cssi/SciSciGPT-SciSciNet huggingface dataset:
Introduction to Gene Editing and Manipulation Using CRISPR/Cas9 Technology

Until very recently, the prospect of introducing mutations or exogenous DNA sequences at precise locations in the genomes of plants and animals was difficult, if not impossible. This rapidly changed with the demonstration that the type II CRISPR-Cas complex, a bacterial anti-viral surveillance system, could be engineered into a simple and robust platform for introducing double-stranded DNA breaks at nearly any position of plant and animal genomes. The prospect of efficiently creating tailored changes to a gene of interest is revolutionizing biomedical research, allowing exciting new questions to be asked. This overview introduces CRISPR-Cas technology as a tool for molecular biology and briefly discusses the advantages of this method over earlier techniques, as well as unique opportunities to create new avenues of research. © 2016 by John Wiley & Sons, Inc.
ON G-SPECTRAL ESTIMATION*

Publisher Summary This chapter discusses a new spectral estimator that appears to be of some value in the problem of spectral estimation. This estimator is closely tied to the ARMA processes, it should be understood that this model is not an underlying assumption. Indeed, the underlying assumption is basically that the spectrum of an associated continuous process satisfies the very general requirement that it is continued fraction integrable. Thus, the method should be fairly robust. The chapter presents the definition of G n - and e n -transformations are defined and some simple examples are given to demonstrate their ability to increase the rate of convergence of certain types of sequences.
Hemostatic Aspects of Sickle Cell Disease

Abstract Sickle cell disease (SCD) is described as a hypercoagulable state. Patients exhibit increased platelet activation, high plasma levels of markers of thrombin generation, depletion of natural anticoagulant proteins, abnormal activation of the fibrinolytic system, and increased tissue factor expression, even in the noncrisis “steady state.” Furthermore, SCD is characterized by an increased risk of thrombotic complications. The pathogenesis of coagulation activation in SCD appears to be multifactorial, with contributions from ischemia-reperfusion injury and inflammation, hemolysis and nitric oxide deficiency, and increased sickle RBC phosphatidylserine expression. Although recent studies in animal models of SCD suggest that coagulation activation may contribute to the pathogenesis of SCD, the data on the contribution of coagulation and platelet activation to SCD-related complications in humans are limited. In this chapter, we review selected complications that may be associated with thrombosis as well as currently available treatments for SCD, including hydroxyurea and red blood cell transfusion. In addition, we review the available data on anticoagulants and antiplatelet agents in patients with SCD.
Organic cation transporter 3 (OCT3) is localized to intracellular and surface membranes in select glial and neuronal cells within the basolateral amygdaloid complex of both rats and mice

Organic cation transporter 3 (OCT3) is a high-capacity, low-affinity transporter that mediates corticosterone-sensitive uptake of monoamines including norepinephrine, epinephrine, dopamine, histamine and serotonin. OCT3 is expressed widely throughout the amygdaloid complex and other brain regions where monoamines are key regulators of emotional behaviors affected by stress. However, assessing the contribution of OCT3 to the regulation of monoaminergic neurotransmission and monoamine-dependent regulation of behavior requires fundamental information about the subcellular distribution of OCT3 expression. We used immunofluorescence and immuno-electron microscopy to examine the cellular and subcellular distribution of the transporter in the basolateral amygdaloid complex of the rat and mouse brain. OCT3-immunoreactivity was observed in both glial and neuronal perikarya in both rat and mouse amygdala. Electron microscopic immunolabeling revealed plasma membrane-associated OCT3 immunoreactivity on axonal, dendritic, and astrocytic processes adjacent to a variety of synapses, as well as on neuronal somata. In addition to plasma membrane sites, OCT3 immunolabeling was also observed associated with neuronal and glial endomembranes, including Golgi, mitochondrial and nuclear membranes. Particularly prominent labeling of the outer nuclear membrane was observed in neuronal, astrocytic, microglial and endothelial perikarya. The localization of OCT3 to neuronal and glial plasma membranes adjacent to synaptic sites is consistent with an important role for this transporter in regulating the amplitude, duration, and physical spread of released monoamines, while its localization to mitochondrial and outer nuclear membranes suggests previously undescribed roles for the transporter in the intracellular disposition of monoamines.
Coordinating Energy Efficiency and Incentive-based Demand Response

Traditionally, energy demand-side management programs are each designed in isolation. Breaking with this tradition, we examine the interactions between long-term energy efficiency upgrades and daily demand response participation at an industrial firm. Using a representative model of the firm’s production and society’s energy generation, we show that energy efficiency and demand response act as substitutes. A larger incentive to participate in demand response leads to a reduced investment in energy efficiency. Upon re-examining the long-studied energy efficiency gap, we find that the gap is typically smaller when demand response is considered. Policies aiming to close or reduce the energy efficiency gap, such as investment subsidies and carbon taxes, may fail to achieve their desired outcomes when firms participate in demand response. We propose an Extended Demand Response Baseline Policy that simplifies the design and implementation of other energy efficiency policy initiatives by removing the firm’s disincentive to install energy efficiency in the presence of demand response.
Unscented Kalman filter for neural decoding of human treadmill walking from non-invasive electroencephalography

The feasibility of decoding lower limb kinematics in human treadmill walking from noninvasive electroencephalography (EEG) has been demonstrated with linear Wiener filter. However, nonlinear relationship between neural activities and limb movements may challenge the linear decoders in real-time brain computer interface (BCI) applications. In this study, we propose a nonlinear neural decoder using an Unscented Kalman Filter (UKF) to infer lower limb joint angles from noninvasive scalp EEG signals during human treadmill walking. Our results demonstrate that lower limb joint angles during treadmill walking can be decoded from the fluctuations in the amplitude of slow cortical potentials in the delta band (0.1–3Hz). Overall, the average decoding accuracy were 0.43 ± 0.18 for Pearson's r value and 1.82 ± 3.07 for signal to noise ratio (SNR), and robust to ocular, muscle, or movement artifacts. Moreover, the signal preprocessing scheme and the design of UKF allow the implementation of the proposed EEG-based BCI for real-time applications. This has implications for the development of closed-loop EEG-based BCI systems for gait rehabilitation after stroke.
Primary Production, Community Respiration, and Net Community Production along Oxygen and Nutrient Gradients: Environmental Controls and Biogeochemical Feedbacks within and across “Marine Lakes”

Declining ocean oxygen content driven by anthropogenic climate change has wide-ranging ramifications for marine ecosystems. These effects are significant but complex at the upper margins of expanding oxygen minimum zones (OMZs), where deoxygenation and biogeochemical feedbacks to low dissolved oxygen (DO) are regulated by biological production and consumption of DO via gross primary production (GPP) and community respiration (CR). We used ‘marine lakes’—bodies of seawater surrounded by land—as a natural experimental system for examining the environmental factors that dictate coupling and de-coupling between GPP and CR. Distinct gradients in DO (from fully oxygenated to anoxic conditions), temperature, light, quantity and quality of organic matter, presence of key nutrients, and microbial community structure occur across multiple stratified meromictic lakes and well-mixed holomictic marine lakes present in Palau. We found consistently high GPP rates in stratified meromictic lakes (>10 mmol O2 m-3 d-1)—especially near the chemocline, where nutrients diffuse upwards from anoxic waters—and a wider range of rates in well-mixed lakes (0.350 to 57.9 mmol O2 m-3 d-1). In contrast to GPP, CR rates were typically lower and less variable across different depths and lakes. Most depths in most lakes were therefore net autotrophic (i.e., net community production [NCP] > 0). However, experimental additions of ammonium (5 μM) and labile organic carbon (100 μM) had strong effects on CR, resulting in (i) several-fold increases in CR, (ii) larger increases in CR in meromictic lakes with chemoclines near the surface, and (iii) the occurrence of net heterotrophy and DO consumption. Our results are indicative of several biogeochemical feedback mechanisms to deoxygenation present at the upper margins of shoaling OMZs that are governed by nutrient turnover. In marine lakes, these feedbacks can have strong effects on nutrient uptake and the production and consumption of oxygen, with implications for carbon, nutrient, and oxygen cycling throughout large areas of the ocean.
Phototherapy for the Elderly Population

Phototherapy is an ideal treatment option for the elderly population for many conditions, such as psoriasis, eczema, and idiopathic pruritus, because, from a medical perspective, phototherapy is systemically safer. However, when considering phototherapy as a treatment option for an elderly patient, it is important to consider physical, logistical, and psychological limitations unique to the elderly, such as issues with mobility, transportation, memory/cognition, and overall access to care.
A complex stereochemical relay approach to the antimalarial alkaloid ocimicide A1. Evidence for a structural revision

Ocimicide A1 (1) and the semisynthetic derivative ocimicide A2 (2) are highly potent antimalarial agents efficacious against chloroquine-sensitive and -resistant Plasmodium falciparum strains with IC50 values in the nanomolar and picomolar range, respectively. Members of this family have demonstrated radical cure in rhesus monkeys, without detectable toxicity, but their structure–function relationships and mechanism of action are unknown. Herein we describe a twelve-step synthesis of an advanced N-acylated pentacyclic precursor to the proposed structure of 1 (11% overall yield). Instability and poor P. falciparum growth inhibition of the corresponding free donor–acceptor cyclopropylamine, and large discrepancies between reported and both experimental and DFT-calculated 13C chemical shifts and coupling constants, suggest that substantial revision of the proposed structures may be necessary.
School Protective Factors and Substance Use Among Lesbian, Gay, and Bisexual Adolescents in California Public Schools.

Abstract Purpose: The majority of studies examining substance use among lesbian, gay, and bisexual (LGB) youth have focused on a wide array of risk factors (e.g., victimization). Few studies have explored the protective role of schools. This study aims to fill this gap in the literature and inform programs aimed at reducing substance use among LGB youth. More specifically, this study explores the extent to which school connectedness and support from teachers and other adults at school are associated with substance use among LGB youth in school and within the past 30 days. Methods: A secondary analysis of the 2013–2015 California Healthy Kids Survey (CHKS) was conducted to examine associations between school protective factors (i.e., school connectedness and adult support) and substance use among LGB youth, above and beyond a key risk factor, school victimization. The study outcomes were past 30-day and in-school use of cigarettes, alcohol, marijuana, inhalants, prescription pain medication, and other ille...
Task-Specific Scoring Functions for Predicting Ligand Binding Poses and Affinity and for Screening Enrichment.

Molecular docking, scoring, and virtual screening play an increasingly important role in computer-aided drug discovery. Scoring functions (SFs) are typically employed to predict the binding conformation (docking task), binding affinity (scoring task), and binary activity level (screening task) of ligands against a critical protein target in a disease’s pathway. In most molecular docking software packages available today, a generic binding affinity-based (BA-based) SF is invoked for all three tasks to solve three different, but related, prediction problems. The limited predictive accuracies of such SFs in these three tasks has been a major roadblock toward cost-effective drug discovery. Therefore, in this work, we develop BT-Score, an ensemble machine-learning (ML) SF of boosted decision trees and thousands of predictive descriptors to estimate BA. BT-Score reproduced BA of out-of-sample test complexes with correlation of 0.825. Even with this high accuracy in the scoring task, we demonstrate that the dock...
A Link Between Childhood Adversity and Trait Anger Reflects Relative Activity of the Amygdala and Dorsolateral Prefrontal Cortex.

Abstract Background Trait anger, or the dispositional tendency to experience a wide range of situations as annoying or frustrating, is associated with negative mental and physical health outcomes. The experience of adversity during childhood is one risk factor for the later emergence of high trait anger. This association has been hypothesized to reflect alterations in neural circuits supporting bottom-up threat processing and top-down executive control. Methods Here, using functional magnetic resonance imaging and self-report questionnaire data from 220 volunteers, we examined how individual differences in top-down prefrontal executive control and bottom-up amygdala threat activity modulate the association between childhood adversity and trait anger during young adulthood. Results We report that the association between childhood adversity and trait anger is attenuated specifically in young adults who have both relatively low threat-related amygdala activity and high executive control–related dorsolateral prefrontal cortex activity. Conclusions These brain activity patterns suggest that simultaneous consideration of their underlying cognitive processes—namely, threat processing and executive control—may be useful in strategies designed to mitigate the negative mental health consequences of childhood adversity.
The future of computing — Arithmetic circuits implemented with memristors

Memristors are non-volatile memory elements. The application of memristors in logic operations have recently gained importance and are being investigated. In applications like mem-computing, where memory acts both as a site for storing data and logic computations, memristors provide a promising future. The work presented in this paper describes multiple techniques of using memristors to build array multipliers. We present designs based on material implication, MAD and current mirror logic and provide a comparative analysis of the described techniques in the context of array multipliers. Metrics like area and latency are compared to previous works.
Human Prostacyclin Receptor: Cloning and Co-Expression with EP3 Prostaglandin Receptor

A variety of agonists are able to activate platelets, including thromboxane A2 and thrombin. Other agents, such as prostaglandins, inhibit platelet aggregation and secretion. All of these responses are mediated through specific receptors on the platelet surface. The primary event coupled with the action of stimulatory agonists is the activation of phospholipase C, whereas activation of adenyl cyclase is the primary event leading to inhibition of platelet activation. The interest of our laboratory is prostaglandin regulation of cAMP metabolism.
Efficiently modeling the noise performance of short-pulse lasers with a computational implementation of dynamical methods

Lowering the output noise of short-pulse lasers has been a long-standing effort for decades. Modeling the noise performance plays a crucial role in isolating the noise sources and reducing them. Modeling to date has either used analytical or semianalytical implementation of dynamical methods or Monte Carlo simulations. The former approach is too simplified to accurately assess the noise performance in real laser systems, while the latter approach is too computationally slow to optimize the performance as parameters vary over a wide range. Here, we describe a computational implementation of dynamical methods that allows us to determine the noise performance of a passively mode-locked laser within minutes on a desktop computer and is faster than Monte Carlo methods by a factor on the order of 103. We apply this method to characterize a laser that is locked using a fast saturable absorber—for example, a fiber-based nonlinear polarization rotation device—and a laser that is locked using a slow saturable absorber—for example, a semiconductor saturable absorbing mirror.
The Value of User Centered Design in Product Marketing: A Simulated Manufacturing Company Product Offering Market Strategy

The field of manufacturing is mainly concern with the creation of products for consumers who demand these items. At Indiana State University’s Advance Manufacturing Management (AMM) Program, phases of the entire value chain are emphasized to students in a senior level undergraduate course structured as a simulated industrial manufacturing company (SIMCO). The course entails design, prototyping, manufacturing and finally marketing of a product. While the first three phases are easily emphasized the final phase, marketing, lacks a holistic strategy that embodies the previous activity. Marketing activities are therefore disjointed, in turn, affecting the potential revenue of the product. This research project originated as a demonstration and proof of concept- human-computer interaction and marketing strategies become equally valuable as the product in the later stages of the value chain, where ecommerce is integrated.
Prevalence and Determinants of Hyperpolypharmacy in Adults with Heart Failure

Introduction Hyperpolypharmacy (HPP), defined as the use of ≥10 medications, is a well-described phenomenon in Geriatrics, that is linked to increased risk for hospitalization, disability, and mortality. Given the number of cardiovascular medications necessary to adhere to clinical practice guidelines, coupled with a high prevalence of non-cardiac comorbidity, adults with CHF may be at elevated risk for HPP. Objective We aimed to assess the prevalence and identify determinants of HPP among adults with CHF. Methods Using 2003-2014 data from NHANES (a cross-sectional survey representative of the non-institutionalized population in the United States), we examined adults aged ≥50 years with self-reported CHF. We defined HPP as the condition of taking ≥10 medications. We used weighted means and percentages to determine population-based characteristics. To identify factors independently associated with HPP, we performed a multivariable Poisson regression analysis, adjusting for sociodemographics, comorbidity, geriatric conditions, and health care utilization. Results We studied 947 participants with CHF, which represented 4.6 million adults with CHF in the USA. The mean age of the population was 70 years, 49% were women, and 77% were white. Most participants had an education level of high school or below (87%), and a substantial proportion (27%) reported an annual household income of Conclusion Hyperpolypharmacy is common in adults with CHF. While its prevalence does not vary according to impairments in function or cognition, low household income and low educational status are independently associated with HPP. This suggests that non-medical factors may be contributing to this potentially harmful practice, and warrants further investigation.
Soft optoelectronic sensory foams with proprioception

In a step toward soft robot proprioception, and therefore better control, this paper presents an internally illuminated elastomer foam that has been trained to detect its own deformation through machine learning techniques. Optical fibers transmitted light into the foam and simultaneously received diffuse waves from internal reflection. The diffuse reflected light was interpreted by machine learning techniques to predict whether the foam was twisted clockwise, twisted counterclockwise, bent up, or bent down. Machine learning techniques were also used to predict the magnitude of the deformation type. On new data points, the model predicted the type of deformation with 100% accuracy and the magnitude of the deformation with a mean absolute error of 0.06°. This capability may impart soft robots with more complete proprioception, enabling them to be reliably controlled and responsive to external stimuli.
On the intersection of electrochemistry and mass spectrometry.

Abstract The application of nanopipettes, developed first as a tool for electrochemistry and electrophysiology, as tools for mass spectrometry is considered. Recent examples of advances in electrospray ionization and sampling for mass spectrometry with nanopipettes is discussed. These examples show a scientific intersection that is ripe for further development.
SRC3 Is a Cofactor for RORγt in Th17 Differentiation but Not Thymocyte Development.

SRC3, a highly conserved member of the steroid receptor coactivator (SRC) family, is recruited by transcription factors to regulate cellular function. Previously, we demonstrated that SRC1, another highly conserved member of the SRC family, interacts with RORγt to regulate Th17 differentiation. However, the relationship between SRC1 and SRC3 in the regulation of Th17 cell function remains unknown. In this study, we demonstrate that mouse SRC3 interacts with RORγt in Th17 cells but not in thymocytes. In addition, Src3-/- mice exhibited defective Th17 differentiation and induction of experimental autoimmune encephalomyelitis but normal thymocyte development. Furthermore, a K313 to arginine mutation of RORγt (RORγt-K313R), which disrupts the interaction of RORγt with SRC3 but not with SRC1, impairs Th17 differentiation but not thymocyte development. These data suggest that SRC3 works with SRC1 to regulate RORγt-dependent Th17 differentiation but is not essential for RORγt-dependent thymocyte development.
Conjoint Analysis and Experimental Data

This chapter introduces the use of indicators to analyze data from conjoint analysis experiments. Conjoint analysis is used in experiments to quantify customer preferences for better design of new products and services.
Long-term outcomes of pediatric kidney transplant recipients with a pretransplant malignancy.

A childhood malignancy can rarely progress to ESRD requiring a KT. To date, few reports describe long-term outcomes of pediatric KT recipients with a pretransplant malignancy. Between 1963 and 2015, 884 pediatric (age: 0-17 years old) recipients received 1055 KTs at our institution. KT outcomes were analyzed in children with a pretransplant malignancy. We identified 14 patients who had a pretransplant malignancy prior to KT; the majority were <10 years old at the time of KT. Ten (71%) patients received their grafts from living donors, the majority of which were related to the recipient. Wilms' tumor was the dominant type of pretransplant malignancy, seen in 50% of patients. The other pretransplant malignancy types were EBV-positive lymphoproliferative disorders, non-EBV-positive lymphoma, leukemia, neuroblastoma, soft-tissue sarcoma, and ovarian cancer. Ten of the 14 patients received chemotherapy as part of their pretransplant malignancy treatment. Graft survival at 1, 3, and 5 years was 93%, 83%, and 72%, respectively. Patient survival at 1, 5, and 10 years was 100%, 91%, and 83%, respectively. Six (40%) patients suffered AR following KT; half of them had their first episode of AR within 1 month of KT. Our single-center experience demonstrates that pediatric KT recipients with a previously treated pretransplant malignancy did not exhibit worse outcomes than other pediatric KT patients.
Blockchain Technology: The Future of Sustainability in the Retail Sector

Many consumers and professionals realize that the state of the world is declining and that change must be adopted. The problem, however, is that it is difficult for consumers to compare brands in the saturated market to make conscious sustainability decisions. This paper will propose an alternative to eco-labelling, the current marketing tool used by companies to inform consumers of their sustainability initiatives. A research model is proposed to understand the effect of Blockchain data on the three elements of ecolabels, and the resulting impact onconsumer behavior compared to the outcome of the traditional ecolabel. Businesses working with blockchain data will be able to identify inefficiencies in their supply chain, which can help determine if any necessary changes should be made.As consumers try to make conscious decisions based on the effect on the environment and society, businesses should try to position themselves within the consumer’s moral interests.
The Natural History of Severe Acute Respiratory Syndrome Coronavirus 2–Related Multisystem Inflammatory Syndrome in Children: A Systematic Review

BACKGROUND: The clinical manifestations and natural history of severe acute respiratory distress syndrome coronavirus 2 (SARS-Cov-2) related Multisystem Inflammatory Syndrome in Children (MIS-C) are poorly defined. Using a systematic review of individual cases and case series and collating elements of the clinical course, the objective of this study was to provide a detailed clinical description and natural history of MIS-C. METHODS: Case reports and series of MIS-C were recovered from repeated MEDLINE searches, a single EMBASE search and table of contents reviews of major general medicine and pediatric journals performed between June 3 and July 23, 2020. Fever, evidence of inflammation, and evidence of organ dysfunction were required for inclusion. RESULTS: MEDLINE and EMBASE searches produced 129 articles and 10 articles were identified from journal contents or article bibliographies; 16 reports describing 505 children with MIS-C comprise this review. Thirty- two children (14.7%) had negative results for SARS-Cov-2 by nucleic acid and/or antibody testing. The weighted median age was 9 years (6 months to 20 years). Clinical findings included fever (100%), gastrointestinal symptoms (88.0%), rash (59.2%), conjunctivitis (50.0%), chelitis/ "strawberry tongue" (55.7%) or extremity edema/erythema (47.5%). Median serum CRP, ferritin, fibrinogen and D dimer concentrations were above the normal range. Intravenous gammaglobulin (78.1%) and methylprednisolone/prednisone(57.6%) were the most common therapeutic interventions ; immunomodulation was used in 24.3% of cases. Myocardial dysfunction requiring ionotropic support (57.4%) plus extracorporeal membrane oxygenation (5.3%), respiratory distress requiring mechanical ventilation (26.1%), and acute kidney injury (11.9%) were the major complications; anticoagulation was used commonly (54.4%) but thrombotic events occurred rarely (3.5%). Seven (1.4%) children died. CONCLUSIONS: MIS-C following SARS-Cov-2 infection frequently presents with gastrointestinal complaints and/or rash; conjunctivitis, chelitis and/or extremity changes also occur frequently. Serious complications occur frequently and respond to aggressive supportive therapy.
Production of Polyhydroxyalkanoates (PHA) by Haloferax mediterranei from Food Waste Derived Nutrients for Biodegradable Plastic Applications

Polyhydroxyalkanoates (PHA) are a family of microbial polyesters that are used as biodegradable plastics in replacement of conventional plastics for various applications. However, the high production cost is the barrier for PHA market expansion. This study aimed to utilize food waste as low-cost feedstock to produce poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) by Haloferax mediterranei. The effects of acetate (Ac), propionate (Pr), butyrate (Bu), and the short-chain carboxylates derived from food waste were examined on the microbial growth and PHBV production. Results showed that a mixture of carboxylates provided a 55% higher PHBV yield than glucose. The food-waste-derived nutrients achieved the yields of 0.41 to 0.54 g PHBV/g Ac from initial loadings of 450 mg/l to 1,800 mg/l Ac of total carboxylates. And the consumption of individual carboxylate varied between different compositions of the carbon source. The present study demonstrates the potential of using food waste as feedstock to produce PHBV by Haloferax mediterranei, which can provide economic benefits to the current PHA industry. Meanwhile, it will also help promote organic waste reduction in landfills and waste management in general.
Sufficient dimension reduction for conditional quantiles with alternative types of data

There is a great amount of work that stands to benefit from quantile regression (QR), especially when the extreme parts of data are of interest. Although QR has been well developed, it has recently...
Constrictive pericarditis in the setting of repeated chest trauma in a mixed martial arts fighter.

BACKGROUND Constrictive pericarditis (CP) is characterized by scarring and loss of elasticity of the pericardium. This case demonstrates that mixed martial arts (MMA) is a previously unrecognized risk factor for CP, diagnosis of which is supported by cardiac imaging, right and left heart catheterization, and histological findings of dense fibrous tissue without chronic inflammation. CASE PRESENTATION A 47-year-old Caucasian male former mixed martial arts (MMA) fighter from the Western United States presented to liver clinic for elevated liver injury tests (LIT) and a 35-pound weight loss with associated diarrhea, lower extremity edema, dyspnea on exertion, and worsening fatigue over a period of 6 months. Past medical history includes concussion, right bundle branch block, migraine headache, hypertension, chronic pain related to musculoskeletal injuries and fractures secondary to MMA competition. Involvement in MMA was extensive with an 8-year history of professional MMA competition and 13-year history of MMA fighting with recurrent trauma to the chest wall. The patient also reported a 20-year history of performance enhancing drugs including testosterone. Physical exam was notable for elevated jugular venous pressure, hepatomegaly, and trace peripheral edema. An extensive workup was performed including laboratory studies, abdominal computerized tomography, liver biopsy, echocardiogram, and cardiac magnetic resonance imaging. Finally, right and left heart catheterization-the gold standard-confirmed discordance of the right ventricle-left ventricle, consistent with constrictive physiology. Pericardiectomy was performed with histologic evidence of chronic pericarditis. The patient's hospital course was uncomplicated and he returned to NYHA functional class I. CONCLUSIONS CP can be a sequela of recurrent pericarditis or hemorrhagic effusions and may have a delayed presentation. In cases of recurrent trauma, CP may be managed with pericardiectomy with apparent good outcome. Further studies are warranted to analyze the occurrence of CP in MMA so as to better define the risk in such adults.
Environmental and Other Causes of Cancer

This chapter focuses on the various factors, including environmental ones, that cause cancer. Polluted air can sometimes cause cancer, and widespread man-made chemicals, which have been shown to cause cancer in animals, are also suspected to cause cancer in humans. Certain pollutants are known to have caused local clusters of a specific malignancy. Arsenic in water has produced bladder cancer in Taiwan and in South America and the use of asbestos mineral as the opaque ingredient in whitewash has produced cases of pleural cancer in certain villages in Southern Europe and New Caledonia. The spill of dioxins at Seveso, Italy, probably resulted in cases of sarcoma and lymphoma. Environmental exposure to ionizing radiation, such as that following the nuclear disaster at Chernobyl in the Ukraine, can cause several forms of cancer, such as specific forms of leukemia, lymphoma, and cancers of the thyroid, lung, and breast. Cancers and other diseases caused by environmental pollution are especially important to identify or rule out. They are likely to be more easily preventable, because they can be eliminated from an entire population by means of a central action, much more efficiently than if each individual's behavior had to be separately modified.
Animal Behavior While Listening to Music and Doing Higher Brain Functions

The understanding of human higher brain function must involve behavioral and neurophysiological studies of higher brain function in other animals. This chapter thus investigates the varied and marvelous higher brain function capabilities of animals. The reliability of animal studies is not confounded by language-analytic reasoning or the cultural biases that can distort human studies. It is shown how both of these factors are important. The studies included in this chapter are limited to discussion of mammals and their response to human music, as well as studies of their higher brain functions. It also includes anecdotes, behavioral observations, and controlled studies. The experimental design is simple and portable and can be repeated in a more natural setting with several primates. Furthermore, in addition to examining group behavior, it is also common to do behavioral experiments with a single subject. The idea with a single subject is that the experiment can be done again and again under very controlled and reproducible conditions, thus single-subject studies can be extremely valuable.
Complex Behavior in Networks with Distributed Routing

The area of distributed systems is the focus of much current interest. However, there exists an apparent discrepancy between the character of these systems and their commonly used formal models as reported, for instance, in [1]. The notion of a global system state in distributed systems is difficult to formulate because of its complexity, non-linearity and unpredictability. Representative challenges include: the need for an integrated theory of correctness, timeliness and reliability at each level of abstraction in large-scale, distributed, dynamic computation; the development of techniques for extracting many states; the construction of heuristic and localized scheduling procedures to overcome the NP-hardness of adaptive scheduling algorithms; and the skillful incorporation of the time metrics to a study of interplays between steps in the reconfiguration — processing cycle. There are also “classic” problems concerning communication, cooperation, and consistency. Above all, there is a desperate need for a descriptive method of complexity.
Ezrin tunes the magnitude of humoral immunity. (IRM8P.709)

Ezrin is a member of the Ezrin-Radixin-Moesin (ERM) family of membrane-actin cytoskeleton crosslinkers that participate in a variety of cellular processes. In B cells, phosphorylation of ezrin at different sites regulates multiple processes such as lipid raft coalescence, BCR diffusion, microclustering, and endosomal JNK activation. In this study, we generated mice with conditional deletion of ezrin in the B cell lineage to investigate the physiological significance of ezrin’s function in antigen receptor-mediated B cell activation and humoral immunity. B cell development, as well as the proportion and numbers of major B cell subsets in peripheral lymphoid organs were unaffected by the loss of ezrin. Using super resolution imaging methods we show that in the absence of ezrin, BCRs respond to antigen binding by accumulating into larger and more stable signaling microclusters. Loss of ezrin led to delayed BCR capping and accelerated lipid raft coalescence. Although proximal signaling proteins showed stronger activation in the absence of ezrin, components of the distal BCR signaling components displayed distinct effects. Ezrin deficiency resulted in increased B cell proliferation and differentiation into antibody-secreting cells ex vivo, and stronger T cell-independent and -dependent responses to antigen in vivo. Overall, our data demonstrate that ezrin regulates amplification of BCR signals and tunes the strength of B cell activation and humoral immunity.
Medical post-traumatic stress disorder: catching up with the cutting edge in stress research

We briefly summarize two original research papers and a review article. We then review the formal structure of the diagnosis of post-traumatic stress disorder (PTSD) and discuss the use of continuous measures of PTSD in comparison with diagnostic instruments. Problems with distinguishing incident from prevalent PTSD cases lead to questions of whether medical PTSD is a new important problem. By examining current studies, we demonstrate that medical PTSD is lagging in fundamental and interventional research but we discuss how medical PTSD has unique opportunities to develop causal models that could inform the greater field of stress studies. We conclude by advocating that future medical PTSD research efforts should focus on understanding how fundamental brain processes are affected during acute medical stress.
On Gramsci’s ‘conceptions of the world’

Antonio Gramsci is widely celebrated for his conceptualisation of hegemony. This paper elucidates a related concept that appears frequently in Gramsci’s prison notebooks yet has been surprisingly under-emphasised: ‘conceptions of the world’. By conceptions of the world, Gramsci refers to things that inform our understanding of the world and our place in it. Each conception of the world is inherently practical and philosophical, relational and political. Gramsci argues that producing a new, effective conception of the world is the key to successfully building communism. It is therefore important to situate this concept in Gramsci’s thought. That is the aim of this paper, which elaborates on the implications of ‘conception of the world’ through a reading of Gramsci’s prison notes – particularly his commentaries on humanity and worldliness.
Proteins Specified by Herpes Simplex Virus X. Staining and Radiolabeling Properties of B Capsid and Virion Proteins in Polyacrylamide Gels

Analyses of the structural proteins of herpes simplex virions and of capsids containing viral DNA (B capsids), after electrophoresis in polyacrylamide gels, revealed considerable variability in their properties with respect to: retention of Coomassie brilliant blue (CBB) and fast green stains during destaining, relative optical absorbance of the CBB-protein complex at different wavelengths, relative efficiency with which /sup 14/C-amino acids are incorporated during early and late periods of the infection cycle, and capacity to be phosphorylated in vivo. In addition, it was found that protein 22a of B capsids, which does not have an electrophoretically identical counterpart in virions, shares a relatively unique set of staining and radiolabeling properties with virion protein 22, which has a slightly more rapid electrophoretic mobility in sodium dodecyl sulfate-polyacrylamide gels. (auth)
Adolescent binge-like alcohol alters sensitivity to acute alcohol effects on dopamine release in the nucleus accumbens of adult rats

Early onset of alcohol drinking has been associated with alcohol abuse in adulthood. The neurobiology of this phenomenon is unclear, but mesolimbic dopamine pathways, which are dynamic during adolescence, may play a role. We investigated the impact of adolescent binge-like alcohol on phasic dopaminergic neurotransmission during adulthood. Rats received intermittent intragastric ethanol, water, or nothing during adolescence. In adulthood, electrically evoked dopamine release and subsequent uptake were measured in the nucleus accumbens core at baseline and after acute challenge of ethanol or saline. Adolescent ethanol exposure did not alter basal measures of evoked dopamine release or uptake. Ethanol challenge dose-dependently decreased the amplitude of evoked dopamine release in rats by 30–50 % in control groups, as previously reported, but did not alter evoked release in ethanol-exposed animals. To address the mechanism by which ethanol altered dopamine signaling, the evoked signals were modeled to estimate dopamine efflux per impulse and the velocity of the dopamine transporter. Dopamine uptake was slower in all exposure groups after ethanol challenge compared to saline, while dopamine efflux per pulse of electrical stimulation was reduced by ethanol only in ethanol-naive rats. The results demonstrate that exposure to binge levels of ethanol during adolescence blunts the effect of ethanol challenge to reduce the amplitude of phasic dopamine release in adulthood. Large dopamine transients may result in more extracellular dopamine after alcohol challenge in adolescent-exposed rats and may be one mechanism by which alcohol is more reinforcing in people who initiated drinking at an early age.
Toll-like receptor 4 activation increases Akt phosphorylation in colon cancer cells

Background: Toll-like receptors (TLRs) are involved in innate immunity. Overexpression of TLRs has been implicated in various types of cancer including colorectal cancer (CRC). The phosphatidylinositol-3'-kinase (PI3K)/Akt signaling pathway is involved in CRC growth and progression. In this study, we determined whether TLR4 signaling and PI3K/Akt pathway activation occur in CRCs. Materials and Methods: Human CRCs and adjacent mucosa were evaluated for TLR4 expression. CRC cell lines were treated with lipopolysaccharide (LPS), endogenous TLR4 ligand, to assess Akt phosphorylation. Results: Human CRCs overexpressed TLR4 compared to matched normal mucosa. Additionally, TLR4 was expressed in CRC cells and LPS treatment increased Akt phosphorylation of TLR4-positive CRCs in a time-dependent manner. Conclusion: Our results identify TLR4 expression in human CRCs and activation of PI3K with LPS treatment. These findings suggest possible treatment strategies targeting TLR4 in CRC.
Arsenate as a potential negative selection agent for deficiency variants in cultured plant cells.

Sodium arsenate is toxic to cultured soybean [Glycine max (L.) Merr.] cells, killing virtually 100% of the cells during a 24-h exposure at a 1–2 mM concentration. However, when growth is previously halted by nitrogen deprivation 50–100% of the cells survive arsenate treatment. Because of this growthdependent toxicity, arsenate has promise as a negative selection agent for cultured plant cells. Using arsenate (2 mM) I was able to select from among 2×107 cells a cell line with a growth requirement for an amino acid mixture. This trait was maintained through 9 months of passage but then was lost.
An Optimal Auction for Complements

Abstract This paper considers the optimal selling mechanism for complementary items. When buyers are perfectly symmetric, the optimal procedure is to bundle the items and run a standard auction. In general, however, bundling the items is not necessarily desirable, and the standard auctions do not maximize revenue. Moreover, the optimal auction allocation may not be socially efficient since the auction must discriminate against bidders who have strong incentives to misrepresent their true preferences. Journal of Economic Literature Classification Number: D44.
Pensamientos sobre el desarrollo de la estadística en el tercer mundo

La matematica es la llave del progreso material humano en el siglo XX, aunque la aplicacion liberal de ese esfuerzo haya realizado tambien avances dramaticos en los ultimos anos. A duras penas nos podemos imaginar el desarrollo de la ciencia e ingenieria en el presente sin un sustrato matematico que le aporte la forma cuantitativa y el rigor necesarios para desarrollar las tecnicas deductivas y predictivas. La contribucion de la estadistica al avance intelectual y tecnologico es evidente, fenomeno altamente relacionado con la violenta penetracion de los metodos estadisticos en otras disciplinas, llevando a cabo una virtual "estadisticalizacion de la civilizacion". Son las tecnicas estadisticas las que han hecho posible el actual progreso de la agricultura; se empiezan a aplicar en las ciencias de las relaciones humanas, que los cientificos no eran capaces de analizar con precision anteriormente; incluso se ha convertido la estadistica en una regla indispensable en el mundo del gobierno, la industria y los negocios (...). [Trabajo presentado en la Conferencia Internacional sobre el Desarrollo de las Matematicas en el Tercer Mundo, Marzo 6-9, 1978, Universidad de Khartoum, Khartoum, Sudan. Traducido por Javier Montero]
Flowering, fruit set, and yield response of 'Bartlett' pear to leaf-scorch damage by twospotted spider mite (Acari: Tetranychidae).

The effect of leaf scorch and defoliation caused by twos potted spider mite, Tetranychus urticae Koch, was investigated on flower production, fruit set, fruit yield, and mean fruit weight of ‘Bartlett’ pear. The level of leaf scorch and defoliation was estimated in autumn, and the number of flowers per flower cluster, fruit set, and fruit yield were determined in the following season. The number of flowers per flower cluster was significantly reduced ( P < 0.05) by leaf scorch and defoliation in the previous summer, but the response was only slight with flower clusters having approximately five flowers per flower cluster. Fruit set per flower cluster, gross fruit yield, and the yield of fruit suitable for canning were Significantly reduced ( P < 0.01) by leaf scorch and defoliation in the previous year. On trees with 80% leaf scorch and defoliation in the previous summer, gross yield and the yield of fruit suitable for canning were reduced to approximately a third of the level determined for trees that experienced no leaf scorch and defoliation in the previous year. Mean fruit weight increased only marginally as fruit density per square meter of planted area decreased, indicating that leaf-scorch damage from twos potted mite may affect fruit growth of ‘Bartlett’ pear in the following year. Fruit set was not responsive to leaf-scorch damage in the second and third years after leaf damage had occurred. The effect of these results on a damage threshold is discussed.
Multiple myeloma in the United States, 1950–1975

A total of 68,400 whites and 10,533 nonwhites were reported to have died from multiple myeloma (MM) in the continental United States between 1950 and 1975 (excluding 1972 because of incomplete case ascertainment). Age-adjusted mortality rates for nonwhites were approximately twice as high as for whites. During the 25-year period of this survey, there was a twofold to threefold increase in MM mortality. The increase was seen in both races, but was greater in nonwhites than whites and primarily occurred in people over 55 years of age. The increases were uniform in all geographic regions and urban/rural categories. MM mortality from 1950--1969 was correlated with geographic, demographic, and occupational factors at the county level. The rates were highest in the far west and mid-central regions for whites and in the northeast for nonwhites. Urban areas had the highest rates and rural areas had the lowest, and positive associations were seen with indices of socioeconomic level and the percentage of residents with Scandinavian ancestry. For white males, MM mortality rates were elevated in areas with high petroleum and paper production, and a slight increase was seen in furniture manufacturing areas.