cssi/SciSciGPT-SciSciNet huggingface dataset:
Receptor Binding Targets for Antipsychotic Efficacy

In order to identify the contribution of individual serotonin and dopamine receptor subtype binding targets to antipsychotic medication efficacy, we analyzed correlations between binding affinity to cloned dopamine and serotonin receptor subtypes and clinically effective drug dose for atypical antipsychotic medications. The strongest correlation was observed between binding affinity to the D3 subtype dopamine receptor and clinically effective atypical antipsychotic medication drug dose (r = 0.77, p = 0.005). In contrast, binding affinity to the D2 (r = 0.59, p = 0.056) and D4 subtype dopamine receptors (r = 0.23, p = 0.23) exhibited lower correlations with atypical antipsychotic medication dosages. No direct correlations were identified between atypical antipsychotic medication dose and binding affinities to serotonin 5-HT1A, 5-HT2A, 5-HT2C, or 5-HT7 receptor subtypes. Highly significant correlations were also observed between atypical antipsychotic medication dose and the ratios of D2/5-HT1A (r = 0.69, p = 0.019); D3/5-HT1A (r = 0.69, p = 0.02); D3 × 5-HT2A (r = 0.71, p = 0.014); (D2 × D3)/5-HT1A (r = 0.81, p = 0.002); (D2 × D3 × 5-HT7)/5-HT1A (r = 0.74, p = 0.010); (D2 × D3 × 5-HT2A)/5-HT1A (r = 0.76, p = 0.007); (D2 × D3 × 5-HT2C)/5-HT1A (r = 0.76, p = 0.007); and (D2 × D3 × 5-HT2A × 5-HT2C)/5-HT1A (r = 0.72, p = 0.013) receptor binding affinities. These observations suggest opposing interactions among three distinct domains of receptor binding targets contribute to the antipsychotic effects of atypical antipsychotic medications: (1) D3 and D2 dopamine receptor binding affinity enhance atypical antipsychotic medication potency. (2) Binding affinity to serotonin 5-HT2A, 5-HT2C, and 5-HT7 receptors also facilitates antipsychotic efficacy. (3) In contrast, enhanced binding affinity to serotonin 5-HT1A receptor reduces antipsychotic medication potency.
Electrical Impedance Tomography During Mechanical Ventilation

Electrical impedance tomography (EIT) is a noninvasive, non-radiologic imaging modality that may be useful for the quantification of lung disorders and titration of mechanical ventilation. The principle of operation is based on changes in electrical conductivity that occur as a function of changes in lung volume during ventilation. EIT offers potentially important benefits over standard imaging modalities because the system is portable and non-radiologic and can be applied to patients for long periods of time. Rather than providing a technical dissection of the methods utilized to gather, compile, reconstruct, and display EIT images, the present article seeks to provide an overview of the clinical application of this technology as it relates to monitoring mechanical ventilation and providing decision support at the bedside. EIT has been shown to be useful in the detection of pneumothoraces, quantification of pulmonary edema and comparison of distribution of ventilation between different modes of ventilation and may offer superior individual titration of PEEP and other ventilator parameters compared with existing approaches. Although application of EIT is still primarily done within a research context, it may prove to be a useful bedside tool in the future. However, head-to-head comparisons with existing methods of mechanical ventilation titration in humans need to be conducted before its application in general ICUs can be recommended.
Cutaneous carcinosarcoma: a series of six cases and a review of the literature.

Background Cutaneous carcinosarcoma is a rare tumor with distinct malignant epithelial and mesenchymal cell populations. The histologic subtypes of epithelial and mesenchymal components in cutaneous carcinosarcoma are variable, as an assortment of carcinomatous and sarcomatous patterns have been described in the literature. Methods Clinical information was obtained from patient charts and archival slides were retrieved and reviewed. Results We present a novel series of six distinct cases of cutaneous carcinosarcoma and review the literature. Our cases consisted of basal cell, pilomatrical, squamous cell, and trichoblastic variants. These cases occurred in elderly men on sun exposed skin with treatment and follow up was available for 4 of 6 cases. The four cases were treated with Mohs micrographic surgery with mean follow up of nine months. Conclusion We report six cases of cutaneous carcinosarcoma with distinctive clinical and histologic characterization not previously described in a single series.
Long-Term Safety and Efficacy of Single Administration of a Fixed Dose Pegfilgrastim (Neulasta) in Inducing Neutrophil Count Recovery after ABVD Chemotherapy in Patients with Hodgkin Lymphoma.

Pegfilgrastim (Neulasta) is a pegylated form of G-CSF that has a long half-life allowing for a single administration per chemotherapy cycle. Although the safety and efficacy of pegfilgrastim has been established in association with chemotherapeutic regimens that are repeated every 3 weeks, its safety in patients receiving chemotherapy regimens every 2 weeks is currently under investigation. Of concern is the possibility of stem cell damage because of the long half life that may overlap with subsequent courses of chemotherapy. ABVD chemotherapy is widely used for the treatment of patients with Hodgkin disease. Up to 65% of patients receiving ABVD will require growth factor support to 1) maintain dose intensity 2) to prevent neutropenic fever and 3) to prevent delays in chemotherapy administration. In this study, we used a single dose per cycle of 6 mg pegfilgrastim in first and subsequent cycles of ABVD. Patients were eligible if they were older than 16 years and had previously untreated Hodgkin’s disease patients who are scheduled to receive standard ABVD chemotherapy, adequate bone marrow reserve (ANC > 1,000/uL, Platelet > 100,000/uL, left ventricular ejection fraction > 50%, serum creatinine
Failure to initiate breastfeeding among high risk obstetrical patients who intended to breastfeed

Background In the US, at the time of discharge from the hospital, 79% of women had initiated breastfeeding. Intention to breastfeed is a strong predictor of breastfeeding initiation; however, we reported initiation failure in 45% of women with pregestational diabetes who intended to breastfeed. Information regarding intention and initiation among women with other high risk obstetrical conditions (HROB) remains scarce. Objective To ascertain demographic and clinical factors associated with breastfeeding initiation failure among women with HROB conditions who intended to breastfeed. Methods The study population is comprised of 89 women with diabetes (DM), 57 who were receiving treatment for substance abuse (SA), 51 women diagnosed with miscellaneous (MISC) conditions and 32 with history of preterm labor/delivery (PTL/D). Intention to exclusively breastfeed or in combination with formula (breastfed/FF) was ascertained prenatally. Breastfeeding was considered initiated if at discharge ≥50% of their infant feedings were maternal milk. Statistics include chi-square, Wilcoxon's and logistic regression (p Results Of all women, 59% initiated any breastfeeding. Intention to breastfeed/FF, lack of mother-infant contact during the first hour following birth and limited lactation consultation were predictive of initiation failure. The odds of initiation failure were 2.3 times higher among women who wished to breastfeed/FF as compared to those who wished to exclusively breastfeed. Women from the SA group had lower rates of initiation failure than the other three HROB groups. Conclusion Intention to breastfeed among women with diverse HROB conditions is similar to that of the general population; however, initiation rates are disappointingly low. Intention to exclusively breastfeed results in fewer initiation failures. Prenatal intention to combine breast and formula feeding characterize women who may benefit from specific educational programs.
Conformational heterogeneity in CCR7 undergoes transitions to specific states upon ligand binding

Abstract Ligand-binding to G protein-coupled receptors (GPCRs) acts as the local driving force that initiates signal transduction through the receptor and mediates its conformational transitions and interactions with various intracellular effectors. In a recent study, We have shown that the binding of ligands CCL19 and CCL21 to CCR7 induces biased triggering of side chain-based molecular switches, which coordinate concerted transmembrane helical domain motions and transitioning of the receptor to distinct conformational states (Gaieb, Z., D.D. Lo, and D. Morikis. 2016. Molecular Mechanism of Biased Ligand Conformational Changes in CC Chemokine Receptor 7. Journal of Chemical Information and Modeling. 56: 1808–1822, DOI: 10.1021/acs.jcim.6b00367). To complement our previous study, we compare the results of the free (apo) CCR7 microsecond molecular dynamics simulations to those of the ligand-bound CCR7, and show that the apo receptor is found in conformational heterogeneity that only exhibits random fluctuations and lacks the coordinated helical motions seen in ligand-bound receptors. We conclude that ligand binding is responsible for coordinating the stochastic conformational nature of CCR7 into specific conformational states, initiated and propagated by specific physicochemical events.
Response to commentaries on Disorientation and Moral Life

In Disorientation and Moral Life, I consider disorientations as experiences of not knowing how to go on following serious life events and experiences like those involved in traumas, grief, illness, education, consciousness raising, and migration. I challenge a history of moral philosophy that I claim has been preoccupied by a focus on the best moral agents as those who are most decisive, wholehearted, and clear about how they ought to act. In this piece, I respond to three commentaries on Disorientation and Moral Life. In particular, I offer reflections on how disorientations might be useful in contexts of disability studies, prison abolitionism, professional philosophy, anti-racist action, and political organizing.
Virus Vector-Mediated Transfer of Drug-Sensitivity Genes for Experimental Brain Tumor Therapy

Publisher Summary This chapter summarizes the gene therapy strategies that employ virus vectors to deliver drug-sensitivity genes into brain tumor cells. Drug-sensitivity genes encode enzymes that activate prodrugs into their toxic metabolites. In order to transfer these genes into tumor cells in vivo , modified viruses and other agents can be employed as vectors. Three types of viral vectors have been reported as efficient vectors when applied to experimental brain tumors: retrovirus, herpes virus, and adenovirus. One major difference among retrovirus, herpes simplex virus, and adenovirus vectors is that with retroviruses, gene expression requires integration into the host cell chromosome and this integration occurs only in dividing cells. This property provides for selectivity in the delivery of drug-sensitivity genes into dividing tumor cells since most endogenous cells in the brain are postmitotic. Issues of safety have been met by genetically modifying and designing Moloney murine leukemia virus-based (MoMLV) vectors and mouse fibroblast packaging cells (ψ CRE/CRIP) to minimize the risk of recombination after infection, which could result in regeneration of pathogenic replication-competent retrovirus. Replication-defective adenovirus vectors have also been employed to deliver the reporter gene, LacZ, into endogenous neural cells, as well as into tumor . This vector can be grown to high titers and does not integrate into the host cell genome. In case of herpes virus, two types have been developed for gene delivery to the central nervous system: replication-defective recombinant viruses and plasmid-derived amplicons. Several types of genes have been shown to possess antitumor effectiveness: (1) drug-enhancing genes encode enzymes, (2) immune-response enhancer genes such as such as interleukin-2, (3) tumor-suppressor genes such as p53, and (4) antisense RNAs such as that to insulin-like growth factor I. Three other gene encoding enzymes that convert prodrugs to drugs are HSVtk Gene, Escherichia coli Cytosine Deaminase (CD) Gene and Escherichia coli GPT Gene, and Cytochrome P450 2B1 Gene.
Biologic therapy of gastrointestinal cancer.

During the last two decades, biologically based cancer therapies have received enormous attention. Advances in laboratory medicine have unveiled new insights into the biological processes that underlie the subcellular circuits involved in signal transduction or in DNA replication, transcription, and translation. We also have improved understanding of structural and functional markers on cancer cells, and of the capacity of immunologically based reagents to diagnose and treat cancer. In some cases, this new knowledge has been effectively put to therapeutic use. Rationally designed therapies based on preclinical efficacy have been successfully translated into clinical efficacy. One example is the use of interleukin-2 (IL-2) and lymphokine activator killer (LAK) cells for the therapy of malignant melanoma and metastatic renal cell cancer [1]. The use of cytokines or immunomodulating agents has also reaped major benefits. Examples include the use of interferon for the treatment of hairy cell leukemia [2] and chronic myelogenous leukemia [3]; these diseases clearly respond to these cytokines, but the mechanism leading to benefit is not completely understood. Another example is the combination of levamisole and 5-fluorouracil (5-FU); this combination has proved to be effective in the adjuvant therapy of stage C colon cancer despite the fact that a potent immunomodulating effect of levamisole has not been demonstrated [4]. Other successful examples of biologically based therapies include the use of monoclonal antibodies both as immunotherapeutic agents and as carriers for radionuclides. Antibodies targeting the CD20 antigen on lymphoma cells have been shown to have therapeutic efficacy in both settings [5,6]. Another therapeutic approach to cancer involves the use of cancer vaccines. For example, immunization with the GM2 ganglioside has produced encouraging results in malignant melanoma [7]; phase III trials are being undertaken to confirm these findings.
Omega-3 Fatty Acid Intake by Age, Gender, and Pregnancy Status in the United States: National Health and Nutrition Examination Survey 2003–2014

Despite the importance of n-3 fatty acids for health, intakes remain below recommended levels. The objective of this study was to provide an updated assessment of fish and n-3 fatty acid intake (i.e., eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and EPA+DHA) in the United States using the 2003–2014 National Health and Nutrition Examination Survey (NHANES) data (n = 45,347)). Over this survey period, toddlers, children, and adolescents (aged 1–19) had significantly lower n-3 fatty acid intake (p < 0.001) compared to adults and seniors, which remained significant after adjusting for caloric intake. Females demonstrated lower n-3 fatty acid intake than males (p < 0.001), with adult and senior women having significantly lower intakes compared to men in the same age categories (p < 0.001) after adjustment for energy intake. Women also consumed less fish than men (5.8 versus 6.1 servings/month, p < 0.001). The estimated intakes of n-3 fatty acids in pregnant women did not differ from non-pregnant women (p = 0.6 for EPA+DHA), although pregnant women reported consuming less high n-3 fatty acid-containing fish than non-pregnant women (1.8 versus 2.6 servings/month, p < 0.001). Our findings indicate that subgroups of the population may be at higher risk of n-3 fatty acid intakes below recommended levels.
Otolaryngology Resident Well-Being and Perceptions of the Clinical Learning Environment.

Objective:To measure the current state of organizational and well-being factors in otolaryngology residency programs and associate these perceptions with demographics, pursuit of subspecialty fello...
Community-based interventions for preventing diarrhoea in people living with HIV in sub-Sahara Africa: A systematic review.

Background High prevalence rates of people living with HIV (PLHIV) are more predominant in sub-Saharan Africa compared to any region globally. Nonetheless, many people in the region have little access to safe water and live in poor sanitation environment. This region is, therefore, faced with a challenge in protecting PLHIV from infectious diseases that are transmitted through unhygienic conditions. Aim This systematic review was conducted to identify effective community-based interventions for the prevention of diarrhoea among PLHIV in sub-Saharan Africa. Methods Studies included in this systematic review were sought from PubMed, EMBASE, PsycINFO, AMED, CINAHL, DOAJ, Web of science, WHO Global Index Medicus Library, Cochrane and ProQuest (GeoRef). Articles were appraised using MMAT scale. Results From a search finding of 3,849 articles, only nine papers whose participants were people living with HIV and had incidence or prevalence of diarrhoea as an outcome met our inclusion criteria. Community-based interventions such as water treatment and safe storage were associated with 20% -53% reduction in diarrhoea episodes among PLHIV. The review has also demonstrated that the impact of hand hygiene and health education on the prevention of diarrhoeal infections is not adequately assessed. Conclusion Future studies are, therefore, warranted to assess the effect of hand hygiene and health education interventions on prevention and reduction of diarrhoea in PLHIV in Sub-Saharan Africa.
Redondoviridae, a Family of Small, Circular DNA Viruses of the Human Oro-Respiratory Tract Associated With Periodontitis and Critical Illness

Summary The global virome is largely uncharacterized but is now being unveiled by metagenomic DNA sequencing. Exploring the human respiratory virome, in particular, can provide insights into oro-respiratory diseases. Here, we use metagenomics to identify a family of small circular DNA viruses—named Redondoviridae—associated with human diseases. We first identified two redondovirus genomes from bronchoalveolar lavage samples from human lung donors. We then queried thousands of metagenomic samples and recovered 17 additional complete redondovirus genomes. Detections were exclusively in human samples and mostly from respiratory tract and oro-pharyngeal sites, where Redondoviridae was the second most prevalent eukaryotic DNA virus family. Redondovirus sequences were associated with periodontal disease, and abundances decreased with treatment. Some critically ill patients in a medical intensive care unit were found to harbor high levels of redondoviruses in respiratory samples. These results suggest that redondoviruses colonize human oro-respiratory sites and can bloom in several human disorders.
Total Hip Arthroplasty in Patients With Osteogenesis Imperfecta

Abstract Background Osteogenesis imperfecta (OI) comprises a spectrum of disorders that result in bone fragility. This presents unique challenges when performing total joint arthroplasty in patients with OI. The purpose of this study is to determine the survivorship and clinical outcomes of total hip arthroplasty (THA) in patients with OI. Methods We retrospectively reviewed our institution’s total joint registry from 1969 to 2018 for all primary THAs in patients with a history of OI. There were 11 patients (13 hips) with a mean follow-up of 13 years (range 6-20). Survivorship free of component revision was determined using Kaplan-Meier analysis. Patient-reported clinical outcomes were assessed using Harris Hip Scores. Results At final follow-up, the status of the implant was known in all 13 hips. One patient (1 hip) was deceased. Four hips (31%) underwent revision surgery at a mean of 9 years (range 5-17). Survivorship free of component revision was 52% at 20 years. Mean Harris Hip Scores at final follow-up were fair (75, 47-97), but significantly improved compared to available preoperative scores (P = .0015). No intraoperative complications occurred during the 13 primary THAs. Conclusion THA in patients with OI is associated with high revision rates and low survivorship at long-term follow-up. Although this is a very challenging patient population, THA provided these patients with improved functional outcomes. To the authors’ knowledge, this is the largest series of primary THA in patients with OI reported in the literature and therefore provides surgeons with important data regarding the expected outcomes following THA in this unique patient population. Level of Evidence Level IV.
HIP ARTHROSCOPY VS. PHYSICAL THERAPY IN PATIENTS WITH FEMOROACETABULAR IMPINGEMENT: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS:

Introduction:Both physical therapy (PT) and surgery appear to have some efficacy in treating femoroacetabular impingement (FAI). Only recently have high-level evidence studies compared these two op...
Ionic Liquid Additives for the Mitigation of NafionSpecific Adsorption on Platinum

Perfluorosulfonic acid (PFSA)-based ionomers, most notably Nafion, provide the ionic connection between catalyst particles and solid polymer ion conducting membrane separators in polymer electrolyt...
Improving understanding of how mentoring works: Measuring multiple intervention processes.

The objective is to develop and test dimensionality and validity of a new measure of five mentoring intervention processes drawn from emphases across prior mentoring efforts that might be the basis for effects: identification with the mentor, social and emotional support, teaching and education, and advocacy, and shared time and activity. Partial validation of value was drawn from moderation role in a meta-analysis of mentoring (Tolan, Henry, Lovegrove, Schoeny, & Nichols, 2014. J. Exp. Criminol., 10, 179-201). Data collected of candidate items completed by 740 mentors and 302 mentees (mean age = 16.59 years) were subjected to confirmatory factor analyses based on the five theorized dimensions. Scales derived from best-fitting solutions were examined for convergent validity in relation to other indicators of mentoring relationship qualities. A bifactor model with five specific factors was supported for adult mentor reports while a simplified single factor model fit youth reports. Correlations between derived scale scores and validity indicators of mentoring relationship qualities were consistent with expectations. Multiple activities that comprise mentoring can be identified in adult mentor reports but not youth reports. This scale provides a promising basis for testing how variation in emphasis during mentoring affects impact and help guide training emphases.
TGFβ3 is neuroprotective and alleviates the neurotoxic response induced by aligned poly-l-lactic acid fibers on naïve and activated primary astrocytes.

Following spinal cord injury, astrocytes at the site of injury become reactive and exhibit a neurotoxic (A1) phenotype, which leads to neuronal death. In addition, the glial scar, which is composed of reactive astrocytes, acts as a chemical and physical barrier to subsequent axonal regeneration. Biomaterials, specifically electrospun fibers, induce a migratory phenotype of astrocytes and promote regeneration of axons following acute spinal cord injury in preclinical models. However, no study has examined the potential of electrospun fibers or biomaterials in general to modulate neurotoxic (A1) or neuroprotective (A2) astrocytic phenotypes. To assess astrocyte reactivity in response to aligned poly-l-lactic acid microfibers, naive spinal cord astrocytes or spinal cord astrocytes primed towards the neurotoxic phenotype (A1) were cultured on fibrous scaffolds. Gene expression analysis of the pan-reactive astrocyte makers (GFAP, Lcn2, SerpinA3), A1 specific markers (H2-D1, SerpinG1), and A2 specific makers (Emp1, S100a10) was done using quantitative polymerase chain reaction (qPCR). Electrospun fibers mildly increased the expression of the pan-reactive and A1-specific markers, showing the ability of fibrous materials to induce a more reactive, A1 phenotype. However, when naive or activated astrocytes were cultured on fibers in the presence of transforming growth factor β3 (TGFβ3), the expression of A1-specific markers was greatly reduced, which in turn improved neuronal survival in culture.
Muscle Loss is Associated with Risk of Orthostatic Hypotension in Older Men and Women

Muscle provides a reservoir for water to maintain fluid volume and blood pressure, so older adults may be at risk for orthostatic hypotension due to muscle loss with age. To evaluate the association between muscle loss with age and postural blood pressure. Longitudinal comparison of overnight changes in hydration, postural blood pressure, and strength. Community field study. Sixty-nine men and women (76.0 ± 0.8 years) with low (Low) or normal (Normal) muscle based on the Lean Mass Index. Body composition was measured with bioelectrical impedance analysis. Postural blood pressure was measured sequentially (lying, sitting, standing). Strength was measured with a handgrip dynamometer, Arm Curl test, and Chair Stand test. On Day 1, Low had less hydration and a significant drop in postural systolic blood pressure compared to Normal (lying to standing: −11.06 ± 2.36 vs. + 1.14 ± 2.20 mmHg, p < 0.001). Overnight, both groups lost significant total body water, while fluid volume was unchanged. On Day 2, both groups experienced significant drops in postural systolic blood pressure, although the drop in Low was more profound and significantly greater than Normal (lying to standing: −16.85 ± 2.50 vs. −3.89 ± 2.52 mmHg, p = 0.001). On both days, Normal compensated for postural changes with increases in postural diastolic blood pressure not observed in Low. Only Low experienced significant overnight decreases in all strength measures. In older men and women, muscle loss with age is accompanied by loss of hydration and less stable early morning postural systolic blood pressure that increase risk for orthostatic hypotension and can also increase risk for falls.
Interpreting the performance of HPF/Fortran 90D

We present a novel interpretive approach for accurate and cost effective performance prediction in a high performance computing environment, and describe the design of a source driven HPF/Fortran 90D performance prediction framework based on this approach. The performance prediction framework has been implemented as part of a HPF/Fortran 90D application development environment. A set of benchmarking kernels and application codes are used to validate the accuracy, utility, usability, and cost effectiveness of the performance prediction framework. The use of the framework for selecting appropriate compiler directives and for application performance debugging is demonstrated.
Pregnancy in an Urban Cohort of Adolescents Living with Human Immunodeficiency Virus: Characteristics and Outcomes in Comparison to Adults

Adolescents (13–24 years of age) account for more than one-fifth of new HIV diagnoses yearly, and the United States has one of the highest rates of adolescent pregnancy among high resource countrie...
A Rare Case of Periprosthetic Joint Infection Caused by a Periodontal Pathogen, Slackia exigua: A Case Report.

Case A 72-year-old woman with a history of right total hip arthroplasty and subsequent revision 18 years ago developed right hip periprosthetic joint infection with significant bone destruction caused by Slackia exigua. She underwent a dental cavity filling without prophylactic antibiotics before presentation that may have contributed to development of the infection. The patient required total hip revision and prolonged antibiotic therapy to eradicate the bacteria. Conclusion This case is an example that certain high-risk patients undergoing invasive dental procedures are at risk of developing prosthetic joint infection.
A new cheilostome bryozoan from a dinosaur site in the Upper Cretaceous (Campanian) Judith River Formation of Montana

Few bryozoans have been described from the Cretaceous Western Interior Seaway (WIS), which is consistent with the low diversity of other typically stenohaline groups in this large expanse of relatively shallow marine water. Here we describe a new cheilostome bryozoan, Conopeum flumineum n. sp., based on well-preserved material from the Campanian Judith River Formation of the Upper Missouri River Breaks National Monument in north-central Montana. The new species shows strong morphological similarities with Conopeum seurati, a Recent species that is often categorized as brackish, but which is euryhaline and can also be found in marine and stenohaline environments. The new Campanian bryozoan species was found in a locality also containing fragmentary remains of dinosaurs and other terrestrial vertebrates, as well freshwater mollusks and terrestrial plant debris. The sedimentology and facies associations of the fossil-bearing site suggest that the depositional setting was a swamp or tidally influenced fluvial backwater on the Judith River coastal plain. The proximity of the site to the western shoreline of the WIS presumably made it susceptible to occasional marine flooding during storms or extreme tides. Previous occurrences of Conopeum in the Cretaceous of the Western Interior have also been associated with dinosaur remains, corroborating the very nearshore and at times even ‘upstream’ distribution of this euryhaline genus. UUID: http://zoobank.org/bb1fdc8a-5017-44c5-9251-9e24ef3995e3.
Postcranial Description and Reconstruction of the Varanodontine Varanopid Aerosaurus wellesi (Synapsida: Eupelycosauria)

The postcranial skeleton of the varanopid synapsid Aerosaurus wellesi is reconstructed based on several specimens, including partly articulated material of an apparently fully adult specimen. Comparisons are made with other known varanopid taxa, reaffirming its position as a basal varanodontine. Aerosaurus was an obligatory sprawling-gaited animal with an extremely long tail and a presacral column that descended posteriorly at an angle of 25o. Aerosaurus shares many synapomorphies with other varanodontines: tall neural spines, double headed ribs, presence of a supraglenoid foramen, broadly expanded proximal and distal heads of humerus, high degree of twist or torque of the humeral heads about the shaft, radius shorter than humerus, expanded heads of femur, femur lacking a sigmoid curvature, and humerus and femur roughly subequal in length. The high degree of torque in the humerus, the extremely long tail, and the subequal lengths of the humerus and femur are considered primitive features of basal tetrapods, whereas the length of the centra being 23 % greater than the width and the expanded clavicular plate are specializations also seen in some later, derived varanodontines.
Simulations of submicron aerosol deposition at an air–liquid interface for in vitro toxicology

Submicron particles released during the lifecycle of nano-enabled products and as a byproduct of air pollution and occupational processes are a potential health risk. Recent advancements to in vitro model systems have been proposed to assess the toxicity of particulate materials resulting from inhalation. The reliability of these models depends on the introduction and deposition of aerosolized particles on cells at an air–liquid interface. However, chamber geometry, gas flow rate, electric field, and other process parameters significantly impact how particles deposit at this interface. Here, we carried out finite element modeling to describe the transport and deposition of submicron aerosolized particles. Simulations were performed using multiphysics software on a typical in vitro exposure chamber design, and results were compared to analytical approximations for deposition efficiency. Deposition experiments were also systematically carried out to validate the modeling predictions. Our results show how deposition depends on various process parameters. To achieve efficient deposition without focusing, the electric field strength and gas flow rate must be balanced; at high gas flow rates, higher electric fields are required to achieve deposition. Further, we find that AC electric fields at the appropriate frequency can increase deposition above DC fields at similar strengths. Overall, the study establishes simulation approaches for the design of in vitro aerosol deposition chambers and relates key process parameters to deposition, which is critical to controlling the dose of submicron aerosols in in vitro toxicology experiments.
Mental Models in Human-Computer Interaction

2.1 Abstract Users of software systems acquire knowledge about the system and how to use it through experience, training, and imitation. Currently, there is a great deal of debate about exactly what users know about software. This knowledge may include one or more of the following: • simple rules that prescribe a sequence of actions that apply in certain conditions, • general methods that fit certain general situations and goals, • “mental models,” knowledge of the components of a system, their interconnection, and the processes that change the components; knowledge that forms the basis for users being able to construct reasonable actions; and explanations about why a set of actions is appropriate. Discovering what users know and how these different forms of knowledge fit together in learning and performance is important. It applies to the problem of designing systems and training programs so that the systems are easy to use and the learning is efficient. Research on the effects of different representations on ultimate performance is mixed. Research on exactly what users know is scattered. Analytical methods and techniques for representing what the user knows are sparse but growing. This paper reviews current work and through the review, identifies several important research needs: • Detail what kinds of mental representations people have of systems that allow them to behave appropriately in using the software. • Detail what a mental model would consist of and how a person would use it to decide what action to take next. • Produce evidence that people have and use mental models. • Determine the behaviors that would demonstrate a mental model's form and the operations used on the model. • Explore alternative views of goal-directed representations (e.g., so-called “sequence/method representations”) and detail the behavior predicted from them. • Expand the types of mental representations that may exist to include those that may not be mechanistic, such as algebraic systems and visual systems. • Determine how people intermix different representations in producing behavior. • Explore how knowledge about systems is acquired. • Determine how individual differences have an impact on learning of and performance on systems. • Explore the design of training sequences for systems. • Provide systems designers with tools to help them develop systems that evoke “good” representations in users. • Expand the task domain of this research to include more complex software.
Nonconvex relaxation for Poisson intensity reconstruction

Critical to accurate reconstruction of sparse signals from low-dimensional Poisson observations is the solution of nonlinear optimization problems that promote sparse solutions. Theoretically, non-convex l p -norm minimization (0 ≤ p 1 -norm relaxation commonly used in sparse signal recovery. In this paper, we propose an extension to the existing SPIRAL-l 1 algorithm based on the Generalized Soft-Thersholding (GST) function to better recover signals with mostly nonzero entries from Poisson observations. This approach is based on iteratively minimizing a sequence of separable subproblems of the nonnegatively constrained, l p -penalized negative Poisson log-likelihood objective function using the GST function. We demonstrate the effectiveness of the proposed method, called SPIRAL-l p , through numerical experiments.
Fungistatic activity of miconazole against Candida albicans in relation to pH and concentration of nonprotonated drug.

Summary: At < 10--5M, miconazole (MCZ) exerts a fungistatic effect on Candida albicans, presumably by interfering with ergosterol biosynthesis. The imidazole moiety of MCZ is subject to protonation (pKa˜6.5). Based on pKa and greater water solubility of protonated (MCZH+) versus nonprotonated (MCZ°) drug, fungistatic action ought to be markedly affected by environmental pH, but apparently it is not. In this report growth phase, pH, and concentrations of MCZ and MCZ° have been studied in relation to fungistasis. Yeasts were grown in a synthetic liquid medium and MCZ effects were monitored by viability determinations. Results showed that fungistatic activity is little affected by growth phase and is largely independent of drug concentration and pH. Antagonism of fungistasis by low pH was demonstrated only at < 10 -7M MCZ. Data supported earlier proposals that MCZ° is required for biological activity and suggested that target sites are saturated at very low levels of drug. Zusammenfassung: Miconazol (MCZ) wirkt bei Konzentrationen < 10--5 M fungistatisch auf Candida albicans, wahrscheinlich uber die Beeintrachtigung der Ergosterol-Biosynthese. Die Imidazolgruppe von MCZ wird dabei protonisiert (pKa ˜ 6.5). Wegen dieses pKa und der hoheren Wasserloslichkeit der protonisierten (MCZH+) im Vergleich zur nicht-protonisierten (MCZ°) Verbindung sollte die fungistatische Wirkung deutlich durch den pH-Wert der Umgebung beeinflust sein, ist es aber offensichtlich nicht. In der vorliegenden Studie wurde die Fungistase in Abhangigkeit von der Wachstumsphase, vom pH sowie von der MCZ- und MCZ°-Konzentration untersucht. Die Hefe wurde in einem synthetischen Flussigmedium angezuchtet, und die MCZ-Wirkung wurde durch Lebendkeimzahlbestimmungen erfast. Die Ergebnisse zeigen, das die fungistatische Aktivitat kaum von der Wachstumsphase beeinflust wird und von der Wirkstoffkonzentration und vom pH weitgehend unabhangig ist. Die Fungistase war lediglich bei niedrigem pH und bei Konzentrationen < 10 -7M MCZ herabgesetzt. Die Ergebnisse stutzen die fruher erhobene These, das MCZ° fur die biologische Aktivitat vorliegen mus und das vermutlich die Zielkonfigurationen bei sehr geringen Wirkstoffkonzentrationen abgesattigt sind.
Improving One's Situation: Some Pragmatic Reflections on the Art of Judging

As legal theorists, we live in an age of self-conscious repetition: everything is "neo" and nothing is new. There are neo-realists, neo-formalists, neo-conservatives, and neo-pragmatists to name just a few. And what is not "neo" is "post" as in post-structuralist, post-colonial, and even postcritical. Indeed, the newest theories sound pointedly antitheoretical as deconstructionists, feminists, and critical legal scholars argue in various ways that conventional theory making is but one more mechanism for oppressing the powerless. In all this theory consciousness, it is difficult to have simple thoughts and it is especially difficult to think simply about judging because judging has been the object of so much theoretical attention. This is too bad. Judging, I think, is a little like riding a bicycle-if you are teetering out of control, it is unlikely that a complicated theory will help to restore the balance. Simple thoughts are more useful; they are easier to internalize and therefore more accessible when needed.
Rule-based topological vulnerability analysis

Attack graphs represent known attack sequences that attackers can use to penetrate computer networks. Recently, many researchers have proposed techniques for automatically generating attack graphs for a given computer network. These techniques either use model checkers to generate attack graphs and suffer from scalability problems, or they are based on an assumption of monotonicity and are unable to represent real-world situations. In this paper, we present a vulnerability analysis technique that is more scalable than model-checker-based solutions and more expressive than monotonicity-based solutions. We represent individual attacks as the transition rules of a rule-based system. We define noninterfering rulesets and present efficient, scalable algorithms for those sets. We then consider arbitrary nonmonotonic rulesets and present a series of optimizations which permit us to perform vulnerability assessment efficiently in most practical cases. We motivate the issues and illustrate our techniques using a substantial example.
The strength factor in digital human modeling and simulation: a case for a new framework

It is not well understood whether strength could ever influence performance in which only sub-maximal, moderate exertions are needed although strength may be indicative of the movement performance at or near the maximal level. In this paper, we present some evidence from two studies suggesting the strength effects on performance strategies in volitional physical tasks, and based on the evidence, a new framework was proposed for human movement modeling and simulation that incorporates the strength factor.
The Effects of pH and Anions on the Properties of the α and β Chains within Human Deoxyhemoglobin

Abstract The reaction of n-butyl isocyanide with deoxyhemoglobin A has been examined as a function of pH and ionic strength in the presence and absence of inositol hexaphosphate. In solutions of high pH (about 9) or of low ionic strength at pH 7 the rates of n-butyl isocyanide binding to the α and β chains within deoxyhemoglobin are almost equal. At pH 7, increase of ionic strength decreases the rate of binding to α chains. The addition of inositol hexaphosphate accentuates this effect, and in its presence the rates of binding and affinities of the α chains are substantially reduced in relation to the corresponding β chain values. Although it is known that organic phosphates bind between the β chains (Arnone, A. (1972) Nature 237, 146–149), the main effect of inositol hexaphosphate is a modification of the ligand-binding properties of the α chains. Similarly, the addition of protons to solutions of deoxyhemoglobin exerts a greater effect on the functional properties of the α chains than on the β chains, even though, at neutral pH 50% of the additional number of protons bound to deoxyhemoglobin are associated with the imidazole group of histidine 146 β (Kilmartin, J. V., and Wootton, J. F. (1970) Nature 228, 766–767). These results show that the functional properties of hemoglobin cannot be explained solely in terms of the perturbation of a single microscopic conformational equilibrium since the properties of the individual α and β chains within deoxyhemoglobin are unequally influenced by anions and protons while those of liganded hemoglobin are not.
Valuation of Technology - Theory and Practice Approaches

There are various methods of valuation of technology and intellectual property. Some of these methods routinely used in practice, at the same time as the other methods are not suitable for a business reality. In this paper, I analyzed the actual methods of valuation techniques used for M&A and tried to systemize these approaches. As it turned out, many theoretical approaches cannot be applied in practice. On the other hand, the rules of the market remain true. By studying the cases of theoretical valuation methods in practice, we can find the most acceptable methods of technology and IP assessment.
Catastrophic caldera-forming eruptions II: The subordinate role of magma buoyancy as an eruption trigger

Abstract Recent analytical investigations have suggested that magma buoyancy is critical for triggering catastrophic caldera forming eruptions. Through detailed assessment of these approaches, we illustrate how analytical models have been misapplied for investigating buoyancy and are, therefore, incorrect and inconclusive. Nevertheless, the hypothesis that buoyancy is the critical trigger for larger eruptions warrants further investigation. As such, we utilize viscoelastic finite element models that incorporate buoyancy to test overpressure evolution and mechanical failure in the roof due to the coalescence of large buoyant magma bodies for two model cases. In the first case, we mimic empirical approaches and include buoyancy as an explicit boundary condition. In the second set of models, buoyancy is calculated implicitly due to the density contrast between the magma in the reservoir and the host rock. Results from these numerical experiments indicate that buoyancy promotes only minimal overpressurization of large silicic magma reservoirs ( 100 km3) they surpass a rheological threshold where their subsequent evolution is controlled by host rock mechanics. Consequently, this results in a thermomechanical division between small systems that are triggered “internally” by magmatic processes and large systems that are triggered “externally” by faulting related to roof uplift or tectonism. Finally, critical assessment of recent analytical approaches illustrates that care must be used when applying previously derived analytical solutions to ensure that assumptions used in the original formulation are not violated during application to new geologic problems.
Optical Imaging of Facial Perfusion in Migraine (P1.257)

Background: Migraine is a disorder of autonomic outflow as well as sensation. Trigeminal and autonomically mediated perfusion changes in the face (e.g. flushing, pallor, conjunctival injection) can be discerned with the naked eye; we reasoned that optical imaging techniques developed for animal models of migraine might be used to image the face in migraineurs. Methods: Von Frey filaments were used to determine each test subject’s baseline pain threshold. Participants were then positioned supine under a CCD camera. EKG leads and a respiratory monitor were attached and the right nostril was occluded. Skin reflectance from the upper two thirds of the subject’s face was recorded for a total of 3 minutes. After 90 seconds of recording, ammonia vapor was inhaled until pain threshold was reached, and recording continued for the remaining 90 seconds. The participant’s mechanical pain thresholds were then reassessed. CCD video images were processed with ImageJ. Anatomically consistent regions of interest were generated for each subject, and percent-change in skin reflectance was measured for baseline and ammonia-stimulated conditions. Results: Mechanical pain thresholds (baseline and post-ammonia inhalation) were significantly lower in migraineurs compared to normal controls in all regions of interest (p < 0.05 for all comparisons; ANOVA with post-hoc Tukey test). Hemodynamic oscillation amplitude and frequency were significantly lower in migraineurs compared to controls (p < 0.05; T-test). Amplitude and duration of ammonia-induced hemodynamic changes did not differ between migraineurs and controls. Conclusions: Our pilot data suggest that migraineurs and controls may be distinguishable based on baseline and stimulus-evoked facial hemodynamic oscillations. Reflectance imaging of facial trigeminal and autonomic function is feasible and may be useful to examine physiological endophenotypes of migraine and other craniofacial neurological disorders. Disclosure: Dr. Peterson has nothing to disclose. Dr. Hunter has nothing to disclose. Dr. Cortez has nothing to disclose. Dr. Theriot has nothing to disclose. Dr. Brennan has received personal compensation for activities with MAP Pharmaceuticals and Allergan, Inc. as an advisory board member.
Squamous cell carcinoma of the supraglottic larynx treated with surgery and/or radiation therapy.

Abstract This is an analysis of 195 patients with squamous cell carcinoma of the supraglottic larynx treated with curative intent at the University of Florida between October 1964 and February 1984. The patients were staged according to the AJCC staging system. There was a minimum follow-up of 2 years, with 76% having at least a 5-year followup. Patients were treated with preoperative irradiation and resection (28), surgery and postoperative irradiation 35), surgery alone (26), or radiation therapy alone, with or without neck dissection(s) (106). This paper will compare the rate of local-regional control, the incidence of complications, voice preservation, and survival for radical irradiation, as opposed to surgery, with or without adjuvant irradiation.