasticity of the glue optimized contributions from glue spreading and bulk cohesion. In this study, we show how glue droplet shape during peeling contributes significantly to capture silk adhesion. Both overspreading and underspreading of glue droplets reduces adhesion through changes in crack propagation and failure regime. Understanding the mechanism of stimuli-responsive adhesion of spider capture silk will lead to new designs for smarter adhesives.
Adolescent's Health Behaviors and Risk for Insulin Resistance: A Review of the Literature.

One-third of US adolescents are obese, and related comorbidities exist in this population. Preventing early indicators of these diseases, such as insulin resistance (IR), may impact future morbidity and mortality. Interventions to date have only focused on diet or exercise. Additional targets to prevent disease are needed. This paper reviews the evidence in adolescents examining multiple health behaviors that have been associated with IR. Health behaviors (i.e., diet, activity, sleep) have been individually examined as possible contributors to disease, but an understanding of the complex interplay between these behaviors is lacking. A better understanding of how multiple health behaviors contribute to IR in adolescents is needed. Future studies using both advanced statistical methodology and robust measures of each health behavior may facilitate better understanding of the impact of lifestyle factors on IR and guide intervention strategies to reduce the risk of disease.
Food safety practices in the U.S. meat slaughter and processing industry: Changes from 2005 to 2015

Meat slaughter establishments use a multipronged approach to ensure beef and pork products are safe for human consumption. To determine the approaches most commonly used, we conducted a national survey of federally inspected meat slaughter and processing establishments (376 completed surveys, 66% response rate) in 2015. We compared the results with a survey that was conducted in 2005, albeit of potentially different establishments, by using a similar questionnaire and similar data collection methods, thus allowing for an evaluation of trends in food safety practices over time. The use of some food safety practices has increased over the 10-yr time period, whereas others remained the same or decreased. For example, the use of chemical sanitizers or hot water for food contact surfaces and tools increased from 51 to 93%. As another example, microbiological testing of raw meat after fabrication, in addition to that required by regulation, increased from 50 to 72%. However, the use of organic acid rinse on carcasses in the slaughter area remained the same, at 66% of establishments. Written policies and procedures to control the use of hazardous chemicals decreased from 75 to 65% of establishments. The survey findings can be used to characterize food safety practices and technologies in the meat slaughter and processing industry and identify areas for improvement.
Supercritical Accretion and its Possible Relation to Quasars and Radio Sources

This paper reviews some of the properties of supercritical accretion which make it a possible model for the quasar optical central source and for producing the jet in radio sources. Some of the problems with this scenario can be remedied with alternative, but related, models.
Moral Disengagement and Discrimination Experiences as Predictors of Bullying Among Korean-American Adolescents

AbstractThis study aimed to examine the relationship between moral disengagement, and discrimination experiences, and bullying experiences among Korean-American adolescents. It was hypothesized that bullies would show higher levels of moral disengagement and discrimination when compared with non-bullies. It was also hypothesized that moral disengagement would be related to discrimination experiences. A secondary data analysis from a survey study of Korean-American adolescents was conducted using a data set that consisted of survey responses on bullying and related experiences from 119 Korean-American junior high school students. The results supported the hypothesis that bullies experienced higher levels of moral disengagement when compared to non-bullies, although bullies did not experience more discrimination than non-bullies. Moral disengagement was not related to discrimination experiences. This study found that gender played a role in moral disengagement. Boy bullies experienced higher levels of moral disengagement than any other comparison group. In general, boys experienced more discrimination than girls. Future studies need to explore these factors along with other social variables, such as family relationships and cultural value orientations, to delineate why certain Korean-American adolescents become bullies and aggressors while others remain intact and resilient to adverse social and school experiences.
Zoo Story: Narrative, Virtue Ethics, and Deconstructing Dualisms in the Journalism of Thomas French

ABSTRACTThis study conducts a textual analysis of Thomas French’s longform journalistic work Zoo Story: Life in the Garden of Captives as an example of how narrative might foster a nuanced understa...
Chapter Sixteen – Advances in Inhibitors of Penicillin-Binding Proteins and β-Lactamases as Antibacterial Agents

Abstract The continued rise of multidrug-resistant bacterial infections poses a significant threat to public health and has prompted the pharmaceutical industry to reinvest in the discovery of new antibiotics with increased potency and expanded spectrum against these lethal pathogens. Although many excellent antibacterial targets exist, the penicillin-binding proteins remain the most clinically successful and most well-understood antibacterial targets currently by researchers. The classic β-lactam motif continues to be a primary driver in this field with N th generation β-lactams as a major focus of research. In addition, the evolution of β-lactamase (BL) resistance-particularly in Gram-negative pathogens-has pushed the industry to develop both non-β-lactam inhibitors of PBPs as well as direct inhibitors of the BL enzymes themselves, dosed concurrently with a BL antibiotic. This review will summarize the most recent advances in the development of BL and non-β-lactam PBP inhibitors and the development of inhibitors of the serine and metallo-β-lactamase enzymes for treatment of bacterial infections.
The effect of intergovernmental aid on city property taxes: new results for minnesota

An earlier study found that certain Minnesota state aid programs stimulated city property tax levies to a high degree. If this is accurate, it suggests potentially serious problems with state property tax relief efforts. This article re-examines this question and finds that most aid programs have little direct effect on property tax levies. However, certain aid formulas that reduce the effective price of property taxes do indirectly stimulate property taxes. Therefore, states need to be careful in designing aid programs intended to reduce property taxes.
Prospects for understanding the role of lymphoid microenvironments in B cell differentiation in vivo.

In this introduction to the section on B cell differentiation, I will focus on one of the traditional subjects of the Germinal Center Conferences — the role of lymphoid tissue microenvironments, and in particular of germinal centers, in controlling the development and differentiation of functional B cell subsets. Gerry Klaus, in his introductory remarks in our abstract books, emphasized the fact that germinal centers seem rather an esoteric topic to many immunologists today — including, undoubtedly, some attending this conference for the first time. This was not always the case, however. Twenty years ago the role of microenvironments in immune responses was a central concern of the immunology community, perhaps equivalent in general interest to the fascination today with lymphokines or the major histocompatibility complex. In this introduction, I will present my own (probably distorted) perspective on why interest in this area has so declined, and why investigations of in vivo microenvironments should hold renewed fascination to immunologists in the future.
The Collaborative Transition Model: An Interdisciplinary Approach to Meeting the Transition Needs of Rural Communities:

The author of this article describes an interdisciplinary transition model which is being utilized in various school districts in rural Wisconsin. The Collaborative Transition Model promotes the fo...
Advancing barrier island habitat mapping using landscape position information

Barrier islands are dynamic ecosystems that change gradually from coastal processes, including currents and tides, and rapidly from episodic events, such as storms. These islands provide many impor...
Laboratory markers as useful prognostic measures for survival in patients with spinal metastases.

Abstract BACKGROUND CONTEXT Laboratory values have been found to be useful predictive measures of survival following surgery. The utility of laboratory values for prognosticating outcomes among patients with spinal metastases has not been studied. PURPOSE To determine the prognostic capacity of laboratory values at presentation including white blood cell count, serum albumin and platelet-lymphocyte ratio (PLR) in patients with spinal metastases. STUDY DESIGN Retrospective review of records from two tertiary care centers (2005–2017). PATIENT SAMPLE Patients, aged 40 to 80, who received operative or nonoperative management for spinal metastases. OUTCOME MEASURES Survival, complications, or hospital readmissions within 90 days of treatment and a composite measure for treatment failure accounting for changes in ambulatory function and mortality at 6 months following presentation. METHODS Multivariable Cox proportional hazard regression analysis was used to analyze the relationship between laboratory values and length of survival, adjusting for confounders. Multivariable logistic regression was used in analyses related to 6-month and 1-year mortality, complications, readmissions, and treatment failure. A scoring rubric was developed based on the performance of laboratory values in the multivariable tests. Internal validation was performed using a bootstrap simulation that consisted of sampling with replacement and 1,000 replications. RESULTS We included 1,216 patients. Thirty-seven percent of patients received a surgical intervention and 63% were treated nonoperatively. Median survival for the cohort as a whole was 255 days (interquartile range 93–642 days). The PLR (hazard ratio [HR] 1.53; 95% confidence interval [CI] 1.29, 1.80; p CONCLUSIONS Individuals with low serum albumin and elevated PLR should be advised regarding the impact of these laboratory markers on outcomes including survival, irrespective of treatments received. An effort should also be made to optimize nutrition and PLR, if practicable, before treatment to minimize the potential for development of adverse events.
Gender Differences Among Adolescent Client Evaluations of the Working Alliance in an Acute Inpatient Treatment Setting

Suicidal adolescents seeking treatment in inpatient hospitals benefit from a strong working alliance with their counselor to meet discharge goals. Professional counselors working in these settings ...
Theory Ordinals Can Replace ZFC in Computer Science

The theory Ordinals can serve as a replacement for the theory ZFC because: • Ordinals are a very well understood mathematical structure. • There is only one model of Ordinals up to a unique isomorphism, which decides every proposition of the theory Ordinals in the model. • The theory Ordinals is much more powerful than ZFC. Standard mathematics that has been carried out in ZFC can more easily be done in Ordinals. Axioms of ZFC are in effect theorems of Ordinals. The type Ordinal is larger than any set in ZFC because no set can be placed in one-to-one correspondence with instances of the type Ordinal. • The theory Ordinals is algorithmically inexhaustible, i.e., it is impossible to computationally enumerate theorems of the theory thereby reinforcing the intuition behind [Franzen, 2004]. Contrary to [Church 1934], the conclusion in this article is to abandon the assumption that theorems of a theory must be computationally enumerable while retaining the requirement that proof checking must be computationally decidable. • There are no “monsters” [Lakatos 1976] in models of Ordinals such as the ones in models of 1st-order ZFC. Consequently unlike ZFC, the theory Ordinals is not subject to cyberattacks using “monsters” in models such as the ones that plague 1st-order ZFC. • The theory Ordinals formally proves its own consistency contra [Godel 1931] • Longstanding issues such as the nonexistence of large cardinals and the nonexistence of nonstandard models [Cohen 1966] are resolved in the theory Ordinals. The theory Ordinals is based on intensional types as opposed to extensional sets of ZFC. Using intensional types together with strongly-typed ordinal induction is key to proving that there is just one model of the theory Ordinals up to a unique isomorphism.
Community engagement and pediatric obesity: Incorporating social determinants of health into treatment

Childhood obesity is a complex and multi-faceted problem, with contributors ranging from individual health behaviors to public policy. For clinicians who treat pediatric obesity, environmental factors that impact this condition in a child or family can be difficult to address in a clinical setting. Community-clinic partnerships are one method to address places and policies that influence a person's weight and health; however, such partnerships are typically geared toward community-located health behavior change rather than the deeper social determinants of health (SDH), limiting effective behavioral change. Community-engaged research offers a framework for developing community-clinic partnerships to address SDH germane to obesity treatment. In this paper, we discuss the relationship between SDH and pediatric obesity treatment, use of community-clinic partnerships to address SDH in obesity treatment, and how community engagement can be a framework for creating and harnessing these partnerships. We present examples of programs begun by one pediatric obesity clinic using community-engagement principles to address obesity.
Roadway Context Classification Approach for Developing Regional Safety Performance Functions for Florida Intersections

Understanding how the type and location of intersections affect crashes is important to reduce these crashes effectively. This paper discusses the development of regional safety performance functio...
INFECTIVE ENDOCARDITIS PRESENTING AS COMPLETE HEART BLOCK

Intracardiac abscess causing 3rd degree AV block is a rare complication that can be seen in infective endocarditis. Epicardial pacing is a potentially feasible alternative to manage heart block in such patients. A 71-year-old male with ESRD on dialysis and recent admission for MRSA bacteremia
Evaluation of plasma ACTH stability using the Roche Elecsys immunoassay

Abstract Background Adrenocorticotropic hormone (ACTH) has been reported to be labile in blood due to proteolytic degradation and stringent procedures are followed to prevent in vitro degradation after sample collection. Objective The purpose of this study was to examine the effect of time and temperature before and after separation of plasma from cells in the quantitation of plasma ACTH. Methods Our current protocol includes sample collection in a pre-chilled tube, transport on ice and immediate centrifugation at 4 °C. These reference conditions were compared against sample processing in tubes and centrifuge set at room-temperature; using delayed centrifugation at 4 °C. ACTH stability was evaluated at ambient and refrigerated temperatures after collection and plasma separation using the reference protocol. Plasma samples were analyzed using the Roche Elecsys ACTH immunoassay. Results Quantification of ACTH was not impacted by the use of non-chilled tubes and centrifuge and up to a 4 h delay in separation of plasma from cells. Average percent differences in plasma ACTH concentration from time 0 was Conclusions As supported by these data, previously recommended strict specimen collection and processing requirements are not necessary for measuring ACTH with the Roche Elecsys immunoassay.
HIF3A DNA methylation, obesity and weight gain, and breast cancer risk among Mexican American women.

Abstract Objective In previous epigenome-wide association studies, Hypoxia inducible Factor 3 Alpha Subunit (HIF3A) DNA methylation has been reported to be associated with body mass index (BMI) and weight change. However, none of these studies have included Mexican Americans. Methods In the current study, we assessed levels of HIF3A methylation in 927 Mexican American women identified from Mano-A-Mano, the Mexican American Cohort study. Results Significantly higher methylation levels at three CpG sites (position 46801557, 46801642, and 46801699) were observed in obese women compared to non-obese women (P Conclusion Thus, our results provide evidence to support the role of HIF3A in obesity, weight gain, and the development of breast cancer.
Does Household Debt Matter to Financial Fragility

Minsky, the father of the financial instability hypothesis was concerned with how instability in business sector balance sheets could contribute to overall financial instability. Minsky did not con...
Engineering a folic acid-decorated ultrasmall gemcitabine nanocarrier for breast cancer therapy: Dual targeting of tumor cells and tumor-associated macrophages

Abstract Combination of passive targeting with active targeting is a promising approach to improve the therapeutic efficacy of nanotherapy. However, most reported polymeric systems have sizes above 100 nm, which limits effective extravasation into tumors that are poorly vascularized and have dense stroma. This will, in turn, limit the overall effectiveness of the subsequent uptake by tumor cells via active targeting. In this study, we combined the passive targeting via ultra-small-sized gemcitabine (GEM)-based nanoparticles (NPs) with the active targeting provided by folic acid (FA) conjugation for enhanced dual targeted delivery to tumor cells and tumor-associated macrophages (TAMs). We developed an FA-modified prodrug carrier based on GEM (PGEM) to load doxorubicin (DOX), for co-delivery of GEM and DOX to tumors. The co-delivery system showed small particle size of ∼10 nm in diameter. The ligand-free and FA-targeted micelles showed comparable drug loading efficiency and a sustained DOX release profile. The FA-conjugated micelles effectively increased DOX uptake in cultured KB cancer cells that express a high level of folate receptor (FR), but no obvious increase was observed in 4T1.2 breast cancer cells that have a low-level expression of FR. Interestingly, in vivo, systemic delivery of FA-PGEM/DOX led to enhanced accumulation of the NPs in tumor and drastic reduction of tumor growth in a murine 4T1.2 breast cancer model. Mechanistic study showed that 4T1.2 tumor grown in mice expressed a significantly higher level of FOLR2, which was selectively expressed on TAMs. Thus, targeting of TAM may also contribute to the improved in vivo targeted delivery and therapeutic efficacy.
Amikacin potentiator activity of zinc complexed to a pyrithione derivative with enhanced solubility

Resistance to amikacin in Gram-negatives is usually mediated by the 69-N-acetyltransferase type Ib [AAC(69)-Ib], which catalyzes the transfer of an acetyl group from acetyl CoA to the 69 position of the antibiotic molecule. A path to continue the effective use of amikacin against resistant infections is to combine it with inhibitors of the inactivating reaction. We have recently observed that addition of Zn2+ to in-vitro enzymatic reactions, obliterates acetylation of the acceptor antibiotic. Furthermore, when added to amikacin-containing culture medium in complex to ionophores such as pyrithione (ZnPT), it prevents the growth of resistant strains. An undesired property of ZnPT is its poor water-solubility, a problem that currently affects a large percentage of newly designed drugs. Water-solubility helps drugs to dissolve in body fluids and be transported to the target location. We tested a pyrithione derivative described previously (Magda et al. Cancer Res. 2008, 68:5318-5325) that contains the amphoteric group di(ethyleneglycol)-methyl ether at position 5 (compound 5002), a modification that enhances the solubility. Compound 5002 in complex with zinc (Zn5002) was tested to assess growth inhibition of amikacin-resistant Acinetobacter baumannii and Klebsiella pneumoniae strains in the presence of the antibiotic. Zn5002 complexes in combination with amikacin at different concentrations completely inhibited growth of the tested strains. However, the concentrations needed to achieve growth inhibition were higher than those required to achieve the same results using ZnPT. Time-kill assays showed that the effect of the combination amikacin/Zn5002 was bactericidal. These results indicate that derivatives of pyrithione with enhanced water-solubility, a property that would make them drugs with better bioavailability and absorption, are a viable option for designing inhibitors of the resistance to amikacin mediated by AAC(69)-Ib, an enzyme commonly found in the clinics.
Beyond Race, Sex, and Sexual Orientation: Legal Equality without Identity

Part I. Identity versus Powers: 1. Suspect class and the dilemma of identity 2. A powers review Part II. Race: 3. How constitutional law rationalizes racism 4. Why racial profiling is based on animus Part III. Sex and Sexuality: 5. The puzzle of intermediate scrutiny 6. Same-sex marriage and the disestablishment of marriage.
What Kinds of Economic Inequality Really Matter

The chapter discusses the major reasons why economic inequality should be a source of concern and the forms of inequality that are principally implicated. It considers ten different arguments as to why inequality matters—two of them moral, two political, three economic, and three social. In each case it discusses the economic variable(s) whose unequal distribution is at issue, whether economic class inequality or ethnic group inequality is most salient, and what part(s) of the unequal distribution are the most problematic—i.e., is the problem primarily poverty at the lower end, privilege at the upper end, bipolarization, or the entire distribution?
Clinical Evaluation of Pediatric Patient with Spondylolisthesis

Pediatric patients presenting with spondylolisthesis require a thorough physical examination. While the majority of these patients will present with back pain, occasionally the initial finding is simply spinal deformity or abnormal gait. Reported symptoms may be minimal in the pediatric population with spondylolisthesis, regardless of the degree of deformity, so a careful and complete physical exam is necessary to document all associated deficits. The exam begins by documenting a thorough history including presenting symptoms, duration, and aggravating or relieving factors. A general inspection of the spinal posture, palpation, spinal range of motion assessment, gait abnormalities, a complete neurologic exam, and special physical exam tests are needed as well. Complaints or findings of motor weakness, sensory changes, or urologic abnormalities which are identified require further evaluation or imaging. In general, despite the range of severity of presenting symptoms found in pediatric patients with spondylolisthesis, evaluating all patients with this thorough physical exam will allow the treating physician to fully assess the impact of the spinal pathology and select appropriate treatment.
Is pregnancy after breast cancer safe

: The impact of treatment on subsequent fertility and the safety of childbearing are major complicating factors for young women diagnosed with breast cancer. As national data indicate women are postponing first pregnancy to older ages; therefore, many young patients are seeking clinical guidance regarding the safety of conception and treatment options that may not prevent subsequent pregnancy. Newly developed chemotherapy protocols of brief duration have improved life expectancy enabling some women to consider childbearing. This study was conducted to compare prognosis among breast cancer patients with and without a subsequent pregnancy. Medical record review of female members of a Northern California prepaid health care plan enabled the identification of 107 women with one or more subsequent pregnancies and 344 cases without a pregnancy, who were diagnosed between 1968 and 1995. Sets were matched on age, year and stage at diagnosis, months of survival and recurrence status at conception. Among the matched sets, neither risk of recurrence nor death differed significantly by subsequent pregnancy history during an average 12 years of follow-up (adjusted hazard ratio [HR] recurrence: 1.2 [0.8, 2.0]; adjusted HR death: 1.0 [0.6, 1.9]). Women interested in preserving their fertility and considering pregnancy are a self-selected population; therefore, to reduce potential bias, cases were matched on recurrence status at time of conception. Although the number of cases was limited, subgroup analyzes indicated a small, nonsignificant adverse effect among women who conceived within 12 months of diagnosis. This analysis of carefully matched cases provides reassurance that long-term prognosis was not adversely affected by subsequent pregnancy.