cssi/SciSciGPT-SciSciNet huggingface dataset:
Computational chemistry applied to studies of organic contaminants in the environment: Examples based on benzo[a]pyrene

The topics of DNA adduct structure, biodegradation mechanisms, photo-chemistry, and adsorption of polycyclic aromatic hydrocarbons (PAHs) are discussed using benzo[a]pyrene and its partial oxidation products as an example. The use of classical mechanical, semi-empirical, and ab initio computational techniques are discussed in terms of their ability to answer important questions regarding the environmental fate of this important carcinogenic compound. The role of H-bonding variation with computational technique was analyzed and significant errors are likely when this parameter is predicted by classical force field simulations or semi-empirical calculations. The stability of the conformations of benzo[a]pyrene also change with computational method although the density functional theory (DFT) and second-order Moller-Plessett (MP2) methods used here converge to similar relative energies. Analysis of the relationship among HOMO-LUMO gaps, triplet and singlet excitation energies, and phototoxicity suggests that the HOMO-LUMO gaps are not the true parameter related to phototoxicity but a correlation between HOMO-LUMO gaps and excitation energies gives the appearance of a cause-and-effect relationship. Methods for predicting the water-soot partition coefficient of PAHs and the complexation of partial oxidation products with cations and metals in the environment are also discussed.
Review of long-term adverse effects associated with the use of chemically-modified animal and nonanimal source hyaluronic acid dermal fillers.

Although only recently introduced, chemically-modified hyaluronic acid dermal fillers have gained widespread acceptance as “redefining” dermal fillers in the fields of dermatology and cosmetic facial surgery. Although hyaluronic acid-based dermal fillers have a low overall incidence of long term side effects, occasional adverse outcomes, ranging from chronic lymphoplasmacytic inflammatory reactions to classic foreign body-type granulomatous reactions have been documented. These long-term adverse events are reviewed.
Footprint evaluation for volume rendering

This paper presents a forward mapping rendering algorithm to display regular volumetric grids that may not have the same spacings in the three grid directions. It takes advantage of the fact that convolution can be thought of as distributing energy from input samples into space. The renderer calculates an image plane footprint for each data sample and uses the footprint to spread the sample's energy onto the image plane. A result of the technique is that the forward mapping algorithm can support perspective without excessive cost, and support adaptive resampling of the three-dimensional data set during image generation.
An Order-Level-Scheduling-Period System with Lost Sales

An order-level-scheduling-period system with lost sales is considered. The zero leadtime case is analyzed first and a method for computing the total average cost is presented. The nonzero leadtime case is then treated for a scheduling period of one time unit. The average cost for this case depends on the distribution of the inventory available on hand. This random variable, on-hand inventory, is denoted by Q and its distribution is given by gQ. Methodologies are presented for finding this distribution for any leadtime L. A comparison of the Markov chain approach and the direct solution approach for finding gQ is also given.
Soil Organic Carbon Changes in Diversified Rotations of the Western Corn Belt

Sequestration and storage of carbon (C) by agricultural soils has been cited as one potential part of the solution to soil degradation and global climate change. However, C sequestration in soils is a slow and dynamic process. The objective of this study was to evaluate the effects of crop rotation and N fertilizer management on soil organic C (SOC) levels at several points in time during 18 yr of a long-term study in the Western Corn Belt. Seven cropping systems (three monoculture, two 2-yr, and two 4-yr rotations) with three levels of N fertilizer were compared. Soil samples were taken in the spring in 1984, 1992, 1998, and 2002 to a depth of 30 cm in 0- to 7.5-, 7.5- to 15-, and 15- to 30-cm increments. No differences were obtained in SOC levels in 1984 at the beginning of the study. After 8 yr, rotation significantly increased SOC 449 kg ha -1 across all cropping systems. From 1992 to 2002, SOC levels in the 0- to 7.5-cm depth decreased by 516 kg ha -1 across all cropping systems. Soil organic C levels in the 7.5- to 15-cm depths in 1992 and 2002 demonstrated similar rotation effects to those in the surface 0- to 7.5-cm, being not significantly affected from 1984 to 1992 but being significantly decreased from 1992 to 2002 (568 kg SOC ha -1 across all cropping systems). Many of the SOC gains in the surface 30 cm measured during the first 8 yr of the study were lost during the next 10 yr in all but the 4-yr cropping systems after 18 yr. The loss of SOC in this latter period occurred when depth of tillage was increased by using a tandem disk with larger-diameter disks. These results demonstrate that more than one point-in-time measurement from long-term experiments is necessary to monitor SOC changes when several management variables, such as cropping system and N fertilizer, are being used. They also indicate that apparent small changes in cultural practices, such as in depth of tillage in this experiment, can significantly change SOC dynamics in the soil. Subtle changes in cultural practices (e.g., tillage depth) can have significant long-term results, but long-term experiments are required to quantify their impact under variable climatic conditions.
Intermittent iterative learning control

In this paper we present a mathematical formulation of the problem of robust iterative learning control (ILC) design when the system is subject to data dropout. It is assumed that an ILC scheme is implemented via a networked control system (NCS) and that during the data transfer from the remote plant to the ILC controller data dropout occurs, resulting in what we call intermittent measurement. Using the Kalman filtering approach, we show that it is possible to design a learning gain such that the system eventually converges to a desired trajectory as long as there is not complete data dropout.
Tidally induced turbulent mixing at Irving Seamount—Modeling and measurements

[1] The relationship of tidal currents and turbulence over Irving Seamount is examined by model and measurement. Surface tides are partially scattered into internal tides and, particularly over the seamount summit, current strength and shear greatly increase. Current shear causes the model's turbulent mixing. At Irving, modeled turbulent mixing, as represented by vertical diffusivity, is largest O(10−3 m2 s−1) in the bottom boundary layer and in a turbulent column rising to the sea surface directly above the seamount. Pockets of less intense mixing occur within the turbulent column, but their locations are highly variable. Field measurements confirm a turbulent mixing column atop Irving of comparable intensity. Increased model diffusivity (average of 7 × 10−5 m2 s−1) also occurs to a distance of several hundred kilometers from the seamount flanks in a band vertically centered at ∼800 m depth.
Sinonasal surfactant protein A1, A2, and D gene expression in cystic fibrosis: a preliminary report.

OBJECTIVE: To measure alterations in SPA1, A2, and D gene expression in various forms of inflammatory chronic rhinosinusitis (CRS).STUDY DESIGN AND SETTING: Sinus mucosal biopsies were performed in patients with allergic fungal rhinosinusitis (AFS), CRS with nasal polyposis, cystic fibrosis (CF), and controls. SP mRNA was measured with quantitative polymerase chain reaction.RESULTS: Patients with CF (n = 4) showed significantly increased SPA1 (82-fold), SPA2 (100-fold), and SPD (47-fold) mRNA (P < 0.05) when compared with controls (n = 5). Patients with CRS with nasal polyposis (n = 5) also demonstrated elevated SPA1 (27-fold), SPA2 (13-fold), and SPD (13-fold). Patients with AFS (n = 7) had increased SPA1 (5-fold), SPA2 (9-fold), and SPD (17-fold), but were not statistically significant.CONCLUSION: SPA1, A2, and D are upregulated in various forms of CRS, but are significantly elevated in cystic fibrosis CRS.SIGNIFICANCE: Understanding the role of SPs in CRS will help develop novel treatment approaches fo...
Collecting Survey Data for Nonmarket Valuation

The unique nature of environmental and natural resource amenities makes valuation a challenge in many respects. Prices reflect aggregate societal values for market goods but nonmarket goods lack an analogous indicator of value. Estimation of nonmarket values requires that the researcher either ask the public about their values for the good of interest or use existing data to infer the values. Either approach is sensitive to the quality of the data used for the estimation, which is why this chapter focuses on how to collect data for estimating nonmarket values. Understanding where such data come from and the procedures used to collect the data will make the descriptions of the nonmarket valuation techniques in Chapters 4–11 more meaningful.
Vulcanization. Part II. Fate of Curing System during Sulfur Curing of Nr Accelerated by MBT Derivatives and Activated by Zinc Stearate

Abstract As discussed in Part I it was generally believed that during the sulfur vulcanization of rubber, important vulcanization intermediates are formed as a result of reactions between components of the various curing systems, e.g., sulfur, accelerator, zinc oxide and elastomer. A variety of reaction products have been postulated, however, actual supporting evidence for most of these postulations is limited. This is not surprising considering that the complexity of the system makes the identification and quantitative determination of these intermediates by conventional analytical techniques difficult. Part I of this paper described some analytical methods and the application of procedures for determining the fate of the curing system throughout the vulcanization of natural rubber in the presence of sulfur and various benzothiazole type accelerators. This study confirmed that important vulcanization intermediates are formed during the vulcanization process and that they play decisive roles in delay acti...
Novel Time-Stamped Digital Card (TSDC) to Determine User’s Identity

Time-stamped digital signature scheme can be employed to derive a new solution that improves the authentication, non-repudiation and data integrity of current payment gateway. This paper suggests designing a new method to process online payment transactions by adding an additional step to the current payment gateway which will verify the bank cardholder’s identity through a trusted third party, a certificate authority (CA). Therefore, a new Time-Stamped Digital Card (TSDC), which relies on the concept of asymmetrical key algorithm to accomplish its task, will be proposed. Time stamp is examined to determine how old the TSDC is and whether it has been previously used or not. It will also be used to prevent replay attack. The protocol of TSDC consists of five steps and has been analyzed. TSDC needs to be generated, signed and submitted to the payment gateway along with the credit card information by the customer prior to processing any online transaction for identification purposes. Therefore, TSDC aims to reduce the high volume of fraud transactions and suspicious activities currently experienced during payment gateway due to lack of identity verification of bank cardholders.
Forbidden Extension Queries

Document retrieval is one of the most fundamental problem in information retrieval. The objective is to retrieve all documents from a document collection that are relevant to an input pattern. Several variations of this problem such as ranked document retrieval, document listing with two patterns and forbidden patterns have been studied. We introduce the problem of document retrieval with forbidden extensions. Let D={T_1,T_2,...,T_D} be a collection of D string documents of n characters in total, and P^+ and P^- be two query patterns, where P^+ is a proper prefix of P^-. We call P^- as the forbidden extension of the included pattern P^+. A forbidden extension query asks to report all occ documents in D that contains P^+ as a substring, but does not contain P^- as one. A top-k forbidden extension query asks to report those k documents among the occ documents that are most relevant to P^+. We present a linear index (in words) with an O(|P^-| + occ) query time for the document listing problem. For the top-k version of the problem, we achieve the following results, when the relevance of a document is based on PageRank: - an O(n) space (in words) index with O(|P^-|log sigma+ k) query time, where sigma is the size of the alphabet from which characters in D are chosen. For constant alphabets, this yields an optimal query time of O(|P^-|+ k). - for any constant epsilon > 0, a |CSA| + |CSA^*| + Dlog frac{n}{D} + O(n) bits index with O(search(P)+ k cdot tsa cdot log ^{2+epsilon} n) query time, where search(P) is the time to find the suffix range of a pattern P, tsa is the time to find suffix (or inverse suffix) array value, and |CSA^*| denotes the maximum of the space needed to store the compressed suffix array CSA of the concatenated text of all documents, or the total space needed to store the individual CSA of each document.
L-Dominance: A New Mechanism Combining ε-Dominance and Pareto Knee Exploitation in Evolutionary Multi-objective Optimization

In Evolutionary Multi-objective Optimization (EMO), the mechanism of -dominance has received a lot of attention because of its ability to guarantee convergence near the Pareto frontier and maintain diversity among solutions at a reasonable computational cost. A significant weakness of this mechanism is its inability to also identify and exploit knee regions of the Pareto frontier, which are frequently the regions of the frontier that are most interesting to the user. We therefore propose a new mechanism—L-dominance, based on the Lame curve—as an alternative to -dominance in EMO. The geometry of the Lame curve naturally supports a greater concentration of solutions in directions of high tradeoff between objectives than a corresponding -box of the same area. This adaptable resolution of solutions in knee regions of the Pareto frontier will result in significant gains in computational efficiency for complex optimization routines in large n-objective design scenarios.
Energy Function Inspired Value Priority Based Global Wide-Area Control of Power Grid

Conventional wide-area control strategies that are deployed to damp inter-area oscillations use fixed a priori schemes based on modal analysis of the power system. As these controllers cannot be tuned online, such schemes fail to perform well during severe dynamic system changes. In this paper, a wide-area control architecture designed based on reinforcement learning and optimal adaptive critic network is proposed, that learns and optimizes the system closed-loop performance. Also, a value priority scheme is designed using a derived Lyapunov energy function for prioritization of local and the proposed wide-area global controller which ensures coherent damping of local and inter-area oscillations. The method increases the reliability and allows for automatic tuning of stabilizing controllers especially in the presence of wide-area monitoring constraints. Simulation results on 8-bus 5-machine and 68-bus 16-machine IEEE test systems highlight the efficiency of the proposed method.
Nonadherence to osteoporosis medications: A critical problem

Nonadherence to medical regimens has been described as an epidemic of the 21st century. The recent Surgeon General's Report on Bone Health and Osteoporosis points out that nonadherence is a problem in the bone field and addresses the need to improve adherence with osteoporosis therapies. Studies show that less than 25% of patients who initiate drug therapy for osteoporosis achieve 1 yr of treatment without interrupting therapy. It is estimated that improving adherence could result in nearly 400,000 fewer fractures each year in the United States. This article addresses strategies that clinicians can use to increase adherence to osteoporosis medications.
Estimating relative renal function.

AbstractRadionuclide measurements of relative renal function have been made using conventional dual-probe renography, computer assisted triple-probe renography, rectilinear kidney scanning and computer assisted gamma camera renography and kidney scanning. The relative area of each kidney from the excretory urogram also has been used to measure relative function.The best correlation between renography and kidney scanning was obtained with the gamma camera computer system. The relative function of each kidney was obtained by outlining regions of interest that corresponded closely to the renal images and subtracting the blood and tissue background activity, using a special background region.Triple-probe renography, using computer assisted blood background subtraction, provides another reliable indicator of relative function, which is considerably more accurate than conventional dual-probe renography.Relative renal function also may be determined, but with less precision, from the relative counts in a rectili...
Enzymatic plasticity of medial gastrocnemius fibers in the adult chronic spinal cat

The metabolic plasticity of single fibers in adult cat medial gastrocnemius (MG) 6 mo after complete spinal cord transection (Sp) at T12-T13 was studied. Some Sp cats were trained to weight support (Sp-WS) 30 min/day beginning 1 mo posttransection. Cross-sectional area, succinate dehydrogenase (SDH), alpha-glycerophosphate dehydrogenase (GPD), and myofibrillar adenosinetriphosphatase (ATPase) activities were determined in fibers identified in frozen serial sections. Fibers were categorized as light or dark based on myosin ATPase staining, alkaline preincubation. The percentage of dark ATPase fibers was higher in Sp and Sp-WS (approximately 85%) than in control (approximately 60%). All dark ATPase fibers reacted positively to a fast myosin heavy chain monoclonal antibody. In both spinal groups, a higher percentage of dark ATPase fibers reacted to both fast and slow myosin heavy chain antibodies than in controls. Neither Sp nor Sp-WS cats showed fiber atrophy. Compared with control, SDH activity was decreased in both fiber types of Sp cats. Daily weight-support training ameliorated this adaptation. There were no differences among the three groups in mean GPD and ATPase activities for either fiber type. There was a slight tendency, however, for spinal cats to have higher GPD and ATPase activities (independent of type) than control, probably reflecting the larger proportion of dark ATPase fibers in these cats. These observations indicate that 6 mo after spinalization in adult cats, some of the fibers of a fast muscle became "faster" and developed oxidative and glycolytic enzyme profiles that normally are exhibited in fast fatigable motor units.(ABSTRACT TRUNCATED AT 250 WORDS)
Antinociceptive effects of topical mepivacaine in a rat model of HIV-associated peripheral neuropathic pain

Background A consequence of HIV infection is sensory neuropathy, a debilitating condition that degrades the quality of life of HIV patients. Furthermore, life-extending antiretroviral treatment may exacerbate HIV sensory neuropathy. Analgesics that relieve other neuropathic pains show little or no efficacy in ameliorating HIV sensory neuropathy. Thus, there is a need for analgesics for people with this particular pain. While lidocaine is used in the management of painful peripheral neuropathies, another local anesthetic mepivacaine, with a potentially improved bioavailability, could be utilized for the management of HIV neuropathic pain. Methods The efficacy of topical anesthetics was evaluated in a preclinical rodent model of painful peripheral neuropathy induced by epineural administration of the HIV envelope protein gp120 delivered using saturated oxidized cellulose implanted around the sciatic nerve. Beginning at 2 weeks following gp120 administration, the effects of local anesthetics topically applied via gauze pads were tested on heat and mechanical hyperalgesia in the hind paw. Rats were tested using several concentrations of mepivacaine or lidocaine during the following 2 weeks. Results By 2 weeks following epineural gp120 implantation, the ipsilateral hind paw developed significant hypersensitivity to noxious pressure and heat hyperalgesia. A short-lasting, concentration-dependent amelioration of pressure and heat hyperalgesia was observed following topical application of mepivacaine to the ipsilateral plantar hind paw. By contrast, topical lidocaine ameliorated heat hyperalgesia in a concentration-dependent manner but not pressure hyperalgesia. Equipotent concentrations of mepivacaine and lidocaine applied topically to the tail of mice significantly increased tail withdrawal latencies in the tail flick test, demonstrating that both local anesthetics attenuate responding to a brief noxious stimulus. Conclusion These findings showed that mepivacaine, rather than lidocaine, consistently attenuated two distinct symptoms of neuropathic pain and suggest that topical formulations of this local anesthetic could have utility in the alleviation of clinical HIV neuropathic pain.
Expanded applications of diagnostic and therapeutic thoracoscopy

From 1971 to 1990, 315 thoracoscopies were performed. Recent advances in optic/video systems and endoscopic operating instruments have made thoracoscopy easier and more accurate than 20 years ago. The operative mortality rate was low (1%) and the diagnostic accuracy high (99%). Thoracoscopy has been performed at an increasing frequency in recent years because of its expanded applications, especially in the areas of therapeutic or operative procedures such as carbon dioxide laser treatment of spontaneous pneumothorax or diffuse bullous emphysema, neodymium:yttrium-aluminum-garnet laser vaporization of pleural malignant tumors, and thoracoscope/laser-aided pleurectomy, pericardiectomy, or lung resection. Further technologic advancement in thoracoscopy will have a considerable impact on the future of thoracic surgery.
Internal Indpendent Assessment Report - CASTLE-PX SQA

This IIA assessed the flow down of institutional 830 Software Quality Assurance requirements through three required document templates to the CASTLE-PX software effort and the implementation of those SQA requirements. The templates flow down the DOE O 414.1D consensus standard requirements for Safety Software. This assessment did not include the flow down of NAP-24, Weapon Quality Policy, requirements. The assessment focused on the CASTLE-PX project’s software development and release processes. It did not assess Pantex’s acceptance or usage of the software. The assessment resulted in 3 Deficiencies, 5 Observations, 1 Recommendation, and 3 Strengths. Overall the CASTLE-PX team demonstrated it values quality and has worked to integrate quality practices into its software development processes. Improvement in documentation will enhance their SQA implementation.
How Fast to Move: A Physicist’s Look at the Economists

Former US President Harry Truman once said that he wished the government had more one-handed economists because his economists were always telling him on the one hand this, on the other hand that. Today, we do have many one-handed economists writing on the economics of taking action now to limit climate change. Unfortunately they seem to fall into camps with different hands. I will call the two camps after the two people who best represent them. One I call the Nordhaus camp after Professor William Nordhaus, the Sterling Professor of Economics at Yale University, and the creator of the Dynamic Integrated model of Climate and the Economy (DICE model) that is used by many to estimate the economic effects of climate change. The other I call the Stern camp after Sir Nicholas Stern, former Head of the UK Government Economics Service, who led the effort to produce the influential 2006 British analysis of climate change impacts called the Stern Report (he is now Lord Stern of Brentford and is at the London School of Economics). The issue is how much the world should be spending now to reduce the emissions that will cause large climate changes in the future. If we could assign a monetary value to future harm, and we used some reasonable discount rate (defined below), we could in principle figure out how much to invest now and in the future to reduce the harm. The Nordhaus camp says that we should be spending a reasonable amount now, but that there is no need to panic. The Stern camp in contrast says that the consequences are so severe as to constitute a global emergency and that drastic action is called for immediately. There is no one among the leaders of the economics profession who says we should do nothing now.
Agency Costs of Moving to Tax Havens: Evidence from Cross‐border Merger Premia

Research Question/Issue This paper explores the valuation effects of the tradeoff between tax avoidance and corporate governance through tax haven M&As. Firms can achieve tax savings by selling to an acquirer based in a tax haven, making the newly created multinational a haven resident. Changing a firm's tax home through a 100% acquisition is also accompanied by a change in legal system and corporate governance. Therefore, tax savings could come at the expense of corporate governance degradation making the value implications of such tax avoidance attempts an important empirical issue. Research Findings/Insights Using an international sample of cross-border M&As from 1989-2012, we find value evidence supporting the agency costs hypothesis. For 100% M&As, a lower target premium is associated with those transactions where the tax haven acquirer has weaker investor protection than the target. Theoretical/Academic Implications Our findings provide value evidence regarding the agency costs of tax motivated M&As as a result of the secrecy laws and limited investor protection of tax havens. Practitioner/Policy Implications This study provides a perspective for executives of multinational firms to take into account the value consequences associated with secrecy laws and weak investor protection while considering a possible relocation to tax havens. It also offers further insight to policy makers concerning the costs of limited investor protection and lack of transparency.
Upon admission coagulation and platelet function in patients with thermal and electrical injuries

Abstract Rational There has been increased focus on hemostatic potential and function in the initial assessment of the patient with traumatic injuries, that not been extensively studied in patients with burns. We proposed to determine the hemostatic potential of patients with burns upon admission to the emergency department and contrasted their condition with that of healthy controls and patients with other traumatic injuries. In addition we assessed differences due to thermal versus electrical injury and evaluated the effect of burn size. Methods This is a patient based prospective observational study conducted with delayed consented. Subjects at the highest level of trauma activation upon admission to the ED had a blood sample collected for research purposes and were subsequently consented. Hemostatic potential was measured by rapid thromelastography (r-TEG®), thrombin generation by calibrated automated thrombogram (CAT) and platelet function by Multiplate® using five activators. Burn subjects were compared to subjects with other traumatic injuries and controls. Within the burn subjects additional analysis compared mechanism (thermal vs. electrical) and burn size. Values are medians (IQR). Results Two hundred and eighty two trauma patients (with burns n = 40, 14%) and 27 controls were enrolled. Upon admission, compared to controls, subjects with burns or trauma were hyper-coagulable based on r-TEG and CAT, with increased rates of clot formation and thrombin generation. There were no differences in burns compared to other traumatic injuries. The presence of hyper-coagulation did not appear to be related to the type of burn or the percentage of total body surface area involved. Employing previous defined cut points for R-TEG driven therapeutic interventions burn patients had similar rates of hyper- and hypo-coagulation noted in patients with traumatic injuries. Conclusion Upon admission patients with burns are in a hyper-coagulable state similar to that of other trauma patients. Employing demonstrated cut points of hemostatic potential in trauma patients associated with increased risk of poor outcomes demonstrated the incidence in burn patients to be similar, suggesting that these values could be used in the early assessment of the patient with burns to guide treatment interventions.
A sustainability comparison of green infrastructure interventions using emergy evaluation

Abstract Green infrastructure (GI) has been touted as a more economically, socially, and environmentally sustainable option for urban stormwater management than more traditional gray infrastructure solutions. There are many types of GI, however, and there has been limited comparison of sustainability between types. This study examines the benefits and detriments of current GI designs (rain gardens, green roofs, porous pavements, and tree plantings) using emergy analysis, an environmental accounting system that evaluates the direct and indirect energy inputs used in the production of goods or services. Results of the analysis revealed inherent differences between the four GI typologies examined and identified system inputs that dominate emergy flows, and thus sustainability outcomes. Porous pavements performed the worst when evaluated using standard emergy-based environmental sustainability indices and the best when using economic indices. Indices calculated for green roofs and tree plantings indicated that these types of green infrastructure might inherently be more environmentally sustainable. Emergy inputs of stone and soil were dominant inputs for all systems, as was the emergy cost of disposal of excavated materials. Porous asphalt was a high emergy input for the porous pavement projects examined. Labor and equipment inputs were high for most projects, but were overshadowed by stone and soil inputs. These dominant emergy inputs show areas where efficiency of designs could be improved by practices such as recycling excavated sediments or utilizing construction materials that are less emergy intensive. In addition, the results of this study show that not all GI projects are created equally. Urban planners and other decision makers can use this information to improve standard design and implementation practices for GI projects.
Using Zebrafish for High-Throughput Screening of Novel Cardiovascular Drugs

Cardiovascular diseases remain a major challenge for modern drug discovery. The diseases are chronic, complex, and the result of sophisticated interactions between genetics and environment involving multiple cell types and a host of systemic factors. The clinical events are often abrupt, and the diseases may be asymptomatic until a highly morbid event. Target selection is often based on limited information, and though highly specific agents are often identified in screening, their final efficacy is often compromised by unanticipated systemic responses, a narrow therapeutic index, or substantial toxicities. Our understanding of complexity of cardiovascular disease has grown dramatically over the past 2 decades, and the range of potential disease mechanisms now includes pathways previously thought only tangentially involved in cardiac or vascular disease. Despite these insights, the majority of active cardiovascular agents derive from a remarkably small number of classes of agents and target a very limited number of pathways. These agents have often been used initially for particular indications and then discovered serendipitously to have efficacy in other cardiac disorders or in a manner unrelated to their original mechanism of action. In this review, the rationale for in vivo screening is described, and the utility of the zebrafish for this approach and for complementary work in functional genomics is discussed. Current limitations of the model in this setting and the need for careful validation in new disease areas are also described. An overview is provided of the complex mechanisms underlying most clinical cardiovascular diseases, and insight is offered into the limits of single downstream pathways as drug targets. The zebrafish is introduced as a model organism, in particular for cardiovascular biology. Potential approaches to overcoming the hurdles to drug discovery in the face of complex biology are discussed, including in vivo screening of zebrafish genetic disease models.
Harnessing legal complexity.

Complexity science has spread from its origins in the physical sciences into biological and social sciences ( 1 ). Increasingly, the social sciences frame policy problems from the financial system to the food system as complex adaptive systems (CAS) and urge policy-makers to design legal solutions with CAS properties in mind. What is often poorly recognized in these initiatives is that legal systems are also complex adaptive systems ( 2 ). Just as it seems unwise to pursue regulatory measures while ignoring known CAS properties of the systems targeted for regulation, so too might failure to appreciate CAS qualities of legal systems yield policies founded upon unrealistic assumptions. Despite a long empirical studies tradition in law, there has been little use of complexity science. With few robust empirical studies of legal systems as CAS, researchers are left to gesture at seemingly evident assertions, with limited scientific support. We outline a research agenda to help fill this knowledge gap and advance practical applications.
Complications and Outcomes After Gynecomastia Surgery: Analysis of 204 Pediatric and 1583 Adult Cases from a National Multi-center Database

Gynecomastia is a common disease that is prevalent across all age groups of boys and men. Although benign in nature, it can lead to psychological and social distress, prompting affected patients to seek medical attention. Management strategies include observation and drug therapy, yet surgical procedures remain the hallmark of treatment. The goal of this study was to analyze patient demographics, outcomes, and complication rates of gynecomastia surgery in a large multi-institutional cohort. We performed a retrospective analysis of the American College of Surgeons National Surgical Quality Improvement Program adult and pediatric databases to produce two cohorts that underwent gynecomastia surgical repair. The two populations were compared for comorbidities, perioperative details, and complication rates. Multivariate analyses helped detect risk factors associated with adverse events. A total of 204 pediatric and 1583 adult male patients were identified in our analysis. Mean ages were 15.8 and 39.6 years, respectively. A BMI of 28.2 in the latter cohort revealed an overweight adult population. Preoperative comorbidities (0.0–4.9% in children, 0.0–6.4% in adults) and American Society of Anesthesiologists scores (ASA 1 + 2: 98.5 and 82.7%) symbolized a healthy population. Procedures were subsequently performed mostly as outpatient (84.3 and 93.9%) and with short hospitalization durations (0.27 and 0.06 days). Our results demonstrated low surgical (3.9 and 1.9%) and medical (0.0 and 0.3%) complications within the standardized 30-day postoperative period. Children and adolescents, however, required double mean operative times compared to adults (111.3 vs 56.7 min). Operative gynecomastia treatment remains a safe treatment modality across all age groups. Patients with known preoperative medical or surgical comorbidities necessitate more extensive perioperative assessment and monitoring. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
Abstract 813: Development of a porcine model for pancreatic cancer

Pancreatic ductal adenocarcinoma (PDAC) remains a lethal disease with a 5-year survival rate of 4%. Without significant advances in early detection and treatment, PDAC is estimated to become the second leading cause of cancer deaths in the United States by 2020. Many advancements in PDAC have come from murine models and retrograde studies of patient samples. A supplemental pig model would allow such studies as noninvasive image-guided technologies, radiation oncology, drug metabolism, surgical experimentation/training, and early detection screening to be more readily performed. Here, we sought to develop an orthotopic model of porcine pancreatic cancer using transformed pancreatic tumor cells to help address some of these issues. We isolated primary porcine epithelial cells from pancreatic ducts harvested from a normal pig. We isolated epithelial cells from fibroblasts by serial dilutions and stained our final population with cytokeratin 19 (specific for pancreatic ductal epithelium), E cadherin, alpha-SMA, and collagen I to show that our population of primary cells were indeed of epithelial origin and not mesenchymal. We used these cells to generate 3 different tumorigenic cell lines: PGKP (contains mutated Kras and p53), PGKPS (PGKP + SMAD4 shRNA), and PGKPSC (PGKPS + p16 shRNA). We tested these cell lines using in vitro assays to test their tumorigenic properties. The PGKP cells outperformed the primary cells in proliferation, population doubling time, and soft agar growth with p-values We used all three cell lines in a subcutaneous injection model in nude mice to determine if they could produce tumors in vivo. We injected 5x106 cells into the hind flanks of mice with groups of 10 mice/cell line. Of the 30 mice injected, 28 grew tumors that were ≥1.8 cm2 in size within 5 weeks. All of the tumors had large necrotic centers, were hypervascular, and mucous producing. Upon HE 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 813. doi:10.1158/1538-7445.AM2017-813
Canine GM2‐Gangliosidosis Sandhoff Disease Associated with a 3‐Base Pair Deletion in the HEXB Gene

Background GM2-gangliosidosis is a fatal neurodegenerative lysosomal storage disease (LSD) caused by deficiency of either β-hexosaminidase A (Hex-A) and β-hexosaminidase B (Hex-B) together, or the GM2 activator protein. Clinical signs can be variable and are not pathognomonic for the specific, causal deficiency. Objectives To characterize the phenotype and genotype of GM2-gangliosidosis disease in an affected dog. Animals One affected Shiba Inu and a clinically healthy dog. Methods Clinical and neurologic evaluation, brain magnetic resonance imaging (MRI), assays of lysosomal enzyme activities, and sequencing of all coding regions of HEXA, HEXB, and GM2A genes. Results A 14-month-old, female Shiba Inu presented with clinical signs resembling GM2-gangliosidosis in humans and GM1-gangliosidosis in the Shiba Inu. Magnetic resonance imaging (MRI) of the dog's brain indicated neurodegenerative disease, and evaluation of cerebrospinal fluid (CSF) identified storage granules in leukocytes. Lysosomal enzyme assays of plasma and leukocytes showed deficiencies of Hex-A and Hex-B activities in both tissues. Genetic analysis identified a homozygous, 3-base pair deletion in the HEXB gene (c.618-620delCCT). Conclusions and Clinical Importance Clinical, biochemical, and molecular features are characterized in a Shiba Inu with GM2-gangliosidosis. The deletion of 3 adjacent base pairs in HEXB predicts the loss of a leucine residue at amino acid position 207 (p.Leu207del) supporting the hypothesis that GM2-gangliosidosis seen in this dog is the Sandhoff type. Because GM1-gangliosidosis also exists in this breed with almost identical clinical signs, genetic testing for both GM1- and GM2-gangliosidosis should be considered to make a definitive diagnosis.
Risk Factors for Infection After Shoulder Arthroscopy in a Large Medicare Population.

Background:Shoulder arthroscopy is well established as a highly effective and safe procedure for the treatment for several shoulder disorders and is associated with an exceedingly low risk of infec...
An axiomatization of plays in repeated games

Abstract Suppose that, in repeated games, players eventually engage in a pattern of action profiles, which we call a convention. Do some conventions seem more plausible than others? We answer axiomatically based on the principles of stability and efficient simplicity. The main solution says that conventions should be constant repetitions of a static Nash equilibrium, or such that players switch between two Pareto unranked profiles (across which they each change action). In some repeated games, this reduces the multiplicity of outcomes and even leads to uniqueness. The paper also reports experimental evidence that supports our findings.
Crystal structure of a mononuclear copper(II) complex with 2-methoxy-N,N-bis­(quinolin-2-yl­meth­yl)­ethyl­amine (DQMEA)

Structural characterization of the compound [Cu(C2H3N)(C23H23N3O)](ClO4)2] or [Cu(C2H3N)(DQMEA)](ClO4)2] [DQMEA = 2-methoxy-N,N-bis­(quinolin-2-ylmeth­yl)ethyl­amine] {systematic name: (aceto­nitrile)[2-methoxy-N,N-bis(quinolin-2-ylmeth­yl)ethyl­amine]­copper(II) diperchlorate} by single-crystal X-ray diffraction reveals a complex cation with a tetra­dentate coordination of the DQMEA ligand along with monodentate coordination of a CH3CN ligand to a single CuII center, with two perchlorate anions providing charge balance. The CuII center has a distorted square-pyramidal geometry in which the nitro­gen atoms of the DQMEA and CH3CN ligands occupy the equatorial positions, while the oxygen atom of the DQMEA ligand resides in the axial position with an elongated Cu—O bond. The quinoline ring systems are nearly co-planar in the structure, while the linear CH3CN ligand is tilted significantly below this plane, and the central nitro­gen of DQMEA is above it. Within the complex, weak C—H⋯N hydrogen bonding takes place between the nitro­gen of CH3CN and a neighboring quinolyl group. The perchlorate ions are disordered within the structure, but undergo a number of weak inter­molecular C—H⋯O hydrogen-bonding inter­actions. Additional weak π-stacking inter­actions between the quinolyl groups of neighboring complexes further stabilize the crystal packing.
Imaging of a high concentration of iron labeled cells with positive contrast in a rat knee.

Purpose The sweep imaging with Fourier transformation (SWIFT) imaging technique has been shown to provide positive contrast from diluted cell suspensions labeled with super-paramagnetic iron oxide (SPIO) in a tissue, as an alternative to T2*-weighted imaging. Here we demonstrate a variation of the SWIFT technique that yields a hyperintense signal from a concentrated cell suspension. The proposed technique provides minimal background signal from host tissue and facilitates visualization of injected cells. Methods The proton resonance frequency and linewidth were determined for SPIO solutions of different concentrations. The original SWIFT sequence was modified and a dual saturation Gaussian shape RF pulse with ~200 Hz bandwidth was incorporated into the acquisition protocol to suppress host tissue and fat signals. This modification of the original acquisition protocol permits the detection of a hyperintense signal from grafted cells with minimal background signal from the host tissue. Results SPIO particles not only induce broadening of NMR line-width but also an initiate proton resonance frequency shift. This shift is linearly proportional to the concentration of the iron oxide particles and induced by the bulk magnetic susceptibility of SPIOs. The shift of the resonance frequency of iron labeled cells allowed us effectively suppress the host tissues with saturation RF pulse to improve MRI detection of grafted cells. Conclusions Iron oxide particles increase the resonance frequency of water proton signal. This shift permitted us to add the tissue/fat saturation RF pulse into the original SWIFT acquisition protocol and detect distinct hyperintense signals from grafted cells with minimal background signal from the host tissue.
Deriving the Practice-Primed Decision Model from a naturalistic decision-making perspective for acute care nursing research.

Abstract Aim The purpose of this article is to present the derivation of the Practice Primed Decision Model from a naturalistic decision-making framework for use in guiding future nursing decision-making research. Background Acute care nurses make decisions in demanding environments under the influence of many factors. The influence of these factors on nurse decision-making is not well understood leading to gaps in understanding how to best support acute care nurse decision-making. Methods The strategy of theory derivation was used in the development of a new model for use in nursing research. This model incorporates important elements identified in naturalistic decision making, a Recognition Primed Decision Model and an integrative review of nurse decision-making literature. Conclusion The new model, Practice Primed Decision Model, provides a new perspective to guide nurse decision-making research. This model includes factors influential to the nurse decision-making process that is more realistic in time limited, high stakes decision-making situations.
Analysis of Kaon fluctuations from the beam energy scan at RHIC

Abstract We analyze the recent STAR collaboration results on net-kaon fluctuations in the framework of the Hadron Resonance Gas (HRG) model. Our purpose is to extract the freeze-out temperature and chemical potential as functions of the collision energy. In our HRG model, we use the complete hadron spectrum from the latest PDG list. These results are compared to the freeze-out parameters obtained from a combined analysis of net-electric charge and net-proton fluctuations. At the highest collision energies, kaons need about 10-15 MeV higher freeze-out temperatures than the light hadrons. Predictions for moment ratios of the net-Lambda multiplicity distribution are obtained along the freeze-out lines. Lambda fluctuations are sensitive to the difference in the freeze-out temperatures observed in our analysis.
Improving patient selection for adjuvant therapy in high-risk renal cell carcinoma.

From 2007 to 2011, the adjuvant sunitinib in high-risk renal cell carcinoma (RCC) after nephrectomy (S-TRAC) investigators conducted a phase 3, randomized, placebo-controlled trial with primary results published in 2016 (1). Patients with completely resected, high-risk RCC defined based on pathologic stage received either adjuvant sunitinib or placebo for a maximum of 1 year.
Residual or Gate? Towards Deeper Graph Neural Networks for Inductive Graph Representation Learning

In this paper, we study the problem of node representation learning with graph neural networks. We present a graph neural network class named recurrent graph neural network (RGNN), that address the shortcomings of prior methods. By using recurrent units to capture the long-term dependency across layers, our methods can successfully identify important information during recursive neighborhood expansion. In our experiments, we show that our model class achieves state-of-the-art results on three benchmarks: the Pubmed, Reddit, and PPI network datasets. Our in-depth analyses also demonstrate that incorporating recurrent units is a simple yet effective method to prevent noisy information in graphs, which enables a deeper graph neural network.