cssi/SciSciGPT-SciSciNet huggingface dataset:
V(D)J hypermutation and DNA mismatch repair: Vexed by fixation

The immune system has adopted a remarkable series of genetic tricks to cope with pathogens, extant and possible. For example, diverse sets of Ig heavy- and light-chain genes are generated by specific DNA recombinations in the developing B lymphocytes present in bone marrow. This process of V(D)J recombination can generate >107 distinct antibody V regions from relatively few (≈102) genetic building blocks and is driven by the punctuated expression of the recombination activating genes Rag1 and Rag2 during B cell genesis (1). Maturing B cells leave the bone marrow and travel to peripheral lymphoid follicles, where they become competent to respond to an antigen. The antigen activates B cells by binding to membrane Ig, inducing migration from follicles into adjacent zones of T lymphocytes and a concerted up-regulation of surface molecules that mediate T and B cell collaboration (2). In the T cell zone, activated antigen-specific B cells provide and receive survival and proliferation signals; the progeny of these cells subsequently specialize to become antibody-secreting plasmacytes or return to the follicle and initiate the germinal center (GC) reaction (2, 3). GCs support another trick for generating Ig diversity: V(D)J hypermutation. B cells in GCs accumulate high frequencies of point mutations (and, less commonly, deletions and insertions); the rate of mutation in the Ig V region is thought to be ≈1 mutation/103 bp/cell division, a rate 106-fold above that for other gene loci. Ig hypermutation usually is restricted to GC B cells and exhibits a distinctive pattern of nucleotide misincorporations by favoring transition mutations and strand polarity (1, 4). The small, GC B cell population undergoes repeated rounds of hypermutation, selection, and proliferation. In this darwinian microcosm, mutations that better the ability of the B cell to bind …
Comparison of magnetic materials for V-groove inductors in optimized high-frequency DC-DC converters

The tradeoff between saturation flux density and resistivity in soft magnetic materials for thin film inductors is examined quantitatively. We use an optimization routine to evaluate the achievable efficiency and power density using designs individually optimized to make best use of particular materials. The optimization selects switching frequency, ripple ratio, inductor dimensions and MOSFET sizes. For the example application of a 3.3- to 1.1-V, 7-A output dc-to-dc converter, Co-Zr-O, Fe-Al-O and Co-Fe-B-Si-O materials are considered. Predicted efficiencies are in the range of 80% to 90% at power densities of 20 W/cm/sup 2/ to 1000 W/cm/sup 2/. Different materials show advantages in different power-density or efficiency ranges.
Incidentally detected gallbladder polyps: is follow-up necessary?--Long-term clinical and US analysis of 346 patients.

Almost all polypoid lesions detected at US are nonneoplastic, representing cholesterol polyps or small stones, and no neoplastic polyps were seen at diameters smaller than 7 mm.
THE BUCKLE-UP PROMISE CARD: A VERSATILE INTERVENTION FOR LARGE-SCALE BEHAVIOR CHANGE

This article discusses one suggestion for improving driver use of safety belts -- the buckle-up promise card. In trial programs a significant number of promise-card signers increased their use of safety belts following their commitment behavior. The front of the buckle-up promise card includes a rationale for the safety belt use, a space for the trainer to sign, and a space for the subject to sign acknowledgment of his or her commitment to safety belt use. The back of the promise card includes a postcard and instructions for obtaining additional cards. This is an attempt to get the subject to participate as an intervention agent. A group at Rensselaer Polytechnic Institute (RPI) modified the promise card to encourage driving sober as well as buckling up.
Complementation of a temperature sensitive Escherichia coli rpoD mutation using Lactobacillus sigma factors

Housekeeping sigma factors in the σ70 family, as components of the RNA polymerase holoenzyme, are responsible for regulating transcription of genes related to vegetative growth. While these factors are well understood in model organisms such as Escherichia coli and Bacillus subtilis , little experimental work has focused on the sigma factors in members of the Lactobacillus genus such as Lactobacillus brevis and Lactobacillus plantarum . This study evaluates the ability of putative σ70 proteins from L. brevis (σ70-Lb) and L. plantarum (σ70-Lp) to complement a temperature sensitive mutation in the E. coli 285c σ70 protein. This report is the first to show that these heterologous sigma factors were capable of restoring the viability of E. coli 285c for growth at 40-43.5 °C, indicating the σ70-Lb and σ70-Lp are capable of initiating transcription in a complex with the E. coli 285c RNA polymerase.These heterologous sigma factors may therefore be useful for improving biochemical knowledge of the sigma factor family or for use in the expression of hetereologous genomic libraries.
Activity and Ranging Patterns of Guerezas in the Kakamega Forest: Intergroup Variation and Implications for Intragroup Feeding Competition

From March 1997 to February 1998, I investigated the activity patterns of 2 groups and the ranging patterns of 5 groups of eastern black-and-white colobus (Colobus guereza), aka guerezas, in the Kakamega Forest, Kenya. Guerezas at Kakamega spent more of their time resting than any other population of colobine monkeys studied to date. In addition, I recorded not one instance of intragroup aggression in 16,710 activity scan samples, providing preliminary evidence that intragroup contest competition may be rare or absent among guerezas at Kakamega. Mean daily path lengths ranged from 450 to 734 m, and home range area ranged from 12 to 20 ha, though home range area may have been underestimated for several of the study groups. Home range overlap was extensive with 49–83% of each group's range overlapped by the ranges of other groups. Despite the high level of home range overlap, the frequently entered areas (quadrats entered on ≥30% of a group's total study days) of any one group were not frequently entered by any other study group. Mean daily path length is not significantly correlated with levels of availability or consumption of any plant part item. Mean daily path length is also not significantly correlated with group size, though the largest group did have the longest mean daily path length. This finding suggests that intragroup scramble competition may have been rare or absent among guerezas at Kakamega except perhaps in the largest group, which was unusually large.
Evaluation of electrodes coated with metal hexacyanoferrate as amperometric sensors for nonelectroactive cations in flow systems

Two electrodes modified with either nickel or cupric hexacyanoferrate films were evaluated and compared as sensors for nonelectroactive cations in a flow-injection system. Both gave responses for group 1A and ammonium ions, but only the electrode modified with cupric hexacyanoferrate was sufficiently stable for use in flowing solutions. This electrode responded to K+, NH, Rb+, and Cs+ ions rather selectively. Within this group, the selectivity could be controlled from general to almost specific toward Cs+ by the potential at which the electrode was poised. The electrode was compatible with a mobile phase of dilute nitric acid commonly used in ion chromatography, and chromatographic detection limits of 2 × 10−7 M and linear responses over two decades were obtained. The electrode was applied to the ion chromatographic analysis of K+ and NH in urine and K+ in blood serum samples.
Managing Self-Confidence: Theory and Experimental Evidence ∗

A large literature in social psychology suggests that agents process information about their own ability in a biased manner. While this finding has generated exciting research in behavioral economics, some of the fundamental evidence has also been criticized as being potentially consistent with Bayesian updating. We reevaluate the evidence from social psychology by conducting a large-scale experiment with 656 undergraduate students. Subjects perform an IQ-test and receive noisy feedback on their performance while we track the evolution of their beliefs. Our experimental design allows us to precisely measure the relevant belief distribution of subjects simply and repeatedly. Our experiment confirms that subjects are asymmetric and put greater weight on positive performance signals compared to negative signals. However, we also find that subjects are conservative and update too little in response to both positive and negative signals. Subjects appear much more Bayesian when receiving feedback about someone else’s performance. We show that these seemingly related phenomena naturally arise in a simple model of biased information processing inspired by the anticipatory utility model of Brunnermeier and Parker (2005). Our model is parsimonious and adds just a single parameter to the standard model. We also find that women are more conservative than men, but not more asymmetric. High-confidence women have a higher value for information than men.
Microbial metaproteomics for characterizing the range of metabolic functions and activities of human gut microbiota

The human gastrointestinal tract is a complex, dynamic ecosystem that consists of a carefully tuned balance of human host and microbiota membership. The microbiome is not merely a collection of opportunistic parasites, but rather provides important functions to the host that are absolutely critical to many aspects of health, including nutrient transformation and absorption, drug metabolism, pathogen defense, and immune system development. Microbial metaproteomics provides the ability to characterize the human gut microbiota functions and metabolic activities at a remarkably deep level, revealing information about microbiome development and stability as well as their interactions with their human host. Generally, microbial and human proteins can be extracted and then measured by high performance MS-based proteomics technology. Here, we review the field of human gut microbiome metaproteomics, with a focus on the experimental and informatics considerations involved in characterizing systems ranging from low-complexity model gut microbiota in gnotobiotic mice, to the emerging gut microbiome in the GI tract of newborn human infants, and finally to an established gut microbiota in human adults.
Exploring nonlinear models in personality assessment: Development and preliminary validation of a negative emotionality scale.

ABSTRACT In this article we discuss the applicability of several new measurement models to the construction of personality scales, and we contrast these models with more traditional approaches in common usage, such as the principal factor analysis model. Our goal is to illustrate how nonlinear item-response models can be profitably used in personality research. We describe the development of a 30-item Negative Emotionality scale that was constructed using nonlinear factor analysis and item-response theory. We also show how traditional (linear) factor analysis can produce misleading results when it is applied to personality items with dichotomous response formats (e.g., true/false, agree/disagree). No formal training in modern measurement theory is assumed of the reader as we describe the nonlinear models that are used in this study in nontechnical language with a minimum of mathematics.
Ribosomal robots: evolved designs inspired by protein folding

The biological process of ribosomal assembly is one of the most versatile systems in nature. With only a few small building blocks, this natural process is capable of synthesizing the multitude of complex chemicals that form the basis of all organic life. This paper presents a robotics design and manufacturing scheme which seeks to capture some of the versatility of the ribosomal process. In this scheme, a custom "printer" folds a long ribbon of material in which control elements such as motors have been embedded into a morphology that is capable of accomplishing a pre-defined task. The evolved folding patterns are encoded with a special kind of compositional pattern producing network (CPPN), which can compactly describe patterns with regularities such as symmetry, repetition, and repetition with variation. This paper tests the efficacy of this design scheme and the effects of different ribbon lengths on the ability to produce walking robot morphologies. We show that a single strip of material can be folded into a variety of different morphologies displaying different forms of locomotion. Thus, the results presented here suggest a promising new method for the automated design and manufacturing of robotic systems.
Meta-Analyses Some Very Good Steps Toward a Bit Longer Journey

The authors' role is to comment on the four articles that compose this feature topic of Organizational Research Methods on meta-analysis. In that spirit, the authors note the common themes addressed in this work and its contribution to a growing body of literature addressing pivotal aspects of meta-analyses. Also, the authors discuss some elements of meta-analysis that may account for its relatively infrequent use by organizational researchers. Last, the authors underscore other features of its use that may be unparalleled when compared to alternative analyses.
Multidisciplinary life cycle metrics and tools for green buildings

Building sector stakeholders need compelling metrics, tools, data, and case studies to support major investments in sustainable technologies. Proponents of green building widely claim that buildings integrating sustainable technologies are cost effective, but often these claims are based on incomplete, anecdotal evidence that is difficult to reproduce and defend. The claims suffer from 2 main weaknesses: 1) buildings on which claims are based are not necessarily ‘‘green’’ in a sciencebased, life cycle assessment (LCA) sense and 2) measures of cost effectiveness often are not based on standard methods for measuring economic worth. Yet, the building industry demands compelling metrics to justify sustainable building designs. The problem is hard to solve because, until now, neither methods nor robust data supporting defensible business cases were available. The US National Institute of Standards and Technology (NIST) Building and Fire Research Laboratory is beginning to address these needs by developing metrics and tools for assessing the life cycle economic and environmental performance of buildings. Economic performance is measured with the use of standard life cycle costing methods. Environmental performance is measured by LCA methods that assess the ‘‘carbon footprint’’ of buildings, as well as 11 other sustainability metrics, including fossil fuel depletion, smog formation, water use, habitat alteration, indoor air quality, and effects on human health. Carbon efficiency ratios and other eco-efficiency metrics are established to yield science-based measures of the relative worth, or ‘‘business cases,’’ for green buildings. Here, the approach is illustrated through a realistic building case study focused on different heating, ventilation, air conditioning technology energy efficiency. Additionally, the evolution of the Building for Environmental and Economic Sustainability multidisciplinary team and future plans in this area are described.
Origins of Life: Chemical and Philosophical Approaches

In this article we address selected important milestones of chemical evolution that led to life. The first such milestone could be achieved by Oparin’s model, which accounts for the early stages of chemical evolution. These occurred at the dawn of development of primitive chemical systems that were pre-RNA. Oparin’s model consists of spontaneous formation of coacervates that encapsulate chemical matter, undergo primitive self-replication, and provide a pathway to a primitive metabolism. We review the experimental updates of his model from our laboratory and discuss types of selection that could have occurred in these primitive systems. Another major milestone in chemical evolution is the transition from abiotic to biotic. This has occurred later, after the RNA world evolved. A controversy of what life is interferes with the efforts to elucidate this transition. Thus, we present various definitions of life, some of which specifically include the requirements and mechanisms for this transition. Self-replication is one of the major requirements for life. In this context we re-examine the question if viruses, which do not have capability to self-replicate, are alive. We draw on philosophy of Hegel, Aristotle, Rescher, Priest, and Fry to guide us in our endeavors. Specifically, we apply Hegel’s law on quantity-to-quality transition to abiotic-to-biotic transition, Aristotle’s philosophy to the definition of life, Priest’s dialetheism to the question if viruses are alive or not, Fry’s philosophy to the beginning of natural selection in chemical evolution, and Rescher’s philosophy to the possible cognitive bias toward simple definitions of life.
ÕProduction Control of Door Manufacturing Line at an Automotive Assembly PlantÕ

Abstract In this paper, we study production control problems under multiple products setting. An application study of control policy for a door manufacturing line at an automotive assembly plant making two distinct types of products is introduced. Using analytical investigations, closed formula for key performance indices are derived and the buffer occupancy are used as control variable to satisfy throughput demand and reduce disruption for downstream production. Sensitivity analysis of such control policies has also been discussed to provide management insights. Using the data collected at plant floor, a discrete event simulation study has been carried out to validate the applicability of the model and control algorithm.
Perceived Stress and Quality of Life among Prostate Cancer Survivors

A convenience sample of 136 prostate cancer survivors participated in this study that assessed their perception of stress and quality of life (QOL). Data were collected via an anonymous questionnaire consisting of the Perceived Stress Scale, the UCLA Prostate Cancer Index Short Form, and demographic variables. The findings revealed low levels of stress with marginal reports of QOL. Significant differences were found in organ-specific functioning (p < 0.001), with respondents indicating that they were experiencing a disproportionately higher rate of sexual problems (sexual performance and sexual satisfaction) compared to bowel and bladder problems. These complaints were highest among patients who had undergone prostatectomy and lowest among patients who had selected watchful waiting. No association was found between stress and QOL, but significantly higher rates of stress were reported by patients who felt they had not received sufficient information before treatment (p < 0.05).
A Modified Autonomous En Transposon in Maize (Zea mays L.) Elicits a Differential Response of Reporter Alleles

Transposable elements in maize are composed of a defined molecular structure that includes coding sequences, determiners of functionality and ordered terminal motifs that provide binding sites for transposase proteins. Alterations in these components change the phenotypic expression of unstable genes with transposon inserts. The molecular basis for the altered timing and frequency of transposition as determined by the size and number of spots on kernels or stripes on leaves has generally been described for defective inserts in genes. Most differential patterns can be ascribed to alterations in the terminal motifs of the reporter allele structure that supplies a substrate (terminal inverted repeat motifs) for transposase activity. For autonomously functioning alleles, the explanations for changes in phenotype are not so clear. In this report, an En-related element identified as F-En is described that shares with En the recognition of a specific defective element c1(mr)888104 but differs from En in that this F-En element does not recognize the canonical c1(mr) elements that are recognized by En. Evidence is provided suggesting that F-En does not recognize other En/Spm-related defective elements, some of whose sequences are known. This modified En arose from a c1-m autonomously mutating En allele.
Image Expansion in Integer Arithmetic

(1991). Image Expansion in Integer Arithmetic. The College Mathematics Journal: Vol. 22, No. 5, pp. 429-435.
Reimplantation of Ureters in Children

Obstruction and reflux at the vesicoureteral junction constitute a very real danger to the kidney; much damage can occur silently over the long term in children with recurrent urinary tract infections, even if these are rendered asymptomatic by medical treatment. The indications for surgery and the necessary evaluative steps are discussed in the context of the case of a child undergoing ureteral reimplantation.
Complement split products and the pathogenesis of SLE.

Complement's role in SLE pathology is not limited to tissue damage at immune complex deposition sites. Circulating split products can cause inflammatory cells to occlude small vessels and damage their endothelium—all in the absence of IC deposition. In SLE, split-product levels reflect disease activity and predict flares better than conventional complement measurements.
Wood Burning, Biomass, Air Pollution, and Climate Change

Domestically and internationally, there is a trend toward greater reliance on the burning of wood as a partial response to the problems of global warming and climate change. But in labeling wood burning as a source of “renewable energy,” consumers and corporations have overlooked a more compelling and immediate health problem. Worldwide, air pollution causes the deaths of approximately seven million people every year, far more than the number of deaths from climate change. Mortality is largely due to air emissions of fine particulate matter. Given the popularity of burning wood and regulatory loopholes, the public health effects of air pollution go underregulated, and often unregulated. As a source of energy that is generated by combustion and results in the direct emission of fine particulates, biomass is like coal, oil, and natural gas (non-renewable energy), and unlike solar and wind (renewable energy). Whether biomass may play a role in an effective climate change strategy is unclear and is the subject of ongoing debate. Recent attempts to address the problem of residential wood burning through the Environmental Protection Agency’s New Source Performance Standards and New York City’s Local Law 38 of 2015 demonstrate the political and legal challenges to regulating emissions from the burning of wood.
Illicit Drug Use and Women’s Sexual and Reproductive Health

Historically, the use of drugs among women has been associated with prescription drugs, whereas drug use among men often is linked to the use of illegal substances such as cocaine, heroin, marijuana, and methamphetamine. Illicit drug use among women and the associated negative health consequences has only recently become a serious topic of investigation. Only since the 1960s have studies on the use of illicit drugs among women become common, a change that coincided with the second wave of the feminist movement in the western world. In most early 1960s/1970s studies, female drug users primarily were included as a comparison sample to male users. Consequently, the findings of these studies tended to emphasize differences between men and women, with female users typically being depicted as much more negative than their male counterparts.
Family-Based Behavioral Interventions

The purpose of this chapter is to review the literature on family-based lifestyle interventions for pediatric obesity, which are currently the most well-established treatments for pediatric obesity to date (9,10). This chapter also explains the specific role of parents as key partners in child weight loss within these interventions, critically reviews the components of family-based behavioral interventions, and finally makes recommendations on how best to expand the current scope, duration, and intensity of treatment to enhance the traditional approaches to losing weight by including weight loss maintenance components within a socio-ecological framework.
Involvement of neuronal Nicotinic cholinergic α4β2 receptors in alcohol and Nicotine addiction and cognition: Preclinical studies

N nicotinic cholinergic receptors have been implicated in alcohol drinking behavior, nicotine addiction and cognitive function. Manipulations of these receptors have been shown to influence both alcohol consumption and cognition. Sazetidine-A [6-(5(((S)-azetidine-2-yl)methoxy)pyridine-3-yl)hex-5-yn-1-ol] and VMY-2-95 are novel compounds that potently and selectively desensitizes neuronal α4β2 nicotinic receptors. The goal of the present study was to examine the effects of these compounds on alcohol consumption in alcohol preferring (P) rats, and on nicotine self-administration and attention in Sprague Dawley rats. In alcohol studies, alcohol preferring rats were given the choice of water or alcohol. Once stable baselines were established, the acute and chronic effects of sazetidine-A and acute effects of VMY-2-95 on alcohol intake were assessed. In addition, the acute effects of sazetidine-A, VMY-2-95 and naltrexone on alcohol intake after alcohol deprivation were evaluated. Our results show that sazetidine-A and VMY-2-95 caused a dose-dependent reduction in alcohol intake. Chronic sazetidine-A also effectively reduced alcohol intake. In the post-deprivation experiment, when the urge for drinking is enhanced, similar to naltrexone, sazetidine-A and VMY-2-95 significantly reduced alcohol intake and preference. In the sustained attention study, using an operant visual signal detection task it was shown that dizocilpine and scopolamine caused significant impairments in performance, which were significantly reversed by an acute dose sazetidine-A. These studies imply an important role for α4β2 nicotinic receptors in improving sustained attention under conditions that disrupt it. Both sazetidine-A and VMY-2-95 when given acutely significantly reduced nicotine intake. In conclusion, very low doses of sazetidine-A and VMY-2-95 may hold promise for the treatment of heavy drinking and nicotine self-administration and sazetidine-A provides therapeutic benefit for reversing attentional impairment in patients with mental disorders suffering from cognitive impairment. (Supported by NIDA U19 grant DA027990 and NIAAAR25AA015512-02).
Clinical and Immunohistochemical Study of Uterine Carcinosarcoma in a Large Academic Women’s Center

Objectives: Uterine carcinosarcomas (UCs) are highly aggressive and rare tumors. The prognostic factors and immunohistochemical (IHC) profile of epithelial and stromal component still remains unknown and may be targeted. Methods: A computer-based search was carried out on our pathology database to retrieve the UCs diagnosed between 2007 and 2012. The clinicopathologic, treatment, and outcome information was obtained from the …
A Network-based Cost Comparison of Resilient and Robust System-of-Systems☆

Abstract Connectivity within systems-of-systems often provides enhanced capabilities, but may also introduce new vulnerabilities. Systems engineers must therefore consider the impact of potential threats to a system, and subsequently identify methods for mitigating the effects of those threats. A common approach is to design for robustness, i.e. designing a system to be insensitive to perturbations, often through system redundancy. An alternative approach is to design for resilience, focusing on adaptation and the ability to recover lost capabilities. This paper represents systems-of-systems as networks and identifies thresholds in which a resilient network design is more cost-effective than a robust one. Resilient networks are defined with network adaptation or link rewiring. Robust networks are defined without adaptation, but instead have high network density or path redundancy. The number of initial and rewired links is used as a proxy for network cost. A command and control (C2) network of unmanned aerial vehicles performing a surveillance mission is used as an application problem. An agent-based model is used to simulate C2 network performance.
Semi-automatic brain morphometry in CT

Presents development and application of a semi-automatic method for estimating volumes of brain tissues from computed tomography (CT) images. The method does not require manual drawing of tissue boundaries. The steps of the new method are: (1) intracranial brain volume is segmented from skull and background using thresholding and morphological operations; (2) noise is suppressed using a nonlinear edge-preserving filter; (3) a histogram of the resulting image is generated and the dominant peak is removed; (4) minima and maxims of the histogram are identified and the brain is segmented into normal tissues, cerebrospinal fluid, and lesions, if present; (5) previous steps are repeated for each slice and volume of each tissue is estimated from the results. The method has shown to be faster and more reproducible than conventional methods. Details and significance of each step of the method are explained. Experimental results using a simulation, a phantom, and selected clinical cases are presented. >
An Oxygen-Dependent Mechanism of Neutrophil-Mediated Cytotoxicity

Human neutophils stimulated with phorbol myristate acetate were able to rapidly destroy autologous red blood cell targets. Neutrophil-mediated cytotoxicity was related to phorbol myristate acetate concentration and neutrophil number. The ability of stimulated neutrophils to lyse red blood cell targets was markedly impaired by catalase or superoxide dismutase but not by heat-inactivated enzymes or albumin. Despite a simultaneous requirement for O2.- and H2O2 in the cytotoxic event, a variety of OH. and 1O2 did not effect cytolysis. The myeloperoxidase inhibitor cyanide did not reduce red blood destruction, while azide consistently impaired cytolysis. The inability of cyanide to reduce cytotoxicity coupled with the protective effect of superoxide dismutase suggests that cytotoxicity is independent of the classic myeloperoxidase-H2O2-halide system. We propose that neutrophils, stimulated with phorbol myristate acetate, generate O2.- and H2O2, which play an integral role in a novel cytotoxic mechanism.
Leukemia Stem Cells in Murine MLL−AF9 AML Are Downstream Myeloid Lineage Cells That Have Acquired Stem−Like Biological and Genetic Properties.

An essential prerequisite for the development of more effective targeted therapies in AML is a characterization of the frequency and biological properties of leukemia stem cells (LSCs), which sustain the disease and mediate relapse. Previous studies have shown that hematopoietic stem cells, as well as progenitors, may be targeted by MLL oncoproteins to give rise to AML, however it was unclear whether these lineage negative cells also functioned as LSCs to sustain disease. To address this issue, we have identified and characterized LSCs in a somatic, genetic mouse model of leukemia that faithfully recapitulates many of the pathologic and clinical attributes of human leukemia initiated by the MLL−AF9 oncogene. In this model, CFCs in the bone marrow and spleen of leukemic mice were demonstrated to be LSCs, based on the observation that secondary transplantation of the progeny of individually isolated AML CFCs cultured in vitro for seven days or longer invariably resulted in transfer of short latency disease. These self−renewing cells were remarkably frequent, accounting for 25–30% of myeloid lineage cells at late−stage disease. Unexpectedly, they expressed mature myeloid lineage antigens (91.3 ± 3.8% Mac1+ Gr1+ immunophenotype, versus fewer than 0.2% lineage negative), placing them downstream of the known hematopoietic progenitor compartment. Furthermore, LSCs in this model generated a phenotypic, morphologic and functional leukemia cell hierarchy loosely defined by expression of c−kit. When compared with immortalized progenitors, LSCs exhibited a markedly enhanced ability to engraft secondary recipients, which was not due to differences in bone marrow homing, which was equivalently poor in the compared populations. Rather, LSCs exhibited an acquired ability to proliferate in response to stromal cell derived cytokines, an enhanced SDF1 induced chemotaxis, and increased proliferation in contact with OP9 stromal cells demonstrating that LSCs exhibit altered microenvironmental interactions by comparison with the oncogene immortalized CFCs that initiated the disease. Thus, the LSCs responsible for sustaining, expanding and regenerating MLL−AF9 AML are downstream myeloid lineage cells, outside of the normal stem and progenitor compartment. They have acquired an aberrant Hox−associated self−renewal program as well as other biologic features of hematopoietic stem cells. Our findings support a revision of the prevailing hypothesis that AML LSCs are always rare and solely located within the most immature bone marrow progenitor compartment. Furthermore, LSCs exhibit markedly different microenvironmental interactions, by comparison with cells simply immortalized by MLL−AF9, indicating that acquisition of sensitivity to stromal derived survival and proliferative signals is a critical feature of LSCs, in addition to their extensive self−renewal capabilities.
Multivariate analysis of gamma spectra to characterize used nuclear fuel

Abstract The Multi-Isotope Process (MIP) Monitor provides an efficient means to monitor the process conditions in used nuclear fuel reprocessing facilities to support process verification and validation. The MIP Monitor applies multivariate analysis to gamma spectroscopy of key stages in the reprocessing stream in order to detect small changes in the gamma spectrum, which may indicate changes in process conditions. This research extends the MIP Monitor by characterizing a used fuel sample after initial dissolution according to the type of reactor of origin (pressurized or boiling water reactor; PWR and BWR, respectively), initial enrichment, burn up, and cooling time. Simulated gamma spectra were used to develop and test three fuel characterization algorithms. The classification and estimation models employed are based on the partial least squares regression (PLS) algorithm. A PLS discriminate analysis model was developed which perfectly classified reactor type for the three PWR and three BWR reactor designs studied. Locally weighted PLS models were fitted on-the-fly to estimate the remaining fuel characteristics. For the simulated gamma spectra considered, burn up was predicted with 0.1% root mean squared percent error (RMSPE) and both cooling time and initial enrichment with approximately 2% RMSPE. This approach to automated fuel characterization can be used to independently verify operator declarations of used fuel characteristics and to inform the MIP Monitor anomaly detection routines at later stages of the fuel reprocessing stream to improve sensitivity to changes in operational parameters that may indicate issues with operational control or malicious activities.
Risk versus benefit or risk versus risk: Risk aversion in the medical decision making process

Psoriasis can be debilitating, as even objectively mild cases can have profound impact on a patient’s activities and social interactions. Highly efficacious treatment options are available (1). Des...
5.7 A 19nV/√Hz-noise 2µV-offset 75µA low-drift capacitive-gain amplifier with switched-capacitor ADC driving capability

This paper describes a capacitive programmable-gain amplifier (CGA) with amplifier common-mode sampling (CMS) and switched-capacitor driving capability, compatible with many conventional switched-capacitor ADC inputs (SCAI) such as delta-sigma modulators or SAR ADCs. CGAs are popular for their low power, low noise and high precision [1,2]. The capacitive gain network is highly linear, does not dissipate static power and can be noiseless. Capacitors have excellent matching and temperature drift, which has a positive impact on offset/gain errors and their drift. They also offer a high input impedance at low frequencies and rail-to-rail operation, which makes them very suitable to interface with different types of sensors.
An Automated Detection of Inconsistencies in SBVR-based Business Rules Using Many-sorted Logic

Business rules control and constrain the behavior and structure of the business system in terms of its policies and principles. Business rules are restructured frequently as per the internal or external circumstances based on market opportunities, statutory regulations, and business focus. The current practice in industry, of detecting inconsistencies manually, is error prone, due to the size, complexity and ambiguity in representation using natural language.
Oligonucleotide therapeutics in neurodegenerative diseases

Therapeutics that directly target RNAs are promising for a broad spectrum of disorders, including the neurodegenerative diseases. This is exemplified by the FDA approval of Nusinersen, an antisense oligonucleotide (ASO) therapeutic for spinal muscular atrophy (SMA). RNA targeting therapeutics are currently under development for amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), and spinocerebellar ataxias. We have used an ASO approach toward developing a treatment for spinocerebellar ataxia type 2 (SCA2), for targeting the causative gene ATXN2. We demonstrated that reduction of ATXN2 expression in SCA2 mice treated by intracerebroventicular injection (ICV) of ATXN2 ASO delayed motor phenotype onset, improved the expression of several genes demonstrated abnormally reduced by transcriptomic profiling of SCA2 mice, and restored abnormal Purkinje cell firing frequency in acute cerebellar sections. Here we discuss RNA abnormalities in disease and the prospects of targeting neurodegenerative diseases at the level of RNA control using ASOs and other RNA-targeted therapeutics.
Core/Shell Bacterial Cables: A One-Dimensional Platform for Probing Microbial Electron Transfer.

Extracellular electron transfer (EET) from electrochemically active bacteria (EAB) plays a critical role in renewable bioelectricity harvesting through microbial fuel cells (MFC). Comprehensive interpretation and interrogation of EET mechanisms can provide valuable information to enhance MFC performance, which however are still restricted by the intrinsic complexity of natural biofilm. Here, we design core/shell EAB-encapsulating cables as a one-dimensional model system to facilitate EET studies, where the local microenvironments can be rationally controlled to establish structure–function correlations with full biological relevance. In particular, our proof-of-concept studies with Shewanella loihica PV-4 (S. loihica) encapsulating cables demonstrate the precise modulation of fiber diameters (from 6.9 ± 1.1 to 25.1 ± 2.4 μm) and bacteria interactions, which are found to play important roles in programming the formation of different intercellular structures as revealed by in situ optical and ex situ electr...
Extranodal Diffuse Large B Cell Lymphoma: Molecular Features, Prognosis, and Risk of Central Nervous System Recurrence.

Diffuse large B cell lymphoma (DLBCL) arises from extranodal organs in about 30% of cases. Its prognosis and risk of recurrence in the central nervous system (CNS) vary according to the primary site of origin. Recent studies begin to clarify these differences using molecular classification. Testicular, breast, and uterine DLBCL (as well as possibly primary cutaneous DLBCL, leg-type) share a high prevalence of the non-germinal center B cell (non-GCB) phenotype and the MYD88/CD79B-mutated (MCD) genotype. These biologic features, which resemble primary CNS lymphoma, may underlie their stage-independent propensity for CNS involvement. Management of these lymphomas should involve CNS prophylaxis, preferably using systemic high-dose methotrexate to prevent intraparenchymal recurrence. Involvement of the kidneys, adrenal glands, ovary, bone marrow, lung, or pleura usually indicates disseminated disease, conferring worse prognosis. Involvement of these sites is often associated with high CNS-International Prognostic Index (IPI), concurrent MYC and BCL2 or BCL6 rearrangements, or intravascular lymphoma—risk factors warranting CNS prophylaxis. In contrast, craniofacial, thyroid, localized bone, or gastric lymphomas have a variable prevalence of the non-GCB phenotype and lack MYD88 mutations. Their outcomes with standard immunochemotherapy are excellent, and the risk of CNS recurrence is low. We recommend individualized consideration of CNS prophylaxis based on the CNS-IPI score and anatomical proximity in cases of epidural, orbital, or skull involvement. Rituximab-containing immunochemotherapy is a standard approach for all extranodal DLBCLs. Surgery is no longer required for any primary site, but routine consolidative radiation therapy is recommended for testicular lymphoma. Radiation therapy also appears to be associated with better progression-free survival in primary bone DLBCL. Future studies should better distinguish primary from secondary sites of extranodal involvement, and investigate the association of newly identified genotypes with the risk of CNS or systemic recurrence.
Cell Adhesion in Epidermal Development and Barrier Formation

Cell–cell adhesions are necessary for structural integrity and barrier formation of the epidermis. Here, we discuss insights from genetic and cell biological studies into the roles of individual cell–cell junctions and their composite proteins in regulating epidermal development and function. In addition to individual adhesive functions, we will discuss emerging ideas on mechanosensation/transduction of junctions in the epidermis, noncanonical roles for adhesion proteins, and crosstalk/interdependencies between the junctional systems. These studies have revealed that cell adhesion proteins are connected to many aspects of tissue physiology including growth control, differentiation, and inflammation.
Activation of Carcinogenic N-Arylhydroxamic Acids by Peroxidase/H2O2/Halide Systems: Route to C-Nitroso Aromatics

Evidence that locally carcinogenic N-arylhydroxamic acids may be activated by oxidants generated by leukocytes has been obtained from model systems including tissue peroxidases, myeloperoxidase (MPO)/H2O2/ halide (X-) or hypohalous acids (HOX). Peroxidative oxidations of N-hydroxy-N-2-fluorenylacetamide (N-OH-2-FAA) via one electron (le-) to equimolar 2-nitrosofluorene (2-NOF) and N-acetoxy-2-FAA, and via oxidative cleavage to 2-NOF were determined. The latter oxidation predominated with peroxidase-rich extracts of rat uterus and mammary gland and with eosinophils from intraperitoneal fluid in the presence of H2O2, Br- and cationic detergent. Contribution to 2-NOF by le- oxidation was up to 50% at 0.1 mM Br- and pH 7.4, but negligible at 10 mM Br- and pH 5.5. Oxidation of N-OH-2-FAA by MPO of human neutrophils in the presence of physiologic concentrations of Cl- (0.1 M) or Br- (0.1 mM) or their mixture was examined in the pH range of 4 to 6.5. At the respective pH optima (4 for Br- and 5 for Cl- or Cl- + Br-), oxidation of N-OH-2-FAA to 2-NOF by MPO/H2O2 was much more rapid with Br- and Br- + Cl- than with C1-. Since HOBr oxidized N-OH-2-FAA to 2-NOF much more rapidly than did HOC1, MPO/H2O2-catalyzed oxidation in the presence of C1-+Br- was possibly due in part to HOBr. le- oxidation of N-OH-2-FAA occurred to a lesser extent in chemical (HOX) than enzymatic systems (MPO/H2O2/X-), in which it appeared to be stimulated by Br- at pH > 5.5. In the presence of taurine, a scavenger of hypohalous acids in vivo, oxidation of N-OH-2-FAA to 2-NOF bv MPO/H2O2 was unaffected with Br-, inhibited with Cl-, and partially inhibited with Cl- + Br-. These results were linked to N-halotaurine formation since it was found that N-bromotaurine, but not N-chloro-taurine, oxidized N-OH-2-FAA chiefly to 2-NOF. The possibility that 2-NOF through its interactions with unsaturated lipids may initiate lipid peroxidation was investigated by measurements of malondialdehyde (MDA), a lipid degradation product, following aerobic incubations of 2-NOF with arachidonic, linolenic or linoleic acid at a molar ratio of 1:1. The amounts of MDA were optimal after 4 hr and were increased by 50% when 2-NOF was preincubated with the fatty acids for 24 hr under anaerobic conditions. Our studies indicate potential significance of: 1) Br--derived oxidants in activation of carcinogenic N-arylhydroxamic acids to C-nitroso aromatics, and 2) interactions of C-nitroso aromatics with unsaturated lipids leading to lipid peroxidation and thus, genotoxicity.
Building an American Empire: The Era of Territorial and Political Expansion. By Paul Frymer. (Princeton, NJ: Princeton University Press, 2017. Pp. vii, 295. $35.00.)

Paul Frymer's newest book examines US territorial expansion over the course of the long nineteenth century. In seven well‐written chapters, the author seeks to address several separate (though broa...
Standardizing documentation and improving communication on an academic inpatient solid tumor oncology consult service.

171Background: As the number of patients living with cancer increases, a growing proportion of hospital inpatients will have an advanced cancer diagnosis. Data suggests that an unscheduled hospitalization for a patient with advanced cancer strongly predicts a median survival of less than 6 months. As hospitalists more frequently become the primary team taking care of admitted cancer patients, communication between a patient's oncologic care team and inpatient primary providers is crucial. We sought to implement and assess the impact of improved oncology consult documentation of patient prognosis on outcomes of advanced cancer patients admitted to our hospitalist medicine teaching services. Methods: We implemented an EMR-based oncology consult note template which required documentation of prognosis, potential future treatment options (if available), and advance care planning. We reviewed all patients with stage IV solid tumors admitted to the hospitalist teaching service for 8 weeks prior and 8 weeks post-...
Real-Time FPGA-Based Rate Adaptive LDPC Coding for Data Center Networks and PONs

We experimentally demonstrate an FPGA-based rate adaptive LOPC coding scheme suitable for data center networks and PONs. The proposed adaptive coding scheme can dynamically determine channel condition and adapt the code rate accordingly in frame-by-frame fashion.
Colonizing Consent : Rape and Governance in South Africa's Eastern Cape

Elizabeth Thornberry uses historical evidence to shed light on South Africa's contemporary epidemic of sexual violence. Drawing on over a thousand cases from a diverse set of courts, Thornberry reconstructs the history of rape in South Africa's Eastern Cape, from the precolonial era to the triumph of legal and sexual segregation, and digs deep into questions of conceptions of sexual consent. Through this process, Thornberry also demonstrates the political stakes of disputes over sexual consent, and the ways in which debates over the regulation of sexuality shaped both white and black politics in this period. From customary authority to missionary Christianity and humanitarian liberalism to segregationism, political claims implied theories of sexual consent, and enabled distinctive claims to control female sexuality. The political history of rape illuminates not only South Africa's contemporary crisis of sexual violence, but the entangled histories of law, sexuality, and politics across the globe.
Kimmel on Climate: Disentangling the Emotional Ingredients of a Satirical Monologue:

This study explored whether satire (an emotional blend of humor/indignation) can minimize the emotional tradeoffs researchers have documented for humorous appeals about climate change. Using a samp...