cssi/SciSciGPT-SciSciNet huggingface dataset:
Lower Late-Life Body-Mass Index is Associated with Higher Cortical Amyloid Burden in Clinically Normal Elderly.

Background Lower body-mass index (BMI) in late life has been associated with an increased risk of dementia, and weight loss has been associated with more rapid decline in Alzheimer's disease (AD) dementia. Objective To explore the association between BMI and cortical amyloid burden in clinically normal (CN) elderly at risk for AD dementia. Methods Cross-sectional analyses were completed using baseline data from the Harvard Aging Brain Study, consisting of 280 community-dwelling CN older adults aged 62-90. Assessments included medical histories and physical exam, Pittsburgh compound B (PiB) positron emission tomography (PET) amyloid imaging, and apolipoprotein E ɛ4 (APOE4) genotyping. For the primary analysis, a general linear regression model was used to evaluate the association of BMI with PiB retention. Covariates included age, sex, years of education, and APOE4 carrier status. Secondary analyses were performed for BMI subdivisions (normal, overweight, obese), APOE4 carriers, and BMI×APOE4 interaction. Results In the primary analysis, greater PiB retention was associated with lower BMI (β = -0.14, p = 0.02). In the secondary analyses, APOE4 carrier status (β= -0.27, p = 0.02) and normal BMI (β= -0.25, p = 0.01), as opposed to overweight or obese BMI, were associated with greater PiB retention. The BMI×APOE4 interaction was also significant (β= -0.14, p = 0.04). Conclusions This finding offers new insight into the role of BMI at the preclinical stage of AD, wherein lower BMI late in life is associated with greater cortical amyloid burden. Future studies are needed to elucidate the mechanism behind this association, especially in those with lower BMI who are APOE4 carriers.
An exact theory of ultrafast electron emission on a biased metal surface

Laser-driven ultrafast electron emission [1, 2] is important to free electron lasers (FELs), laser acceleration of relativistic electrons, and ultrafast electron diffraction. It would enable exciting technological development on four-dimensional (4D) time-resolved electron microscopy [3]. We constructed an analytic solution for the highly nonlinear electron emission from a metal surface that is exposed to both a dc biased electric field and a single frequency laser field [4]. The solution is valid for arbitrary combinations of dc electric field, laser electric field, laser frequency, metal work function and Fermi level. Various emission mechanisms, such as multiphoton absorption or emission, optical or dc field emission, are all included in this single formulation. The time-dependent emission current reveals that intense current modulation may be possible even with a low intensity laser, by merely increasing the applied dc bias.
The Bible in Psycho-Spiritual Perspective: News from the World of Biblical Scholarship

Since 1991 a new discipline of interest to pastoral psychologists has been brewing in the haunts of biblical scholarship. It is called Psychological Biblical Criticism. The history of this new field and the prospects of future research are chronicled in my book, Soul and Psyche: The Bible in Psychological Perspective (Fortress, 1999). The present article highlights four themes of the book: a) the history of psychological approaches to scripture from Tertullian to the twentieth century; b) Freud and Jung, forerunners of psychological biblical criticism; c) psychological biblical criticism today; and d) revisioning the Bible as a “soul book.”
Characterization of traps in scaled NMOS transistors with ultra-thin high-K dielectrics and metal gate electrodes

At the ITRS 45nm technology node, NMOS transistors with high-K dielectrics have an effective oxide thickness (EOT) less than 1nm. An increase in trap density, both at the interface and in the film, is observed as a result of the incorporation of high-K materials into these devices. In our research, several experimental methods have been used to study these on scaled NMOS transistors — devices with ultra-thin high-k dielectric layer and metal gate. These methods include 1/f noise characterization, charge pumping and subthreshold region characterization.
Abstract B102: A microengineered human lymph node-on-a-chip to study cancer immunotherapy

Preclinical studies in cancer immunotherapy, such as those involving checkpoint blockade are usually conducted and validated in mice; however, rodent immune responses do not faithfully mimic those observed in humans. The overall goal of this project is to leverage recent advances in human organ-on-chip technology to create a human lymph-node-on-chip (hLN-on-chip) that exhibits complex human immune functionality. For maximum applicability, we have started with human peripheral blood mononuclear cells (PBMC) such that these devices may be widely used as non-invasive surrogates for patient testing. We have optimized matrix, cellular composition, chip design and microfluidic perfusion to induce B cell clusters reminiscent of follicles found in the lymph node. T and B cell function is maintained in the hLN-on-chip as evidenced by IL-2 and immunoglobulin M production in response to heat killed formalin fixed Staph aureus Cowan I (SAC), commonly used to induce a T cell dependent antibody response. Current studies are focused on defining the alterations in sensitivity and activity of the T cells. For instance, lymph node resident T and B cells are known to be polarized. Thus, we have tested if coinhibitory receptors such as CTLA-4, known to be important in anti-tumor immunity are also polarized under tissue like conditions. We also present preliminary data on optimizing the perfusion of the lymphocyte parenchyma with microengineered channels lined with lymphatic and vascular endothelial cells to model antigen delivery and immune cell trafficking. These devices will enable near real-time assessment of secreted factors, cell trafficking and high-resolution imaging of dynamic cellular interactions that occur in the human lymph node, and hence, they should prove invaluable in studying human cancer response to anti-cancer immunotherapies in the future. Citation Format: Girija Goyal, Donald Ingber. A microengineered human lymph node-on-a-chip to study cancer immunotherapy [abstract]. In: Proceedings of the Second CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference: Translating Science into Survival; 2016 Sept 25-28; New York, NY. Philadelphia (PA): AACR; Cancer Immunol Res 2016;4(11 Suppl):Abstract nr B102.
Acute Ankle Instability/Ankle Sprains in Athletes

Ankle ligament injuries are common amongst athletes. Low ankle sprains typically involve the anterior talofibular ligament and the calcaneofibular ligament while high ankle sprains involve the syndesmosis. These injuries present with focal tenderness, swelling over the involved ligaments, and pain with weight bearing. Specialized physical exam maneuvers and radiographic imaging can aid in the diagnosis of these injuries. Non-operative management includes immobilization followed by stretching, proprioception training and peroneal strengthening. Furthermore, ankle braces and proprioception training prevent repeat injury. Surgical management includes multiple procedures ranging from ankle arthroscopy to anatomic reconstruction.
Examples of Advanced Applications: Plates with Piezoelectric Sensors and Actuators and Functionally Graded Plates

While the previous chapters attempt to provide a comprehensive formulation of the theory of plates applied to isotropic and composite material structures, this chapter illustrates representative areas of recent research and development. Naturally, the list of such areas is extensive, including solutions where the response of plate materials is elastic-plastic, viscoelastic or viscoplastic, plates formed of several materials and incorporating inclusions of various shapes, textile composites, shape memory alloy structures, etc. In this chapter we concentrate on two developments, i.e. plates with piezoelectric sensors and actuators and functionally graded material plates. The former area is particularly relevant to thin-walled aerospace structures whose dynamic response can be monitored and controlled by piezoelectric sensors and actuators. It is also applicable to energy harvesting and structural health monitoring systems. Functionally graded plates possess a number of potential advantages over conventional composite plate designs, including elimination of delamination tendencies present in laminated structures, reduced thermal residual stresses and improved thermal response during lifetime, possible enhancement in fatigue and fracture characteristics, etc. Since functionally graded plates are often applied in thermal applications, the discussion is centered on relevant problems.
Agostino Scilla: A Baroque Painter in Pursuit of Science

Agostino Scilla (1629–1700), a disciple of Antonio Barbalunga in Messina and Andrea Sacchi in Rome, was a prolific painter, well-known numismatist, and the author of one of the most important publications on fossils in the seventeenth century. Scilla’s Vain Speculation Undeceived by Sense (1670) helped to usher in a new understanding of fossils in the seventeenth century. Cited approvingly by Leibniz and to some degree plagiarized by John Woodward (who eventually acquired Scilla’s fossils and drawings), Vain Speculation added further weight to the argument that fossils were remnants or imprints of living beings. This article examines Scilla’s work as an important example of a painter’s understanding of nature in Baroque Italy. It explores Scilla’s claim to be a better interpreter of nature than any scholar in light of his relationship to the scientific communities in Messina and Rome, and his understanding of art and science in the works of Leonardo, Galileo, the Accademia dei Lincei and Accademia del Cimento.
Providing guidance for genomics-based cancer treatment decisions: insights from stakeholder engagement for post-prostatectomy radiation therapy

Despite the emergence of genomics-based risk prediction tools in oncology, there is not yet an established framework for communication of test results to cancer patients to support shared decision-making. We report findings from a stakeholder engagement program that aimed to develop a framework for using Markov models with individualized model inputs, including genomics-based estimates of cancer recurrence probability, to generate personalized decision aids for prostate cancer patients faced with radiation therapy treatment decisions after prostatectomy. We engaged a total of 22 stakeholders, including: prostate cancer patients, urological surgeons, radiation oncologists, genomic testing industry representatives, and biomedical informatics faculty. Slides were at each meeting to provide background information regarding the analytical framework. Participants were invited to provide feedback during the meeting, including revising the overall project aims. Stakeholder meeting content was reviewed and summarized by stakeholder group and by theme. The majority of stakeholder suggestions focused on aspects of decision aid design and formatting. Stakeholders were enthusiastic about the potential value of using decision analysis modeling with personalized model inputs for cancer recurrence risk, as well as competing risks from age and comorbidities, to generate a patient-centered tool to assist decision-making. Stakeholders did not view privacy considerations as a major barrier to the proposed decision aid program. A common theme was that decision aids should be portable across multiple platforms (electronic and paper), should allow for interaction by the user to adjust model inputs iteratively, and available to patients both before and during consult appointments. Emphasis was placed on the challenge of explaining the model’s composite result of quality-adjusted life years. A range of stakeholders provided valuable insights regarding the design of a personalized decision aid program, based upon Markov modeling with individualized model inputs, to provide a patient-centered framework to support for genomic-based treatment decisions for cancer patients. The guidance provided by our stakeholders may be broadly applicable to the communication of genomic test results to patients in a patient-centered fashion that supports effective shared decision-making that represents a spectrum of personal factors such as age, medical comorbidities, and individual priorities and values.
Simulation of complex incompressible flows using a finite element solver on MIMD machines

Publisher Summary An incompressible flow solver based on unstructured grids is implemented on parallel distributed-memory computer architecture. An important phase in the flow solver is the solution of the elliptic equations for the velocities and pressures. This elliptic solver is parallelized and incorporated into both the explicit and implicit versions of the incompressible flow solver. Performance and scalability studies are carried out on both Intel iPSC 860 and the Intel Delta prototype and show that the code is scalable. A parallelizable load balancing algorithm is developed to be used in conjunction with the incompressible flow solver. Steady and unsteady flows over a tri-element airfoil and NACA0012airfoil are computed using the parallel incompressible flow solver. The parallel flow solver is extended to 3D for simulation of flow past a fully appended submarine. The chapter concludes that the future developments will be focused on the incorporation of adaptive regridding in 2D and the parallel implementation of 3-D incompressible flow solver.
Building a Six-Junction Inverted Metamorphic Concentrator Solar Cell

We propose practical six-junction (6J) inverted metamorphic multijunction (IMM) concentrator solar cell designs with the potential to exceed 50% efficiency using moderately high quality junction materials. We demonstrate the top three junctions and their monolithic integration lattice matched to GaAs using 2.1-eV AlGaInP, 1.7-eV AlGaAs or GaInAsP, and 1.4-eV GaAs with external radiative efficiencies >0.1%. We demonstrate tunnel junctions with peak tunneling current >400 A/cm2 that are transparent to V OC = 5.15 V, and a promising pathway toward >50% efficiency at high concentrations is presented.
The Locational Impact of Site-Specific PEGylation: Streamlined Screening with Cell-Free Protein Expression and Coarse-Grain Simulation.

Although polyethylene glycol (PEG) is commonly used to improve protein stability and therapeutic efficacy, the optimal location for attaching PEG onto proteins is not well understood. Here, we present a cell-free protein synthesis-based screening platform that facilitates site-specific PEGylation and efficient evaluation of PEG attachment efficiency, thermal stability, and activity for different variants of PEGylated T4 lysozyme, including a di-PEGylated variant. We also report developing a computationally efficient coarse-grain simulation model as a potential tool to narrow experimental screening candidates. We use this simulation method as a novel tool to evaluate the locational impact of PEGylation. Using this screen, we also evaluated the predictive impact of PEGylation site solvent accessibility, conjugation site structure, PEG size, and double PEGylation. Our findings indicate that PEGylation efficiency, protein stability, and protein activity varied considerably with PEGylation site, variations tha...
Examining the Incremental Benefits of Administering a Maze and Three versus One Curriculum-Based Measurement Reading Probes When Conducting Universal Screening.

A primary problem with special education placement is that it is a solution that comes too late for children who are first noticed by their kindergarten teachers as lacking prerequisite skills. It ...
Psychiatric Emergencies and Crisis Management in a Neurological Practice

The complexities of neurological practice have increased considerably in the 21st century. There is now greater awareness of links between neurological and psychiatric disorders as the branch of neuropsychiatry has moved ahead. It is well known, for example, that patients with dementia, Parkinson’s disease, multiple sclerosis, and other disorders may have various behavioral problems well before the diagnosis is confirmed. This results in an increased need for having an understanding of psychological issues that neurological patients have. Depression commonly is associated with chronic pain and medical illnesses. This chapter focuses on these issues, as well as threatened violence and aggressive behavior in patients with traumatic brain injury (TBI).
Unusual Adrenal Tumors

A variety of unusual mesenchymal tumors involve the adrenal gland primarily, such as hemangiomas, Kaposi sarcomas, angiosarcomas, and benign and malignant smooth muscle and neural tumors. Malignant melanoma is an extraordinarily rarely reported primary in the adrenal gland; most malignant melanomas involving the adrenal gland are metastatic. Rare cases of primary lymphoma of the adrenal gland also have been reported. Other unusual tumors in the adrenal gland are teratomas and adenomatoid tumors. Adenomatoid tumors usually are identified in the urogenital system but may occur at a variety of sites, including the adrenal gland. Although a variety of unusual tumors rarely may be primary to the adrenal gland, the histologic and immunophenotypic features of these tumors are characteristic of the tumor and enable their identification.
Violence and the Nursing Curriculum: Nurse Educators Speak Out.

Violent crime in the United States is increasing at an alarming rate. Nurses are the first to encounter its victims--but are they prepared for them? Two activities at the 1995 NLN convention gathered the opinions, concerns, and recommendations of nurse educators about how education can help better equip nurses to perform the role of violence preventer and care provider.
Nasal polyp fibroblasts modulate epithelial characteristics via Wnt signaling.

Background While essential to the normal differentiation of ciliated airway epithelial cells, upregulated Wnt signaling in chronic rhinosinusitis with nasal polyps (CRSwNP) has been proposed to result in abnormal epithelial morphology and dysfunctional mucociliary clearance. The mechanism of epithelial Wnt signaling dysregulation in CRSwNP is unknown, and importantly cellular sources of Wnt ligands in CRSwNP have not yet been investigated. Methods Human sinonasal epithelial cells (hSNECs) and human sinonasal fibroblasts (hSNFs) were collected from 34 human subjects (25 control and 9 CRSwNP) and differentiated as primary air-liquid interface (ALI) and organoid co-cultures. hSNECs were isolated to the apical compartment of the transwell and hSNFs were isolated to the basolateral compartment. After 21 days of ALI culture, ciliary expression and sinonasal epithelial morphology were examined by immunohistochemistry (IHC) and quantitative real-time polymerase chain reaction (qRT-PCR). An organoid model was used to evaluate proliferation of basal cells in presence of hSNFs. Results Epithelial cells co-cultured with CRSwNP-hSNFs revealed significantly decreased ciliated cells, altered epithelial cell morphology, and increased colony forming efficiency compared to epithelial cells co-cultured with control-hSNFs. CRSwNP-hSNFs showed significantly higher messenger RNA (mRNA) expression of canonical WNT3A. A Wnt agonist, CHIR99021, replicated CRSwNP-hSNF co-cultures, and treatment with the Wnt inhibitor IWP2 prevented abnormal morphologies. Conclusion These results suggest that abnormal interactions between epithelial cells and fibroblasts may contribute to CRSwNP pathogenesis and supports the concept that dysregulated Wnt signaling contributes impairment to epithelial function in CRSwNP.
Use of Intravenous Anti-RhD Immunoglobulin (RhIG) in the Treatment of Primary Immune Thrombocytopenia

Commercialized intravenous immunoglobulin (IVIG) products have been used since the early 1980s for various patient treatment options, specifically to induce an immunomodulatory and therapeutic effect. IVIG, a pooled immunoglobulin G (IgG) preparation, is used for patients with immune deficiencies, inflammatory conditions, and autoimmune disorders such as primary immune thrombocytopenia (ITP). Front-line therapies for ITP include corticosteroids, IVIG, or anti-RhD immune globulin (RhIG). WinRho SDF (Cangene Corporation, Winnipeg, Manitoba, Canada), a RhIG preparation, was FDA-approved for use in 2005 and is used for treatment of patients with ITP through what is called a Fc blockade mechanism. After intravenous WinRho administration, patient platelets are spared from clearance by the spleen and with a good response to treatment, the patient9s platelet count increases. WinRho is not without potential side effects and also impacts the transfusion service pre-transfusion testing in the event that the patient undergoing treatment requires red cell transfusion. In 2010, a work group of experts reviewed the warnings associated with RhIG and concluded that assuming that patients are appropriate candidates for RhIG, monitored in a clinical setting for 8 hours after administration, RhIG products such as WinRho are considered a very effective front-line therapy for ITP.1 Effective first line therapies can circumvent the necessity for less-desirable second line therapies such as an invasive splenectomy or life-long treatment with thrombopoietin-receptor agonists (TPO-RAs) to increase platelet counts. ABBREVIATIONS:IVIG – intravenous immunoglobulin, ITP – primary immune thrombocytopenia, RhIG – Rh immune globulin, TPO-RAs – thrombopoietin-receptor agonists, MPV – mean platelet volume, RBC – red blood cell, HUS – hemolytic uremic syndrome, TTP – thrombotic thrombocytopenic purpura, DIC – disseminated intravascular coagulation, CBC – complete blood count, PT – prothrombin time, APTT – activated partial thromboplastin time, FDA – Food and Drug Administration
Evolving skill sets and job pathways of technical communicators

Recent research in technical communication (TC) indicates that the field has become more varied than ever in terms of job titles, job skills, and levels of involvement in the design and production process. Here, we examine this diversity by detailing the results of a small-scale anonymous survey of individuals who are currently working as technical communicators (TCs). The purpose of our survey was to discover what job titles people who identify as TCs have held and the skills required of those positions. The study was conducted using the online survey platform Qualtrics. Survey results found that TCs occupy jobs and use skills that are often quite different from "traditional" TC careers. Results further support previous research that these roles and responsibilities continue to evolve. However, results also suggest that this evolution is more sweeping than previously realized---moving TCs away from not only the traditional technical writing role but also the "technical communicator" role as it has been understood for the past 20--25 years.
Tau repeat regions contain conserved histidine residues that modulate microtubule-binding in response to changes in pH

Tau, a member of the MAP2/tau family of microtubule-associated proteins, stabilizes and organizes axonal microtubules in healthy neurons. In neurodegenerative tauopathies, tau dissociates from microtubules and forms neurotoxic extracellular aggregates. MAP2/tau family proteins are characterized by three to five conserved, intrinsically disordered repeat regions that mediate electrostatic interactions with the microtubule surface. Here, we used molecular dynamics, microtubule-binding experiments, and live-cell microscopy, revealing that highly-conserved histidine residues near the C terminus of each microtubule-binding repeat are pH sensors that can modulate tau-microtubule interaction strength within the physiological intracellular pH range. We observed that at low pH ( 7.5), tau deprotonation decreased binding to microtubules both in vitro and in cells. Electrostatic and hydrophobic characteristics of histidine were both required for tau-microtubule binding, as substitutions with constitutively and positively charged nonaromatic lysine or uncharged alanine greatly reduced or abolished tau-microtubule binding. Consistent with these findings, tau-microtubule binding was reduced in a cancer cell model with increased intracellular pH but was rapidly restored by decreasing the pH to normal levels. These results add detailed insights into the intracellular regulation of tau activity that may be relevant in both normal and pathological conditions.
Neighborhood-conditioned phonetic enhancement of an allophonic vowel split.

Vowels are enhanced via vowel-space expansion in perceptually difficult contexts, including in words subject to greater lexical competition. Yet, vowel hyperarticulation often covaries with other acoustic adjustments, such as increased nasal coarticulation, suggesting that the goals of phonetic enhancement are not strictly to produce canonical phoneme realizations. This study explores phonetic enhancement by examining how speakers realize an allophonic vowel split in lexically challenging conditions. Specifically, in US English, /ae/ is raising before nasal codas, such that pre-nasal and pre-oral /ae/ are moving apart. Speakers produced monosyllabic words varying in phonological neighborhood density (ND), a measure of lexical difficulty, with CaeN or CaeC structure to a real listener interlocutor in an interactive task. Acoustic analyses reveal that speakers enhance pre-oral /ae/ by lowering it in Hi ND words; meanwhile, pre-nasal /ae/ Hi ND words are produced with greater degrees of nasalization and increased diphthongization. These patterns indicate that ND-conditioned phonetic enhancement is realized in targeted ways for distinct allophones of /ae/. Results support views of hyperarticulation in which the goal is to make words, that is, segments in their contexts, as distinct as possible.
Synthesis of sulfur and silicon SAM precursors for molecular electronics applications

AbstractThis review largely covers the synthesis of sulfur and silicon containing small molecules that have subsequently been used as components of a number of molecular circuits. In some cases, it...
A High Performance Ultrasonic System for Flaw Detection

In ultrasonic Nondestructive Evaluation (NDE), high frequency acoustic waves are used to test the integrity of materials. The detection of flaw echoes in the presence of high microstructure scattering noise is a challenging problem that requires advanced signal processing methods such as statistical analysis and pattern recognition algorithms. In this study, we designed and implemented a reconfigurable, high performance and low cost ultrasonic NDE platform based on Xilinx ZYNQ SoC. The system can generate high voltage pulses for exciting the ultrasonic transducers, receive the low voltage ultrasonic backscattered echoes, process the acquired data, and transmit and store the processed data to a host computer. in this study, we used machine learning algorithms as an alternate to conventional target echo recognition methods. In particular, Multilayer Perceptron Neural Network (MLPNN) is designed for ultrasonic flaw echo detection. The input to MLPNN is segments of backscattered signals, and regions within the Split Spectrum Processing (SSP) 2D distribution. The experimental results show that MLPNN can detect the flaw echo in the backscattered signal with very high precision.
Polymorphisms in the ACE2 Locus Associate with Severity of COVID-19 Infection

The mechanisms underlying risk of developing severe outcomes due to COVID-19 have not yet been fully elucidated. The SARS-CoV-2 virus has a marked affinity to the human angiotensin-converting enzyme 2 (ACE2) receptor. The ACE2 locus is highly polymorphic, and this genetic variability may affect COVID-19 disease severity. Here, we analyzed associations between polymorphisms in the ACE2 locus and COVID-19 severity in 62 patients found to be COVID-19 positive by polymerase chain reaction. Of these patients, 23 required hospitalization due to COVID-19 infection. Of 61 ACE2 single nucleotide polymorphisms (SNPs) genotyped in this patient cohort, 10 were significantly associated with tissue expression of ACE2. Logistic regression adjusted for age and sex identified six of these ten SNPs to be significantly associated with hospitalization. These results provide preliminary evidence of a link between the ACE2 genotype and COVID-19 disease severity and suggest that the ACE2 genotype may inform COVID-19 risk stratification and need for more intense therapy.
Balancing Religious Freedoms and Public Health Protections During the COVID-19 Pandemic

Extraordinary responses to the COVID-19 pandemic are generating substantial debates over the scope and reach of public health powers and religious freedoms. Emergency declarations at every level of government to limit societal impacts of COVID-19 may shift constitutional norms, but do not completely negate rights to free exercise or assemble. Yet, no one has an unmitigated right to harm others in pursuit of their faith. Somewhere between individual religious rights and communal public health objectives lies a legally viable balance. Finding it during the pandemic is controversial. Among the most contentious issues are governments’ temporary orders suspending large religious gatherings to maintain social distances. While many religious leaders have complied, others have vociferously objected. Reaching accord begins with an assessment of legal principles of separation of church and state, especially concerning claims of religious rights to assemble despite unprecedented public health risks.
Methylene Blue Inhibits In Vitro the SARS-CoV-2 Spike - ACE2 Protein-Protein Interaction - A Mechanism That Can Contribute to Its Antiviral Activity Against COVID-19

Abstract Due to our interest in the chemical space of organic dyes to identify potential small-molecule inhibitors (SMIs) for protein-protein interactions (PPIs), we initiated a screen of such compounds to assess their inhibitory activity against the interaction between SARS-CoV-2 spike protein and its cognate receptor ACE2, which is the first critical step initiating the viral attachment and entry of this coronavirus responsible for the ongoing COVID-19 pandemic. As part of this, we found that methylene blue, a tricyclic phenothiazine compound approved by the FDA for the treatment of methemoglobinemia and used for other medical applications (including the inactivation of viruses in blood products prior to transfusion when activated by light), inhibits this interaction. We confirmed that it does so in a concentration-dependent manner with a low micromolar half-maximal inhibitory concentration (IC50 = 3 μM) in our protein-based ELISA-type setup, while chloroquine, siramesine, and suramin showed no inhibitory activity in this assay. Erythrosine B, which we have shown before to be a promiscuous SMI of PPIs, also inhibited this interaction with an activity similar, possibly slightly higher, than those found for it for other PPIs. This PPI inhibitory activity of methylene blue could contribute to its antiviral activity against SARS-CoV-2 even in the absence of light by blocking its attachment to ACE2-expressing cells and making this inexpensive and widely available drug potentially useful in the prevention and treatment of COVID-19 as an oral or inhaled medication.
An Alternative Molecular View of Evolution: How DNA was Altered over Geological Time

Four natural phenomena are cited for their defiance of conventional neo-Darwinian analysis: human intelligence; cat domesticity; the Cambrian explosion; and convergent evolution. 1. Humans are now far more intelligent than needed in their hunting–gathering days >10,000 years ago. 2. Domestic cats evolved from wildcats via major genetic and physical changes, all occurring in less than 12,000 years. 3. The Cambrian explosion refers to the remarkable expansion of species that mystifies evolutionists, as there is a total lack of fossil evidence for precursors of this abundant new life. 4. Convergent evolution often involves formation of complex, multigene traits in two or more species that have no common ancestor. These four evolutionary riddles are discussed in terms of a proposed “preassembly” mechanism in which genes and gene precursors are collected silently and randomly over extensive time periods within huge non-coding sections of DNA. This is followed by epigenetic release of the genes, when the environment so allows, and by natural selection. In neo-Darwinism, macroevolution of complex traits involves multiple mutation/selections, with each of the resulting intermediates being more favorable to the species than the previous one. Preassembly, in contrast, invokes natural selection only after a partially or fully formed trait is already in place. Preassembly does not supplant neo-Darwinism but, instead, supplements neo-Darwinism in those important instances where the classical theory is wanting.
Does agricultural value-added induce environmental degradation? Evidence from Azerbaijan

This study empirically analyzes the long-term relationship between agricultural production and carbon dioxide (CO2) emissions in Azerbaijan using annual data covering the period of 1992–2014. Additionally, real income and energy consumption variables were included in the model in testing the existence of the environmental Kuznets curve (EKC) hypothesis. Autoregressive distributed lag (ARDL) method is undertaken to reveal the existence of the long-term relationship between the CO2 and its determinants. The ARDL mechanism shows that gross domestic product (GDP) and energy consumption have a positive and statistically significant effect on carbon dioxide emissions. However, agricultural production and the square of GDP have a negative impact on air pollution. Furthermore, when the coefficients of real GDP and squared GDP included in the model were examined to analyze the inverted-U-shaped relationship between economic growth and environmental pollution, the EKC hypothesis was confirmed to be valid. According to Toda-Yamamoto causality test results, there is a bidirectional relationship between GDP, the square of GDP, and carbon emissions. From energy consumption and agricultural value-added to CO2 emissions, a unidirectional Granger causality relationship was found. Ultimately, the findings suggest that policies and reforms that increase or support agricultural production will help lower the country’s CO2 emissions level.
Potential Application of USP Paddle and Basket Dissolution Methods in Discriminating for Portioned Moist Snuff and Snus Smokeless Tobacco Products

The focus of the study was to develop discriminatory dissolution methods for portioned snus and moist snuff sub-categories of smokeless tobacco products (STPs) using USP basket and paddle apparatuses. Skoal Classic Wintergreen (SCW) and CORESTA CRP1.1 pouches were used as test products. The dissolution was performed at 10, 20, 30, 40, and 50 rpm basket or paddle speed in 500 ml artificial saliva pH 6.8. The products were also characterized for assay, pH, particle size, and loss on drying. The dissolution profiles were evaluated for amount/% of nicotine dissolved, time to reach plateau, and profiles comparison by f2 and f1 factors. The nicotine assay was 13.3 ± 0.2 and 7.6 ± 0.1 mg/pouch for SCW and CRP1.1, respectively. The nicotine dissolved in 30 min from SCW and CRP1.1 were 38.4–81.8 and 37.6–88.1, and 50.5–64.9 and 72.3–92.1% by paddle and basket methods, respectively. The f2 and f1 values were ≤ 39.2 and ≥ 42.1 and ≤ 43.2 and ≥ 34.1 for basket methods and paddle methods. RSD were less than 20% at all points of dissolution profiles, and dissolution plateau were achieved in 30 min at some of the tested conditions. In summary, dissolution methods based on basket and paddle can be used as a performance test for STPs.
How the Removal of a Market Barrier Enhanced Market Efficiency: The Case of WTI and Brent Crude Oil Prices

If the world oil market is efficient, arbitrage should lead the West Texas Intermediate and Brent crude oil price indexes to converge whenever they stray apart. From the beginning of the sample on May 20, 1987 until December 1, 2010 when U.S. oil production began to accelerate due to hydraulic fracturing (fracking), the two series were cointegrated. However, from this point formerly nonbinding constraints became binding. The domestic and world markets were well adapted to the U.S. being a large importer of oil, but the increased production from fracking disrupted this equilibrium, making the decades old U.S. ban on crude oil exports and pipeline capacity from the new well sites to the existing refineries binding. From late 2010 until the crude export ban was lifted on December 18, 2015, the two price series were not cointegrated. From the lifting of the ban through October 31, 2016, the end of the sample, the two prices were again cointegrated, indicating the transatlantic market for crude oil was operating more efficiently. The convergence in the two series was occurring more quickly in this last period than in the first period, suggesting another source of efficiency gains.
CSDMS: A community platform for numerical modeling of Earth-surface processes

Abstract. Computational modelling occupies a unique niche in Earth and environmental sciences. Models serve not just as scientific technology and infrastructure, but also as digital containers of the scientific community's understanding of the natural world. As this understanding improves, so too must the associated software. This dual nature–models as both infrastructure and hypotheses–means that modelling software must be designed to evolve continually as geoscientific knowledge itself evolves. Here we describe design principles, protocols, and tools developed by the Community Surface Dynamics Modeling System (CSDMS) to promote a flexible, interoperable, and ever-improving research software ecosystem. These include a community repository for model sharing and metadata, interface and ontology standards for model interoperability, language bridging tools, a modular programming library for model construction, modular software components for data access, and a Python-based execution and model-coupling framework. Methods of community support and engagement that help create a community-centered software ecosystem are also discussed.
Executive functions and imaginative play: Exploring relations with prosocial behaviors using structural equation modeling.

Abstract Background : Policy makers have long considered how to best educate children for success. Thus, this research explored whether imaginative play serves as a positive context for developing executive functions (EF) and prosocial behaviors necessary for academic success. Specifically, we hypothesized that EF would explain links between imaginative play and prosocial behaviors. Method : 284 preschool children and their teachers completed measures of imaginative play, EF, and prosocial behaviors. Structural Equation Modeling examined mediational links between these constructs. Results : Imaginative play predicted both hot and cool EF, as well as prosocial behavior, even after controlling for age and vocabulary; furthermore, the relationship between imaginative play and prosocial behavior was fully mediated by hot EF. Conclusion : Results suggest that imaginative play may serve as a positive context for developing EF and prosocial behaviors. Curricula and teachers should consider encouraging imaginative play to facilitate the development of EF and prosocial behaviors.
The Changing Face of Terrorism in the 21st Century: The Communications Revolution and the Virtual Community of Hatred

There are no psychological characteristics or psychopathology separating terrorists from the general population. Rather, it is group dynamics, with a particular emphasis on collective identity, that helps to explain terrorist psychology. Just as there is a diverse spectrum of kinds of terrorism, so too is there a spectrum of terrorist psychologies. Some terrorists, those in nationalist-separatist groups, such as Fatah and the IRA, are continuing with the mission of their parents who are dissident to the regime. The opposite generational provenance is seen among social-revolutionary terrorists, such as the Weather Underground and the Red Army Faction in Germany, who are rebelling against their parents' generation, which is loyal to the regime. Four waves of terrorism can be distinguished: the "anarchist wave"; the "anti-colonial wave" (nationalist-separatist), with minority groups seeking to be liberated from their colonial masters or from the majority in their country; the "new left" wave (social-revolutionary); and now the "religious" wave. With the communications revolution, a new phenomenon is emerging which may presage a fifth wave: lone wolf terrorists who through the Internet are radicalized and feel they belong to the virtual community of hatred. A typology of lone wolf terrorism is proposed.
Computer Simulation of Convection and Diffusion Effects on Velocity Estimations from X-Ray Contrast Density Time Curves

The problem of velocity measurement in X-ray angiography using the leading edge of the contrast bolus is considered. The velocity obtained from the ratio of the temporal derivative to the spatial derivative of the contrast concentration curves is shown to reflect the transport velocity, which is the basis for an estimate of the true blood velocity in X-ray angiography. The contrast distribution along the vessel cross section affects the value of transport velocity. Under laminary flow conditions, the measured transport velocity of the leading edge has been found to be between the average and the peak (central) fluid velocities. Simulation studies of the bolus in laminar flow through a straight tube are presented in this paper to provide further proof of the higher transport velocity of the bolus leading edge. The simulation studies confirm observations made previously from X-ray images of contrast passage through simple tubes.
The University of Illinois' Graduate School of Library and Information Science at TREC 2014

Abstract : The University of Illinois' Graduate School of Library and Information Science (uiucGSLIS) participated in TREC's Federated Web (FedWeb) and Knowledge Base Acceleration (KBA) tracks in 2014. Specifically, we submitted runs for the FedWeb resource selection and KBA cumulative citation recommendation (CCR) tasks.
Formalin treatment for massive bladder hemorrhage: Complications

Abstract A case is reported of severe bilateral ureterohydronephrosis secondary to formalin instillation in the bladder for massive hematuria. A review of the literature on the use of formalin intravesically, with emphasis on complications and dosage, is reported.
AGGREGATE EQUILIBRIUM AND A SIMPLE KEYNESIAN MODEL

Publisher Summary This chapter describes aggregate demand as a catalyst of the Keynesian model. Until full employment is attained, supply is accommodative. An increase in aggregate demand leads to an increase in output and real income. The pre-Keynesian view was that supply creates its own demand. However, the Keynesian view turns it around. Until the full-employment capacity of an economy is reached, demand creates its own supply. This chapter discusses the concept of equilibrium introduced by the Keynesian model. Equilibrium within the Keynesian model is not dependent on full employment. It is not expected that full employment would be associated with the equilibrium income level. When unemployment is present, falling wages would not restore full employment because wage cuts would serve to reduce income, thereby reducing aggregate demand. The interest rate would not be able to equate saving and investment. The level of saving would be determined by income, and investment would be determined by the prospect for profit. When an economy is slipping into a recession, falling interest rates may fail to bring saving and investment to equality.
Development of a Maleimide Amino Acid for Use as a Tool for Peptide Conjugation and Modification

An amino acid possessing a maleimide side chain was developed and synthesized in good yield. With a propensity to undergo the Michael addition reaction, the creation of a maleimide amino acid derivative was targeted for use as a highly functional tool for enabling peptide conjugation and structural modifications. After addressing the inherent potential side reactions of maleimides during solid phase peptide synthesis, the ability to incorporate the maleimide amino acid in an RGDS peptide sequence was demonstrated. 1H NMR and mass spectroscopic techniques enabled thorough characterization of the peptide sequence, confirming the presence of the maleimide functionality. Once characterized, the ability to use the maleimide moiety as a peptide modification tool was investigated. Specifically, it was shown that the maleimide functional group could be exploited, given the proper reaction conditions, to anchor a peptide to a surface and create a cyclic conformation from a linear sequence. Furthermore, bioactivity of the peptide containing maleimide amino acid was evaluated by studying cellular interactions with surfaces functionalized with an integrin binding sequence.
The geometric signature: Quantifying landslide-terrain types from digital elevation models

Topography of various types and scales can be fingerprinted by computer analysis of altitude matrices (digital elevation models, or DEMs). The critical analytic tool is the geometric signature, a set of measures that describes topographic form well enough to distinguish among geomorphically disparate landscapes. Different surficial processes create topography with diagnostic forms that are recognizable in the field. The geometric signature abstracts those forms from contour maps or their DEMs and expresses them numerically. This multivariate characterization enables once-in-tractable problems to be addressed. The measures that constitute a geometric signature express different but complementary attributes of topographic form. Most parameters used here are statistical estimates of central tendency and dispersion for five major categories of terrain geometry; altitude, altitude variance spectrum, slope between slope reversals, and slope and its curvature at fixed slope lengths. As an experimental application of geometric signatures, two mapped terrain types associated with different processes of shallow landsliding in Marin County, California, were distinguished consistently by a 17-variable description of topography from 21×21 DEMs (30-m grid spacing). The small matrix is a statistical window that can be used to scan large DEMs by computer, thus potentially automating the mapping of contrasting terrain types. The two types in Marin County host either (1) slow slides: earth flows and slump-earth flows, or (2) rapid flows: debris avalanches and debris flows. The signature approach should adapt to terrain taxonomy and mapping in other areas, where conditions differ from those in Central California.
Clinical and hemodynamic course of infants and children with anomalous left coronary artery

The clinical history of all 17 patients with anomalous left coronary artery presenting over the last 20 years was studied, with special emphasis on those who underwent reimplantation of the anomalous coronary artery into the aorta, a procedure that became our “treatment of choice” during this period. These patients were also evaluated for ventricular performance, residual mitral regurgitation, and wall integrity. Early in our experience with reimplantation, two patients died while we waited for them to achieve a more favorable size for surgery. Eight of nine survived reimplantation; three of these were under 1 year of age when operated upon. One of these eight patients has required additional mitral valvuloplasty, but all are doing well clinically up to 12 years after operation. Preoperative left ventricular ejection fraction of 0.37 ± 0.16 increased to 0.67 ± 0.07 (p < 0.001) by 1 year after surgery, despite ventricular wall abnormalities in four patients. Thus reimplantation of the anomalous left coronary artery should be undertaken upon diagnosis, since surgery can be performed successfully in infancy, with resultant improvement in ventricular function and an adequate clinical condition for at least 12 years.