cssi/SciSciGPT-SciSciNet huggingface dataset:
Formulation Development and Optimization of Ibuprofen Poloxamer Melt Granules Using Hydrophilic Excipients

The focus of this research work was to develop a melt granulation technique to enhance solubility, dissolution rate and associated flowability concerns of Ibuprofen. Hydrophilic excipients like xylitol and lactose anhydrous were added to the binary mixture of conventional low melting surfactant Poloxamer 407 and Ibuprofen. Physical mixtures of Ibuprofen and Poloxamer 407 were prepared in ratios of 1:0.25, 1:0.5 and 1:0.75 using a water-jacketed high shear mixer. For each ratio of Ibuprofen and Poloxamer 407, xylitol and lactose anhydrous were added separately at two levels (75 mg and 150 mg) per unit dose containing 200 mg drug. Phase solubility studies revealed linearity in drug solubility enhancement with Poloxamer 407 concentration. In vitro dissolution studies were carried out for drug, physical mixtures (PM) and melt granules (MG) for all ratios in de-ionized water and 0.1 N HCl (pH=1.2). Solid state characterization was performed using Fourier transform infrared spectroscopy (FTIR), modulated differential scanning calorimetry (mDSC) and powder X-ray diffraction (PXRD) methodologies. Powder rheology studies were performed conventionally by measuring Carr’s index and Hausner’s ratio. Basic flowability energy values were calculated using a powder rheometer to corroborate flowability data measured by conventional methods. Particle morphological studies were done by Scanning electron microscope (SEM) and Fluid imaging technologies. In-vitro dissolution studies showed approximately 7 fold drug release in water and 19 fold drug release in acidic media for MG 1:0.75 at hydrophilic excipient level of 150 mg compared to that of neat Ibuprofen in respective dissolution media. mDSC and PXRD data confirms crystalline nature of drug in the formulations. FTIR data confirms no interactions between drug and excipients used during processing. Particle morphology analysis confirms absence of rhombic Ibuprofen crystals in formulations. Dissolution rate and solubility enhancement was seen due to synergistic effects of Poloxamer 407 and hydrophilic excipients incorporated in formulations.
A Survey on HTTPS Implementation by Android Apps: Issues and Countermeasures

Abstract As more and more sensitive data is transferred from mobile applications across unsecured channels, it seems imperative that transport layer encryption should be used in any non-trivial instance. Yet, research indicates that many Android developers do not use HTTPS or violate rules which protect user data from man-in-the-middle attacks. This paper seeks to find a root cause of the disparities between theoretical HTTPS usage and in-the-wild implementation of the protocol by looking into Android applications, online resources, and papers published by HTTPS and Android security researchers. From these resources, we extract a set of barrier categories that exist in the path of proper TLS use. These barriers not only include improper developer practices, but also server misconfiguration, lacking documentation, flaws in libraries, the fundamentally complex TLS PKI system, and a lack of consumer understanding of the importance of HTTPS. Following this discussion, we compile a set of potential solutions and patches to better secure Android HTTPS and the TLS/SSL protocol in general. We conclude our survey with gaps in current understanding of the environment and suggestions for further research.
Obstructive Nephropathy Without Hydronephrosis: Suspicion Is the Key

Urinary tract obstruction leading to acute kidney injury is usually associated with bilateral hydroureters and hydronephrosis, often accompanied by oliguria. We present an atypical case of obstructive uropathy without these features that presented with severe acute kidney injury. A 64-year-old male with no known medical history has presented with a 2-week history of nausea, decreased appetite, flank pain, and lower extremity edema, and was found to have an elevated creatinine of 10.5 mg/dL. Renal ultrasound showed mild prominence of the bilateral renal collecting systems with no evidence of hydronephrosis. Computed tomography scan showed findings suggestive of retroperitoneal fibrosis involving ureteral region and bilateral ureteral stent placement has led to dramatic improvement of creatinine to 1.3 mg/dL over the next 4 days.
Establishing Content Validity of the Quality Indicators for Classrooms Serving Students With Autism Spectrum Disorders Instrument

The purpose of this study was to provide content validation for quality indicators included in an observation instrument developed to evaluate classrooms serving students with autism spectrum disor...
Abstract WP246: Acute Ischemic Stroke Patients With a Primary Language Other Than English Do Not Have Significantly Increased Door-to-Needle Times for Intravenous TPA

Background: Rapid administration of intravenous alteplase (IV tPA) leads to better outcomes, but language barriers have the potential to introduce delays and to hinder effective communication with ...
Estimating Trends in Progress Monitoring Data: A Comparison of Simple Line-Fitting Methods.

Four simple line-fitting procedures are presented for practitioners to quickly summarize student time series performance data. Two are in common use — Koenig's “quarter-intersect” and White's “spli...
Investigating detailed interactions between novel PAR1 antagonist F16357 and the receptor using docking and molecular dynamic simulations.

Abstract Currently, Vorapaxar is the only recently FDA-approved antiplatelet drug targeting Protease-activated receptor 1 (PAR1). However, a novel antagonist, F16357, has been shown to prevent painful bladder syndrome, also known as interstitial cystitis (IC). Unfortunately, there is no high resolution structure of the F16357-receptor complex, hindering its optimization as a therapeutic agent. In this study, we used docking and molecular dynamic (MD) simulations to investigate the detailed interactions between F16357 and PAR1 at a molecular level. The recently solved crystal structure of human PAR1 complexed with Vorapaxar was used in our docking of F16357 into the binding pocket of the receptor. To enhance binding pose selection, F16357 was docked first without constraints and then with a positional constraint to invert its orientation to become similar to that of Vorapaxar. The three systems, with crystal Vorapaxar, F16357 and an inverted F16357, were subjected to 3.0 μs MD simulations. The MM-GBSA binding energy analysis showed that F16357 binds more strongly in a pose obtained from an unrestrained docking than in the inverted pose from a restrained docking; and Vorapaxar binds more strongly than F17357. This ordering is consistent with the experimental pIC 50 values. Our structural data showed subtle changes in the binding pose between Vorapaxar and F16357. Transmembrane helices 1, 2, 5, and 7 were most significantly affected; most notably a large kink at F279 5.47 in TM helix 5 of the Vorapaxar complex was completely absent in the F16357 complex. The results of this study facilitate the future development of other therapeutic PAR1 antagonists.
Preschool Executive Function Predicts Childhood Resting-State Functional Connectivity and Attention-Deficit/Hyperactivity Disorder and Depression

Abstract Background Measures of executive function (EF), such as the Behavior Rating Inventory of Executive Function, distinguish children with attention-deficit/hyperactivity disorder (ADHD) from control subjects, but less work has examined relationships to depression or brain network organization. This study examined whether early childhood EF predicted new onset or worsening of ADHD and/or depression and examined how early childhood EF related to functional connectivity of brain networks at school age. Methods Participants included 247 children who were enrolled at 3 to 6 years of age from a prospective study of emotion development. The Behavior Rating Inventory of Executive Function Global Executive Composite score was used as the measure of EF in early childhood to predict ADHD and depression diagnoses and symptoms across school age. Resting-state functional magnetic resonance imaging network analyses examined global efficiency in the frontoparietal, cingulo-opercular, salience, and default mode networks and six “hub” seed regions selected to examine between-network connectivity. Results Early childhood EF predicted new onset and worsening of ADHD and depression symptoms across school age. Greater EF deficits in preschool predicted increased global efficiency in the salience network and altered connectivity with four regions for the dorsal anterior cingulate cortex hub and one region with the insula hub at school age. This altered connectivity was related to increasing ADHD and depression symptoms. Conclusions Early executive deficits may be an early common liability for risk of developing ADHD and/or depression and were associated with altered functional connectivity in networks and hub regions relevant to executive processes. Future work could help clarify whether specific EF deficits are implicated in the development of both disorders.
Submucosal gland mucus strand velocity is decreased in chronic rhinosinusitis.

BACKGROUND Chronic rhinosinusitis (CRS) may be initiated by innately impaired host defense mechanisms that predispose the upper airways to infection. Recent evidence suggests tethering of submucosal gland mucus strands represents an inciting event within cystic fibrosis (CF) airways, occurring prior to onset of chronic infection. Submucosal gland hypertrophy and defective mucociliary clearance (MCC) are present in actively inflamed sinuses, but mucus strand velocity may also be affected as a secondary event, further contributing to chronic disease. The objective of this study is to assess whether mucus strand velocity is decreased in patients with CRS. METHODS Mucosal explants from patients with and without CRS were submerged in Ringer's solution mixed with fluorescent nanospheres. Methacholine was then added, and videos demonstrating strand growth and detachment were generated from a time-lapse of Z-stack images using a multiphoton confocal microscope. Dynamic mucus strands were identified and individual velocities quantified with the MTrackJ plug-in of ImageJ. RESULTS Fifteen patients met criteria for ex vivo analysis of mucus strand velocities (CRS, n = 9 vs controls, n = 6). Mucus strands were recorded (pixels/second) streaming from the submucosal gland openings. Average mucus strand velocities were significantly decreased in patients with CRS (1.53 ± 0.67 vs controls, 4.86 ± 1.68 pixels/second; p < 0.001). CONCLUSION This study is the first to report evidence of abnormal mucus strand velocity from submucosal glands in diseased sinonasal mucosa. Future pharmacologic studies targeting this critical component of MCC are warranted.
Acceptability of Health Kiosks Within African American Community Settings: A Pilot Study.

Introduction:Health kiosks have been increasingly adopted to provide health-care services to those with limited access. Kiosks have the potential to reach people who may have undiagnosed health con...
Role of Angiotensin II in Fibrous Tissue Formation Following Myocardial Infarction

Traditional views of circulating angiotensin (Ang) II have focused on its endocrine properties in classical target tissues (e.g., kidneys and vasculature), where resident cell populations express Ang II receptors. More recent evidence supports its role in nonclassical tissues (e.g., adipose and connective tissues). Moreover, de novo generation of Ang peptides by cellular constituents of these nonclassical tissues has drawn attention to autocrine and paracrine properties of Ang II mediated by AT1 receptor-ligand binding at these sites. Fibrous tissue formation, regulated by phenotypically transformed fibroblast-like cells termed myofibroblasts, represent such nonclassical tissue and cells. Herein we address a role for local Ang II in tissue repair following myocardial infarction. The article further draws attention to the importance of chronic elevations in circulating Ang II, associated with activation of the renin– angiotensin–aldosterone system, that promote unwanted cardiac fibrosis. Genetic risk for adverse cardiovascular structural remodeling and thereby such events as myocardial infarction, stroke, and hypertension may be related to iterations in genes encoding angiotensin-converting enzyme and angiotensinogen. Potentials for gene therapy that could prevent fibrosis and thereby be cardioprotective are also briefly considered.
Characterization of multiple regulatory networks and responses to environmental signals in Pseudomonas syringae during its association with plants

Pseudomonas syringae is a model bacterial plant pathogen that is adapted for growth and survival on leaf surfaces and in the leaf interior of its host plants. P. syringae likely experiences distinct environmental conditions in different phases of its interaction with plants. In this study, we used global transcriptome profiling of P. syringae pv. syringae B728a to analyze genes and traits that were responsive to growth and survival on the leaf surface versus in the leaf apoplast. We found that the epiphytic environment specifically favors active relocation via flagellar motility, swarming motility, chemosensing, and chemotaxis, whereas the apoplastic environment favors traits contributing to virulence including the synthesis of two phytotoxins and syingolin A as well as the degradation of an alternative amino acid that suppresses virulence. Through comparing the transcriptomes of in planta cells to those of cells exposed to various stresses in culture media, we found that water limitation is a major stress that limits B728a growth and survival in these leaf habitats. P. syringae can adapt to water stress by the production of a potent compatible solute, trehalose. Distinct P. syringae strains vary in their ability to tolerate water stress, possibly due, in part, to differences in the production or regulation of trehalose. To investigate this possibility, we compared the relative contribution of the trehalose biosynthetic pathways to trehalose synthesis in two closely related P. syringae strains B728a and DC3000 and characterized an apparent interdependency between these pathways. Our data showed that, of the two trehalose biosynthesis pathways, only one was required for trehalose production in B728a whereas both were needed in DC3000, and moreover that differences in trehalose production may help explain differences in their water stress tolerance. Lastly, to understand the
Thermal hybrid power systems using multiple heat sources of different temperature: Thermodynamic analysis for Brayton cycles

Abstract Past studies on hybrid power cycles using multiple heat sources of different temperatures focused mainly on case studies and almost no general theory about this type of systems was developed. This paper is a study of their general thermodynamic performance, with comparison to their corresponding single temperature heat source reference system, focusing on the Brayton cycles: simple Brayton cycle, and Brayton cycle with intercooling, reheat and heat regeneration. The generalized expressions for the energy and exergy efficiency difference between the hybrid and the corresponding single heat source reference systems were developed, which allow easy determination of the extent of relative desirability of the hybrid systems in that respect. The design and operating conditions under which the hybrid systems become more efficient than the non-hybrid reference ones were found. A number of case studies were simulated (after validation) to help basic understanding and confirm the thermodynamic generalization of the results. One of the results showed that the largest exergy destruction occurs in the combustors (67% to total exergy destruction) and can be reduced by using additional heat sources (AHS) that are of lower temperature difference between the heating and heated streams, and/or renewable energy. The sensitivity analysis results further suggested that efforts should be made to increase the energy conversion efficiency of the AHS. The effects of AHS input and temperature on energy efficiency, fuel depletion and emissions were studied and compared with the conventional Brayton cycles. It was found that addition of the AHS, i.e. cycle hybridization, reduces emissions and fuel depletion and thus has an advantage over conventional non-hybrid Brayton cycles. A thermodynamic foundation of such hybrid systems was laid, and some easy guidance was provided for use in their preliminary design, before their highly time-consuming and expensive detailed analysis, simulation, and experiments.
Practical Strategies to Improve Your Writing: Lessons Learned From Public Health Practitioners Participating in a Writing Group.

Many public health professionals (researchers and practitioners) do not regularly spend time writing. We often receive no formal training in the practices that lead one to become a productive write...
Systematic examination of the links between composition and physical properties in surrogate fuel mixtures using molecular dynamics

Abstract Due to the complexity of conventional and alternative hydrocarbon fuels, simplified mixtures known as surrogates are often used to gain insight into the effect of fuel composition on thermophysical properties and combustion behavior. Atomistic simulations are uniquely suited to map changes in both physical properties and liquid structure to compositional changes within mixtures. Here, molecular dynamics simulations are used to examine several hydrocarbon mixtures of n-alkanes, n-alkylcyclohexanes, and n-alkylbenzenes, as well as their pure components. The simulations accurately predict relevant thermophysical properties such as density, bulk modulus, and excess molar volume as a function of n-alkylbenzene side-chain length, length of the n-alkane, and composition. In addition, the molecular-scale structure of the liquids is characterized via angular radial distribution functions and histograms of molecular volumes. Changes in fluid structure are used to rationalize non-intuitive trends in thermophysical properties, such as the opposite trends in density of pure n-alkylbenzenes and n-alkylcyclohexanes as a function of alkyl chain length, minima in bulk modulus as a function of composition, and mixtures whose density does not follow the same trend as their pure components. This work demonstrates the usefulness of molecular dynamics in fuel-surrogate development, by accurately predicting important fuel properties and, in addition, linking changes in molecular-level liquid structure to changes in fuel properties.
Conversion of Carbon Dioxide into Liquid Hydrocarbons Using Cobalt-Bearing Catalysts

There is an increasing interest in carbon dioxide (CO2) capture and subsequent conversion into value-added chemicals and fuels. Cobalt-based catalysts are widely used in Fischer-Tropsch synthesis of liquid fuels from syngas (CO + H2) as they have high activity, good selectivity, and superior stability for the hydrogenation of CO to long-chain hydrocarbons. However, the hydrogenation of CO2 into long-chain hydrocarbons involves both reverse water-gas shift reaction and Fischer-Tropsch synthesis. As a cobalt catalyst lacks the ability to catalyze the reverse water-gas shift reaction, an active component for catalyzing reverse water-gas shift reaction such as iron and copper can be incorporated to a cobalt-based catalyst for CO2 hydrogenation. Proper catalyst supports, structures, and pretreatment can further improve the performance of cobalt-based catalysts for CO2 hydrogenation. The pressure and composition of the feed gas were found to have significant effects on the distribution of Fischer-Tropsch synthesized hydrocarbons during CO2 hydrogenation.
Ecobehavioral Assessment of Paraeducator Behaviors That Support Engagement of Students With Disabilities

Due to a shortage of special education teachers and an increase in the number of students with disabilities, the use of paraeducators is common. Paraeducators frequently provide instruction, under ...
Conflict and adaptation at the intersection of motherhood and conservation leadership

Abstract Conservation leadership science has focused on identifying behaviors and characteristics that make individual leaders effective, but has yet to address contextual challenges that differentially shape various groups' pathways to leadership positions. We sought to understand one such challenge, how motherhood affects women's careers, by conducting interviews with 56 women conservation leaders in the United States and analyzing the data using grounded theory. All participants described how conflict between motherhood and conservation expectations affects women's leadership, particularly for mothers of young children. Mothers in conservation reported experiencing stress from this conflict and so pursued adaptive responses, including gradually returning from maternity leave, restructuring schedules, working part-time, reducing travel, foregoing opportunities, and occasionally changing jobs. These adaptations were shaped by multilevel systems factors at individual, family, organization, and conservation profession scales. We found that having to navigate these factors can undermine women's wellbeing and lead them to restructure their careers, which may jeopardize organizations' abilities to fulfill their conservation objectives. Conversely, our results suggest that greater compatibility between women's motherhood and conservation leadership work may make conservation practitioners and institutions more effective. As more women advance in conservation leadership, the profession should consider ways to better integrate motherhood to support a more sustainable and diverse conservation movement.
Cardiorespiratory fitness, adiposity, and ambulatory blood pressure in adolescents.

BACKGROUND This study examined the association of cardiorespiratory fitness (fitness) and adiposity (Body Mass Index [BMI] and waist circumference [WC]) with ambulatory blood pressure (ABP) and tested the moderating effect of adiposity on the association between fitness and ABP. METHODS A cross-sectional study was conducted with 370 adolescents aged 11-16 years. Fitness was assessed by a height-adjusted step test and estimated by heart rate recovery, defined as the difference between peak heart rate during exercise and heart rate two minutes postexercise. Adiposity was measured using dichotomized values for percentiles of BMI (≥85th) and WC (≥50th). ABP was measured every 30-60 minutes over 24 hours on a school day. Mixed-effects regression analysis was used. RESULTS Each unit increase in fitness was associated with a decrease of systolic blood pressure (SBP) [-0.058 mmHg, P=0.001] and diastolic blood pressure (DBP) [-0.043 mmHg, P<0.001] after adjustment for WC and covariates. Each unit increase in fitness was associated with a decrease in SBP [-0.058 mmHg, P=0.001] and DBP [-0.045 mmHg, P<0.001] after adjustment for BMI and covariates. Fitness and BMI≥85th percentile (or WC ≥ 50th percentile) interactions were not associated with ABP after adjustment for covariates. CONCLUSIONS Our findings indicate a small but statistically significant inverse effect of fitness on ABP in adolescents. No evidence of a modifying effect of adiposity on this association suggesting that fitness and weight management have essential roles for maintaining lower ABP in adolescents.
Integral Geometry and Tomography

The problems of integral geometry are to determine a function given (weighted) integrals of this function over a “rich” family of manifolds. These problems are of importance in medical applications (tomography), and they are quite useful for dealing with inverse problems in hyperbolic differential equations (integrals of unknown coefficients over ellipsoids or lines can be obtained from the first terms of the asymptotic expansion of rapidly oscillating solutions and an information about first-arrival times of a wave). There has been significant progress in the classical Radon problem when manifolds are hyperplanes and the weight function is the unity; there are interesting results in the plane case when a family of curves is regular (resembling locally the family of straight lines) or in case of the family of straight lines with an arbitrary regular attenuation. Still there are many interesting open questions about the problem with local data and simultaneous recovery of density of a source and of attenuation. We give a brief review of this area, referring for more information to the books of Natterer [Nat] and Sharafutdinov [Sh].
Light-matter interactions in two-dimensional layered WSe2 for gauging evolution of phonon dynamics.

Phonon dynamics is explored in mechanically exfoliated two-dimensional WSe2 using temperature-dependent and laser-power-dependent Raman and photoluminescence (PL) spectroscopy. From this analysis, phonon lifetime in the Raman active modes and phonon concentration, as correlated to the energy parameter E0, were calculated as a function of the laser power, P, and substrate temperature, T. For monolayer WSe2, from the power dependence it was determined that the phonon lifetime for the in-plane vibrational mode was twice that of the out-of-plane vibrational mode for P in the range from 0.308 mW up to 3.35 mW. On the other hand, the corresponding relationship for the temperature analysis showed that the phonon lifetime for the in-plane vibrational mode lies within 1.42× to 1.90× that of the out-of-plane vibrational mode over T = 79 K up to 523 K. To provide energy from external stimuli, as T and P were increased, peak broadening in the PL spectra of the A-exciton was observed. From this, a phonon concentration was tabulated using the Urbach formulism, which increased with increasing T and P; consequently, the phonon lifetime was found to decrease. Although phonon lifetime decreased with increasing temperature for all thicknesses, the decay rate in the phonon lifetime in the monolayer (1L) material was found to be 2× lower compared to the bulk. We invoke a harmonic oscillator model to explain the damping mechanism in WSe2. From this it was determined that the damping coefficient increases with the number of layers. The work reported here sheds fundamental insights into the evolution of phonon dynamics in WSe2 and should help pave the way for designing high-performance electronic, optoelectronic and thermoelectric devices in the future.
Consequences of suboptimal communication for patients with limited English proficiency in the intensive care unit and suggestions for a way forward: A qualitative study of healthcare team perceptions

Abstract Purpose To understand the healthcare team's perceptions of the negative consequences of suboptimal communication and their recommendations to improve communication with patients and families who have Limited English Proficiency (LEP) in the Intensive Care Unit (ICU). Materials and methods We performed a qualitative study using semi-structured interviews of physicians, nurses, and interpreters from 3 ICUs at Mayo Clinic Rochester, between November 2017 and April 2018. Results We identified 5 consequences of suboptimal communication: 1) Suboptimal assessment and treatment of patient symptoms, 2) Unmet patient and family expectations, 3) Decreased patient autonomy, 4) Unmet end of life wishes and 5) Clinician Distress. Recommendations to improve communication include: 1) Education and training for patients,families, clinicians and interpreters, 4) Greater integration of interpreters into the ICU team 5) Standardized timeline for goals of care conversations with patients and families with LEP. Conclusions Patients with LEP are at risk of experiencing suboptimal communication with the healthcare team in the ICU. There are several educational and quality improvement strategies that ICUs and institutions can take to mitigate these issues.
Teaching Assistants' Performance at Identifying Common Introductory Student Difficulties in Mechanics Revealed by the Force Concept Inventory.

Graduate teaching assistants are more accurate at predicting the popularity of incorrect answers on the Force Concept Inventory than random guessing, but they did not identify many common difficulties that occur among introductory physics students.
Hidden Realities and the Language of the Prophets of Science: in Search of the Mythos of Modernity

The cosmological narrative, based on scientific theories, reaches deep into the fabric of the modern world. From university lecture halls to movie theatres, from astronomical observatories on isolated mountain tops to public talks, "Prophets of Science" captivate the imagination of millions. The following essay is aimed at describing the social dimension, distribution and consequences of scientific knowledge. To accomplish this goal, I will compare the mythological lore present in the Amazon Basin and the scientific worldview of the industrialized West. Such juxtaposition is focused on western science, where references to another knowledge system are used to enrich the overall argument and as a catalyst of effective self-reflection on modern society. In the course of the essay, I intend to communicate the heterogeneity of both Amazonian and Western societies. The specific examples will be aimed at underscoring the contexts and mechanisms of knowledge distribution, rather than the content. In the first part, I will discuss the role of metaphor in scientific discourse. Subsequently, I will describe variations in lay and expert interpretations of knowledge. The essay will be concluded with an overview of the literature interpreting science as mythology.
Carnitine Responsive Migraine Headache Syndrome: Case Report and Review of the Literature.

To review carnitine’s role in migraine and headache, present a case of a patient with intractable chronic migraine refractory to medications but exquisitely responsive to mitochondrial cofactors with a particularly prompt response to L-carnitine supplementation with dose response, and suggest scenarios where L-carnitine could be considered for prophylactic treatment in migraine and intractable headache with migraine features. Multiple treatments modalities are used to treat migraine, including nutraceutical therapies. Mitochondrial supplements are often used to treat migraine, based on controlled trials. One of the nutraceutical therapies used in neurological and non-neurological conditions is L-carnitine. A few studies have examined the effect of carnitine in patients with migraine. We present a case of a patient with chronic migraine-like headaches found to have carnitine deficiency whose headaches greatly improved with carnitine supplementation. This case suggests that secondary carnitine deficiency may cause chronic migraine. Energy deficiency states occur with migraine, and replenishment of energy substrates has demonstrated some improvement in migraine. Recent studies suggest that L-carnitine with other mitochondrial cofactors may be migraine preventives. The exact link between carnitine and migraine is unknown. Perhaps carnitine deficiency should be in the differential for refractory migraine. Supplementation with L-carnitine merits exploration as a nutraceutical treatment of chronic migraine. Our case suggests that there may be a dose-dependent response to L-carnitine.
Space-occupying brain lesions, trauma-related tau astrogliopathy, and ARTAG: a report of two cases and a literature review

Astrocytes with intracellular accumulations of misfolded phosphorylated tau protein have been observed in advanced-stage chronic traumatic encephalopathy (CTE) and in other neurodegenerative conditions. There is a growing awareness that astrocytic tau inclusions are also relatively common in the brains of persons over 70 years of age—affecting approximately one-third of autopsied individuals. The pathologic hallmarks of aging-related tau astrogliopathy (ARTAG) include phosphorylated tau protein within thorn-shaped astrocytes (TSA) in subpial, subependymal, perivascular, and white matter regions, whereas granular-fuzzy astrocytes are often seen in gray matter. CTE and ARTAG share molecular and histopathologic characteristics, suggesting that trauma-related mechanism(s) may predispose to the development of tau astrogliopathy. There are presently few experimental systems to study the pathobiology of astrocytic-tau aggregation, but human studies have made recent progress. For example, leucotomy (also referred to as lobotomy) is associated with a localized ARTAG-like neuropathology decades after the surgical brain injury, suggesting that chronic brain injury of any type may predispose to later life ARTAG. To examine this idea in a different context, we report clinical and pathologic features of two middle-aged men who came to autopsy with large (> 6 cm in greatest dimension) arachnoid cysts that had physically displaced and injured the subjects’ left temporal lobes through chronic mechanical stress. Despite the similarity of the size and location of the arachnoid cysts, these individuals had dissimilar neurologic outcomes and neuropathologic findings. We review the evidence for ARTAG in response to brain injury, and discuss how the location and molecular properties of astroglial tau inclusions might alter the physiology of resident astrocytes. These cases and literature review point toward possible mechanism(s) of tau aggregation in astrocytes in response to chronic brain trauma.
Non-Platinum Chemotherapeutic Metallopharmaceuticals

Despite the resounding success of cisplatin and closely related platinum antitumor agents,1-3 the movement of other transition-metal antitumor agents toward the clinic has been exceptionally slow. Keppler has pointed out the inherent bias in testing metal compounds in cell and animal systems, which have been proven sensitive to cisplatin, and the difficulty in formulating metal complexes, particularly those with low solubility.4 Also, most metallopharmaceuticals have emanated from academic rather than from commercial pharmaceutical laboratories. Earlier reviews have suggested possible advantages in using transition-metal ions other than platinum, which may involve (1) additional coordination sites, (2) changes in oxidation state, (3) alterations in ligand affinity and substitution kinetics, and (4) photodynamic approaches to therapy.5-12 While the latter may become a clinically useful method,13 it is not addressed here as a chemotherapeutic approach. Broadening the chemotherapeutic arsenal depends on understanding existing agents with a view toward developing new modes of attack. Indeed, few of the compounds covered here may function in a manner analogous to cisplatin, which appears to bend DNA by cross-linking adjacent guanines, thereby causing a class of DNA binding proteins to adhere to the site.1-3 This review focuses on possible mechanistic approaches to chemotherapeutic anticancer drugs involving non-platinum metal ion complexes exclusive of metalloproteins or metal-activated antibiotics. Since DNA has often been proposed as the target of these agents, there is a particular emphasis on those that can interact with nucleic acids. Nevertheless, heavy metals are generally toxic by binding to sulfur and nitrogen sites on proteins and, thus, can interfere with a number of modes of metabolism. Several metals also exhibit action through redox activity, and gallium appears to operate through the displacement of metal ions in iron metabolism or bone.
Case Report of Transient Acute Parkinsonism in the setting of West Nile Virus Encephalitis (P1.9-039)

Objective: Acute onset of Parkinsonism is an uncommon presentation to the emergency department, and is usually secondary to various conditions. These include but are not limited to: acute vascular pathology, structural lesions (e.g. obstructive hydrocephalus, pontine myelinolysis, etc.), medications, and viral infections. We present a case of acute Parkinsonism secondary to a viral infection. Background: NA Design/Methods: NA Results: A 56-year-old chef, with no prior history of movement disorders, presented to the hospital with ongoing confusion and tremors in both arms for one week. Two weeks prior to presentation, patient had a fever, vomiting and diarrhea, all of which had resolved. Neurologic examination was significant for impaired delayed recall, decreased attention, cogwheel rigidity in both arms along with a low amplitude, medium frequency resting, postural, and action tremors in both upper extremities, right greater than left. No gait abnormality was noted. Magnetic resonance imaging (MRI) of the brain was unremarkable. Cerebrospinal fluid analysis showed 31 leukocytes/mm (98% lymphocytes), a glucose level of 51 mg/dL, and a protein level of 98 mg/dL. Cerebrospinal fluid cultures for bacteria, viruses, and fungi were negative. West Nile Virus (WNV)–specific immunoglobulin (Ig) M was present on the New York State Encephalitis Panel. The patient was discharged home with supportive care. In ambulatory follow-up 3 weeks later, cognition and muscle tone were normal. Resting and action tremors had also resolved, however bilateral mild postural tremors persisted in the upper extremities, right greater than left. Conclusions: Most common viral encephalitis associated with acute Parkinsonism are WNV, Coxsackie virus, Japanese Encephalitis Virus, Influenza, and Human Immunodeficiency Virus. Acute onset of Parkinsonian features during WNV encephalitis likely follows the virus-induced death of dopaminergic neurons, resulting in the acute loss of dopamine signaling. We stress that viral etiologies such as WNV should be considered in a patient presenting with encephalopathy and acute Parkinsonism. Disclosure: Dr. Vanguru has nothing to disclose. Dr. Lopez has nothing to disclose. Dr. Gudlavalleti has nothing to disclose. Dr. Sanders has received personal compensation for consulting, serving on a scientific advisory board, speaking, or other activities with PsyBar, Dane Street, Professional Disability Associates, and Academic Insurance.
AWOKE: A theory of representation and process in intelligence as adaptation to the environment

Abstract This article proposes a theory (AWOKE) of mental representation and process in the functioning of intelligence as adaptation. It opens with some background, considering alternative metaphors of mind that have been used in the psychological literature to characterize intelligence. It then considers the epistemological underpinnings of the proposed theory. Next the article considers two alternate ways of knowing: internal coherence and external correspondence. It discusses both declarative and procedural aspects of such knowing in the service of intelligence as adaptation. Next the article considers how the two ways of knowing fit together. Then the article considers what it means for behavior to be adaptively intelligent in the first place. The article next discusses two other ways of knowing—dogma and authority—and why they are not included in the theory as central to intelligence as adaptation. The article then considers how the new theory fits into existing theoretical frameworks, and then how one might measure internal coherence and external correspondence in the service of intelligence as adaptation. Finally, the article draws some conclusions.
Pipedream: An interactive digital twin model for natural and urban drainage systems

Abstract Faced with persistent flooding and water quality challenges, water managers are now seeking to build digital twins of surface water systems that combine sensor data with online models to better understand and control system dynamics. Towards this goal, this study presents pipedream—an end-to-end simulation engine for real-time modeling and state estimation in natural/urban drainage networks. The engine combines (i) a new hydraulic solver based on the one-dimensional Saint-Venant equations and (ii) a Kalman filtering scheme that efficiently updates hydraulic states based on observed data. Using sensor data from a real-world watershed, we find that the simulation engine is effective at both interpolating hydraulic states and forecasting future states based on current measurements. By providing a complete, real-time view of system hydraulics, our software will enable rapid detection of flooding, improved characterization of maintenance and remediation needs, and robust real-time control for both small-scale (stormwater) and large-scale (river/reservoir) networks.
Hospital Meaningful Use Incentive Dollars and HIT-Related Capital Expenditures

Hospital Meaningful Use incentives were positively correlated with health information technology-related capital expenditures. Take-Away Points: • No other known research has demonstrated a relationship between the Hospital MU incentive program and HIT-related capital expenditures. • Our main finding that showed a positive correlation between MU incentives and HIT-related capex may provide some support for policy-makers evaluating the effectiveness of the MU incentive program to stimulate HIT-related capital investments at hospitals and offset some of those hospital costs. • Our second most important finding that demonstrated hospital executives increased and then decreased HIT-capital spending as the MU incentive dollars increased and then decreased highlights a need to understand whether the MU incentives appropriately prepared hospitals for EHR adoption. NOTE: Funding Sources: This publication was supported by the Health Resources and Services Administration (HRSA) of the U.S. Department of Health and Human Services (HHS) as part of the National Telehealth Center of Excellence Awards (U66 RH31458 – MUSC; U66RH31459 – UMMC). The contents are those of the author(s) and do not necessarily represent the official views of, nor an endorsement, by HRSA, HHS or the U.S. Government. This publication was also partially supported by the South Carolina Clinical & Translational Research (SCTR) Institute, with an academic home at the Medical University of South Carolina, through NIH - NCATS Grant Number UL1 TR001450. Data analytic support for the study was provided through support for the CEDAR core funded by the MUSC Office of the Provost.
Cytokinins in Plants

Publisher Summary This chapter focuses on the group of plant hormones called cytokinins, which are defined as compounds that induce cell division in plant cells in cooperation with an auxin. Gibberellins move in plants in a nonpolar fashion, whereas the cytokinins have been reported to move like auxins in a basipetal polar fashion. Cytokinins are extensively metabolized by plant tissues should be kept in mind in studying their transport. In connection with the movement of cytokinins in plants, it is important to note that cytokinins are also transported through the xylem in intact plants, as cytokinin-like compounds have been detected in the sap of several plants. Adenine derivatives with substituents at positions 2, 7, and 9 are inactive, whereas 1-benzyladenine and 1-(3,3-dimethylallyl) adenine showed cytokinin activity, and 3-(3,3-dimethylallyl)adenine (triacanthine), which occurs naturally in plants, showed cytokinin activity only after its conversion, through autoclaving, to the 6-isomer. The chapter discusses the biological effects of cytokinins, metabolism and intracelldar localization of cytokinins in plants, mechanism of action of cytokinins, and metabolic effects of cytokinins.
Ototoxic Drugs and Noise

Drugs that produce tinnitus can be subdivided into those which produce temporary or permanent hearing loss and those which apparently do not cause any hearing loss. The tinnitus occurring with drugs of the first group is probably secondary to the hearing loss. However, most of the drugs that produce tinnitus without an accompanying hearing loss probably do so because of their effect on biogenic amines in the central nervous system and/or as an extension of their proconvulsant side-effects. A pre-existing cochlear impairment is the underlying factor in most patients who experience tinnitus. Not only can ototoxic drugs or high levels of noise produce cochlear impairment but the interaction of the two can place humans in more jeopardy than when exposed to either agent alone. Chloramphenicol has little ototoxic potential when administered systemically in humans. However, our studies show that when chloramphenicol is combined with noise exposure in rats, considerably more cochlear damage results than from the noise alone (chloramphenicol alone does no produce any cochlear damage). We are presently conducting more detailed studies of this ototoxic interaction to determine whether it occurs with other antibiotics (such as erythromycin) which are also commonly considered to have minimal ototoxicity.
Effect of leading-edge geometry on boundary-layer receptivity to freestream sound

The receptivity to freestream sound of the laminar boundary layer over a semi-infinite flat plate with an elliptic leading edge is simulated numerically. The incompressible flow past the flat plate is computed by solving the full Navier-Stokes equations in general curvilinear coordinates. A finite-difference method which is second-order accurate in space and time is used. Spatial and temporal developments of the the Tollmien-Schlichting wave in the boundary layer, due to small-amplitude time-harmonic oscillations of the freestream velocity that closely simulate a sound wave travelling parallel to the plate, are observed. The effect of leading-edge curvature is studied by varying the aspect ratio of the ellipse. Boundary layer over the flat plate with a sharper leading edge is found to be less receptive. The relative contribution of the discontinuity in curvature at the ellipse-flat-plate juncture to receptivity is investigated by smoothing the juncture with a polynomial. Continuous curvature leads to less receptivity. A new geometry of the leading edge, a modified super-ellipse, which provides continuous curvature at the juncture with the flat plate, is used to study the effect of continuous curvature and inherent pressure gradient on receptivity.
Markets, information, and uncertainty: Existence and optimality of a general equilibrium with endogenous uncertainty

Kenneth Arrow once said that uncertainty about prices may be the most important form of economic uncertainty. Yet tI1e treatment of uncertainty in Arrow-Debreu markets reflects only nature's moves. It therefore neglects price uncertainty, because prices depend on human behavior. This chapter attempts to close the gap. It defines a new concept of general equilibrium in markets where traders are uncertain about prices, and proves the existence of such an equilibrium. Traders do not know the possible equilibrium prices a priori. The state space which represents price uncertainty, and the financial instruments used to hedge this uncertainty, are all defined endogenously as part of a market equilibrium. To motivate the problem,I show in Proposition 1 that trying to hedge price uncertainty within an Arrow-Debreu framework leads to paradoxical outcomes, which are connected with Russell's paradox in logics. Thus a new framework is needed.
On-chip monolithic filters for receiver interference suppression using bond-wire inductors

Two passive LC filters are fabricated in a 0.18 /spl mu/m BiCMOS process for interference suppression in WCDMA applications. A single-pole filter achieves an insertion loss of 1dB at 2.14GHz and suppression of 12dB at 1.95GHz, while the three-pole filter has insertion loss of 8dB at 2.3GHz and provides a suppression of 23dB at 2.1GHz. Both filters are implemented using MIM capacitors and bond wire inductors.