cssi/SciSciGPT-SciSciNet huggingface dataset:
On the formation of a tip-vortex

The helicopter-rotor wake is among the most complex flowfields in aerodynamics. Despite the fact that a large amount of computational and experimental work on the rotor wake has been published, little of a quantitative nature is known about the origin of the main component of the rotor wake, the tip-vortex, as a function of the rotor speed, rotor blade geometry, and angle of attack. The objective of this paper is to investigate whether classical inviscid lifting surface methods applied locally near the wing tip can describe the origin of the tip vortex. Correlation of experimental data by several workers has revealed little dependence on the Reynolds number. Of course, this lack of dependence on Reynolds number will hold only if the flow remains substantially unseparated, though it may be noted that drag coefficients of blaff bodies are remarkably constant over wide range of Reynolds number. The rotor blade is assumed to be of large aspect ratio and the methdd of Matched Asymptotic Expansions is used to calculate the bound circulation near the wing tip. The primary objective of this work is to predict the formation of the rotor tip vortex as a function of physical parameters such as angle of attack, rotor speed, and blade aspect ratio. While the rotor-blade tip-vortex is of primary interest here, the techniques developed are applied first to the simple problem of the aircraft wing. Results for the bound circulation on a rotary wing are presented subsequently.
Effect of spleen aminopeptide on asthmatic children with recurrent respiratory infection

Objective To study the efficacy of spleen aminopeptide on children with bronchial asthma complicated byrecurrent respiratory infection.Methods 296 asthmatic children with recurrent respiratory infection were randomly divided into observation group(149cases)and control group(147cases).The observation group accepted spleen aminopeptide and the control group accepted placebo at the same frequency.The severity of asthma and recurrent respiratory infection,T lymphocyte subgroup ratio were investigated.Results The number of asthma and respiratory tract infections in the observation group were significantly less than that of the control group(P0.05),The coughing,wheezing,and fever aspects of the degree of improvement in the observation group were significantly better than that of the control group(P0.05).After 6months of treatment,the CD+3、CD+4and CD+8of the observation group were all increased than before treatment(P0.05).Their degree of change in T cell subsets in the observation group was more obvious than that in the control group.Adverse reactions of the two groups were not statistically significant difference(P0.05).Conclusion It will be feasible that spleen aminopeptidecan be used to treat children with bronchial asthma complicated by recurrent respiratory infection.
Clinical efficacy of high frequency jet ventilation during extracorporeal shock wave lithotripsy of renal and ureteral calculi: a comparison with conventional mechanical ventilation.

AbstractThe use of high frequency jet ventilation compared to conventional mechanical ventilation during general anesthesia for extracorporeal shock wave lithotripsy of renal or ureteral calculi can reduce stone movement. This decrease in stone movement theoretically lessens the total shock and energy requirements for stone fragmentation and perirenal tissue damage. To assess these theoretical advantages of high frequency jet ventilation, we studied patients undergoing extracorporeal shock wave lithotripsy to determine differences in stone movement during high frequency jet and conventional mechanical ventilation (30 patients), and in total shock requirements (1, 174 patients). Mean stone movement in the 30 patients was 34.3 ±4.3mm. during conventional mechanical ventilation compared to 4.1 ± 1.9mm. during high frequency jet ventilation (p less than 0.001). Mean total shocks were 1, 542 ± 212 (452 patients) during conventional mechanical ventilation compared to 1, 217 ± 165 (722 patients) during high freq...
The Media and Human embryology

Clearly, there is a major problem. The public knows little about Human Embryology, although some ignorant writers think they know more than they actually show. If these writers would make even a little effort and seek basic information, much of the problem would be relieved. It is not going to be solved by seeking out political analysts, politicians and ethicists.
An Introduction: (Re)envisioning Chicana/Latina Feminist Methodologies

The articles in this special issue of JOLLAS center on critical methodologies in educational research. As Chicana/Latina scholars have reimagined pedagogical spaces, so too have they reinvented the methodologies needed for such rearticulations. Each of the authors in this special issue provides ways in which to navigate methodological landscapes and offers discussions on the critical conversations necessary to forge a space for Chicana/Latina feminist perspectives in qualitative research. In particular, the scholars focus on anticolonial conversations, critical ethnography, theories and methods of the flesh, critical reflexivity, and Chicana feminist film-making methodologies as well as urge us to consider the global North/South divide by decolonizing conocimiento and forming global alliances.
Characterization of germanium-silicon alloy thin films grown by laser-photochemical vapor deposition

The current interest in germanium-silicon alloy thin films and multilayers is motivated by the dependence of their structural, optical, and electrical properties on alloy composition. This tunability makes them potentially useful for IR-photodetector, solar cell, and optoelectronic applications.
Sociology as the Study of Morality

This article reviews the substantive empirical and theoretical research programs and disputes within the sociology of morality. Specifically, research is reviewed in the areas of moral emotions, reputations and identities, at the social psychological level, and in the areas of political economy, religion and values at the cultural level. In addition, three areas of theoretical controversy are discussed—contentions over the primacy of culture over structure, over the primacy of subliminal versus reflective displays of moral behavior and over the ontological, metatheoretical nature of morality itself. The article ends with a proposed general, interdisciplinary, and integrative theoretical framework for the study of morality in sociology.
A Prehistoric Shell and Bone Necklace from a Burial Exposed in a Bank of the San Pedro River, Arizona

ABSTRACTFacts have recently come to the author's attention which may add some heretofore unknown details concerning the manufacture and use of cup-shaped beads that make up part of an ancient shell and bone necklace found associated with a burial exposed by erosion in the banks of the San Pedro River in southeastern Arizona.
Adaptive Significance of Ethics and Aesthetics

Abstract The question of whether ethical behavior is biologically determined may refer either to the capacity for ethics (ie, the proclivity to judge human actions as either right or wrong), or to the moral norms accepted by human beings for guiding their actions. It is proposed (1) that the capacity for ethics is a biological attribute of human nature; and (2) that moral norms are products of cultural evolution, not of biological evolution. Humans exhibit ethical behavior by nature because their biological makeup determines the presence of three necessary conditions for ethical behavior: the ability (1) to anticipate the consequences of one's own actions; (2) to make value judgments; and (3) to choose between alternative courses of action. Ethical behavior came about in evolution not because it is adaptive in itself, but because it is a necessary consequence of the eminent intellectual abilities of humans, which are an attribute directly promoted by natural selection. That is, morality evolved as an exaptation, not as an adaptation. It is difficult to determine when morality emerged in human evolution. The capacity for appreciating the aesthetic qualities of objects, motions, and sounds is a human universal. The capacity for producing aesthetic items is also universal. Sculptors, painters, dancers, and musicians are pervasive in all human cultures, although they represent a small fraction of any human population. Neither fossil nor archaeological records make it possible to determine when the capacity first evolved for appreciating landscapes, motions, songs, or objects created by artisans. Homo habilis are the first humans to make tools in the Oldowan culture starting somewhat earlier than 2.5 Ma. But there is no evidence of intentional beauty. Tools with delicate symmetry appear first around 100,000 years ago. The exquisite cave paintings of El Castillo, Altamira, Lascaux, and Chauvet climaxed around 14,000 years ago, the Magdalenian culture.
Multimodal Imaging in Focal Therapy Planning and Assessment in Primary Prostate Cancer.

There is increasing interest in focal therapy (male lumpectomy) of localized low-intermediate risk prostate cancer. Focal therapy is typically associated with low morbidity and provides the possibility of retreatment. Imaging is pivotal in stratification of men with localized prostate cancer for active surveillance, focal therapy, or radical intervention. This article provides a concise review of focal therapy and the evolving role of imaging in this clinical setting. We performed a narrative and critical literature review by searching PubMed/Medline database from January 1997 to January 2017 for articles in the English language and the use of search keywords “focal therapy,” “prostate cancer,” and “imaging.” Most imaging studies are based on multiparametric magnetic resonance imaging. Transrectal ultrasound is inadequate independently, but multiparametric ultrasound may provide new prospects. Positron emission tomography with radiotracers targeted to various underlying tumor biological features may provide unprecedented new opportunities. Multimodal Imaging appears most useful in localization of intraprostatic dominant index lesions amenable to focal therapy, in early assessment of therapeutic efficacy and potential need for additional focal treatments or transition to whole-gland therapy, and in predicting short-term and long-term outcomes. Multimodal imaging is anticipated to play an increasing role in the focal therapy planning and assessment of low-intermediate risk prostate cancer and thereby moving this form of treatment option forward in the clinic.
ENERGY RECOVERY FROM SANITARY LANDFILLS - A REVIEW

The state-of-the-art of in-situ methane production and extraction from municipal solid waste landfills is reviewed. Characteristics of municipal solid waste and the landfill environment are discussed in light of their influence on methane gas generation. Gas extraction and cleaning methods currently being used are presented and options available for gas utilization are cited. Current experiences with large-scale extraction from California landfills are cited. A preliminary evaluation of this potential source of energy is given in light of net energy yields.
Performance portable sparse approximate inverse preconditioner for EFIE equations

A block base sparse approximate inverse preconditioner for the electric field integral equations is documented and tested. It utilized the Kokkos library for performance portability and shows superior performance when compared to a direct method, 36x faster for a 112K DOF problem. Furthermore, due to the abstractions available in the Kokkos library it allows one to migrate from CPU to GPU in a trivial way.
On the boundaries of social entrepreneurship: a review of relationships with related research domains

Social entrepreneurship represents a unique and distinctive domain within the broader discipline of entrepreneurship research. The sub-field of social entrepreneurship also shares many commonalities with various sub-fields of larger fields of research such as corporate social responsibility, base of pyramid, non-profit management, social innovation, and impact investing. Understanding the boundaries of social entrepreneurship as well as its relations to these other areas of research is increasingly important as these sub-fields continue to evolve. We provide a clear and concise delineation of social entrepreneurship as a research domain to aid future researchers attempting to understand how social entrepreneurship connects to these other streams of research. Finally, we conclude by outlining research questions that exist at the boundaries of social entrepreneurship and these related sub-fields of research.
Increased risk of respiratory diseases in adults with Type 1 and Type 2 diabetes

Abstract Aims Diabetes is linked with decreases in lung elasticity and in capacity to transfer carbon monoxide. Systemic inflammation, a common concern with diabetes, may contribute to airflow obstruction. We examined the association of self-reported diabetes with self-reported respiratory diseases (RDs) among 53,146 adults from the C8 Health Project. Methods Participants were categorized into three groups: Type 1 (T1D, n = 781), Type 2 (T2D, n = 4277), or no diabetes (n = 48,088). ORs (95% CIs) for the association of diabetes with four RDs were computed: emphysema, chronic obstructive pulmonary disease (COPD), chronic bronchitis (CB), and asthma. Covariates controlled for were age, sex, estimated glomerular filtration rate, C-reactive protein, smoking history, BMI, and perfluorooctonaoic acid (C8). Results RDs were present in 26%, 21% and 13% of persons with T1D, T2D, and no diabetes, respectively. In multivariable analyses, persons with T1D were 62% more likely to have any RD (OR: 1.62, CI: (1.36–1.93)), while those with T2D were 1.3 times as likely (OR: 1.26, CI: 1.15–1.37)). Compared to those without diabetes, in those with T1D and T2D diabetes respectively, ORs (CIs) for COPD were 1.89 (1.38–2.57), 1.45 (1.23–1.71), asthma: 1.51 (1.21–1.87), 1.38 (1.24–1.53), CB: 1.96 (1.57–2.45), 1.35 (1.20–1.52) and emphysema: 1.25 (0.85–1.82), 1.31 (1.10–1.56). Population attributable risks for any RDs associated with a history of smoking were 19%, 30%, and 26% for those with Type 1, Type 2, and no diabetes respectively. Conclusions Diabetes, more so in T1D, appears to increase RD risk. Smoking is an important risk factor, but not as informative in Type 1 diabetes.
Tumor Retention of Enzyme-Responsive Pt(II) Drug-Loaded Nanoparticles Imaged by Nanoscale Secondary Ion Mass Spectrometry and Fluorescence Microscopy

In nanomedicine, determining the spatial distribution of particles and drugs, together and apart, at high resolution within tissues, remains a major challenge because each must have a different label or detectable feature that can be observed with high sensitivity and resolution. We prepared nanoparticles capable of enzyme-directed assembly of particle therapeutics (EDAPT), containing an analogue of the Pt(II)-containing drug oxaliplatin, an 15N-labeled monomer in the hydrophobic block of the backbone of the polymer, the near-infrared dye Cy5.5, and a peptide that is a substrate for tumor metalloproteinases in the hydrophilic block. When these particles reach an environment rich in tumor associated proteases, the hydrophilic peptide substrate is cleaved, causing the particles to accumulate through a morphology transition, locking them in the tumor extracellular matrix. To evaluate the distribution of drug and EDAPT carrier in vivo, the localization of the isotopically labeled polymer backbone was compared to that of Pt by nanoscale secondary ion mass spectrometry (NanoSIMS). The correlation of NanoSIMS with super-resolution fluorescence microscopy revealed the release of the drug from the nanocarrier and colocalization with cellular DNA within tumor tissue. The results confirmed the dependence of particle accumulation and Pt(II) drug delivery on the presence of a Matrix Metalloproteinase (MMP) substrate and demonstrated antitumor activity. We conclude that these techniques are powerful for the elucidation of the localization of cargo and carrier, and enable a high-resolution assessment of their performance following in vivo delivery.
New Treatment Options for Ovarian Cancer

Abstract Epithelial ovarian cancer continues to have a very high mortality rate, partly due to the challenges of early stage diagnosis as well as the low cure rate of standard treatments to date. This chapter will concentrate on the recent updates in the molecular classification of epithelial ovarian cancer, approval of novel targeted agents, and emerging therapeutic modalities.
Automatic Hand Skeletal Shape Estimation from Radiographs

Rheumatoid arthritis (RA) is an autoimmune disease whose common manifestation involves the slow destruction of joint tissue, damage that is visible in a radiograph. Over time, this damage causes pain and loss of functioning which depends, to some extent, on the spatial deformation induced by the joint damage. Building an accurate model of the current deformation and predicting potential future deformations is an important component of treatment planning. Unfortunately, this is currently a time consuming and labor intensive manual process. To address this problem, we propose a fully automated approach for fitting a shape model to the long bones of the hand from a single radiograph. Critically, our shape model allows sufficient flexibility to be useful for patients in various stages of RA. Our approach uses a deep convolutional neural network to extract low-level features and a conditional random field (CRF) to support shape inference. Our approach is significantly more accurate than previous work that used hand-engineered features. We demonstrate this on two large datasets of hand radiographs and highlight the importance of the low-level features, the relative contribution of different potential functions in the CRF, and the accuracy of the final shape estimates. Our approach is nearly as accurate as a trained radiologist and, because it only requires a few seconds per radiograph, can be applied to large datasets to enable better modeling of disease progression. We will release our code and trained models upon acceptance of this paper.
Working memory capacity is enhanced by distributed prefrontal activation and invariant temporal dynamics

The amount of information that can be stored in working memory is limited but may be improved with practice. The basis of improved efficiency at the level of neural activity is unknown. To investigate this question, we trained monkeys to perform a working memory task that required memory for multiple stimuli. Performance decreased as a function of number of stimuli to be remembered, but improved as the animals practiced the task. Neuronal recordings acquired during this training revealed two hitherto unknown mechanisms of working memory capacity improvement. First, more prefrontal neurons became active as working memory improved, but their baseline activity decreased. Second, improved working memory capacity was characterized by less variable temporal dynamics, resulting in a more consistent firing rate at each time point during the course of a trial. Our results reveal that improved performance of working memory tasks is achieved through more distributed activation and invariant neuronal dynamics.
Building Interpersonal Relationship Development Support for an Online Research Community

Although online communities have been thought of as a new mode of collaboration in the scientific world. They suffer from the problem of motivating members to visit and contribute regularly. The main purposes of this study are to explore factors that contribute to online relationship development and to design and evaluate system features to encourage relationship development. This extended abstract first presents the research motivation in introduction section. A theoretical framework to guide the work is described, based on theories from the computer mediated communication field. A field study and the system design based on the framework is then introduced, followed by the research methodology that will be used to evaluate the effectiveness of the framework and the communication features based upon it. Finally, the research timetable will be presented.
Human Monoclonal Antibodies Potently Neutralize Zika Virus and Select for Escape Mutations on the Lateral Ridge of the Envelope Protein.

The mosquito-borne Zika virus (ZIKV) has been causing epidemic outbreaks on a global scale. Virus infection can result in severe disease in humans, including microcephaly in newborns and Guillain-Barre syndrome in adults. Here, we characterized monoclonal antibodies isolated from a patient with an active Zika virus infection that potently neutralized virus infection in Vero cells at the nanogram-per-milliliter range. In addition, these antibodies enhanced internalization of virions into human leukemia K562 cells in vitro, indicating their possible ability to cause antibody-dependent enhancement of disease. Escape variants of the ZIKV MR766 strain to a potently neutralizing antibody, AC10, exhibited an amino acid substitution at residue S368 in the lateral ridge region of the envelope protein. Analysis of publicly availably ZIKV sequences revealed the S368 site to be conserved among the vast majority (97.6%) of circulating strains. We validated the importance of this residue by engineering a recombinant virus with an S368R point mutation that was unable to be fully neutralized by AC10. Four out of the 12 monoclonal antibodies tested were also unable to neutralize the virus with the S368R mutation, suggesting this region to be an important immunogenic epitope during human infection. Last, a time-of-addition infection assay further validated the escape variant and showed that all monoclonal antibodies inhibited virus binding to the cell surface. Thus, the present study demonstrates that the lateral ridge region of the envelope protein is likely an immunodominant, neutralizing epitope. IMPORTANCE Zika virus (ZIKV) is a global health threat causing severe disease in humans, including microcephaly in newborns and Guillain-Barre syndrome in adults. Here, we analyzed the human monoclonal antibody response to acute ZIKV infection and found that neutralizing antibodies could not elicit Fc-mediated immune effector functions but could potentiate antibody-dependent enhancement of disease. We further identified critical epitopes involved with neutralization by generating and characterizing escape variants by whole-genome sequencing. We demonstrate that the lateral ridge region, particularly the S368 amino acid site, is critical for neutralization by domain III-specific antibodies.
Price’s Law on Black Hole Space-Times

The aim of the talk was to provide an overview of recent and ongoing work concerning global in time decay properties for the wave equation on asymptotically flat space-times. Parts of this work are joint with the following collaborators: Jeremy Marzuola, Jason Metcalfe and Mihai Tohaneanu. Some of this research was motivated by problems in general relativity concerning the decay properties for the wave equation on Schwarzschild and Kerr backgrounds. Partly for this reason, all the results are presented in 3 + 1 space dimensions.
Telemedicine Versus Clinic Visit: A Pilot Study of Patient Satisfaction and Recall of Diet and Exercise Recommendations From Survivorship Care Plans.

Background Telemedicine is a growing approach to providing health care but a relatively new model for cancer survivorship services. Objectives This quantitative, quasiexperimental pilot research study compared patient satisfaction and recall of nutrition and exercise recommendations for in-person clinic visits versus telemedicine appointments. Methods Participants were stage 0-III cancer survivors who received their survivorship care plans from a nurse practitioner (NP). Following their clinic or telephone appointment, patients were sent a link to a survey that included demographic, patient satisfaction, and recall of diet and exercise recommendation questions. Fifty-two survivors completed the survey, of whom 38 had a clinic appointment and 14 had a telephone appointment. Findings There was no statistically significant difference between the mean patient satisfaction or recall of healthy weight, exercise, and nutrition recommendations between cancer survivors receiving their survivorship care plan by telephone versus a clinic appointment with an NP.
Resisting Compliance: Learning to Teach for Social Justice in a Neoliberal Context

Background/ContextThis study examines education in the context of neoliberalism and how current educational policies such as high-stakes testing and mandated curriculum create schooling environment...
Improving Time to Hospital Admission from the Pediatric Emergency Department at a Large Academic Children’s Center

INTRODUCTION: Increased lengths of stay in the emergency department (ED) correlate with decreased patient satisfaction and worse patient outcomes. The ED boarding time (time from admission order to ED departure) at an urban, academic, tertiary-care children’s hospital was 10% longer than the national benchmark. Resident physicians hold an important role in hospital admission workflow at academic hospitals. Inefficient resident communication was identified by ED nursing staff as a barrier to timely admission. The aim of this study was to …
Never Ending Care Work

Some people provide a lot more care than others throughout their lifetimes. All of the grandparents we interviewed for this book are providing care to grandchildren with disabilities. Most of them are also caring for their other grandchildren, particularly the siblings of their grandchildren with disabilities. Sometimes those siblings get along, making their jobs a bit easier, other times siblings are at loggerheads, making grandparenting that much more challenging. Many of the grandparents we interviewed are also caring for their own parents, siblings, or partners. Indeed, they are juggling multiple care roles. Some feel they are in a club sandwich generation, caught in the middle, supporting multiple generations older and younger than themselves. Some are simultaneous care workers, caring for multiple family members at once. Others are sequential care workers, caring for multiple family members one after another after another. As they look to the future, nearly all expect to continue caring for their grandchildren with disabilities for as long as they are able. Only a few expect their grandchildren to become independent adults; most are uncertain what the future holds. The most common plan is to remain available as needed. For many of these grandparents, care work provides a constant drumbeat across their days and years.
Channel Leakage, Information-Theoretic Limitations of Obfuscation, and Optimal Privacy Mask Design for Streaming Data

In this paper, we first introduce the notion of channel leakage as the minimum mutual information between the channel input and channel output. As its name indicates, channel leakage quantifies the minimum information leakage to the malicious receiver. In a broad sense, it can be viewed as a dual concept of channel capacity, which characterizes the maximum information transmission to the targeted receiver. We obtain explicit formulas of channel leakage for the white Gaussian case, the colored Gaussian case, and the fading case. We then utilize this notion to investigate the fundamental limitations of obfuscation in terms of privacy-distortion tradeoffs (as well as privacy-power tradeoffs) for streaming data; particularly, we derive analytical tradeoff equations for the stationary case, the non-stationary case, and the finite-time case. Our results also indicate explicitly how to design the privacy masks in an optimal way.
Peripartum Cardiomyopathy: Management Strategies for Pregnancy Termination.

Some women have underlying cardiovascular disease that leads to increased morbidity and mortality with pregnancy. These women may choose to terminate a pregnancy rather than face this increased ris...
Temporary intravascular shunts after civilian arterial injury: A prospective multicenter Eastern Association for the Surgery of Trauma study.

Abstract Introduction We sought to determine the impact of the indication for shunt placement on shunt-related outcomes after major arterial injuries. We hypothesized that a shunt placed for damage control indications would be associated with an increase in shunt-related complications including shunt dislodgement, thrombosis, or distal ischemia. Patients & methods A prospective, multicenter study (eleven level one US trauma centers) of all adult trauma patients undergoing temporary intravascular shunts (TIVS) after arterial injury was undertaken (January 2017-May 2019). Exclusion criteria included age Results The 66 patients who underwent TIVS were primarily young (30years [IQR 22-36]) men (85%), severely injured (ISS 17 [10-25]) by penetrating mechanisms (59%), and had their shunts placed for damage control (41%). After a median SDT of 198min [89-622], 9% experienced shunt-related complications. Compared by shunt placement indication (damage control shunts [n=27] compared to non-damage control shunts [n=39]), there were no differences in gender, mechanism, extremity AIS, MESS score, fractures, or surgeon specialty between the two groups (all p>0.05). Patients with shunts placed for damage control indications had more severe injuries (ISS 23.5 compared to 13; SBP 100 compared to 129; GCS 11 compared to 15; lactate 11.5 compared to 3.6; all p Conclusion Shunts placed for damage control indications were not associated with shunt complications in this prospective, multicenter study.
Is A Better than B? How Affect Influences the Marketing and Pricing of Financial Securities

We investigate the role of affect on asset prices through a natural experiment inherent in the designation of dual-class IPOs and its impact on IPO underpricing. We show that issuers of dual-class IPOs could and do take consumer psychology into account and manage to sell inferior securities at higher prices via branding. In the marketing of dual-class IPOs with inferior voting rights shares, Class A shares are much more frequently adopted and, at issue date, much less underpriced than Class B shares. Class A inferior voting shares enjoy higher valuation than Class B inferior voting shares for years after IPOs. Our results are statistically and economically significant and cannot be explained by a host of firm characteristics. The evidence supports the hypothesis proposed by Statman, Fisher, and Anginer (2008) that affect has a role in the pricing of financial assets. Marketing financial securities has much in common with marketing consumer products. It is the perception, or cache, that commands price premium, not necessarily actual quality.
Considerations for the Nonclinical Safety Evaluation of Antibody–Drug Conjugates

The targeted delivery of drugs by means of linking them to antibodies (Abs) to form antibody–drug conjugates (ADCs) has become an important approach in oncology and could potentially be used in other therapeutic areas. Targeted therapy is aimed at improving clinical efficacy while minimizing adverse reactions. The nonclinical safety assessment of ADCs presents several unique challenges involving the need to examine a complex molecule, each component of which can contribute to the effects observed, in appropriate animal models. Some considerations for the nonclinical safety evaluation of ADCs based on a literature review of ADCs in clinical development (currently or previously) are discussed.
Introduction to computational epidemiology

Most compartment models in epidemiology characterize the time evolution of their populations through a set of coupled nonlinear ordinary differential equations. Except for the SIS model, these equations have no analytical solution and we generally solve them numerically. Here we introduce the basic concepts of numerical methods for first order differential equations and illustrate explicit and implicit time integration schemes to solve them. To demonstrate the features of different classes of numerical methods, we derive and compare the explicit forward Euler, implicit backward Euler, and midpoint methods for the SIS model. We calculate their errors compared to the analytical solution and discuss concepts of convergence and accuracy. The learning objectives of this chapter on computational epidemiology are to
Specific Laminin Domains Mediate Endothelial Cell Adhesion, Alignment and Angiogenesis

The stability and integrity of blood vessels is maintained by many factors in the blood and by an important extracellular layer, the basement membrane, which underlies the endothelium of the vessels. Basement membranes are composed of an organized network of collagen (type IV), heparan sulfate proteoglycan, and glycoproteins such as entactin, fibronectin, and laminin. Laminin is one of the most important and abundant substances in basement membranes. It has a direct role in cell attachment, migration, and induction of the differentiated phenotype of many cells. We have examined and defined the role(s) of laminin and its specific cell-binding sites at the biochemical level using an in vitro angiogenic model. This model involves the differentiation of cultured endothelial cells on a laminin rich reconstituted basement membrane matrix, Matrigel, into capillary-like structures. Synthetic peptides derived from sequences in the laminin A and B1 chains (CTFALRGDNP and CDPGYIGSR) were able to block cell attachment to Matrigel and cell-cell alignment (early events in vessel formation), respectively, and thus inhibit subsequent tube formation. The third biologically active site CSRARKQAASIKVAVSADR) induced the endothelial cells to become migratory and invade into the Matrigel, forming sprouts from the primary capillary-like network. This site also induces angiogenesis in the chick chorioallantoic membrane (CAM) assay. Thus, endothelial cells interact with at least three different sites in laminin and these interactions are important in vessel maintenance and repair.
Functional measurements on the enlarged endothelial cells of corneal transplants.

PURPOSE: To measure the morphologic and functional status of the endothelium of long-term corneal transplants. METHODS: We induced hypoxic corneal edema and measured corneal deswelling (expressed as percent recovery per hour, PRPH, over 7 hours) with a modified optical pachometer in 12 corneas of 8 patients transplanted 7-18 years previously and in 21 normal adult control subjects. Fluorophotometry and specular microscopy were also performed on each eye. Results in the 2 groups were compared with a 2-tailed Student T test for means. RESULTS: The transplanted corneas had significantly decreased PRPH, induced swelling, endothelial permeability to fluorescein, and endothelial cell density compared to the controls, despite a similar estimated open-eye steady-state thickness. CONCLUSIONS: The markedly enlarged endothelial cells of long-term corneal transplants have a reduced ability to deturgesce the cornea and decreased permeability to small solutes. These findings could result from a reduction in intercellular space that occurs when the number of cells lining the posterior surface of the cornea is substantially decreased.
Towards a New Conceptual Framework for Studying Administrative Authority

The influence of civil servants upon policy making has increased substantially in the course of the twentieth century and this influence is no longer limited to senior level officials. Surprisingly, the study of administrative authority has dwindled to almost nothing, focusing on very specific aspects instead of the phenomenon in all its manifesta tions. This emphasis in the last sentence indicates that authority is generally considered as a single concept. We will show that it really is a compound concept. In this article we categorize existing meanings of authority into four main categories: property, place, people, and process. Each of these categories are analyzed in terms of their time of origin, their content, and their main authors. The most recent of these four categories is authority as process. This last one is vital to understanding the fundamentally negotiable nature of authority and the authoritative in contemporary society. The article concludes with a theoretical framework for future analysis of administrative authority. In the Western world the administrative state is feared and reviled as well as embraced and admired. Its civil servants, the archetypical ap pointed officeholders of the administrative state, meet with scorn, suspi cion and sometimes with outright hostility when discussed in the
Rat liver chromatin. Distribution of histone and nonhistone proteins in eu- and heterochromatin.

Abstract Rat liver chromatin was sheared and separated into template-active (euchromatin) and template-inactive (heterochromatin) fractions by glycerol gradient centrifugation. Chromosomal proteins associated with the chromatin fractions were analyzed by sodium dodecyl sulfate-polyacrylamide-gel electrophoresis. Histone composition did not vary qualitatively, but more histone protein was consistently found associated with the euchromatin fractions. Nonhistone protein banding patterns for these chromatin fractions exhibited marked heterogeneity, with a number of bands unique to either eu- or heterochromatin.
265010 JoynerRef: Text Message Reference Service @ ECU

Many libraries have embraced email and IM reference service, but have yet to offer reference via text message. But like e-mail and IM, text messaging represents just another method among a suite of online options to meet the reference needs of library patrons. In fact, if a library is already able to receive IMs via American Online’s Instant Messenger (AIM) then it already is able to offer text messaging as a free service. This article explains how a recent AIM modification, or “hack”, has given libraries and patrons access to a feature that was previously unavailable. AIM is by far the most popular IM client, with more than 55 million active users. A recent study at UNC – Chapel Hill’s House Undergraduate Library found that students prefer using AIM because its familiarity allows multitasking and lacks formality
Abstract 15712: Sirt2 Regulates Cardiac Hypertrophic in Response to Pressure Overload

Background: Heart failure is associated with a change in cardiac energy metabolism and increased oxidative stress. Sirtuins (SIRTs) are NAD+-dependent deacetylases and critical regulators of energy metabolism and oxidative stress response. Accumulating evidence indicates that SIRT family members play different roles in cardiac remodeling in response to stress. However, the function of SIRT2, the only cytosolic protein in the family, in regulating cardiac hypertrophy is largely unknown. Methods and results: To explore the role of SIRT2 in the development of cardiac hypertrophy, we examined the response of SIRT2-/- mice and their littermate controls to sustained pressure overload by transaortic constriction (TAC). SIRT2-/- mice displayed normal adult appearance and cardiovascular parameters at baseline. However, in response to TAC, SIRT2-/- mice displayed resistant to the pathological hypertrophic response, whereas their littermate controls developed cardiac hypertrophy and heart failure. Furthermore, SIRT2-/- mice had lower heart weight/body weight ratio, diminished wall thickness (0.96±0.074 vs 0.8±0.051mm), and sustained cardiac contractility compared to control mice. After 28 days of TAC, percentage of fractional shortening decreased to 16.47±1.78 in control mice, but remained at 26.17± 4.03 in SIRT2-/- mice. Additionally, the mRNA levels of atrial natriuretic factor (ANF) and B-type natriuretic peptide (BNP) were decreased in SIRT2-/- mice compared to wild type mice 4 weeks after TAC, indicating a stronger reduction of fetal gene expression. Finally, phospho-Akt levels were lower in SIRT2 -/- mice compared to wild type mice after TAC. Conclusion: Our results suggest that SIRT2 plays a role in the development of heart failure after TAC and that its deletion exerts protection against cardiac dysfunction, most likely through Akt pathway.
Transformation of Emergency Department processes of care with EHR, CPOE, and ER event tracking systems.

Mercy Medical Center – North Iowa implemented electronic health records (EHR), computerised provider order entry (CPOE) and event tracking systems in the emergency department (ED) as part of hospital-wide implementation of clinical information systems. This case study examines the changes in outcomes and processes in the ED following implementation. Although the system was designed to enhance effi ciency, there was a signifi cant increase in the mean length of stay (about 17 minutes, or 15%) in the ED after implementation. This surprising fi nding was examined in relationship to the multiple process-of-care changes in the ED.
Sarco-endoplasmic reticulum Ca2+ ATPase (SERCA) inhibitors identify a novel calcium pool in the central nervous system

Ca2+ uptake into the endoplasmic reticulum (ER) is mediated by Ca2+ ATPase isoforms, which are all selectively inhibited by nanomolar concentrations of thapsigargin. Using ATP/Mg2+-dependent 45Ca2+ transport in rat brain microsomes, tissue sections, and permeabilized cells, as well as Ca2+ imaging in living cells we distinguish two ER Ca2+ pools in the rat CNS. Nanomolar levels of thapsigargin blocked one component of brain microsomal 45Ca2+ transport, which we designate as the thapsigargin-sensitive pool (TG-S). The remaining component was only inhibited by micromolar thapsigargin, and thus designated as thapsigargin resistant (TG-R). Ca2+ ATPase and [32P]phosphoenzyme assays also distinguished activities with differential sensitivities to thapsigargin. The TG-R Ca2+ uptake displayed unique anion permeabilities, was inhibited by vanadate, but was unaffected by sulfhydryl reduction. Ca2+ sequestered into the TG-R pool could not be released by inositol-1,4,5-trisphosphate, caffeine, or cyclic ADP-ribose. The TG-R Ca2+ pool had a unique anatomical distribution in the brain, with selective enrichment in brainstem and spinal cord structures. Cell lines that expressed high levels of the TG-R pool required micromolar concentrations of thapsigargin to effectively raise cytoplasmic Ca2+ levels. TG-R Ca2+ accumulation represents a distinct Ca2+ buffering pool in specific CNS regions with unique pharmacological sensitivities and anatomical distributions.
Analysis of reactive oxygen species in cell death.

Publisher Summary This chapter analyzes the reactive oxygen species in cell death. The ability of oxidants to trigger apoptosis depends on the extent of the oxidative stress. Higher oxidant concentrations lead to necrosis and the “window” for induction of apoptosis may be small, depending on the cell type and the oxidant investigated. Mammalian cells possess multiple sources of reactive oxygen species (ROS), including, among others, xanthine oxidase, mitochondrial NADH oxidoreductase, microsomal NADPH oxidoreductase, and plasma membrane-bound NADH/NADPH oxidases. Evidence suggests that plasma membrane-associated oxidases may provide one source of ROS associated with cell resistance to triggers of apoptosis. NADH and NADPH oxidases may provide candidate sources of superoxide anion production associated with cell resistance to apoptosis. This chapter discusses the role of NADH and NADPH oxidases in the regulation of sensitivity to apoptosis. The chapter provides a method to measure the redox state of the active site cysteine of caspases. This chapter discusses the method based on the ability of iodoacetic acid (IAA) to react with reduced but not oxidized thiols and the visualization of IAA incorporation by its ability to shift the mobility of the target protein on an isoelectric focusing (IEF) gel.
Decision‐Making Skills in ASD: Performance on the Iowa Gambling Task

Decision making plays a key role in daily function, but little is known regarding how individuals with autism spectrum disorder (ASD) make decisions. The present studies examined decision making in persons with ASD using the Iowa Gambling Task (IGT), a computerized card game with the goal of earning money by deciding among decks of cards. To be successful, players need to figure out which decks are associated with winning and which are associated with losing money in the long run. Results of Study 1 indicated that participants with ASD made poorer decisions and showed slower learning of which decks earned more money compared with participants with typical development. Additionally, they made more frequent shifts between decks compared with participants with typical development. In Study 2, undergraduate students with typical development completed the IGT to examine whether instructing them to make frequent shifts between decks early in the IGT would negatively impact their decision making. Results of Study 2 suggested that when participants with typical development were required to make frequent shifts, they exhibited a slower rate of learning and poorer decision making, thus emulating participants with ASD in Study 1. The combined results suggest that the way that persons with ASD explore and attend to their environment may be related to poor decision making. Implications for cognitive learning styles are discussed.
Physiologic response to the inotropic and vasodilator properties of enoximone

Abstract In patients with chronic cardiac failure, improvement in ventricular function is observed after the administration of enoximone, a phosphodiesterase inhibitor with inotropic and vasodilator properties. The relative contributions of positive inotropy and vasodilation to the improvement in pump performance, however, remain uncertain. Therefore, findings from a series of dog experiments designed to resolve this issue are reviewed. Also, our current understanding of the physiologic response to enoximone in patients with cardiac failure, including the responses of myocardial oxygen consumption and efficiency, are considered. It is concluded that, enoximone produces a substantial (66 ± 2% in dogs) increase in contractility, a relatively minor increase in heart rate (0 to 12%) and a decrease in systemic vascular resistance (−28 to −49%). These are the ranges of average responses based on review of published findings. These physiologic responses lead to an improvement in the pumping function of the failing heart; cardiac output (23 to 83%) and stroke work index (17 to 88%) are increased, and pulmonary capillary wedge pressure (−19 to −59%) and right atrial pressure (−29 to −60%) are decreased. The influence of enoximone on myocardial oxygen consumption is less consistent (−18 to +33%). Nevertheless, enoximone improves the efficiency of the failing heart.
Feedback control of important plasma instabilities

Some of the important residual instabilities of Tokamak and Tandem Mirror fusion devices are trapped particle modes. We discuss control schemes for these instabilities using a Langmuir probe sensor and a Langmuir probe or a pair of electrostatic plates as a suppressor in the low temperature plasma of Linear Machines. We describe a remote suppressor of modulated neutral beam which appears to be highly promising in the context of high temperature fusion plasma of Tokamak and Tandem Mirror reactors.