cssi/SciSciGPT-SciSciNet huggingface dataset:
A Sparse-Data-Driven Approach for Fault Location in Transmission Networks

This paper proposes an efficient wide-area fault location method to find single- and double-fault locations in transmission networks. Unlike earlier conventional fault location methods, we only require capturing the phasors in a limited number of buses by phasor measurement units (PMUs). The measured voltage phasors and impedance matrix of the system yield an underdetermined system of equations that can be solved by sparse representation recovery methods. The solution gives a sparse fault current vector whose nonzero elements assign the probable faulty zones. For areas with no faults, current phasors measured by PMUs are sufficiently accurate to calculate the adjacent bus voltages. The new calculated voltages and the measured data are used to estimate the faulted lines accurately. The substitution theorem and least-squares method are used to calculate the differences between pre- and during-fault voltages, and currents in both ends of the faulted lines. Transmission line equations developed based on distributed line parameters are then used to pinpoint the fault location along each faulted line. We demonstrate the satisfactory performance of our noniterative methodology and its low computational load using simulations of the IEEE 39-bus test system with noisy measurements, multiple combinations of all fault types, and different resistances.
Parathyroid hormone mediates changes in calcium transport in uremic rat brain synaptosomes

In previous studies, we showed that Ca2+ transport by both Na+ gradient-stimulated Ca2+ uptake and ATP-stimulated Ca2+ uptake was increased in synaptosomes from uremic rat brain. The possible role of parathyroid hormone (PTH) in this observation was investigated by performing Ca2+ transport studies in synaptosomes by these two mechanisms. Studies were performed in vesicles from rats that were either normal, uremic, uremic parathyroidectomized (PTX-U), or uremic parathyroidectomized but treated with PTH. In uremic rats, transport by both Na+ gradient-stimulated Ca2+ uptake and ATP-stimulated Ca2+ uptake was increased by 30 and 47%, respectively, whereas uptake was returned to base line in synaptosomes from PTX-U rats. Additionally, the administration of PTH to PTX-U rats resulted in a significant increase (P less than 0.001) of 36 and 41%, respectively, above the values observed in PTX-U rats. To determine whether the increased accumulation of Ca2+ in synaptosomes in uremia was a result of PTH alone and/or...
Evaluation of a new blood autotransfusion device

A new autotransfusion device was evaluated in dogs. The device uses citrate phosphate dextrose as the blood anticoagulant and automatically delivers the agent in a ratio approximating that found in banked blood. Bleeding, aspiration, and autotransfusion of approximately 3 estimated blood volumes produced small changes in hematologic and coagulation studies. Blood electrolytes stayed within normal ranges. Activated clotting times stayed within normal range after autotransfusion of 2 blood volumes but increased slightly after 3 blood volume transfusions. No significant histopathologic changes were found in any organ system. Rapid infusion of citrated blood causes myocardial depression, which can be reversed by giving calcium. Overall performance of the device was excellent, suggesting further documentation in a clinical setting and evaluation with human blood.
Developing constitutive model parameters via a multi-scale approach

Computing the mechanical response of materials requires accurate constitutive descriptions, especially their plastic behavior. Furthermore, the ability of a model to be used as a predictive, rather than a descriptive, tool motivates the development of physically based constitutive models. This work investigates combining a homogenized viscoplastic self-consistent (VPSC) approach to reduce the development time for a high-resolution viscoplastic model based on the fast Fourier transform (FFT). An optimization scheme based on a least-squares algorithm is presented. The constitutive responses of copper, interstitial-free steel, and pearlite are investigated, and the model parameters are presented. Optimized parameters from the low-fidelity model provide close agreement (<2 MPa, ~1 % error) with stress-strain data at low strains (<10 %) in the high-fidelity FFT model. Simple adjustments to constitutive law parameters bring the FFT stress-strain curve in alignment with experimental data at strains greater than 10 %. A two-phase constitutive law is developed for a pearlitic steel using a single stress-strain curve, supplemented by data for the constituent phases. Sources of error and methods of using material information are discussed that lead to optimal estimates of initial parameter values.
New species and nomenclatural notes in Pabstiella (Orchidaceae: Pleurothallidinae) from Brazil

Two new species, Pabstiella calimanii and Pabstiella recurviloba, are described and illustrated. One new combination, Pabstiella deltoglossa, is proposed. Eight species and one variety are proposed as synonyms. They are listed in alphabetical order: Pabstiella avenacea, P. leucosepala and Pleurothallis mathildae as synonyms of Pabstiella elegantula; Pabstiella cipoensis as a synonym of P. pristeoglossa; Pleurothallis magnicalcarata and Pabstiella mentigera as synonyms of P. calcarata; Pabstiella pterophora and Pleurothallis pterophora var. minor as synonyms of Pabstiella leucopyramis, and Pabstiella podoglossa as a synonym of P. versicolor. Lectotypes are selected for four species: Pleurothallis avenacea, P. mentigera, P. pristeoglossa and P. pterophora. An epitype is selected for Pleurothallis pristeoglossa. Illustrations and taxonomic discussions are also provided.
The Role of Mitochondrial Metabolism and Redox Signaling in Iron Deficiency Anemia

Several clinical observations illustrate the link between iron and erythropoietin (EPO)-mediated signaling in committed erythroid progenitor cells. In iron deficiency anemia (IDA), erythropoiesis is blocked despite increased serum EPO concentrations. Intravenous iron improves the effectiveness of exogenous EPO in patients with EPO-refractory anemia of chronic disease. These clinical observations suggest that iron dominantly regulates EPO-receptor signaling. However, the mechanism of this iron-mediated signaling remains unclear. We recently demonstrated that 1) the aconitases, multifunctional iron-sulfur cluster proteins that convert citrate into isocitrate are essential in the iron- EPO-signaling pathway in erythroid progenitor cells, and that 2) isocitrate, the product of aconitase, can enhance the effectiveness of EPO during iron deficiency in vitro and in mice with IDA and in rats with the anemia of chronic inflammation. These observations suggest that isocitrate, or its derivatives that synergize with erythropoiesis stimulating agents, have important therapeutic application in the treatment of anemia. New data shows that cellular iron restriction regulates mitochondrial oxygen consumption rates (OCR) differentially over time during erythropoiesis, suggesting a novel link between mitochondrial function and erythropoeisis. It is unknown how iron deficiency induced inhibition of mitochondrial aconitase (ACO2) regulates mitochondrial metabolism during RBC production. Pilot data show that ACO2 inhibition by cellular iron deprivation or pharmacological inhibition of ACO2 decreases mitochondrial respiratory rates (RRs) and alters reactive oxygen species (ROS) production. Further, isocitrate normalizes mitochondrial RRs and ROS and restores RBC production. Importantly, disruption of mitochondrial ROS generation with a mitochondrial-specific anti-oxidant blocks RBC production and a subset of oxidant generators promote erythropoiesis. Targeted reduction of ACO2 protein expression and enzyme activity in iron replete stably transduced K562 cells decreases OCRs. This confirms the link between ACO2 and mitochondrial metabolism in human erythroid cells. These data inform our overarching hypothesis that iron-restriction inhibits ACO2, thereby inhibiting mitochondrial metabolism, resulting in the loss of a mitochondrial ROS signal that is required for erythropoiesis. The loss of this critical mitochondrial ROS signal inhibits the EPO signaling that is required for RBC production. These data also suggest that ACO2 is an iron-sensing regulator of mitochondrial metabolism and ROS signaling. Disclosures No relevant conflicts of interest to declare.
Cranial nerve involvement in Charcot-Marie-Tooth Disease.

Abstract Background Charcot–Marie–Tooth Disease (CMT) is a rare disorder with less than 200,000 cases reported in the US every year, making diagnosis challenging. MR and CT imaging has become more common in the evaluation of CMT to identify areas of disease involvement. Case report A 27-year-old female from Guatemala with a past history of polio initially presented to the emergency room for necrotizing pneumonia. MRI images demonstrated smoothly enlarged, mildly enhancing trigeminal nerves. CT showed bony widening of the skull base foramina. The patient was noted to have atrophy and weakness of her extremities with decreased sensation, distal more than proximal, and pes cavus. An electromyogram demonstrated absent response in the right median, ulnar, peroneal, and tibial motor studies and bilateral radial and right sural sensory studies. MRI of the spine demonstrated smooth, symmetric enlargement and mild enhancement of the distal spinal nerve roots and cauda equine. Discussion CMT is a group of disorders with a wide range of clinical presentations and abnormalities. Cranial nerve involvement is infrequently described in CMT 1A. In our case and prior studies, there does not appear to be a correlation between cranial nerve involvement and symptoms. Trigeminal neuralgia has been described in patients in CMT, but is not common and was not seen in our patient despite abnormal trigeminal nerve findings on imaging. Our patient also demonstrated involvement of the facial nerve without facial muscle weakness. Clinical features are key in distinguishing CMT 1A from other forms of HMSN.
Validation of a parametric finite element human femur model.

ABSTRACTObjective: Finite element (FE) models with geometry and material properties that are parametric with subject descriptors, such as age and body shape/size, are being developed to incorporate population variability into crash simulations. However, the validation methods currently being used with these parametric models do not assess whether model predictions are reasonable in the space over which the model is intended to be used. This study presents a parametric model of the femur and applies a unique validation paradigm to this parametric femur model that characterizes whether model predictions reproduce experimentally observed trends.Methods: FE models of male and female femurs with geometries that are parametric with age, femur length, and body mass index (BMI) were developed based on existing statistical models that predict femur geometry. These parametric FE femur models were validated by comparing responses from combined loading tests of femoral shafts to simulation results from FE models of t...
The dynamics of Wikipedia article revisions: an analysis of revision activities and patterns

To study the dynamics of revision activities of Wikipedia articles, we define 14 revision actions, annotate 6,950 revisions from 20 articles in four quality ranks (C, B, GA, and FA), and analyse revisions and revision actions in ten consecutive time periods. We identify four revision patterns: 1) revision actions at the sentence and link levels appear in similar paces; 2) the numbers of revision actions at sentence and link levels comparatively evenly grow with the article's age prior to the last time period; 3) the paces of media and reference-level actions tend to be lagged behind sentence and link-level actions; 4) before being promoted to the GA or FA rank, articles nominated to the GA or FA rank exhibit a significant rising pattern in amounts of revisions and revision actions. This pattern is validated with a larger set of 533 articles.
Revealing Abrupt and Spontaneous Ruptures of Protein Native Structure under picoNewton Compressive Force Manipulation

Manipulating protein conformations for exploring protein structure–function relationship has shown great promise. Although protein conformational changes under pulling force manipulation have been extensively studied, protein conformation changes under a compressive force have not been explored quantitatively. The latter is even more biologically significant and relevant in revealing protein functions in living cells associated with protein crowdedness, distribution fluctuations, and cell osmotic stress. Here we report our experimental observations on abrupt ruptures of protein native structures under compressive force, demonstrated and studied by single-molecule AFM-FRET spectroscopic nanoscopy. Our results show that the protein ruptures are abrupt and spontaneous events occurred when the compressive force reaches a threshold of 12–75 pN, a force amplitude accessible from thermal fluctuations in a living cell. The abrupt ruptures are sensitive to local environment, likely a general and important pathway ...
Functional promoter rs189037 variant of ATM is associated with decrease in lung diffusing capacity after irradiation for non-small-cell lung cancer.

Objective: Single-nucleotide polymorphisms (SNPs) in the ataxia telangiectasia-mutated gene ATM have been linked with pneumonitis after radiotherapy for lung cancer but have not been evaluated in terms of pulmonary function impairment. Here we investigated potential associations between SNPs in ATM and changes in diffusing capacity of the lung for carbon monoxide (DLCO) in patients with non-small-cell lung cancer (NSCLC) after radiotherapy. Methods: From November 1998 through June 2009, 448 consecutive patients with inoperable primary NSCLC underwent definitive (≥60 Gy) radiotherapy, with or without chemotherapy. After excluding patients with a history of thoracic surgery, radiation, or lung cancer; without DNA samples available for analysis; or without pulmonary function testing within the 12 months before and the 12 months after radiotherapy, 100 patients were identified who are the subjects of this study. We genotyped two SNPs of ATM previously found to be associated with radiation-induced pneumonitis (rs189037 and rs228590) and evaluated potential correlations between these SNPs and impairment (decreases) in DLCO by using logistic regression analysis. Results: Univariate and multivariate analyses showed that the AA genotype of ATM rs189037 was associated with decreased DLCO after definitive radiotherapy than the GG/AG genotypes [univariate coefficient, -0.122; 95% confidence interval (CI), -0.236 to -0.008; P = 0.037; and multivariate coefficient, -0.102; 95% CI, -0.198 to -0.005; P = 0.038]. No such correlations were found for rs228590 (univariate coefficient, -0.096; 95% CI, -0.208 to 0.017; P = 0.096). Conclusions: The AA genotype of ATM rs189037 was associated with higher risk of lung injury than were the GG/AG genotypes in patients with NSCLC treated with radiotherapy. This finding should be validated prospectively with other patient populations. Key words: Non-small-cell lung cancer; Radiation therapy; Ataxia telangiectasia-mutated gene; Single-nucleotide polymorphisms
Trends in Prescription Pain Medication Use by Race/Ethnicity Among US Adults With Noncancer Pain, 2000-2015.

Objectives. To examine national trends in the use of various pharmacological pain medication classes by race/ethnicity among the US pain population.Methods. We used data from the Medical Expenditure Panel Survey to conduct a nationally representative, serial cross-sectional study of the noninstitutionalized US adult population from 2000 to 2015. We identified adults with moderate or severe self-reported pain and excluded individuals with cancer. We used complex survey design to provide national estimates of the percentage of adults with noncancer pain who received prescription pain medications among 4 groups: non-Hispanic White, non-Hispanic Black, Hispanic or Latino, and other.Results. The age- and gender-adjusted percentage of prescription opioid use increased across all groups, with the greatest increase among non-Hispanic White individuals. By 2015, the percentage of non-Hispanic Black adults using opioids approximated that of non-Hispanic White adults—in 2015, approximately 23% of adults in these 2 g...
Development of a High-Resolution Laser Absorption Spectroscopy Method With Application to the Determination of Absolute Concentration of Gaseous Elemental Mercury in Air

Isotope dilution-cold-vapor-inductively coupled plasma mass spectrometry (ID-CV-ICPMS) has become the primary standard for measurement of gaseous elemental mercury (GEM) mass concentration. However, quantitative mass spectrometry is challenging for several reasons including (1) the need for isotopic spiking with a standard reference material, (2) the requirement for bias-free passive sampling protocols, (3) the need for stable mass spectrometry interface design, and (4) the time and cost involved for gas sampling, sample processing, and instrument calibration. Here, we introduce a high-resolution laser absorption spectroscopy method that eliminates the need for sample-specific calibration standards or detailed analysis of sample treatment losses. This technique involves a tunable, single-frequency laser absorption spectrometer that measures isotopically resolved spectra of elemental mercury (Hg) spectra of 6 1S0 ← 6 3P1 intercombination transition near λ = 253.7 nm. Measured spectra are accurately modeled...
CYGNSS data map flood inundation during the 2017 Atlantic hurricane season.

The 2017 Atlantic Hurricane Season was one of the most active and destructive on record, leading to significant flooding in many parts of the United States and the Caribbean. During flooding events such as these, there is an urgent need to quickly map in detail which areas have been severely affected, yet current satellite missions are not capable of sampling the global land surface at high enough spatio-temporal scales for flooding applications. Here, we demonstrate a novel approach to high-resolution flood mapping by repurposing data from the new NASA mission, CYGNSS. The CYGNSS multi-satellite constellation was designed for frequent temporal sampling of the ocean surface in the tropics. We demonstrate that CYGNSS data provide clear signals of surface saturation and inundation extent over land at higher spatio-temporal resolution than radiometers like SMAP. Using a simple thresholding technique, we are able to estimate that approximately 32,580 km2 of land area in Texas flooded during Hurricane Harvey, and approximately 7210 km2 of land area flooded in Cuba during Hurricane Irma, or about 7% of Cuba’s total area.
Stem Cells, Angiogenesis, and Neurogenesis in Tumors

Stem and progenitor cells promote repair of injured tissues by contributing to new blood vessel, muscle, and nerve formation. These same cells may contribute to tumor growth and spread by promoting new blood vessel growth and stimulating tumor invasiveness. Tumors can express factors that simultaneously induce both angiogenesis and neurogenesis, such as guidance receptors and ligands that regulate branching morphogenesis in neuronal and vascular systems. Vascular endothelial growth factor, brain-derived neurotrophic factor, Neuropilins, Semaphorins, Netrins, and Slit/Robos can promote branching morphogenesis of both neurons and blood vessels. Some of these factors can stimulate stem or progenitor cells to promote tumor angiogenesis and neurogenesis as well as tumor growth and spread. Innervation of tumors promotes cancer pain and can contribute to tumor spread along axons. An understanding of the mechanisms promoting development of neurons and blood vessels during tumor progression will assist in the development of new cancer therapies.
Anti-tumor necrosis factor agents in sarcoidosis: A systematic review of efficacy and safety.

Abstract Background Though anti-tumor necrosis factor agents (anti-TNFs) have been recommended as third-line therapy for sarcoidosis, an up-to-date systematic synthesis of their efficacy and safety is lacking. Objectives To systematically review the literature to characterize the efficacy and safety of anti-TNFs in sarcoidosis. Settings All countries and treatment settings were included. Methods We searched MEDLINE, EMBASE, CINAHL, Web of Science, ClinicalTrials.gov, Cochrane Library, and Google Scholar from inception to November 27, 2017. Studies of five or more cases of sarcoidosis treated with anti-TNFs were included. Descriptive statistics were performed. Results Sixty-five studies (including five randomized controlled trials [RCTs]) were identified, comprising 1525 patients. For pulmonary sarcoidosis, one RCT found infliximab (IFX) significantly improved vital capacity vs. placebo; a second detected no difference. In non-randomized studies, IFX improved pulmonary function in 79% of patients. For cutaneous sarcoidosis, compared to placebo, adalimumab (ADA) showed greater Physician Global Assessment response and significantly reduced target lesion area, and IFX significantly decreased Sarcoidosis Area and Severity Index induration and erythema scores. In non-randomized studies of cutaneous, ocular, neurologic, and multisystem sarcoidosis, IFX improved 89%, 69%, 77%, and 71% of cases, respectively. ADA improved 77% of ocular sarcoidosis cases. IFX displayed a steroid-sparing effect. Half of patients relapsed after discontinuation of IFX, ADA, etanercept, or certolizumab pegol. In RCTs, compared to placebo, anti-TNFs had comparable overall and serious adverse events and slightly more serious infections. Conclusions Available evidence suggests the efficacy and safety of IFX in pulmonary, cutaneous, ocular, neurologic, and multisystem sarcoidosis, and ADA in cutaneous and ocular sarcoidosis.
Discovering de novo peptide substrates for enzymes using machine learning

The discovery of peptide substrates for enzymes with exclusive, selective activities is a central goal in chemical biology. In this paper, we develop a hybrid computational and biochemical method to rapidly optimize peptides for specific, orthogonal biochemical functions. The method is an iterative machine learning process by which experimental data is deposited into a mathematical algorithm that selects potential peptide substrates to be tested experimentally. Once tested, the algorithm uses the experimental data to refine future selections. This process is repeated until a suitable set of de novo peptide substrates are discovered. We employed this technology to discover orthogonal peptide substrates for 4'-phosphopantetheinyl transferase, an enzyme class that covalently modifies proteins. In this manner, we have demonstrated that machine learning can be leveraged to guide peptide optimization for specific biochemical functions not immediately accessible by biological screening techniques, such as phage display and random mutagenesis.
Reproductive performance among color morphs of Diaphorina citri Kuwayama, vector of citrus greening pathogens.

Abstract Diaphorina citri Kuwayama, commonly known as Asian citrus psyllid (ACP), transmits the bacterium Candidatus Liberibacter asiaticus (CLas), one of the causative agents of Huanglongbing (HLB) to citrus trees. Within ACP populations, three adult abdominal color polymorphisms: gray/brown, blue/green, and orange/yellow have been described. Despite the economic importance of this insect, the molecular mechanisms governing reproduction and vitellogenesis are not well understood. The current results describe the expression patterns of VgA1-like and Kr-h1, ovary morphology, and oviposition behavior in two different ACP morphotypes. Our results showed that VgA1-like exhibited female sex-specific expression, was upregulated more in blue/green than gray/brown females, and increased in expression with age only in blue/green morphs. The transcription factor Kr-h1, associated with reproduction in some insect species, was expressed in both sexes, was upregulated in 1 and 7 days old blue/green compared to gray/brown females, and exhibited reduced expression by 14 days of age in both morphotypes. Our results demonstrated an association between VgA1-like expression, oocyte development, and the blue green abdominal color of D. citri, which were linked to higher reproductive output than observed in gray/brown females. Overall, this study described the importance of the genes VgA1-like and Kr-h1 in D. citri vitellogenesis, and explained the mechanisms underlying differential reproductive performance among D. citri abdominal color morphs.
Oxidative Stress and Parkinson's Disease

Parkinson’s disease (PD) is a progressive neurodegenerative disorder affecting primarily the dopamine (DA) neurons that arise in the midbrain (mesencephalon) and project to the putamen and caudate regions (the striatum) of the brain, areas concerned with the control of motor movements (Hornykiewicz and Kish, 1986). Unaffected (or minimally affected) by the disease are DA neurons that arise in the midbrain and project to cortical and limbic regions; overactivity of the latter neuronal circuits has been implicated in schizophrenia (e.g., Lozoncy et al., 1987). Also unaffected are other monoaminergic neurons, specifically the norepinephrine (NE)-secreting and serotonin-secreting neurons of the brain. The DA neurons that degenerate in PD arise in the substantia nigra, a local region of the midbrain. As its name implies, this region is normally heavily pigmented; the pigment is readily visible to the unaided eye as a brown-to-black region of the mesencephalon. The pigment is an insoluble polymer that is related to melanin of skin, and has been termed neuromelanin. However, unlike skin, the pigment is not derived by enzymatic synthesis from L-dopa catalyzed by tyrosinase, because tyrosinase is absent from the brain. Rather, neuromelanin appears to be formed via a slow, nonenzymatic process based on the autoxidation and spontaneous polymerization of the catecholamine DA (Graham, 1978). As with melanin of skin, quinoidal intermediates react with soluble tissue thiols, such as glutathione and cysteine, to incorporate sulfur residues into the matrix of the polymer (Carstam et al., 1992).
Error Assessment of Drug Dose in Pharmaceutical Mixtures

This chapter describes a unique method to calculate the maximum potential error associated with drug dose in pharmaceutical mixtures and unit dosage forms, composed of an infinite number of ingredients that are measured on multiple balances of variable sensitivities, and thus provides instant guidance on the pharmaceutical ingredient preparation. The method also determines the sensitivity of the instruments measuring each of the components and the least allowable weight (LAW) of the drug within the predetermined assay standard. A great variety of solved examples with capsules, creams, and ointments as the finished products are used to demonstrate a step-by-step application of the method. The method was written in such a way to help you better understand the principles of balance operation, comprehend the relationship of the sensitivity requirement (SR) of a balance and the maximum allowable error in the dose, appreciate that sequential measurements carry a complicated error propagation on the result, and sharpen up your critical thinking by having to consider all possible consequences of any action involved in prescription preparation prior to actually performing relevant calculations. What follows is the description of the aliquot method of weighing based on the LAW as a method that allows weighing a drug quantity smaller than the sensitivity of the balance. Although the concept of the aliquot method of weighing based on the least allowable weight has been around for more than 50 years, this is really the first time that the theory of the method is developed and applied correctly. The method as described elsewhere ignores errors associated with multiple weighing of drug-excipient mixtures, and as a result, the dose error in the final product is underestimated. The topics are advanced but extremely important.
Photochemical synthesis of a zirconium cyclobutadienyl complex

Photolysis of (MePMPMe)2ZrBn2 (MePMPMe = 3,5-dimethyl-2-(2-pyridyl)pyrrolide) in the presence of diphenylacetylene yields the first η4-cyclobutadienyl zirconium complex, (MePMPMe)2Zr(η4-C4Ph4), through formal [2+2] cycloaddition of two alkynes at a putative low-valent zirconium intermediate. This unique reactivity expands the scope of alkyne coupling reactions at low-valent zirconium centers that traditionally produce zirconacyclopentadienes.
Hartree-Fock instabilities and the diagonal Born-Oppenheimer correction

The NO and NO2 radicals are used to demonstrate how instabilities in Hartree-Fock wavefunctions can result in unsatisfactory, or even unphysical, values of the diagonal Born-Oppenheimer correction ...
Targeting MAPK/MKP Signaling as a Therapeutic Axis in Periodontal Disease

Periodontal pathogens stimulate inflammatory cytokine and chemokine production within the periodontal microenvironment producing chronic inflammation and subsequent bone loss. In stimulated cells, the maximal induction of cytokine/chemokine expression requires activation of the p38 mitogen-activated protein kinase (MAPK) pathways. The clinical relevance of p38 MAPK activation was demonstrated by our group where excessive MAPK correlated with human periodontal disease severity. Importantly, MAPK signaling contributes toward the expression of multiple gene targets including (interleukin)-1β, IL-6, tumor necrosis factor (TNF)-α, matrix metalloproteinase (MMP)-13, receptor activator of nuclear factor kappa-Β (RANKL), and other inflammatory mediators that can contribute toward periodontal inflammation and bone destruction. Once MAPK activation and substrate phosphorylation occur, MAPK inactivation occurs through specific phosphatase activity via a family of dual-specificity MAPK phosphatases (MKPs) that target the regulatory sites of these kinases. In this chapter, the therapeutic potential to control the MAPK/MKP signaling axis of innate immunity is explored through various therapeutic platforms including small molecule inhibitors, RNA interference, gene therapy, and nanoparticle encapsulation of small molecules.
Trajectories of co-occurring psychopathology symptoms in autism from late childhood to adulthood

Given high rates of co-occurring conditions in youth and adults with autism spectrum disorder (ASD), it is critical to examine the developmental trajectories of these symptoms of psychopathology. Using data from a cohort of participants (n = 194), most of whom were first assessed for ASD in very early childhood, we investigated the trajectories of co-occurring depressive, anxiety, and attention-deficit hyperactivity disorder (ADHD) symptoms from late childhood to adulthood. Additionally, childhood predictors and adult outcomes associated with these symptom trajectories were examined. Using group-based trajectory modeling, we found two distinct classes of individuals exhibiting each of these co-occurring symptom patterns: one class exhibited fairly low symptoms across time, and one class with elevated symptoms with varied fluctuation across time (ADHD symptoms starting high but decreasing, anxiety symptoms high and stable, and depressive symptoms fluctuating but peaking at clinically significant levels in young adulthood). All high trajectory classes were associated with age 9 adaptive skills; verbal IQ predicted higher anxiety and depressive symptom classes. After accounting for verbal IQ, all high symptom trajectory classes were negative predictors of objective adult outcomes. These findings call for wide-ranging considerations of the needs of individuals across ability levels, autism symptoms, and behavioral and emotional challenges.
Correction of Doi–Edwards' Green function for a chain in a harmonic potential and its implication for the stress‐optic rule

We show that the stress-optic rule is violated in a theoretical model of polymer melts that uses a harmonic potential to confine a polymer chain in a tube-like domain of surrounding entangled polymers. This is the model first proposed by Doi and Edwards (DE) [J. Chem. Soc. Farad. Trans. II 1978, 74, 1802] and later extended by Ianniruberto and Marrucci (IM) [J. Non-Newton. Fluid Mech. 1998, 79, 225]. We first provide a rigorous Green function for such a chain, which is a correction to that derived by DE. The modification guarantees chain continuity. Second, we show that the stress-optic rule is violated in the IM model if the modified Green function is used and an unnecessary assumption employed by IM is avoided. Our result contradicts that of IM. The violation is due to the presence of the virtual springs to confine the chain in the tube rather than the anisotropy of the confinement potential. On the other hand, DE used the virtual-spring model only for estimation of the monomer density along the primitive path where we find just a small correction. As they did not use it for rheological calculations, the stress-optic rule appears to be safe for the Doi–Edwards model. The result might be useful for extracting tube potentials from atomistic simulations. © 2014 Wiley Periodicals, Inc. J. Polym. Sci. Part B: Polym. Phys. 2014, 52, 460–469
An artificial intelligence-driven agent for real-time head-and-neck IMRT plan generation using conditional generative adversarial network (cGAN).

PURPOSE To develop an artificial intelligence (AI) agent for fully automated rapid head-and-neck intensity-modulated radiation therapy (IMRT) plan generation without time-consuming dose-volume-based inverse planning. METHODS This AI agent was trained via implementing a conditional generative adversarial network (cGAN) architecture. The generator, PyraNet, is a novel deep learning network that implements 28 classic ResNet blocks in pyramid-like concatenations. The discriminator is a customized four-layer DenseNet. The AI agent first generates multiple customized two-dimensional projections at nine template beam angles from a patient's three-dimensional computed tomography (CT) volume and structures. These projections are then stacked as four-dimensional inputs of PyraNet, from which nine radiation fluence maps of the corresponding template beam angles are generated simultaneously. Finally, the predicted fluence maps are automatically postprocessed by Gaussian deconvolution operations and imported into a commercial treatment planning system (TPS) for plan integrity check and visualization. The AI agent was built and tested upon 231 oropharyngeal IMRT plans from a TPS plan library. 200/16/15 plans were assigned for training/validation/testing, respectively. Only the primary plans in the sequential boost regime were studied. All plans were normalized to 44 Gy prescription (2 Gy/fx). A customized Harr wavelet loss was adopted for fluence map comparison during the training of the PyraNet. For test cases, isodose distributions in AI plans and TPS plans were qualitatively evaluated for overall dose distributions. Key dosimetric metrics were compared by Wilcoxon signed-rank tests with a significance level of 0.05. RESULTS All 15 AI plans were successfully generated. Isodose gradients outside of PTV in AI plans were comparable to those of the TPS plans. After PTV coverage normalization, Dmean of left parotid (DAI = 23.1 ± 2.4 Gy; DTPS = 23.1 ± 2.0 Gy), right parotid (DAI = 23.8 ± 3.0 Gy; DTPS = 23.9 ± 2.3 Gy), and oral cavity (DAI = 24.7 ± 6.0 Gy; DTPS = 23.9 ± 4.3 Gy) in the AI plans and the TPS plans were comparable without statistical significance. AI plans achieved comparable results for maximum dose at 0.01cc of brainstem (DAI = 15.0 ± 2.1 Gy; DTPS = 15.5 ± 2.7 Gy) and cord + 5mm (DAI = 27.5 ± 2.3 Gy; DTPS = 25.8 ± 1.9 Gy) without clinically relevant differences, but body Dmax results (DAI = 121.1 ± 3.9 Gy; DTPS = 109.0 ± 0.9 Gy) were higher than the TPS plan results. The AI agent needed ~3 s for predicting fluence maps of an IMRT plan. CONCLUSIONS With rapid and fully automated execution, the developed AI agent can generate complex head-and-neck IMRT plans with acceptable dosimetry quality. This approach holds great potential for clinical applications in preplanning decision-making and real-time planning.
Survey of Ant Genera and Biodiversity in Toco

Tropical regions are widely known for their high species diversity, which is often threatened by the growth and encroachment of human activity into natural areas. The ants of Trinidad have been studied, but most surveys and records are restricted to the Port of Spain area on the northeastern coast. This study is focused on the ant biodiversity in northeastern Trinidad, a region approximately 87 km from Port of Spain. Over the course of seven days, ants were surveyed on the Jammev Beach Resort property (Toco) using baited ground pitfall traps, baited arboreal pitfall traps, and from freely collected specimen. A total of 298 specimens were collected, representing 12 genera and tribes of Formicidae. The most prevalent ants were Tertamorium sp with 105 specimens and unidentifiable Formicinae with 88 specimens. A Shannon Diversity Index of 1.925 was obtained, indicating an average amount of diversity.
Quantifying Variational Approximation for Log-Partition Function

Variational methods, such as mean-field (MF) and tree-reweighted (TRW), provide computationally efficient approximations of the log-partition function for generic graphical models but their approximation ratio is generally not quantified. % As the primary contribution of this work, we provide an approach to quantify their approximation ratio for any discrete pairwise graphical model with non-negative potentials through a property of the underlying graph structure $G$. % Specifically, we argue that (a variant of) TRW produces an estimate within factor $1/\sqrt{\kappa(G)}$ where $\kappa(G) \in (0,1]$ captures how far $G$ is from tree structure. % As a consequence, the approximation ratio is $1$ for trees, $\sqrt{(d+1)/2}$ for graphs with maximum average degree $d$ and $1+1/(2\beta)+o_{\beta\to \infty}(1/\beta)$ for graphs with girth at least $\beta \log N$. % The quantity $\kappa(G)$ is the solution of a min-max problem associated with the spanning tree polytope of $G$ that can be evaluated in polynomial time for any graph. % We provide a near linear-time variant that achieves an approximation ratio depending on the minimal (across edges) effective resistance of the graph. We connect our results to the graph partition approximation method and thus provide a unified perspective.
Dominantly inherited Alzheimer's disease: a compass for drug development.

The first phase 3 trial of amyloid-β-targeting monoclonal antibodies in dominantly inherited Alzheimer’s disease failed to slow cognitive decline in patients. Could it still help to inform future study design and drug development in this setting?
Initial analysis of the dosimetric benefit and clinical resource cost of CBCT-based online adaptive radiotherapy for patients with cancers of the cervix or rectum

Purpose This provides a benchmark of dosimetric benefit and clinical cost of cone-beam CT-based online adaptive radiotherapy (ART) technology for cervical and rectal cancer patients. Methods An emulator of a CBCT-based online ART system was used to simulate more than 300 treatments for 13 cervical and 15 rectal cancer patients. CBCT images were used to generate adaptive replans. To measure clinical resource cost, the six phases of the workflow were timed. To evaluate the dosimetric benefit, changes in dosimetric values were assessed. These included minimum dose (Dmin) and volume receiving 95% of prescription (V95%) for the planning target volume (PTV) and the clinical target volume (CTV), and maximum 2 cc's (D2cc) of the bladder, bowel, rectum, and sigmoid colon. Results The average duration of the workflow was 24.4 and 9.2 min for cervical and rectal cancer patients, respectively. A large proportion of time was dedicated to editing target contours (13.1 and 2.7 min, respectively). For cervical cancer patients, the replan changed the Dmin to the PTVs and CTVs for each fraction 0.25 and 0.25 Gy, respectively. The replan changed the V95% by 9.2 and 7.9%. The D2cc to the bladder, bowel, rectum, and sigmoid colon for each fraction changed -0.02, -0.08, -0.07, and -0.04 Gy, respectively. For rectal cancer patients, the replan changed the Dmin to the PTVs and CTVs for each fraction of 0.20 and 0.24 Gy, respectively. The replan changed the V95% by 4.1 and 1.5%. The D2cc to the bladder and bowel for each fraction changed 0.02 and -0.02 Gy, respectively. Conclusions Dosimetric benefits can be achieved with CBCT-based online ART that is amenable to conventional appointment slots. The clinical significance of these benefits remains to be determined. Managing contours was the primary factor affecting the total duration and is imperative for safe and effective adaptive radiotherapy.
Ruxolitinib Ameliorates Airway Hyperresponsiveness and Lung Inflammation in a Corticosteroid-Resistant Murine Model of Severe Asthma

Asthma prevalence has increased considerably over the decades and it is now considered as one of the most common chronic disorders in the world. While the current anti-asthmatic therapies are effective for most asthma patients, there are 5-10% subjects whose disease is not controlled by such agents and they account for about 50% of the asthma-associated healthcare costs. Such patients develop severe asthma (SA), a condition characterized by a dominant Th1/Th17 cytokine response that is accompanied by Type 2 (T2)-low endotype. As JAK (Janus Kinase) signaling is very important for the activation of several cytokine pathways, we examined whether inhibition of JAKs might lessen the clinical and laboratory manifestations of SA. To that end, we employed a recently described murine model that recapitulates the complex immune response identified in the airways of human SA patients. To induce SA, mice were sensitized with house dust mite extract (HDME) and cyclic (c)-di-GMP and then subsequently challenged with HDME and a lower dose of c-di-GMP. In this model, treatment with the JAK inhibitor, Ruxolitinib, significantly ameliorated all the features of SA, including airway hyperresponsiveness and lung inflammation as well as total IgE antibody titers. Thus, these studies highlight JAKs as critical targets for mitigating the hyper-inflammation that occurs in SA and provide the framework for their incorporation into future clinical trials for patients that have severe or difficult-to manage asthma.
Development of a Debye heat capacity model for vibrational modes with a gap in the density of states

Low-energy vibrational modes that have a gap in the density of states (DOS) have often been observed in heat capacity data in the form of 'boson' peaks, but the functions used to model these modes are often inadequate or are not physically meaningful. We have adapted the Debye model to represent these gapped modes and have derived the heat capacity equations for these modes in one, two, and three dimensions. Applying these equations to the low-temperature heat capacity data fitting for a large variety of materials substantially improves the fit quality relative to conventional fits. From the fitting parameters, the underlying DOS were estimated, which we show to be comparable to those reported in the literature. This model expands the methods of theoretical low-temperature heat capacity data analysis and improves the procedure of approximating a material's DOS from its low-temperature heat capacity.
Unifying morality’s influence on non-moral judgments: The relevance of alternative possibilities

Past work has demonstrated that people's moral judgments can influence their judgments in a number of domains that might seem to involve straightforward matters of fact, including judgments about freedom, causation, the doing/allowing distinction, and intentional action. The present studies explore whether the effect of morality in these four domains can be explained by changes in the relevance of alternative possibilities. More precisely, we propose that moral judgment influences the degree to which people regard certain alternative possibilities as relevant, which in turn impacts intuitions about freedom, causation, doing/allowing, and intentional action. Employing the stimuli used in previous research, Studies 1a, 2a, 3a, and 4a show that the relevance of alternatives is influenced by moral judgments and mediates the impact of morality on non-moral judgments. Studies 1b, 2b, 3b, and 4b then provide direct empirical evidence for the link between the relevance of alternatives and judgments in these four domains by manipulating (rather than measuring) the relevance of alternative possibilities. Lastly, Study 5 demonstrates that the critical mechanism is not whether alternative possibilities are considered, but whether they are regarded as relevant. These studies support a unified framework for understanding the impact of morality across these very different kinds of judgments.
Disability and Impairment: Working with Children and Families: Peter Burke. London: Jessica Kingsley Publishers, 2008. 168 pp., paperback, $35.00.

The coming into force of the United Nation's Convention on the Rights of Persons with Disabilities, early this year, sets the stage for Peter Burke's book to play an important role in the way we en...
Abstract 4296: Correlation of the apparent diffusion coefficient of water assessed by diffusion-weighted imaging with treatment outcome in refractory lymphoma patients

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA The contrast of MR images can be made sensitive to the average motion of water molecules (diffusivity) giving rise to diffusion-weighted imaging (DWI). Intensity maps of the apparent diffusion constant (ADC) of water can be generated from the DWI information and average ADC values of anatomical regions can be assessed. Malignant tissues generally exhibit hypercellularity, increased nucleus-to-cytoplasm ratios, and an increased amount of macromolecules resulting in decreased water diffusivity (lower ADC). Additionally, a response-related ADC increase has been demonstrated in malignancies under therapy. We previously reported that the ADC mean value (in 10-3 mm2 s-1 [SD, n]) of masses of refractory lymphoma patients prior to a new treatment was lower than the ADC mean value of lymph nodes of healthy volunteers (0.91 [0.23, 15] vs. 1.13 [0.14, 10], respectively). This difference was significant (p 75 days. The ADC mean value [SD, n] in patients with TTF ≤ 75 days was 0.73 [0.20, 5] while in those with TTF > 75 days was 1.04 [0.20, 7]. These mean values were significantly different (p 75 days was not. Discussion: Our results demonstrate that refractory lymphoma patients with tumor masses displaying abnormally low ADC values prior to the start of treatment have poorer treatment outcome than those patients with ADC tumor values that are comparable to those in normal lymph nodes. If low ADC is due to increased tumor cellularity in patients with poorer outcome, this could produce reduced drug availability, thus explaining the substandard outcome. Our results demonstrate an important predictive value of the ADC determination by DWI in refractory lymphoma patients. This together with the fact that DWI is a noninvasive technique and its acquisition is fairly quick makes the ADC a parameter that could become critical for the clinical examination of the patient with refractory lymphoma. Citation Format: Fernando Arias-Mendoza, Hamed Mojahed, Ahmed Sawas, Owen A. O'Connor. Correlation of the apparent diffusion coefficient of water assessed by diffusion-weighted imaging with treatment outcome in refractory lymphoma patients. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4296. doi:10.1158/1538-7445.AM2014-4296
The structure of a symplectic manifold on the space of loops of 7-manifold

We define a symplectic structure on the space of non parametrized loops in $G_2$ manifold. We also develop some basics of intersection theory of Lagrangian submanifolds.