cssi/SciSciGPT-SciSciNet huggingface dataset:
Mitoapocynin Treatment Protects Against Neuroinflammation and Dopaminergic Neurodegeneration in a Preclinical Animal Model of Parkinson’s Disease

Mitochondrial dysfunction, oxidative stress and neuroinflammation have been implicated as key mediators contributing to the progressive degeneration of dopaminergic neurons in Parkinson’s disease (PD). Currently, we lack a pharmacological agent that can intervene in all key pathological mechanisms, which would offer better neuroprotective efficacy than a compound that targets a single degenerative mechanism. Herein, we investigated whether mito-apocynin (Mito-Apo), a newly-synthesized and orally available derivative of apocynin that targets mitochondria, protects against oxidative damage, glial-mediated inflammation and nigrostriatal neurodegeneration in cellular and animal models of PD. Mito-Apo treatment in primary mesencephalic cultures significantly attenuated the 1-methyl-4-phenylpyridinium (MPP+)-induced loss of tyrosine hydroxylase (TH)-positive neuronal cells and neurites. Mito-Apo also diminished MPP+-induced increases in glial cell activation and inducible nitric oxide synthase (iNOS) expression. Additionally, Mito-Apo decreased nitrotyrosine (3-NT) and 4-hydroxynonenol (4-HNE) levels in primary mesencephalic cultures. Importantly, we assessed the neuroprotective property of Mito-Apo in the MPTP mouse model of PD, wherein it restored the behavioral performance of MPTP-treated mice. Immunohistological analysis of nigral dopaminergic neurons and monoamine measurement further confirmed the neuroprotective effect of Mito-Apo against MPTP-induced nigrostriatal dopaminergic neuronal loss. Mito-Apo showed excellent brain bioavailability and also markedly attenuated MPTP-induced oxidative markers in the substantia nigra (SN). Furthermore, oral administration of Mito-Apo significantly suppressed MPTP-induced glial cell activation, upregulation of proinflammatory cytokines, iNOS and gp91phox in IBA1-positive cells of SN. Collectively, these results demonstrate that the novel mitochondria-targeted compound Mito-Apo exhibits profound neuroprotective effects in cellular and pre-clinical animal models of PD by attenuating oxidative damage and neuroinflammatory processes.
The computation of Mössbauer spectra, II

Abstract The extension of the computer programs UNIXTL, LVSPHS and PDRHXT to deal with transitions of mixed multipolarity, and the use of density matrices to calculate Mossbauer spectra in the case where neither source nor absorber is a single unpolarized line are discussed. Methods for testing the programs and finding errors are outlined.
A safer world

The Global Burden of Disease and Injury project (GBD) is a monumental undertaking. First commissioned by the World Bank in 1990, and more recently supported by the Bill and Melinda Gates Foundation, this study aims to quantify the global burden and distribution of mortality, morbidity and disability attributable to a comprehensive set of diseases, conditions and risk factors. Results are most commonly presented as disability adjusted life years (DALYs), a common metric that accounts for years of life lost and for years of life lived with pain, impairment or other disability. Causes are grouped into three large domains: (1) communicable, neonatal, maternal and nutritional disorders; (2) non-communicable diseases and (3) injuries. The methods employed to generate these estimates are both state-of-the-art and daunting, involving huge human and computational resources.1 The raw data are amassed from vital registries, community and household surveys, hospital discharge abstracts and a host of other sources, including published epidemiological studies. These data are fed into sophisticated modelling programmes that generate global, regional, national and—in some cases—subnational—estimates, along with appropriate uncertainty intervals. In some cases this means extrapolating assumptions from one country or region to another. In others, it means glossing over the important—but unmeasured—differences that occur within countries and among demographic subpopulations. These methods have been presented by the authors in multiple venues over the years and, while not without controversy, are generally seen as the best available …
On the Mechanism of Crystalline Polymorph Selection by Polymer Heteronuclei

The phase-selective crystallization of acetaminophen (ACM) using insoluble polymers as heteronuclei was investigated in a combined experimental and computational effort to elucidate the mechanism of polymer-induced heteronucleation (PIHn). ACM heteronucleates from supersaturated aqueous solution in its most thermodynamically stable monoclinic form on poly(n-butyl methacrylate), whereas the metastable orthorhombic form is observed on poly(methyl methacrylate). When ACM crystals were grown through vapor deposition, only the monoclinic polymorph was observed on each polymer. Each crystallization condition leads to a unique powder X-ray diffraction pattern with the major preferred orientation corresponding to the crystallographic faces in which these crystal phases nucleate from surfaces of the polymers. The molecular recognition events leading to these outcomes are elucidated with the aid of computed polymer–crystal binding energies using docking simulations. This investigation illuminates the mechanism by w...
Magnetic Field Dependence of Critical Current Density of TFA-MOD Processed YBCO Coated Conductors

YBCO films on LaAlO3and IBAD (YSZ/Hastelloy) substrate were made by TFA-MOD (metalorganic deposition using trifluoroacetate) process. Improved coating solution resulted in high Jc at 77.3K and 0T of 7 MA/cm2 and 1.7 MA/cm2 for LaAlO3 and IBAD substrates, respectively. The magnetic field dependence of Jc at 77.3K also showed superior property: 105 A/cm2 at 4T (B//c-axis) for the LaAlO3substrate and at 3T (B//c-axis)) for IBAD substrate. Furthermore, the difference in Jc between single crystal LaAlO3and IBAD was small up to 3T. The present results imply that TFA-MOD process is promising for the practical YBCO coated conductor process.
Endoscopic solutions to challenging enteral feeding problems.

Purpose of reviewEnteral nutrition support is often required in patients who are unable to meet their own nutritional requirements. Endoscopists play a key role in the placement of enteral feeding catheters. This review focuses on the recently published solutions to common problems encountered durin
Multilevel summation with B-spline interpolation for pairwise interactions in molecular dynamics simulations

The multilevel summation method for calculating electrostatic interactions in molecular dynamics simulations constructs an approximation to a pairwise interaction kernel and its gradient, which can be evaluated at a cost that scales linearly with the number of atoms. The method smoothly splits the kernel into a sum of partial kernels of increasing range and decreasing variability with the longer-range parts interpolated from grids of increasing coarseness. Multilevel summation is especially appropriate in the context of dynamics and minimization, because it can produce continuous gradients. This article explores the use of B-splines to increase the accuracy of the multilevel summation method (for nonperiodic boundaries) without incurring additional computation other than a preprocessing step (whose cost also scales linearly). To obtain accurate results efficiently involves technical difficulties, which are overcome by a novel preprocessing algorithm. Numerical experiments demonstrate that the resulting method offers substantial improvements in accuracy and that its performance is competitive with an implementation of the fast multipole method in general and markedly better for Hamiltonian formulations of molecular dynamics. The improvement is great enough to establish multilevel summation as a serious contender for calculating pairwise interactions in molecular dynamics simulations. In particular, the method appears to be uniquely capable for molecular dynamics in two situations, nonperiodic boundary conditions and massively parallel computation, where the fast Fourier transform employed in the particle–mesh Ewald method falls short.
Juvenilizing activity of compounds related to the juvenile hormone against pupae of the stable fly.

Of 62 compounds tested topically against pupae of Stomoxys calcitrans (L.) for morphogenetic activity (expressed by production of pupal-adult intermediates), 6 were highly active at a dose of 10 ng, Five of the 6 were epoxides of arylterpenoid compounds with a 9-carbon backbone, and 1 was an aryl carbamate N -substituted by an 8-carbon epoxide. The 6 compounds had either no or para substituents on the phenyl ring. Substitutions made at the meta and ortho position, reduced the morphogenetic activity.
Visual hallucinations in photographs in Parkinson's disease

Visual hallucinations are reported in 16-37% of drug-treated patients with Parkinson's disease (PD) and are the most common hallucinations in PD. We report two patients with PD with symptoms that uniquely integrate visual hallucinations and delusions. We report two cases of patients with PD with visual hallucinations who saw the persistence of these hallucinations in photographs. These pictures were taken to prove the absence of these hallucinations. We believe this is the first description of this peculiar phenomenon, in which hallucinations or illusions could be replicated in photographs. Both patients had delusions associated with the images and we speculate that the images they saw in the photographs represent a further delusion, hence a 'delusional hallucination' or 'delusional illusion.' We believe that delusions fostering hallucinations are rare.
A Formative Evaluation of the Prairie Science Class

The Prairie Science Class is a formal partnership between the U.S. Fish and Wildlife Service's Prairie Wetlands Learning Center and the Fergus Falls Independent School District 544. Its mission is ...
Synthesis and Characterization of bis(Tetrahydrofurfuryl) Ether

Despite the availability of a large number of alkyl tetrahydrofurfuryl ethers that have a wide range of applications, pure bis(tetrahydrofurfuryl) ether (BTHFE) has not been previously synthesized. Here, we report the synthesis of BTHFE (consisting of the RR, SS, and meso stereoisomers) at greater than 99 % purity from tetrahydrofurfuryl alcohol, using (tetrahydrofuran-2-yl)methyl methanesulfonate as an intermediate. Additionally, we demonstrate that BTHFE can be used as a non-volatile solvent in poly(3,4-propylenedioxythiophene)-based supercapacitors. Supercapacitor devices employing solutions of the ionic liquid 1-ethyl-3-methyl-imidizolium bis(trifluoromethylsulfonyl)imide in BTHFE display similar performances to those prepared by using the neat ionic liquid as an electrolyte, although solution-based devices exhibit a somewhat higher resistance.
Myocardial Mechanical, Ionic, Metabolic and Electrical Correlates in Response to Coronary Ischemia

The experiments to be presented were carried out employing the blood perfused dog Langendorff preparation. Myocardial performance was monitored using a strain gauge arch sewn to the wall of the ventricle with the preload set at about 130% of resting fiber length. Blood was diverted from the coronary inflow and coronary outflow lines and passed through a Guyton A-VO2 analyzer to continuously monitor coronary arteriovenous O2 difference and the blood then returned to the dog which perfused the isolated heart. The A-VO2 difference of the preparation at normal coronary blood flow was approximately 7 to 8 volumes percent. This along with coronary blood flow provided us with a continuous measurement of myocardial oxygen consumption. Myocardial arteriovenous blood potassium difference was continuously monitored using an on-line automated flame photometery system. To obtain measurements of the myocardial transmembrane potential, the technique of PRUETT and WOOD was employed. This is a technique in which a micromanipulator is mounted on a small plastic disc and the disc in turn sewn to the wall of the ventricle. Under any given experimental condition several myocardial cells were penetrated for potential measurements. The potentials were analyzed primarily in terms of the first derivative and the duration of the action potential plateau. Unless indicated otherwise heart rate was maintained constant through external pacing. Coronary perfusion pressure was altered by a clamp on the coronary inflow line.
Retinopathy of Prematurity

Retinopathy of prematurity (ROP) is a proliferative disorder involving the developing vasculature of premature infants that can result in retinal detachment and blindness. Timely screening for ROP and prompt treatment of severe ROP can decrease the prevalence of unfavorable retinal structural and poor visual outcome. The criteria for treatment of ROP has evolved from classic threshold ROP, as defined in the Multicenter Trial of Cryotherapy for ROP, to type 1 prethreshold ROP, as defined in the Early Treatment of ROP randomized trial, with incremental improvement in the overall treatment outcome. The mode of treatment has also transitioned from the use of cryotherapy to laser photocoagulation. The mouse model of oxygen-induced retinopathy has elucidated the pathogenesis of ROP and led to new interventions and screening approaches. Pharmacotherapy using the intravitreal injection of bevacizumab, an antibody to vascular endothelial growth factor, appears to be superior to laser photocoagulation for type 1 ROP in zone I but equivalent to laser therapy for type 1 ROP in zone II. However, the systemic risks associated with bevacizumab are uncertain. New screening algorithms based on the rate of postnatal growth of at risk infants are being developed in order to reduce the percentage of infants screened while maintaining efficacy. Digital fundus photography has a high degree of accuracy for the detection of treatment warranting ROP. Validation studies for the reliability and accuracy of telemedicine for ROP are under way.
Nanometallic Particles for Oligodynamic Microbial Disinfection

Publisher Summary This chapter reveals that nanotechnology has enabled the development of a new class of atomic scale materials capable of fighting waterborne disease-causing microbes. Oligodynamic metallic nanoparticles such as silver, copper, zinc, titanium, nickel, and cobalt are among the most promising nanomaterials with bactericidal and viricidal properties owing to their charge capacity, high surface-to-volume ratios, crystallographic structure, and adaptability to various substrates for increased contact efficiency. Given the cost and known problems with disinfection by-products of conventional chemical disinfection systems, nanoscale oligodynamic disinfection could serve as a viable alternative for point-of-use (POU) applications. This chapter covers the synthesis, impregnation onto various substrates, and application of antimicrobial metallic nanoparticles for water disinfection.
Chapter 19 – Manganese-Induced Oxidative Stress

Some regions of the brain, especially the basal ganglia, are particularly susceptible to excess manganese, and excessive accumulation there may result in the neurodegenerative disorder manganism. Research efforts into the poorly understood molecular mechanisms by which elevated manganese levels in the brain could cause neuronal dysfunction and death have increased. The most popular model suggests that excess manganese causes imbalance of the mitochondrial redox activity, which may then lead to proliferation of cellular oxidative stress (OS). Such a mitochondrial event may be a key step in the demise of the affected central nervous system (CNS) cells. This chapter discusses the sources, absorption, and transportation of manganese, as well as the nature of manganese toxicities reported in humans. The chapter also addresses the mechanistic hypothesis that manganese induces OS in areas of the brain where it accumulates most, thereby leading to the onset of neurotoxicity.
Assessment of the Interrater Reliability of the Congress of Neurological Surgeons Microanastomosis Assessment Scale.

Background The potential for simulation-based learning in neurosurgical training has led the Congress of Neurosurgical Surgeons to develop a series of simulation modules. The Northwestern Objective Microanastomosis Assessment Tool (NOMAT) was created as the corresponding assessment tool for the Congress of Neurosurgical Surgeons Microanastomosis Module. The face and construct validity of the NOMAT have been previously established. Objective To further validate the NOMAT by determining its interrater reliability (IRR) between raters of varying levels of microsurgical expertise. Methods The NOMAT was used to assess residents' performance in a microanastomosis simulation module in 2 settings: Northwestern University and the Society of Neurological Surgeons 2014 Boot Camp at the University of Indiana. At Northwestern University, participants were scored by 2 experienced microsurgeons. At the University of Indiana, participants were scored by 2 postdoctoral fellows and an experienced microsurgeon. The IRR of NOMAT was estimated by computing the intraclass correlation coefficient using SPSS v22.0 (IBM, Armonk, New York). Results A total of 75 residents were assessed. At Northwestern University, 21 residents each performed microanastomosis on 2 model vessels of different sizes, one 3 mm and one 1 mm. At the University of Indiana, 54 residents performed a single microanastomosis procedure on 3-mm vessels. The intraclass correlation coefficient of the total NOMAT scores was 0.88 at Northwestern University and 0.78 at the University of Indiana. Conclusion This study indicates high IRR for the NOMAT. These results suggest that the use of raters with varying levels of expertise does not compromise the precision or validity of the scale. This allows for a wider adoption of the scale and, hence, a greater potential educational impact.
Neutrophil Integrins and Matrix Ligands and NET Release.

Neutrophils are motile and responsive to tissue injury and infection. As neutrophils emigrate from the bloodstream and migrate towards a site of affliction, they encounter the tissue extracellular matrix (ECM) and thereby engage integrins. Our laboratory studies the neutrophilic response to the fungal pathogen Candida albicans either in the filamentous state of the microbe or to the purified pathogen-associated molecular pattern, β-glucan. We have gained an appreciation for the role of integrins in regulating the neutrophil anti-Candida response and how the presence or absence of ECM can drive experimental outcome. The β2 integrin CR3 (Complement Receptor 3; αMβ2; Mac-1; CD11b/CD18) plays an important role in fungal recognition by its ability to bind β-glucan at a unique lectin-like domain. The presence of ECM differentially regulates essential neutrophil anti-fungal functions including chemotaxis, respiratory burst, homotypic aggregation, and the release of neutrophil extracellular traps (NETosis). We have shown that NET release to C. albicans hyphae or immobilized β-glucan occurs rapidly and without the requirement for respiratory burst on ECM. This is in contrast to the more frequently reported mechanisms of NETosis to other pathogens without the context of ECM which occur after a prolonged lag period and require respiratory burst. As expected for an ECM-dependent phenotype, NETosis and other neutrophil functions are dependent on specific β1 integrins. The focus of this review is the role of ECM ligation by neutrophil integrins as it pertains to host defense functions with an emphasis on lessons we have learned studying the anti-Candida response of human neutrophils.
I Had to Get Cancer to Become a More Empathetic Doctor

I am 80 and a retired infectious diseases physician. I have always thought of myself as caring, compassionate, and warm. I thought I knew what patients were feeling, but only now that I have a life...
Allylation and Alkylation of Biologically Relevant Nucleophiles by Diallyl Sulfides

Allyl sulfides are bioactive phytochemicals found in garlic, onion, and other members of the genus Allium. Here we showed that diallyl disulfide and diallyl trisulfide can transfer allyl side chains to low molecular weight thiols. Diallyl monosulfide is inert with respect to this allyl transfer reaction. On the other hand, diallyl sulfone, a known metabolite of diallyl monosulfide, alkylates both amines and thiols under physiologically relevant conditions via isomerization to an electrophilic vinyl sulfone.
Abstract A85: Metabolic wiring dictates GOT1 dependency in pancreatic cancer

Pancreatic Ductal Adenocarcinoma (PDA) is an extremely aggressive disease. The 5-year survival rate is a shockingly low 8%, a number that has hardly increased in the last 30 years. This owes in large part to the fact that effective treatment options for PDA do not exist. A hallmark of pancreatic cancers, and one that contributes to this resistance, is the metabolic environments that they create locally and systemically. Pancreatic tumors exist in a highly inflammatory environment, are under severe physical and oxidative stress, and do not have functional vasculature to deliver oxygen and nutrients. Despite these unfavorable circumstances for growth, these tumors thrive. Clearly metabolism is rewired in unique ways to facilitate survival and growth in this unusual and hostile environment. Based on this framework, we have been mapping the metabolic pathways in PDA to identify aspects of metabolism that are unique or highly over-utilized. Previously, we defined a novel pathway used by PDA cells to maintain redox balance via NADPH generation. Inhibition of a central enzyme in this pathway, cytosolic aspartate aminotransferase (GOT1), dramatically impairs growth in vitro and in vivo. Importantly, these effects can be completely reversed by supplying PDA cells with antioxidants. We also found that this pathway is regulated by mutant KRAS in PDA and, accordingly, non-transformed pancreatic epithelial cells are unresponsive to GOT1 inhibition. Subsequently, we interrogated GOT1 dependence in another KRAS transformed cancer, colon cancer, and found that they, like non-transformed cells, do not respond to GOT1 inhibition. Through a detailed series of metabolomics and functional assays, we ultimately found that colon cancers bypass GOT1 dependence favoring flux through ATP citrate lyase (ACL), a mechanism dictated not at the transcriptional level but by the metabolic wiring in these cells. Furthermore, ACL knockdown dramatically sensitizes colon cancer cells to GOT1 inhibition mediated redox and growth defects. In addition to revealing novel aspects of tissue specific metabolic pathway regulation, this analysis also illustrated novel metabolic dependencies that can be exploited for therapeutic gain. Citation Format: Costas A. Lyssiotis.{Authors}. Metabolic wiring dictates GOT1 dependency in pancreatic cancer. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2016 May 12-15; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2016;76(24 Suppl):Abstract nr A85.
A polarimeter for protons between 100 and 800 MeV

Abstract A carbon polarimeter has been built and used for protons with energies between 100 and 800 MeV. The polarimeter accepts scatters in the carbon analyzer up to 30° lab , with negligible instrumental asymmetries. Drift chambers 60 cm square were used with a system for resolving the left-right ambiguity inherent in drift chambers. A hardware system for rejecting small angle scatters is described. The polarimeter is routinely used to measure spin transfer parameters with a typical precision of ±0.03 in about eight hours of low-duty LAMPF beam.
Derrida and the Question of Philosophy’s History

Hegel remarks somewhere that all facts and personages of great importance in world history occur, as it were, twice. He forgot to add: the first time as tragedy, the second as farce. (Karl Marx, The Eighteenth Brumaire of Louis Bonaparte)1
Microprecipitation and δ 18 O analysis of phosphate for paleoclimate and biogeochemistry research

Abstract Phosphate oxygen isotope ratios provide a powerful tool for paleoclimate reconstruction and the study of phosphorus biogeochemistry in aquatic systems. The temperature dependent offset between the oxygen isotope composition of phosphate and water in biogenic minerals and in solutions has been used extensively in paleoclimate research and the study of phosphorus cycling in aquatic and soil environments. Sample sizes are small in many applications, e.g., serial sampling of mammalian tooth enamel for paleoseasonality studies, the use of conodont elements for climate and ocean δ 18 O reconstruction, or the isolation and analysis of dissolved phosphate from marine and freshwater environments in biogeochemistry studies. This has pushed the development of techniques that allow for processing and analysis of a few micromoles of phosphate. Current approaches to phosphate oxygen isotopic composition (δ 18 O p ) determination require purification of phosphate as silver phosphate (Ag 3 PO 4 ). The techniques for the final precipitation of Ag 3 PO 4 fall into two categories: slow vs. rapid microprecipitations. We have tested both and identify artifacts that impact measured δ 18 O p values resulting from commonly used methods for rapid Ag 3 PO 4 precipitation. In particular, commonly used methods are prone to (a) incomplete precipitation of phosphate, with associated isotopic fractionation, and (b) the production of silver oxide contaminants whose oxygen isotope composition is sensitive to the δ 18 O of water used to prepare the precipitation reagent solution. These artifacts are commonly on the order of 0.5 to 2‰, which is subtle enough to go undetected in many studies, but large enough to cause errors in temperature estimates on the order of 2–8 °C. Slow microprecipitations lead to complete precipitation of phosphate without contaminating O-bearing phases. We develop a rapid precipitation technique that avoids the problems noted above. Both the slow microprecipitation and the rapid microprecipitation developed herein lead to δ 18 O p measurements that are indistinguishable from those made on conventional large-batch precipitations of Ag 3 PO 4 .
Dynamic Modeling of Conditional Quantile Trajectories, with Application to Longitudinal Snippet Data

ABSTRACTLongitudinal data are often plagued with sparsity of time points where measurements are available. The functional data analysis perspective has been shown to provide an effective and flexible approach to address this problem for the case where measurements are sparse but their times are randomly distributed over an interval. Here we focus on a different scenario where available data can be characterized as snippets, which are very short stretches of longitudinal measurements. For each subject the stretch of available data is much shorter than the time frame of interest, a common occurrence in accelerated longitudinal studies. An added challenge is introduced if a time proxy that is basic for usual longitudinal modeling is not available. This situation arises in the case of Alzheimer's disease and comparable scenarios, where one is interested in time dynamics of declining performance, but the time of disease onset is unknown and chronological age does not provide a meaningful time reference for lon...
Injury risk factors to farm and ranch operators in the Central United States

Background This study focused on risk factors for serious injuries in farm and ranch operators in the central United States. Methods The Central States Center for Agricultural Safety and Health, in collaboration with the National Agricultural Statistics Service, sent mail surveys to 6953, 6912, and 6912 farms/ranches in 2011-2013, respectively, covering seven Midwestern states. Results The average survey response rate was 35%. The average annual incidence rate (injuries/100 workers) was 6.91 for all injuries and 2.40 for serious injuries. Univariate analyses determined several demographic and farm production-related risk factors for serious injury. Adjusted analysis showed a greater risk of serious injury for operators of age 45-54 years (vs. 65 and higher), those who worked 75-99% of their time (vs. less time), and those who operated larger land areas (vs. smaller). Conclusion The identified risk factors should be considered when targeting injury prevention programs.
Purely sequential bounded-risk point estimation of the negative binomial mean under various loss functions: one-sample problem

A negative binomial (NB) distribution is useful to model over-dispersed count data arising from agriculture, health, and pest control. We design purely sequential bounded-risk methodologies to estimate an unknown NB mean $$\mu (>0)$$ under different forms of loss functions including customary and modified Linex loss as well as squared error loss. We handle situations when the thatch parameter $$\tau (>0)$$ may be assumed known or unknown. Our proposed methodologies are shown to satisfy properties including first-order asymptotic efficiency and first-order asymptotic risk efficiency. Summaries are provided from extensive sets of simulations showing encouraging performances of the proposed methodologies for small and moderate sample sizes. We follow with illustrations obtained by implementing estimation strategies using real data from statistical ecology: (1) weed count data of different species from a field in Netherlands and (2) count data of migrating woodlarks at the Hanko bird sanctuary in Finland.
Evaluation of three imidazolinone herbicides for control of yellow and purple nutsedge in woody and herbaceous landscape plants.

Abstract Foliar-applications of Pursuit applied at 280 and 560 g/ha (4 and 8 oz/A) provided 97% purple nutsedge and 86% yellow nutsedge control at 560 g/ha (8 oz/A). Foliar-applications of Cadre ap...
Hypomethylating Agents in Combination With Immune Checkpoint Inhibitors in Acute Myeloid Leukemia and Myelodysplastic Syndromes

Immune checkpoint inhibitors, as single-agent therapy, have shown modest clinical efficacy in the treatment of acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). As has been successfully shown in other less immunogenic hematologic malignancies, rationally designed combination approaches may be more effective than single-agent checkpoint inhibitors, and may be the approach to pursue in AML/MDS. Hypomethylating agents (HMAs) such as azacitidine, while enhancing anti-tumor immune response, concurrently dampen immune response by upregulating inhibitory immune checkpoint molecule expression. Immune checkpoint molecule upregulation may be an important mechanism of azacitidine resistance. These findings have resulted in multiple clinical trials combining HMAs with immune checkpoint blockade. Clinical trial data have shown encouraging response rates and durable responses without resorting to stem cell transplant. In this review, we discuss preclinical data supporting the use of these agents in combination, and focus on clinical and correlative data emerging from numerous clinical trials investigating HMA-immune checkpoint inhibitor combinations in AML/MDS.
Structural study of agmatine iminohydrolase from Medicago truncatula, the second enzyme of the agmatine route of putrescine biosynthesis in plants

Plants are unique eukaryotes that can produce putrescine (PUT), a basic diamine, from arginine via a three-step pathway. This process starts with arginine decarboxylase that converts arginine to agmatine. Then, the consecutive action of two hydrolytic enzymes, agmatine iminohydrolase (AIH) and N-carbamoylputrescine amidohydrolase, ultimately produces PUT. An alternative route of PUT biosynthesis requires ornithine decarboxylase that catalyzes direct putrescine biosynthesis. However, some plant species lack this enzyme and rely only on agmatine pathway. The scope of this manuscript concerns the structural characterization of AIH from the model legume plant, Medicago truncatula. MtAIH is a homodimer built of two subunits with a characteristic propeller fold, where five αββαβ repeated units are arranged around the fivefold pseudosymmetry axis. Dimeric assembly of this plant AIH, formed by interactions of conserved structural elements from one repeat, is drastically different from that observed in dimeric bacterial AIHs. Additionally, the structural snapshot of MtAIH in complex with 6-aminohexanamide, the reaction product analog, presents the conformation of the enzyme during catalysis. Our structural results show that MtAIH undergoes significant structural rearrangements of the long loop, which closes a tunnel-shaped active site over the course of the catalytic event. This conformational change is also observed in AIH from Arabidopsis thaliana, indicating the importance of the closed conformation of the gate-keeping loop for the catalysis of plant AIHs.
Promoting Mathematical Explorations through Children's Literature.

Children's tant vehicle to use when exploring various mathematical concepts (Whitin and Wilde 1992). Stories can help students understand the meaningful contexts that support mathematical thinking. They will see mathematics not as a prescribed set of algorithms to master but as a way of thinking about their world. Children' s literature presents a nonthreatening avenue to test out current notions about important mathematical concepts. The following two classroom scenarios occurred in Cassandra Gary's first-grade classroom in Irmo, South Carolina. She used two pieces of literature, The Line-up Book (Russo 1986) and The Doorbell Rang (Hutchins 1986), on two different occasions as springboards for mathematical thinking. The first book enabled her students to explore the concept of length, and the second story reinforced the concept of partitioning. Although each book has a mathematical dimension, it is important to remember that they are, first and foremost, good pieces of literature. Each book is a unique literary experience and should be enjoyed for its own sake first. Gary read each story to the class several times and let the students voice their personal, spontaneous observations and predictions. By so doing, the integrity of the literature is respected and preserved.
A Solid-State Gas Generator Actuated Deorbiter for CubeSats

A solid-state actuated deorbiter for SmallSats and CubeSats has been developed, the Solid State Inflation Balloon deobriter (SSIB). The device reduces orbital lifetime by increasing the frontal surface area of spacecraft and thereby increasing drag in the upper atmosphere Surface area is increased by inflating a gossamer inflation balloon and this method can reduce orbital lifetime by over an order of magnitude, dependent on the size of the balloon. The balloon in inflated with a custom MEMS device, the Solid-State Gas Generator (SSGG), which creates dry Nitrogen gas on-demand by thermally decomposing Sodium Azide crystals. The SSGG consists of an array of individually addressable micro-heaters which provide the thermal energy to generate gas. The SSIB was developed and prototyped at the University of Arkansas under a development grant from NASA. Prototypes were tested at NASA Ames’ Research Center and successfully passed thermal, vibrational, shock, and vacuum deployment testing.
How Machine Learning Will Transform Biomedicine

This Perspective explores the application of machine learning toward improved diagnosis and treatment. We outline a vision for how machine learning can transform three broad areas of biomedicine: clinical diagnostics, precision treatments, and health monitoring, where the goal is to maintain health through a range of diseases and the normal aging process. For each area, early instances of successful machine learning applications are discussed, as well as opportunities and challenges for machine learning. When these challenges are met, machine learning promises a future of rigorous, outcomes-based medicine with detection, diagnosis, and treatment strategies that are continuously adapted to individual and environmental differences.
Squigonometry: Trigonometry in the p-Norm

We can define the traditional trigonometric functions in several different ways: via differential equations, via an arclength definition on the unit circle x2 + y2 = 1, or via an analytic approach. In this project, we adapt these approaches to define analogous functions for a unit squircle |x|p + |y|p = 1, p ≥ 1. As we develop these functions using only elementary calculus, we will ponder the importance and role of π, and glimpse some very deep ideas in elliptic integrals, special functions, non-Euclidean geometry, number theory, and complex analysis.
Patient DNA cross-reactivity of CDC SARS-nCoV2 extraction control leads to potential false negative results

Abstract Detecting RNA viruses such as SARS-nCoV2 requires careful handling of inherently labile RNA. Molecular tests incorporate controls to verify the presence of intact RNA and ensure that all steps of an assay have succeeded. The Centers for Disease Control and Prevention (CDC)-specified extraction control recognizes both reverse-transcribed RNA and human genomic DNA. Human DNA copurified from nasopharyngeal swabs by multiple clinically-used RNA extraction approaches, is sufficient for a strong “extraction control positive” signal using the CDC design, creating the potential for false-negative results. Moreover, DNA cross-reactivity precludes control of RNA integrity in real-world samples. A properly designed control that monitors sample collection, extraction, reverse transcription, and qPCR processes is essential and demonstrated here. This control can be immediately implemented in the CDC testing workflow. One Sentence Summary A widely-used COVID-19 diagnostic is misdesigned and can report “assay okay, virus not detected” from virus-containing samples – but it’s fixable
Immunomodulatory Dual-Sized Microparticle System Conditions Human Antigen Presenting Cells Into a Tolerogenic Phenotype In Vitro and Inhibits Type 1 Diabetes-Specific Autoreactive T Cell Responses.

Current monotherapeutic agents fail to restore tolerance to self-antigens in autoimmune individuals without systemic immunosuppression. We hypothesized that a combinatorial drug formulation delivered by a poly-lactic-co-glycolic acid (PLGA) dual-sized microparticle (dMP) system would facilitate tunable drug delivery to elicit immune tolerance. Specifically, we utilized 30 µm MPs to provide local sustained release of granulocyte-macrophage colony-stimulating factor (GM-CSF) and transforming growth factor β1 (TGF-β1) along with 1 µm MPs to facilitate phagocytic uptake of encapsulated antigen and 1α,25(OH)2 Vitamin D3 (VD3) followed by tolerogenic antigen presentation. We previously demonstrated the dMP system ameliorated type 1 diabetes (T1D) and experimental autoimmune encephalomyelitis (EAE) in murine models. Here, we investigated the system's capacity to impact human cell activity in vitro to advance clinical translation. dMP treatment directly reduced T cell proliferation and inflammatory cytokine production. dMP delivery to monocytes and monocyte-derived dendritic cells (DCs) increased their expression of surface and intracellular anti-inflammatory mediators. In co-culture, dMP-treated DCs (dMP-DCs) reduced allogeneic T cell receptor (TCR) signaling and proliferation, while increasing PD-1 expression, IL-10 production, and regulatory T cell (Treg) frequency. To model antigen-specific activation and downstream function, we co-cultured TCR-engineered autoreactive T cell "avatars," with dMP-DCs or control DCs followed by β-cell line (slox5) target cells. For G6PC2-specific CD8+ avatars (clone 32), dMP-DC exposure reduced Granzyme B and dampened cytotoxicity. GAD65-reactive CD4+ avatars (clone 4.13) exhibited an anergic/exhausted phenotype with dMP-DC presence. Collectively, these data suggest this dMP formulation conditions human antigen presenting cells toward a tolerogenic phenotype, inducing regulatory and suppressive T cell responses.
Impact of Community Structure on Consensus Machine Learning.

Consensus dynamics support decentralized machine learning for data that is distributed across a cloud compute cluster or across the internet of things. In these and other settings, one seeks to minimize the time $\tau_\epsilon$ required to obtain consensus within some $\epsilon>0$ margin of error. $\tau_\epsilon$ typically depends on the topology of the underlying communication network, and for many algorithms $\tau_\epsilon$ depends on the second-smallest eigenvalue $\lambda_2\in[0,1]$ of the network's normalized Laplacian matrix: $\tau_\epsilon\sim\mathcal{O}(\lambda_2^{-1})$. Here, we analyze the effect on $\tau_\epsilon$ of network community structure, which can arise when compute nodes/sensors are spatially clustered, for example. We study consensus machine learning over networks drawn from stochastic block models, which yield random networks that can contain heterogeneous communities with different sizes and densities. Using random matrix theory, we analyze the effects of communities on $\lambda_2$ and consensus, finding that $\lambda_2$ generally increases (i.e., $\tau_\epsilon$ decreases) as one decreases the extent of community structure. We further observe that there exists a critical level of community structure at which $\tau_\epsilon$ reaches a lower bound and is no longer limited by the presence of communities. We support our findings with empirical experiments for decentralized support vector machines.
Bayes and Popper

There has been little direct confrontation between Bayesians and Popperians. No doubt Popper views the Bayesian approach as a species of inductivism and therefore not to be countenanced. But while Bayesians evaluate hypotheses primarily in terms of their probability, their position rests on no obscure ‘principle of induction’, but on Bayes’ rule. For a Bayesian, ‘learning from experience’ can only mean modifying prior probabilities by conditionalizing on observed experimental outcomes. On the other hand, the implications of Bayes’ rule for scientific method often have a distinctly Popperian ring, fostering the suspicion that many of the differences between the two schools are, at worst, merely verbal, and, at best, but differences of emphasis. We shall have something to say about this, but, in a more positive vein, we wish to explore here the extent to which Bayesian and Popperian viewpoints can be reconciled.
The patient experience in a cytopathologist-performed ultrasound-guided fine needle aspiration clinic: potential complications and feedback

Introduction The number of fine needle aspirations (FNAs) being performed by cytopathologists has been increasing in recent years. As the advantages of cytopathologist-performed FNAs such as more frequent sample adequacy, appropriate specimen triage for ancillary testing, and optimal turnaround time are recognized, little has been reported from the patient’s perspective. This study aimed to characterize the patient experience in a cytopathologist-run FNA clinic. Materials and methods Patient responses were collected as part of routine post-procedure telephone follow-up. Patient demographics, clinical history, reported complications, general feedback, and procedural data were documented. Results Of 303 patients, 126 (41.6%) were available for follow-up. One or more minor complications including pain or soreness, swelling, and bruising at the biopsy site was reported by 46 patients (36.5%). No patients required additional medical treatment. For the patients who were unavailable for telephone follow-up, review of medical records showed 158 (89.3%) had at least one subsequent clinical visit and 1 reported bruising at the FNA site. Overall, none of the 284 patients with available follow-up information reported any major complications related to the FNA procedure. All patients had a generally positive experience, specifically citing the cytopathology team’s thorough explanation of the procedure, cytopathologist ability to address questions and concerns, and professionalism. Conclusions Overall, the patient experience at our cytopathologist-run FNA clinic was positive. Minor procedure-related complications were reported in a subset of patients. No major complications were recorded, underscoring the safety of this procedure.
Research on Startup Control Strategy of Inverter Hybrid Cascade LCC-MMC UHVDC Transmission System

A novel inverter hybrid cascaded LCC-MMC UHVDC system is studied in this paper. The rectifier of the system is consisted of LCC; the inverter is consisted of LCC and parallel MMCs. Based on the analysis of the coordinated control strategy of LCCs and MMCs, a detailed startup control strategy for the inverter hybrid cascaded LCC-MMC UHVDC system is proposed. The startup control strategy is divided into 4 periods: MMC uncontrolled charging period, MMC unlocking period, DC loop closing period and power boosting period. In order to verify the performance of the proposed startup strategy, a model of the inverter hybrid cascaded LCC-MMC UHVDC system based on detailed engineering parameters was established in the PSCAD/EMTDC environment. The simulation results show that the system has a good dynamic performance except that MMCs may exchange power during power boosting period. However, after adopting the optimized startup strategy, the power exchange between MMCs has been significantly suppressed.
Clinical manifestations, risk factors, and prognostic factors of cytomegalovirus enteritis.

BACKGROUND To comprehensively analyze the risk factors, clinical characteristics, outcomes, and prognostic factors of Cytomegalovirus (CMV) enteritis. METHODS This retrospective cohort study enrolled patients who had undergone pathological examinations for CMV enteritis. They were divided into CMV and non-CMV groups according to immunohistochemistry staining results. The risk factors, clinical presentations, endoscopic features, treatments, outcomes, and prognostic factors of CMV enteritis were then analyzed. RESULTS Forty-two patients (18 CMV, 24 non-CMV group) were included in the study. Major clinical presentations in the CMV group included gastrointestinal bleeding (72.2%), abdominal pain (55.6%), and fever (33.3%); ulcers (72.2%) were the most common endoscopic findings. In-hospital and overall mortality rates were 27.8% and 38.9%, respectively; and longer hospital stays and higher overall mortality rates were observed. Radiotherapy and C-reactive protein levels were prognostic factors for in-hospital mortality. The risk factors for CMV enteritis included immunocompromised status (p = 0.013), steroid use (p = 0.014), shock (p = 0.031), concurrent pneumonia (p = 0.01), antibiotic exposure (p < 0.001), radiotherapy (p = 0.027), chronic kidney disease (p = 0.041), and CMV colitis (p = 0.031). CONCLUSIONS Physicians should pay attention to the characteristics of CMV enteritis in high-risk patients to make an early diagnosis and potentially improve the clinical outcome.
Working: The Role of Occupational Epidemiology.

The COVID-19 pandemic redemonstrated the importance of work as a determinant of health. Extant disparities were accentuated, as the workforce was divided into the roughly 50% who could safely work from home and those who could not. With the spotlight on work, one might wonder where all the occupational epidemiologists have gone. To answer, we point to diminished research support and more limited workplace access that have led many to shift away from a focus on workers towards other vulnerable populations. We build on the renewed interest in work as a driver of health and inequality during the pandemic to highlight contributions of occupational epidemiology to public health. Consider: (1) etiologic studies of chronic disease based on employment records to define cohorts and reconstruct long-term exposure; (2) studies of hypothetical interventions particularly appropriate for evaluating potential regulations to reduce workplace exposures; and (3) studies of disparities that take advantage of work as a potential source of social stratification and economic opportunity. As we have learned during COVID-19, workplaces can become venues for public health messaging and delivering interventions to enumerated populations of adults. By starting with COVID-19 prevention policies, we have a chance to protect public health and rethink work.