cssi/SciSciGPT-SciSciNet huggingface dataset:
Polypyrrole coated phase-change contrast agents for sono-photoacoustic imaging (Conference Presentation)

A new light and sound sensitive nanoemulsion contrast agent is presented. The agents feature a low boiling point liquid perfluorocarbon core and a broad light spectrum absorbing polypyrrole (PPy) polymer shell. The PPy coated nanoemulsions can reversibly convert from liquid to gas phase upon cavitation of the liquid perfluorocarbon core. Cavitation can be initiated using a sufficiently high intensity acoustic pulse or from heat generation due to light absorption from a laser pulse. The emulsions can be made between 150 and 350 nm in diameter and PPy has a broad optical absorption covering both the visible spectrum and extending into the near-infrared spectrum (peak absorption ~1053 nm). The size, structure, and optical absorption properties of the PPy coated nanoemulsions were characterized and compared to PPy nanoparticles (no liquid core) using dynamic light scattering, ultraviolet-visible spectrophotometry, transmission electron microscopy, and small angle X-ray scattering. The cavitation threshold and signal intensity were measured as a function of both acoustic pressure and laser fluence. Overlapping simultaneous transmission of an acoustic and laser pulse can significantly reduce the activation energy of the contrast agents to levels lower than optical or acoustic activation alone. We also demonstrate that simultaneous light and sound cavitation of the agents can be used in a new sono-photoacoustic imaging method, which enables greater sensitivity than traditional photoacoustic imaging.
Innovative models for providing clinical pharmacy services to remote locations using clinical video telehealth.

Purpose The use of videoconferencing and other telehealth technologies to expand access to clinical pharmacy services at multiple Veterans Affairs (VA) clinics in rural areas of Alaska and the northwestern United States is described. Summary Beginning in 2014, clinical pharmacy specialists at a regional VA Telehealth Hub based at Boise VA Medical Center in Idaho have provided telehealth services for 16 clinics. In one telehealth model, a pharmacist and other remotely located primary care team members (a medical provider, a medical support assistant, a social worker, and a psychologist) conduct telehealth visits with veterans located at VA clinics, with support provided by clinic-based nursing staff; this model has been used to improve medication management services for veterans in sparsely populated areas. In the second VA telehealth model, a remotely located pharmacist uses telehealth technology to participate in clinical encounters along with primary care team members located at the patient site; this model allows on-demand remote coverage in the event of planned or unplanned absences of clinic-based pharmacists. Since the Telehealth Hub was established, pharmacists have engaged in video encounters and provided other telehealth-based clinical services to more than 1,200 veterans with diabetes, hyperlipidemia, hypertension, and other chronic conditions. Conclusion Within the VA healthcare system, telehealth technology has been demonstrated to be a cost-effective and well-received means of providing clinical pharmacy services in rural areas.
Initial Shield Woodland

relative time period: Chronologically overlaps and then follows the Shield Archaic tradition; partially overlaps but largely precedes the historical period
Water-soluble-template-derived nanoscale silicon nanoflake and nano-rod morphologies: Stable architectures for lithium-ion battery anodes

Earth abundant and economical rock salt (NaCl) particles of different sizes (<3 μm and 5–20 μm) prepared by high energy mechanical milling were used as water-soluble templates for generation of Si with novel nanoscale architectures via low pressure chemical vapor deposition (LPCVD). Si nanoflakes (SiNF) comprising largely amorphous Si (a-Si) with a small volume fraction of nanocrystalline Si (nc-Si), and Si nanorods (SiNR) composed of a larger volume fraction of crystalline Si (c-Si) and a small volume fraction of a-Si resulted from modification of the NaCl crystals. SiNF yielded first-cycle discharge and charge capacities of ∼2,830 and 2,175 mAh·g−1, respectively, at a current rate of 50 mA·g−1 with a first-cycle irreversible loss (FIR loss) of ∼15%–20%. SiNR displayed first-cycle discharge and charge capacities of ∼2,980 and ∼2,500 mAh·g−1, respectively, at a current rate of 50 mA·g−1 with an FIR loss of ∼12%–15%. However, at a current rate of 1 A·g−1, SiNF exhibited a stable discharge capacity of ∼810 mAh·g−1 at the end of 250 cycles with a fade rate of ∼0.11% loss per cycle, while SiNR showed a stable specific discharge capacity of ∼740 mAh·g−1 with a fade rate of ∼0.23% loss per cycle. The morphology of the nanostructures and compositions of the different phases/phase of Si influence the performance of SiNF and SiNR, making them attractive anodes for lithium-ion batteries.
Buyid Silk and the Tale of Bibi Shahrbanu: Identification of Biomarkers of Artificial Aging (Forgery) of Silk

Buyid silk forgery is one of the most famous silk forgeries in the world. In 1924–1925, excavation of the Bibi Shahrbanu site in Iran unearthed several silk textiles. The silks were thought to be of the Buyid period (934–1062 BCE) of the Persian Empire and have since been known as the “Buyid silks”. In the 1930s, more silk appeared and was reported as being from the Buyid period as well. Controversy over the authenticity of these silks escalated after the purchase of the silks by museums throughout the world. Extensive investigations of several of these silks have been conducted over the years with respect to iconography, weaving patterns, dyes/mordant, style, and even radiocarbon dating. It was found that most of the silks are not from Buyid period. To test the authenticity of these silk fabrics, the recently developed silk dating technique using amino acid racemization (AAR) in conjunction with capillary electrophoresis mass spectrometry was applied to 13 Buyid silk specimens from the Textile Museum col...
The physics of an academic career

We adopted well-known physics equations to illustrate concepts for developing a successful academic career plan. Formulas for distance, force, momentum, and power are used to explain how to define goals and set a pace that maximizes success potential. Formulas for synergy, balance, and stress are used to highlight common obstacles encountered by both junior (untenured and early career) and established faculty and provide ways to circumvent or limit damage from setbacks. Combined, these formulas provide tips for thriving in an academic environment.
Gothic Romance and Retribution in the Short Fiction of Isabella Valancy Crawford

This chapter focuses on the short fiction of Isabella Valancy Crawford, and how Crawford used the Gothic romance genre to craft fictional heroines who gain more autonomy and greater freedom than their late eighteenth- and early nineteenth-century literary forbears. The chapter examines two early stories by Crawford, “The Perfect Number Seven” (1880) and “Sevres Fulkes” (1885), as well as two of her final stories which are set in distinctly Canadian settings, “Extradited” (1886) and “In the Breast of a Maple” (c. 1887). These stories show that not only did Crawford manage to succeed in the competitive world of popular magazines, becoming one of the first Canadian women writers to make her career as an author, but she also was integral to the creation of a more progressive imagining of the Gothic heroine.
Application of Advanced. Turbulence Models in Determining the Structure and Dispersion of Heavy Gas Clouds

The present paper reviews the use of a particular form of higher order turbulence modelling in heavy gas dispersion, and demonstrates its potential for use in complex situations. It is also shown how such models can be used to provide more general information on the detailed turbulence structure within a heavy gas cloud. A currently available 3D heavy gas dispersion model is also described, and examples given of typical applications.
3 – Nitric Oxide as a Communication Signal in Vascular and Neuronal Cells

This chapter elaborates the role of nitric oxide as a communication signal in vascular and neuronal cells. One of the most intriguing features of NO, considering the simplicity of the molecule, is that it elicits so many different regulatory functions and other effects. At relatively low concentrations, NO functions as a vasodilator, inhibitor of platelet adhesion and aggregation, inhibitor of neutrophil adhesion, a neuromodulator in the CNS, and possibly as an NANC neurotransmitter and neurotransmitter in other neuronal pathways as well. At relatively high concentrations, NO functions in a pathophysiological manner as a cytosolic product of cytokineactivated macrophages and possibly neutrophils and other phagocytic cells such as hepatic Kupffer cells. This chapter begins with a discussion on evidence that endothelium-derived relaxing factor is nitric oxide or a labile nitroso precursor. It also describes biosynthesis and metabolism of endothelium-derived nitric oxide. An overview of unique chemical properties for a ubiquitous and general physiological mediator is also presented in this chapter. The chapter reviews, in detail, about signal transduction mechanisms for transcellular communication. The chapter concludes with a discussion on nitric oxide as a neuronal messenger.
Interleukin-2 based therapy for kidney cancer.

Interleukin-2 (IL-2) is a 15 kDa glycoprotein, originally characterized as T-cell growth factor,’ and is produced in response to T-cell activation. Interleukin-2 binds to cells through T-cell receptors which are up-regulated with activation, and through these receptors, signals clonal expansion of T-cells, with specific and non-specific immunity, and expansion of natural killer (NK) cells, all with cytotoxic activity.2In addition, secondary cytokines are released, such as interferon-gamma, tumor necrosis factor, and interleukin-1, among others.’ Recombinant DNA technology has allowed the production of IL-2 in large quantities, allowing for clinical investigation of this agent.’ The most generally used formulation is that produced by Chiron, Proleukin®. Subsequent to this, clinical trials have demonstrated efficacy in the treatment of metastatic renal cell cancer and melanoma, and IL-2 was approved for these indications. The initial approval was for therapy with high dose IL-2, to be described below, which remains the gold standard for IL-2 administration in renal cell causes and melanoma. This approval is based on the durability of the responses that are produced. However, due to the toxicity and the need for patient selectivity with high dose IL-2, a variety of regimens exploring lower doses and different schedules and combinations have been investigated. These will be summarized.
Synchronous Capacitor-Clamped GaN Electrostatic Energy-Harvesting Power Stage

This paper presents a proposed power stage for an electrostatic energy harvester that uses Gallium Nitride transistors. It provides a review of various energy-harvesting sources, electrostatic energy harvesting, and previous research. It has been well demonstrated that the higher the harvesting voltage the greater the amount of energy harvested from the environment. The simulations show that the proposed circuit can increase the energy harvested per cycle by an order of magnitude, up to 220 nJ/cycle
Murine (Endemic) Typhus

Murine (endemic) typhus is a rickettsial disease with a worldwide distribution. The etiologic agent, Rickettsia typhi , is harbored by rodents and transmitted to humans by fleas. The disease occurs in epidemics and may be clinically mild, although it can cause severe and fatal cases. Recent outbreaks have been reported in China, Kuwait, Thailand, and Australia. Cases in the United States have diminished, with the highest number reported in Los Angeles and Orange County, California, and South and Central Texas.
Extreme Thrombocytosis after Pediatric Pancreatectomy with Islet Autotransplantation Is Unique Compared to Other Postsplenectomy States.

Abstract Background Hematologic trends after pancreatectomy with islet autotransplantation (IAT), which involves splenectomy, have been rarely studied. Reactive thrombocytosis (RT, platelets ≥ 500 K/μL) often occurs postoperatively, similar to other postsplenectomy states, but the degree of similarities and true incidence are unknown. Study design A single-site, retrospective, observational cohort study of patients who underwent total splenectomy between 2010 and 2018 was performed. Thrombocytosis incidence and pharmacologic management strategies were evaluated, including cohort-based analyses for IAT versus other splenectomy indications. Results Analyses included 112 patients overall, 42 of whom underwent IAT. RT occurred frequently (93.8%) despite most patients having normal preoperative platelet counts. IAT patients had significantly higher peak platelet counts compared to non-IAT patients and the rate of platelet rise for IAT patients was significantly faster. IAT was uniquely predictive of developing extreme thrombocytosis (ExT, platelets ≥ 1000 K/μL, 90% vs. 15.7%, risk ratio 4.11, P Conclusions RT was common regardless of splenectomy indication but ExT was uniquely associated with IAT despite cytoreductive pharmacotherapy. These results strongly suggest that splenectomy is unlikely to be the sole contributor to post-IAT RT but further investigations into this phenomenon are needed. Level-of-Evidence rating Treatment study, Level III (retrospective comparative study).
Lessons Learned from Providing Hundreds of Hours of Diversity Training

The past thirty years have seen many advances in our understanding of issues that impede diversity, as well as interventions that can remove or mitigate those impediments. The advances are generally presented in psychology journals and are under-consumed by computing educators, leading to the need for diversity training tailored to said educators. We have hundreds of hours of experience providing diversity training to computing educators, and have learned many lessons about how training should and should not be delivered to engage participants in understanding diversity-impeding forces and implementing interventions to improve the attraction and retention of diverse students. This paper is a collection of those lessons learned. We focus on concrete approaches to presenting material rather than on training organization or content, including a dozen specific practices that have proven particularly effective or ineffective in reaching diverse audiences. Examples include how how to avoid offending participants, how to help experts not lose their audience, how to pace and organize material for maximum impact, how we tie many topics into a single cognitive framework, and how we've learned to handle participant-raised objections. We also include commentary as to why we believe they did or did not work. We also describe possible future research to validate and expand on our observations and a few open questions for diversity training.
Real Time Accident Prediction and Related Congestion Control Using Spark Streaming in an AWS EMR cluster

This paper focuses on real-time cloud based analytics of live video feeds from the cameras of self-driven autonomous vehicles using the Spark framework on Amazon’s Elastic Mapreduce (EMR). We use deep-learning methodologies for real-time object detection on the streamed images, to classify and predict traffic incidences, leading to subsequent congestion control. Results on a benchmark application: traffic congestion aware navigation using 10 self-driving vehicles with their own camera feeds as they drive around in Manhattan, show a 60% improvement in performance on the AWS-EMR based Spark framework, when compared to cloud processing on single instance of EC2 server on the AWS.
Is Intensive Care Unit Admission Necessary After Removal of Mandibular Distraction Devices in Infants With Robin Sequence

Objective:Intensive care unit (ICU) care is routinely required after the operation to initiate mandibular distraction osteogenesis (MDO) in infants with Robin sequence (RS). Many patients are also ...
Longitudinally Variable Polarization Optics

We introduce a new class of polarizing elements (analyzers and retarders) that virtually rotate their orientation as a function of the propagation distance, thus expanding the scope of conventional polarization devices into 3D space.
The Association Between BMI and Inpatient Mortality Outcomes in Older Adults With COVID-19.

Background and aim Coronavirus disease 2019 (COVID-19) is known to cause a broad spectrum of illnesses. There is evidence that obesity-related conditions may increase the severity of COVID-19 disease, especially in those below the age of 60. However, there has been limited research on mortality rate based on body mass index (BMI) in the older adult population, defined as age over 65. The objective of this study was to characterize outcomes in older adults infected with COVID-19 based on BMI. Study design and methods It is a single-center retrospective cohort study of older adults with COVID-19 infection. The primary outcome was hospital mortality. Secondary outcomes assessed were oxygen requirements, need for mechanical ventilation, duration of mechanical ventilation, and hospital length of stay. Data were analyzed with the Student's t-test, Fisher's exact test, and multiple logistic regression analyses as appropriate. Results A total of 290 patients were included in this study. The mean age was 77.6 years. The median BMI was >30 kg/m2. The primary outcome of hospital mortality occurred in 49.7% of patients. BMI was not found to be a predictor of mortality. Age 75-79 and age ≥ 85 were associated with an increased risk of mortality (OR: 2.58; 95% CI: 1.15 - 5.79; OR: 3.17; 95% CI: 1.35 - 7.44, respectively). Patients with a BMI < 18.5, BMI 18.5 - 25, and age ≥ 85 were less likely to require mechanical ventilation (OR: 0.06; 95% CI: 0.00 - 0.83; OR:0.11; 95% CI: 0.02 - 0.64 and OR:0.28; 95% CI: 0.09 - 0.92, respectively). Past medical history was not associated with mortality. Conclusion In a cohort of older adults with COVID-19 disease, BMI was not an independent predictor of in-hospital mortality. Patients with BMI ≤ 25 and age ≥ 85 years were less likely to require mechanical ventilation.
The science of crystallization : macroscopic phenomena and defect generation

This book, together with its companion volume The Science of Crystallization: Microscopic Interfacial Phenomena, make up a complete course that will teach an advanced student how to understand and analyse scientifically any of the phenomena that are observed during natural or technological crystallization from any medium and via any technique. It is an advanced text that goes into considerable detail concerning the many elements of knowledge needed to understand both quantitatively and qualitatively a crystallization event. Both the present book and its companion volume are sufficiently broad to provide the scientific basis necessary to address any area of application. The book and its companion can be used independently of each other, and together they provide the basis for advanced courses on crystallization in departments of materials science, metallurgy, electrical engineering, geology, chemistry, chemical engineering and physics. In addition the books will be invaluable to scientists and engineers in the solid state electronics, optoelectronics, metallurgical and chemical industries involved in any form of crystallization and thin film formation.
Arthroscopic Biologic Interpositional Tuberosity Graft for the Treatment of Irreparable Rotator Cuff Tears

Abstract Massive, irreparable rotator cuff tears in younger, more active patients present a unique treatment challenge to shoulder surgeons. In the past few years, new techniques continue to emerge to address this challenging problem. The superior capsular reconstruction technique has been accepted as an option for addressing this problem. While initial results are encouraging, pitfalls remain regarding technical challenges, healing and protracted rehabilitation due to delayed motion protocols. We present an alternative approach to the massive, irreparable rotator cuff tears using a biologic interpositional humeral -based graft.
Election Administration and Public Records Responsiveness

Is there an optimum method to elicit public records from election officials? Using a field experiment that randomly assigned the wording and email domains used to solicit public records, we test ho...
Population Informative Markers Selected Using Wright's Fixation Index and Machine Learning Improves Human Identification Using the Skin Microbiome.

Microbial DNA, shed from human skin, can be distinctive to its host and, thus, help individualize donors of forensic biological evidence. Previous studies have utilized single-locus microbial DNA markers (e.g., 16S rRNA) to assess the presence/absence of personal microbiota to profile human hosts. However, since the taxonomic composition of the microbiome is in constant fluctuation, this approach may not be sufficiently robust for human identification (HID). Multimarker approaches may be more powerful. Additionally, genetic differentiation, rather than taxonomic distinction, may be more individualizing. To this end, the nondominant hands of 51 individuals were sampled in triplicate (n = 153). They were analyzed for markers in the hidSkinPlex, a multiplex panel comprising candidate markers for skin microbiome profiling. Single-nucleotide polymorphisms (SNPs) with the highest Wright's fixation index (FST) estimates were then selected for predicting donor identity using a support vector machine (SVM) learning model. FST is an estimate of the genetic differences within and between populations. Three different SNP selection criteria were employed: SNPs with the highest-ranking FST estimates (i) common between any two samples regardless of markers present (termed overall); (ii) each marker common between samples (termed per marker); and (iii) common to all samples used to train the SVM algorithm for HID (termed selected). The SNPs chosen based on criteria for overall, per marker, and selected methods resulted in an accuracy of 92.00%, 94.77%, and 88.00%, respectively. The results support that estimates of FST, combined with SVM, can notably improve forensic HID via skin microbiome profiling. IMPORTANCE There is a need for additional genetic information to help identify the source of biological evidence found at a crime scene. The human skin microbiome is a potentially abundant source of DNA that can enable the identification of a donor of biological evidence. With microbial profiling for human identification, there will be an additional source of DNA to identify individuals as well as to exclude individuals wrongly associated with biological evidence, thereby improving the utility of forensic DNA profiling to support criminal investigations.
Abdominal subcutaneous adipose tissue negatively associates with subclinical coronary artery disease in men with psoriasis.

Abstract Objective Understand the relationship between abdominal subcutaneous adipose tissue (ASAT) and coronary atherosclerosis defined as noncalcified and lipid-rich necrotic core burden in psoriasis. Methods We performed a cross-sectional study of 232 participants (92 women) with psoriasis and without known cardiovascular disease. Participants underwent coronary computed tomography angiography to characterize coronary atherosclerosis burden and low dose abdominal computed tomography to quantify subcutaneous and visceral adipose tissue. Fat depot volumes were first adjusted for each participant's BMI (ASATadjBMI). Results In women, there was a positive correlation between ASATadjBMI and systemic inflammation as assessed by hs-C-reactive protein (r=0.30; p=.004) and GlycA (r=0.29; p=.007) as well as total cholesterol (r=0.24; p=.02) and low-density lipoprotein cholesterol (r=0.22; p=.04). In men, ASATadjBMI correlated with hs-C-reactive protein (r=0.18; p=.04) and insulin resistance (r=0.17; p=.04). In models fully adjusted for traditional cardiovascular risk factors, ASATadjBMI negatively associated with noncalcified and lipid-rich necrotic core burden in men (β= -0.17; p=.03, β= -0.20; p=.03, respectively), but not women (β= -0.06; p=.57, β= 0.09; p=.49, respectively) with psoriasis. Conclusions For a given BMI, ASAT negatively associated with coronary atherosclerosis burden in male participants with psoriasis. The observed sex-specific effects warrant further study of ASAT in states of chronic inflammation.
Platelet-derived growth factor receptor β inhibition increases tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) sensitivity: Imatinib and TRAIL dual therapy

BACKGROUND: There is a crucial need for better therapeutic approaches for the treatment of Ewing sarcoma (EWS). Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) induces apoptosis in EWS cells in vitro. However, in vivo, acquired resistance to TRAIL is a major limiting factor. Platelet-derived growth factor receptor-β (PDGFR-β) is highly expressed on EWS cells. Thus, the authors evaluated whether PDGFR-β blockade could sensitize EWS cells to TRAIL-induced apoptosis in vitro and in vivo. METHODS: The effect of combined imatinib mesylate (Gleevec) and TRAIL on EWS cell growth and apoptosis was tested in vitro. Stable PDGFR-β knockdown in EWS cells was achieved by short-hairpin RNA transduction, and TRAIL sensitivity of these cells was measured. Expression of death receptors was measured by fluorescence-activated cell-sorting (FACS) analysis, and caspase 8 activity was evaluated by Western blot analysis. An orthotopic human xenograft model of EWS growth and spontaneous metastasis in nude mice was used to assess the in vivo affect of combined imatinib mesylate and TRAIL. RESULTS: Imatinib mesylate induced a significant TRAIL proapoptotic effect in EWS cells in vitro. Specific PDGFR-β silencing in EWS cells enhanced the effects of TRAIL, possibly through an increase in the expression of death receptors 4 and 5. The combination of imatinib mesylate and TRAIL significantly inhibited the growth of primary tumors and decreased the incidence of spontaneous EWS pulmonary metastasis compared with either drug alone. CONCLUSIONS: PDGFR-β blockade combined with TRAIL resulted in antihuman EWS activity in vitro and in vivo, suggesting the possibility that combining these treatments will improve anti-EWS therapy. Cancer 2010. © 2010 American Cancer Society.
Los circulos del aparato circulatorio

Luz en lo alto. Juan Felipe Robledo. Universidad Externado de Colombia, Coleccion Un libro por centavos, numero 23, Bogota, 2006, 68 pags.
Actin-membrane cytoskeletal dynamics in early sea urchin development.

Publisher Summary Eggs and embryos have been used in a vast array of biochemical, biophysical, and cytological studies to ask and answer seminal questions on fertilization, signal transduction, cell cycle regulation, exocytosis, gene expression, cellular induction, and differentiation. Historically, the echinoderm egg and embryo have been particularly fruitful in pushing the envelope of the understanding of complex synergistic interactions among cell signaling events, membrane traffic, and cytoskeletal reorganizations that occur during the course of normal cellular and embryonic differentiation. Nowhere is this better exemplified than in the extraordinary works of Rappaport, Hiramoto, and others who have shown the important relationship that exists between the mitotic spindle and the cortical membrane actin cytoskeleton leading to the induction and formation of the contractile apparatus driving cytokinesis. This chapter focuses on the actin cytoskeleton and its interaction with egg and embryonic membranes during fertilization and morphogenesis. It highlights the known sea urchin egg actin-binding proteins and discusses their structural, functional, and regulatory cytoskeletal-membrane dynamics during development. Fertilization serves as the starting point for reviewing the dynamic interplay between physiological activation and reorganization of the cortical actin-membrane cytoskeleton (filament assembly, cortical granule exocytosis, microvillar elongation, membrane uptake, vesicle sorting) that follows sperm-egg fusion. The chapter provides an appreciation of the sea urchin egdembryo as a cell and developmental model for studying the mechanisms underlying cytoskeletal membrane reorganization and its importance to early embryonic morphogenesis and differentiation.
A SURVEY OF OUR PRESENT SOURCES OF INFORMATION ON THE CONVERSION CONSTANT, A(=lambda(g)/lambda(s)) AND THE ABSOLUTE WAVELENGTHS OF X-RAY EMISSION LINES.

Origin of the "X-Unit" and the Scale of X-Ray Wavelengths. - The wavelengths of X-ray emission lines measured relative to each other by the high precision methods of crystal diffraction are mostly known with a precision of 1 part in 10^(4) to 10^(5). By refined and very careful measurements with the 2-crystal spectrometer, an imprecision approaching and in some cases perhaps even smaller than a part in a million can be obtained.
Quantitative Structure–Activity Relationships and Computational Methods in Drug Discovery

Quantitative structure–activity relationships (QSARs) are mathematical equations or other types of functions (such as the weights of connections in artificial neural networks) relating chemical structures to their biological activity. The purpose of QSAR studies is to predict novel structures with either beneficial activity as drugs for human or veterinary medicine (bactericides, antiviral or anticancer drugs, and metabolic regulators, such as hypoglycemics, hypotensives, etc.), or selective toxicity for various unwanted higher organisms (pesticides such as fungicides, insecticides, acaricides, weed killers, etc.) Quantitative structure–property relationships (QSPRs) are similar, but the property may be physical or chemical. The main problems involve finding a mathematical representation of chemical structures (usually organic molecules), represented either as molecular graphs by their constitution or connectivity without considering the three-dimensional (3-D) (stereochemical) factors, or as 3-D objects including stereochemical information; measuring the biological activities of a series of molecules; finding the QSAR between each type of biological activity and the most convenient molecular descriptors. Physicochemical parameters that are closely related to drug transport and ligand binding include lipophilicity, polarity, polarizability, and electronic influence on hydrogen-donor and hydrogen-acceptor binding. The next task is to use the QSAR to predict which novel structures to prepare in order to obtain molecules with the desired biological activity. Then the cycle is usually repeated, because a single pass seldom affords the optimal solution. The main mathematical descriptors and the techniques for obtaining QSARs are reviewed. An important molecular parameter, which may be measured experimentally or computed from the chemical structure, is lipophilicity or hydrophobicity; Hansch introduced the n-octanol–water partition coefficient as a measure of this property, which, to a large extent, determines the ability of molecules to penetrate the lipophilic, bilayer, extra- or intracellular membranes. Lipophilicity levels that are too high lead to insolubility in water, i.e. it is difficult to administer the drug orally via the digestive tract. The main constitutional and 3-D molecular descriptors are described and examples are given. To be statistically valid, correlations must involve orthogonal or orthogonalized descriptors. Linear, multilinear, and nonlinear types of correlations are reviewed. Screening of virtual combinatorial libraries together with high-throughput combinatorial synthesis and testing provides modern tools for more efficient drug design. Keywords: QSAR; isomers; chemical graphs; hydrophobicity; molecular descriptors; topological indices; molecular similarity/dissimilarity; computer-assisted drug design; chemoinformatics
What synaptic lipid signaling tells us about seizure-induced damage and epileptogenesis.

Abstract Glutamate, the most abundant excitatory neurotransmitter in the mammalian CNS, plays a central role in many neuronal functions, such as long-term potentiation, which is necessary for learning and memory formation. The fast excitatory glutamate neurotransmission is mediated by ionotropic receptors that include AMPA/kainate and N-methyl-Daspartate (NMDA) receptors, while the slow glutamate responses are mediated through its interaction with metabotropic receptors (mGluRs) coupled to G-proteins. During seizures, massive release of glutamate underlies excitotoxic neuronal damage as it triggers an overflow of calcium in postsynaptic neurons mediated by NMDA-gated channels. The early upstream postsynaptic events involve the activation of phospholipases, with the release of membrane-derived signaling molecules, such as free arachidonic acid (AA), eicosanoids, and platelet-activating factor (PAF). These bioactive lipids modulate the early neuronal responses to stimulation as they affect the activities of ion channels, receptors, and enzymes; and when released into the extracellular space, they can contribute to the modulation of presynaptic neurotransmitter release/re-uptake, and/or affect other neighboring neuronal/glial cells. The downstream postsynaptic events target the nucleus, leading to activation of gene-expression cascades. Syntheses of new proteins are the basis for seizure-induced sustained physiological and/or pathological changes that occur hours, days, or months later, such as synaptic reorganization and repair, and apoptotic/necrotic neuronal death. The intricate mesh of signaling pathways converging to the nucleus, and connecting upstream to downstream synaptic events, are at present the focus of many research efforts. We describe in this chapter how seizure-induced glutamate release activates the hydrolysis of membrane AA-phospholipids via phospholipase A2 (PLA2), PLC, and PLD, thus releasing bioactive lipids that, in turn, modulate neurotransmission. We discuss mechanisms through which lipid messengers, such as AA and PAF, may turn into injury mediators participating in seizure-induced brain damage.
Conservation Through Collusion: Antitrust Barriers to Cooperative Fishery Management

Antitrust law aims to protect consumers from anti-competitive conduct that can restrict output and increase price. Conservation, on the other hand, often requires restrictions on output in order to maintain resource consumption at a sustainable level. Thus, while antitrust and environmental law both seek to advance the public interest, in the context of resource conservation they can conflict. Collective arrangements among private firms to reduce output or allocate market shares are inherently suspect, even if the intent or effect is to conserve an otherwise threatened ecological resource. This paper examines the tension between resource conservation and antitrust in the context of marine fisheries. Beginning in the 1930s, fishing unions and cooperatives have been prosecuted for setting prices or restricting output, even where such arrangements have served conservation purposes. By limiting the sorts of cooperative arrangements that fishers or other common pool resource users may adopt to limit access or utilization of the underlying resource, antitrust law may inhibit the development of more effective self-governing institutions.
Coating Electrospun Chitosan Nanofibers with Polyelectrolyte Multilayers Using the Polysaccharides Heparin and N,N,N‐Trimethyl Chitosan

A new method is presented for functionalizing electrospun nanofibers with GAGs and growth factors by PEM deposition. Electrospun chitosan nanofibers, spun from trifluoroacetic acid and dichloromethane, were coated with PEMs, using the polysaccharides heparin and N,N,N-trimethyl chitosan. FGF-2 was adsorbed on the PEM-coated nanofibers. Nanofiber neutralization, PEM construction, and FGF-2 adsorption were monitored using FT-IR spectroscopy and X-ray photoelectron spectroscopy. Alcian blue staining was used to confirm the presence of heparin. SEM was used to study nanofiber morphology.
Photo-n-p junctions in ZnTe

We have demonstrated ZnTe devices with efficient (about 1%) light emission at 77 °K in which the injection mechanism is a forward-biased photo-n-p junction. In one, Al and Cd are diffused into highly p-type ZnTe:P to produce an AI-doped region 70µm deep with a 20µm surface layer of average composition Zn0.5Cd0.4Te. Light emission (575 nm) is observed for 2.5 V. Similar results are obtained when Al alone is diffused in from an evaporated layer to a depth of about 50µm. This latter device was earlier thought to operate by avalanche injection. Both structures with In contacts to the Al layer give open-circuit photovoltages of over 1.8 V at 77 °K. The all-ZnTe device, however, requires over 7 V to sustain light emission. While it is possible that efficient ZnTe devices made by vapor diffusing the Al are avalanche injection structures, efficient avalanche injection in a II-VI device has yet to be conclusively demonstrated.
Can prototypes inform moral developmental theory

L. J. Walker and R. C. Pitts (1998) suggest that research on prototypes of moral excellence can lead to important new insights for accounts of moral development that are unlikely to emerge from the efforts of theorists working within psychological or philosophical paradigms. In this commentary, I argue that (a) experts in philosophical and psychological paradigms can and do contribute to revisions of theories of moral excellence, and (b) the study of prototypes has limited value for resolving some important theoretical issues. Three research topics that can be informed by the investigation of prototypes of moral excellence are described.
The evolution of professional training in the American Dance Therapy Association

Since its inception in 1966, the American Dance Therapy Association (ADTA) has worked to develop standards of professional training. The initiation of a registry procedure was the organization’s first attempt to identify and set forth standards for clinical training. This task was often difficult due to three important factors: (1) the lack of in-depth training opportunities during the early years of the association; (2) the desire and motivation of the ADTA to establish a professional identity; and (3) the lack of a clearly defined body of knowledge. The emergence of graduate programs in dance therapy has positively affected the quality of training, lent credibility to the profession, and facilitated the discovery and exploration of a body of knowledge. This paper traces the historical development of dance therapy training in the ADTA.
Impression creep of β-tin single crystals

Abstract The impression creep of β-tin single crystals was studied in three orientations: [001], [100] and [110]. The temperature dependence of the steady state impression velocity showed two parallel processes. The activation enthalpy for the high temperature process was 25 – 26 kcal mol −1 for all three orientations and showed no obvious effects of stress. The value is comparable to that for self-diffusion, 25.6 kcal mol −1 . For the low temperature process, the activation enthalpy was stress dependent. Some values are 8.2 kcal mol −1 for the [001] orientation at 16 – 20 MN m −2 , 10 kcal mol −1 for [001] at 12 – 16 MN m −2 and 9.4 kcal mol −2 for [110] at 16 – 20 MN m −1 . For all orientations and all temperatures, the stress dependence of the impression velocity obeyed a power law with stress exponents between 3.6 and 5.0, in general agreement with previously reported results from conventional creep tests. Slip lines developed around the impression were more numerous at low temperatures than at high temperatures. Pencil slip was observed at low temperatures but not at high temperatures in the [001] orientation. It is suggested that the low temperature process involves dislocation slip and the high temperature process involves dislocation climb.
Effects of intraocular tetrodotoxin on dendritic spines in the developing rat visual cortex: a Golgi analysis

The effect of tetrodotoxin (TTX)-induced monocular impulse blockade on the growth of dendritic spines in the developing rat primary visual cortex was analysed by quantitative Golgi techniques. Between 5 and 21 days postnatal (dpn), rats were injected with TTX every 2 days into the right eye to chronically eliminate optic impulses. Effectiveness of TTX was monitored by loss of the pupillary light reflex. At 21 dpn, the number of spines located on the portion of the apical dendrite within layers III, IV and the superficial region of layer V was reduced by approximately 26%. These decreases were found on the apical dendrites of both large and medium sized pyramidal cells. TTX also reduced the number of spines on the proximal portion of oblique dendrites in layer IV by 16%, yet did not change the number of spines on basilar dendrites. No evidence of transneuronal degeneration was seen following long-term TTX treatment. These data indicate that dendritic spine development in the visual cortex is sensitive to the loss of optic impulses and that the decrease in spine population is principally due to a reduction in spine growth.
Modified rapid deployment hemostat bandage terminates bleeding in coagulopathic patients with severe visceral injuries.

Background We recently reported that a new dressing, the Modified Rapid Deployment Hemostat (MRDH) controlled bleeding in hypothermic coagulopathic swine after traumatic liver avulsion. The purpose of this study was to evaluate the MRDH in coagulopathic trauma patients undergoing abbreviated laparotomy. Methods A prospective, observational clinical trial of the MRDH dressing was performed at our Level One Trauma Center in patients with high-grade visceral injuries with coagulopathy who failed conventional therapy and required packing. Attending surgeons graded the injury and the adequacy of hemostasis following application of the dressing. Patients were followed until discharge or death. Results Ten patients were enrolled: nine severe hepatic injuries, and one major abdominal vascular injury. All patients were hypothermic, acidotic, and clinically coagulopathic. Intraoperative hemostasis was immediately obtained after MRDH placement in all cases except one. There was one death. Conclusion The Modified Rapid Deployment Hemostat terminates bleeding from severe visceral injuries in coagulopathic patients undergoing abbreviated laparotomy.
Predicting returns in the stock and bond markets

Abstract Several predetermined variables that reflect levels of bond and stock prices appear to predict returns on common stocks of firms of various sizes, long-term bonds of various default risks, and default-free bonds of various maturities. The returns on small-firm stocks and low-grade bonds are more highly correlated in January than in the rest of the year with previous levels of asset prices, especially prices of small-firm stocks. Seasonality is found in several conditional risk measures, but such seasonality is unlikely to explain, and in some cases is opposite to, the seasonal found in mean returns.
High-power piezoelectric acoustic-electric power feedthru for metal walls

ABSTRACT Piezoelectric acoustic-electric power feed-through devices transfer electric power wirelessly through a solid wall using elastic waves. This approach allows for the elimination of the need for holes through structures for cabling or electrical feed-thrus . The te chnology supplies power to electric equipment inside sealed containers, vacuum or pressure vessels, etc where holes in the wall are prohibitive or may result in significant performance degradation or requires complex designs. In the our previous work, 100-W of elec tric power was transferred thr ough a metal wall by a small, piezoelectric device with a simple-structure. To meet requirements of higher power applications, the feasibility to transfer kilowatts level power was inve stigated. Pre-stressed longitudinal piezoelectric feed-thru devi ces were analyzed by finite element modeling. An equivalent circuit model wa s developed to predict the char acteristics of power transfer to different electric loads. Based on the analytical results, a prototype device was designed , fabricated and successfully demonstrated to transfer electric power at a level of 1-kW. Methods of minimizing plate wave excitation on the wall were also analyzed. Both model analysis and experime ntal results are presented in detail in this paper. KEYWORD : piezoelectric devices, acoustic wave, electric powe r supply, wireless power feed, pressure vessels.
Sexual life events and schizophrenia.

A large body of clinical literature would imply that life events in the sexual sphere are of major significance for schizophrenic patients. However, the best known reports of life events associated with the onset of schizophrenia do not seem to support the significance of life events in the sexual sphere in the onset, early course, or exacerbation of schizophrenia. Methodologically, however, these studies have focused on the precipitating event, rather than on the amount of life stress induced by the serial occurrence of life events. This suggests the possibility that if life events in schizophrenic patients are examined in their totality, conclusions as to the relationship between sexual life events and schizophrenia might be different. As part of an international collaborative study twenty subjects receiving an ICD-9 diagnosis of schizophrenia, hospitalized for the first time in their lives for functional psychiatric disorder, were evaluated on the basis of a structured interview to assess symptoms and psychiatric history, including life events. Almost half (920) of these schizophrenic patients were found to have experienced life events occurring in the sexual sphere. At the customary P < .05 level of significance, the presence of life events in the sexual sphere was independent of gender, marital status, and race, as well as age. If sexual sphere events were to be excluded completely from the ratings, 18 of 20 would still have had ratable life events. These data suggest the importance of relating specific categories of events to specific subject characteristics or to specific populations. They also point to the importance of life events in the sexual sphere as stressors for first-admission schizophrenic patients. Difficulties in more fully understanding the importance of life events in the sexual sphere can be approached via both a social model entailing prohibition of communication, and a psychopathological model involving the nature of the schizophrenic or preschizophrenic psychological processes.
Lognormality of the scalar dissipation pdf in turbulent flows

It is shown that measurements of lower‐dimensional projections of the scalar gradient in an isotropic conserved scalar field ζ(x,t) are sufficient to construct the probability density function (pdf) for the true scalar dissipation χ. With this general method, the true scalar dissipation pdf is obtained from the result reported recently for the approximate pdf based on ‖∇ζ‖2≈3⋅(∂ζ/∂x)2. Results show that (i) the pdf of the true scalar dissipation is virtually lognormal and (ii) the most probable value of χ increases and the rms fluctuations of χ decrease in comparison with their one‐dimensional estimates.
Introduction to the special section on the emotional concomitants of brain damage.

The purpose of this introduction is to emphasize the theoretical and clinical implications of studying emotion after brain damage. Theoretically, it is one way of elucidating critical neural substrates of emotion and the interaction of cognitive and noncognitive determinants. Clinically, the cognitive and other behavioral changes associated with certain types of brain damage may make traditional methods of assessing emotion inaccurate. This special section is designed to review current knowledge regarding these issues and to emphasize their theoretical and clinical importance.