cssi/SciSciGPT-SciSciNet huggingface dataset:
Maneuvering Spacecraft Tracking via State-Dependent Adaptive Estimation

In this study, an adaptive estimation algorithm is developed to estimate the state of a spacecraft that performs impulsive maneuvers. The accurate tracking of a maneuvering spacecraft with impulsive burns is a challenging problem since the magnitude and the time of occurrence of impulsive maneuvers are usually unknown a priori. To deal with this problem, an adaptive state estimation algorithm is developed in this study using a bank of extended Kalman filters along with interacting multiple models that account for spacecraft motion with and without impulsive maneuvers. Motivated by the fact that impulsive maneuvers usually occur when certain conditions on the spacecraft state are satisfied, the multiple extended Kalman filters are systematically blended using a state-dependent transition probability. Since the information about the conditions based on which impulsive maneuvers occur is explicitly used in the state-dependent transition probability, the proposed algorithm can predict the impulsive maneuvers ...
Sunscreen Product Performance and Other Determinants of Consumer Preferences

Importance Sunscreen use is a modifiable behavior that can help reduce the risk for skin cancer, prevent sunburns, mitigate photoaging, and treat photosensitive dermatoses. A better understanding of consumer sunscreen preferences would inform dermatologists in their own recommendations. Objective To determine the characteristics and the most commonly cited positive and negative features of highly rated sunscreens described by consumers. Design, Setting, and Participants The top 1 percentile of sunscreen products on Amazon.com as of December 2015 was selected according to average consumer review (≥4 stars) and the highest number of consumer reviews. Descriptive data for each product were collected from the product page and manufacturer claims. The top 5 “most helpful” reviews (positive and critical) were analyzed and coded by a consensus qualitative coding scheme, which included positive and negative descriptors in 6 major categories according to consumer comments: affordability, cosmetic elegance, separate ratings, product ingredients, product performance, and skin compatibility. Main Outcomes and Measures The Kruskal-Wallis test was performed to determine whether characteristics of each product (eg, American Academy of Dermatology [AAD] criteria, sun protection factor [SPF], or vehicle) could be used to predict price per ounce. The number (percentage) of comments categorized by major themes and subthemes was determined. Illustrative consumer comments were also collected. Results There were 6500 products categorized as sunscreens in the Amazon.com, online catalog. Of the 65 products evaluated, the median price per ounce was $3.32 (range, $0.68-$23.47). Of products, 40% (26 of 65) did not adhere to AAD guidelines (broad spectrum, SPF ≥30, and water resistant) for sunscreens. Vehicles, fulfillment of AAD criteria, and sunscreen type predicted a higher price per ounce. Cosmetic elegance was the most cited positive feature (198 of 325 [61%] comments) followed by product performance (146 of 325 [45%] comments) and skin type compatibility (78 of 325 [24%] comments). Conclusions and Relevance In this cohort of highly rated sunscreen products, a significant proportion did not adhere to AAD guidelines, mostly attributable to a lack of water resistance. The most striking variation in this cohort was price, which varied by more than 3000%. Dermatologists should balance the importance of cosmetic elegance, cost, and AAD guidelines for sun protection in making their recommendations to consumers.
CHAPTER 10 – Peptide-Based Instruction of Suppressor Commitment in Naïve T Cells

Publisher Summary This chapter focuses on the generation of CD25+ suppressor cells by exogenous antigens in the fully mature immune system, as well as with their in vivo stability and function. Evidence suggests that CD25+ suppressor cells represent a suitable tool to induce antigen-specific immunologic tolerance in the fully mature immune system in the absence of general immune suppression, which often has undesired side effects ranging from increased risk of infection to development of life-threatening lymphoma. The fact that CD4+25+ FoxP3-expressing suppressor cells have an essential role in preventing the early onset of autoimmune disease in mammals, and the fact that these cells can be artificially induced through subimmunogenic presentation of TCR agonist ligands, opens new possibilities to exploit these cells to induce specific tolerance in the fully mature immune system. This may become a powerful tool in the prevention of allergies and transplant rejection. Inducing such cells by organ-specific antigens, may become an effective means to prevent autoimmunity in patients. However, such attempts have had success in animal models of disease but not in clinical trials.
The Culture Based Model: A Framework for Designers and Visual ID Languages

The globalization of instructional design is the direction for the 21st century and beyond. Future designs of instruction, like the emerging VIDL, must consider culture as an integral component to the design process. Culture is a core construct of all design decisions; however its potential to improve the design process has been mostly ignored in the field of instructional design (Subramony 2004; Young, in press-a). This lack of interest in culture as a design construct may be prevalent for various reasons. First, designers are not sure how to represent culture in the design process, what to look for, nor what to include. Second, there may be conflicts between the culture of the target audience and the technology; and many designers are grappling with how to bridge these communication connections (Chu & Reeves, 2000). Third, a comprehensive framework in which to integrate culture into the analysis, design, development, implementation and evaluation (ADDIE) process has not been available. Finally, the inclusion of “cultural frames abstract
Aesthetics, Propaganda and Culture in Mass Dictatorships

In many places across the globe, culture between the two world wars possessed a set of common characteristics that were both novel and unique to this particular time period. The cataclysm of the First World War had redrawn the map and unsettled social hierarchies. New governments replaced old empires with the promise to remake and renew humanity. At the same time, social and gender relations were transformed and the “New Woman” claimed a more active role in the public and social spheres. Simultaneously, there were substantial advances in mass media. Advertising techniques spread, film and radio became ever-more popular and more prevalent, and elaborate civic celebrations and mass festivals became an ever-more common feature around the world.
Racial and Ethnic Disparities in Infant Mortality, 1990–2004: Low Birth Weight, Maternal Complications and Other Causes

Demographers have long been interested in understanding persistent racial and ethnic gaps in infant mortality, which are likely a reflection of disproportionately distributed resources across groups. Using micro-level cohort linked birth-death files from the National Center for Health Statistics (NCHS) for the years 1990, 2000, and 2004, we estimate multinomial logistic regressions to examine race and ethnicity-specific trends in risk of infant death due to low birthweight , maternal complications, and other causes over time. We further investigate whether or not a survival advantage by gestational age and birthweight varies across racial and ethnic groups. We found that risk of death has increased for non-Hispanic black infants, and that the beneficial effect of Hispanic ethnicity is reduced over time. We further found that both race and ethnicity interact with preterm and/or low birthweight delivery to magnify risk of death due to several causes in later years. Overall, this research confirms the presence of an increasing black-white infant mortality gap, lends support to findings of a survival disadvantage in Black infants, and calls attention to a survival disadvantage in Hispanic infants. Additional attention to the mechanisms that generate magnified risk of infant death among racial and ethnic minorities who experience compromised births, i.e. preterm or low birthweight, is needed.
Teaching Justice and Drawing Change in Teacher Education

This final chapter pulls together the way that comics (or another alternative compositional mode, beyond the alphanumeric norm) could offer a new vantage point from which we might observe our collaborative socius – and thus imagine our collaborative project of teacher education for social justice. This chapter centers a theme of creativity, of doing things not done before, of refusing to repeat and questioning assumptions of conditions being fixed.
Influence of viscosity and pressure on prosthetic valve regurgitation

Blood viscosity varies during the course of artificial heart implants and is affected by pathological conditions. To gauge the potential effect of changing viscosity on valve performance, leakage rates were measured across a closed Medtronic-Hall valve with water, water/glycerol and fresh whole bovine blood for aortic and pulmonary pressure ranges. As might be expected from the low Reynolds numbers (< 140), losses across the valve were found to be primarily viscous. For the two Newtonian fluids, leakage was slightly less than linearly proportional to pressure. This is comparable with empirical data for orifice flow, which predicts three fifths power dependence on pressure. For blood, however, the greater than linear dependence on pressure found suggests that the pseudoplasticity (shear-thinning behavior) of blood is important. These data provide evidence that the viscous and non-Newtonian properties of blood must be taken into account in modelling prosthetic valve performance and may affect the test methods and flow regulation strategies for prosthetic blood pumps.
Bacterial d-amino acids suppress sinonasal innate immunity through sweet taste receptors in solitary chemosensory cells

In the upper respiratory epithelium, bitter and sweet taste receptors present in solitary chemosensory cells influence antimicrobial innate immune defense responses. Whereas activation of bitter taste receptors (T2Rs) stimulates surrounding epithelial cells to release antimicrobial peptides, activation of the sweet taste receptor (T1R) in the same cells inhibits this response. This mechanism is thought to control the magnitude of antimicrobial peptide release based on the sugar content of airway surface liquid. We hypothesized that d-amino acids, which are produced by various bacteria and activate T1R in taste receptor cells in the mouth, may also activate T1R in the airway. We showed that both the T1R2 and T1R3 subunits of the sweet taste receptor (T1R2/3) were present in the same chemosensory cells of primary human sinonasal epithelial cultures. Respiratory isolates of Staphylococcus species, but not Pseudomonas aeruginosa, produced at least two d-amino acids that activate the sweet taste receptor. In addition to inhibiting P. aeruginosa biofilm formation, d-amino acids derived from Staphylococcus inhibited T2R-mediated signaling and defensin secretion in sinonasal cells by activating T1R2/3. d-Amino acid-mediated activation of T1R2/3 also enhanced epithelial cell death during challenge with Staphylococcus aureus in the presence of the bitter receptor-activating compound denatonium benzoate. These data establish a potential mechanism for interkingdom signaling in the airway mediated by bacterial d-amino acids and the mammalian sweet taste receptor in airway chemosensory cells.
Wolfenden’s Witnesses: homosexuality in postwar Britain

In recent years, interest in queer British history has resulted in the publication of a number of important studies by Matt Cook, Laura Doan, Matt Houlbrook and Rebecca Jennings, among others. Appe...
Valganciclovir Use Among Commercially and Medicaid-insured Infants With Congenital CMV Infection in the United States, 2009–2015

Abstract Purpose The aim of this study was to assess the clinical characteristics and trends in valganciclovir use among infants diagnosed with congenital cytomegalovirus (CMV) disease in the United States. Methods We analyzed data from medical claims dated 2009–2015 from the Truven Health MarketScan® Commercial Claims and Encounters and Medicaid databases. We identified infants with a live birth code in the first claim who were continuously enrolled for at least 45 days. Among infants diagnosed with congenital CMV disease, identified by an ICD-9-CM or ICD-10-CM code for congenital CMV infection or CMV disease within 45 days of birth, we assessed data from claims containing codes for any CMV-associated clinical condition within the same period, and data from claims for hearing loss and/or valganciclovir within the first 180 days of life. Findings In the commercial and Medicaid databases, we identified 257 (2.5/10,000) and 445 (3.3/10,000) infants, respectively, diagnosed with congenital CMV disease, among whom 135 (53%) and 282 (63%) had ≥1 CMV-associated condition, 30 (12%) and 32 (7%) had hearing loss, and 41 (16%) and 78 (18%) had a claim for valganciclovir. Among infants with congenital CMV disease who had a claim for valganciclovir, 37 (90%) among commercially insured infants and 68 (87%) among Medicaid-insured infants had ≥1 CMV-associated condition and/or hearing loss. From 2009 to 2015, the percentages with a claim for valganciclovir increased from 0% to 29% among commercially insured infants and from 4% to 37% among Medicaid-insured infants (P Implications During 2009–2015, there was a strong upward trend in valganciclovir claims among insured infants who were diagnosed with congenital CMV disease, the majority of whom had CMV-associated conditions and/or hearing loss.
The Case for Predictive Database Systems: Opportunities and Challenges

This paper argues that next generation database management systems should incorporate a predictive model management component to effectively support both inward-facing applications, such as self management, and user-facing applications such as data-driven predictive analytics. We draw an analogy between model management and data management functionality and discuss how model management can leverage profiling, physical design and query optimization techniques, as well as the pertinent challenges. We then describe the early design and architecture of Longview, a predictive DBMS prototype that we are building at Brown, along with a case study of how models can be used to predict query execution performance.
Corneal wound healing after excimer laser ablation. Effects of nitrogen gas blower.

Purpose: To examine the effects of blowing nitrogen gas over the cornea during photorefractive keratectomy. Methods: Excimer laser ablations for myopia were performed on rabbit corneas with or without the blowing of nitrogen across the surface of the cornea. All eyes underwent a 5-diopter myopic ablation; in 8 eyes, a ring was used to blow nitrogen gas across the cornea, and, in 8 eyes, the same ring was used, but no nitrogen gas was blown. Results: Epithelial healing occurred more rapidly in the eyes that were not treated with the gas (3.8 ± 1.3 days) than in the gas-treated group (6.1 ± 0.8 days; P = 0.0025). Corneal haze was greater in the group treated with gas. Results of histologic examination showed the ablated area to have a smoother surface when nitrogen was not blown across the cornea surface. Conclusion: Superficial corneal deturgescence produced by the nitrogen gas appears to result in a rougher surface immediately postoperatively with undesirable effects on surface healing, but further studies will be necessary to determine the applicability of these results to humans.
Soret Spectroscopic and Molecular Graphic Analysis of Human Semi-β-Hemoglobin Formation

The interaction of heme-free α (αo) and heme-containing β (βh) chains of human hemoglobin has been monitored in 0.1 M potassium phosphate buffer, pH 7 or 8, at [5°C. Soret zero and first-derivative spectra were consistent with a uniform association reaction. Stopped-flow investigations demonstrated association rates on the order of 107 M−1 s−1. This was 100-fold more rapid than the reported rate of combination of αh and βh proteins. This encounter-like rate of semi-β-hemoglobin (αoβh) formation was increased by raising the pH from 7 to 8. pH change is known to affect the spatial arrangement of AB—GH helical entities. Molecular graphic analysis of modeled αo protein superimposed over native αh protein revealed an apo Mb-like structure with well-defined AB—GH segments. Repositioning of these core helical segments, resulting in increased conformational freedom of the α1β1 interface, was apparently responsible for the enhanced association properties of the αo protein.
Peritoneal Dialysis in Adolescents with End-Stage Renal Disease

Adolescents with chronic illnesses, including ESRD, are a unique group of patients. Caretakers should be sensitive to their emotional and psychological needs and be cognizant of the toll chronic dialysis can take on them. This chapter discusses peritoneal dialysis treatment in adolescents. It addresses the advantages and challenges of the treatment in this age group in addition to patient selection, physiology, training, monitoring, and complications of treatment.
iPLA2β and its role in male fertility, neurological disorders, metabolic disorders, and inflammation.

The Ca2+-independent phospholipases, designated as group VI iPLA2s, also referred to as PNPLAs due to their shared homology with patatin, include the β, γ, δ, e, ζ, and η forms of the enzyme. The iPLA2s are ubiquitously expressed, share a consensus GXSXG catalytic motif, and exhibit organelle/cell-specific localization. Among the iPLA2s, iPLA2β has received wide attention as it is recognized to be involved in membrane remodeling, cell proliferation, cell death, and signal transduction. Ongoing studies implicate participation of iPLA2β in a variety of disease processes including cancer, cardiovascular abnormalities, glaucoma, and peridonditis. This review will focus on iPLA2β and its links to male fertility, neurological disorders, metabolic disorders, and inflammation.
Parent-Reported Symptoms and Effectiveness of Treatment in Children Hospitalized with Advanced Heart Disease

Purpose Patient perceived effectiveness of care is increasingly recognized as a measure of quality. There is little data on the frequency or treatment of symptoms in children with advanced heart disease. We sought to evaluate parental report of symptoms and successful treatment of those symptoms in their children hospitalized with advanced heart disease (AHD). Methods We performed a prospective cohort survey of parents of children hospitalized with AHD at a single institution. Parents were approached if their child was (1) admitted for > 7 days with single ventricle physiology, pulmonary vein stenosis, or pulmonary hypertension, or (2) had ICU stay >30d, mechanical circulatory support, >3 surgeries/ admissions in the last year, mechanical ventilator support >14d, or listed for heart transplant. Information was collected regarding symptoms, suffering from those symptoms, and whether symptoms were addressed and treated by medical providers. Results 112 parents participated, with the majority ward admissions (60%). 51% of parents reported that their child was experiencing ‘a great deal’ or ‘a lot’ of symptoms related to their heart disease. Frequent symptoms reported included: fatigue (76%), feeding difficulties (67%), irritability (66%), pain (65%), and dyspnea (64%). The percentage suffering from the symptoms was fairly consistent across individual symptoms (37-47%). The least often treated symptoms were sadness/depression (47%), fatigue (49%), and sleep disturbances (52%), and these were some of the least likely to be reported as successfully treated (31-33%) (Fig). Conclusion Fatigue, pain, dyspnea, irritability and feeding difficulties are the symptoms most frequently identified by parents caring for children with AHD in the hospital setting, with pain and dyspnea most often being the symptoms treated successfully. Our data suggest that cardiologists may inadequately assess and treat mental health symptoms associated with hospitalization for advanced heart disease.
Plasma technology as a tool to decrease the sensitivity to water of fish protein films for food packaging

Abstract Proteins films have been developed for use in food packaging materials in order to replace synthetic polymers because of environment pollution. Despite their advantages, the use of protein films in a wide range of food products is still limited due to their hydrophilic behavior. Thus, this study aimed to decrease the sensitivity of fish protein films to water through the application of glow discharge plasma. Plasma parameters (power, pressure and time of exposure) were studied according to a 23 factorial design, and the physicochemical properties of the films including moisture content, water vapor permeability, and solubility in water were evaluated. The microstructure and thermal properties of the films were also characterized. In general, glow discharge plasma caused different effects in films properties, such as cleaning and etching which were responsible for the changes observed in physicochemical properties. Power and time of exposure, as well as their interaction, were the most influent parameters. Decrease in water vapor permeability and solubility were observed in some treatments, which are important characteristics for a material to be used as food packaging. Then, the plasma setting might be changed through the adjustment of parameters of exposure according to the specificity of the application intended.
Organ Dysfunction Trials: Background, Historical Barriers, Progress in Overcoming Barriers, and Suggestions for Future Trials

In the past, patients with cancer, who also have hepatic or renal dysfunction, have carried a triple burden. Not only have they suffered from cancer and organ dysfunction, but until recently, their oncologists have had inadequate information to tailor doses of drugs to their degree of organ dysfunction. In the past, phase 1 clinical trials in patients with organ dysfunction were either performed long after drug approval or not at all. This chapter provides background, a review of barriers to the conduct of clinical trials in this population, information about how these barriers have been largely overcome, and suggestions for conducting organ dysfunction trials in the future.
An activatable PET imaging radioprobe is a dynamic reporter of myeloperoxidase activity in vivo.

Myeloperoxidase (MPO) is a critical proinflammatory enzyme implicated in cardiovascular, neurological, and rheumatological diseases. Emerging therapies targeting inflammation have raised interest in tracking MPO activity in patients. We describe 18 F-MAPP, an activatable MPO activity radioprobe for positron emission tomography (PET) imaging. The activated radioprobe binds to proteins and accumulates at sites of MPO activity. The radioprobe 18 F-MAPP has a short blood half-life, remains stable in plasma, does not demonstrate cytotoxicity, and crosses the intact blood–brain barrier. The 18 F-MAPP imaging detected sites of elevated MPO activity in living mice embedded with human MPO and in mice induced with chemical inflammation or myocardial infarction. The 18 F-MAPP PET imaging noninvasively differentiated varying amounts of MPO activity, competitive inhibition, and MPO deficiency in living animals, confirming specificity and showing that the radioprobe can quantify changes in in vivo MPO activity. The radiosynthesis has been optimized and automated, an important step in translation. These data indicate that 18 F-MAPP is a promising translational candidate to noninvasively monitor MPO activity and inflammation in patients.
Recurrent Urinary Tract Infection in Women: Primary Care Referral Patterns in a Tertiary Care Center.

ObjectivesWith more than 150 million urinary tract infections (UTIs) diagnosed globally per year, the impact on patient care is significant. We sought to examine appropriateness of management of recurrent UTI before referral to a female pelvic medicine and reconstructive surgery practice, as well as
Functional RDL of FOPLP by Using LTPS-TFT Technology for ESD protection Application

This study realized a functional RDL structure in FOPLP for the first time. It shows not only the potentials and advantages of small generation display factory to produce IC packaging by FOPLP in the future, but also a new concept of hetero-integration by combining display and RDL technologies. The ESD protection circuit formed by LTPS-TFT can discharge large than 0.5 A in a nano-second for protecting die to die I/Os of multi-chips in assembly process of RDL first packaging.
Safety II: A Novel Approach to Reducing Harm

Traditional safety efforts in healthcare have relied on learning from mistakes. This method (termed “Safety I”) includes error identification and reporting, investigation, and subsequent policy and procedure revisions if needed. Believing the Safety I approach can eliminate harm derives from evidence that standardizing work improves reliability and quality, which both affect safety. However, the Safety I approach has limitations due to the complexity of patients and healthcare delivery, making pre-planned, stable solutions to every possible situation impossible. Furthermore, as harm events become increasingly rare, there is less opportunity to learn from each occurrence, with events becoming “one-offs” unrelated to prior harm. Thus, if an organization’s goal is zero harm, the Safety I approach alone may be insufficient to reach that ambitious target. The solution may lie in a new approach – “Safety II.” The key philosophy of Safety II is that individuals and systems usually perform well, even under varying conditions. By understanding why things usually go right, even when they might not, and increasing the capability to handle unanticipated or unusual scenarios, patient safety will improve. Safety II leaders (psychologists, philosophers, systems and resilience engineers, and healthcare professionals) have proposed four highly interrelated activities believed to increase odds that systems will succeed during unpredictable conditions and improve outcomes: Monitor, Anticipate, Respond, and Learn. By using an illustrative case example, we will outline how Safety II practices can avoid harm in the healthcare setting.
MM-378: Inhibitory and Stimulatory Interplay Between Myeloma Tumor and T Cells

Context: T cells engineered to express chimeric antigen receptors (CAR-Ts) offer hope for improved outcomes in multiple myeloma. Patients relapse despite 80% or better response rates from CAR-Ts in clinical trials. Improvements in CAR design may come from a better understanding of the interplay between T cells and the tumor microenvironment. Objective: To describe this interplay, we deeply characterized the surfaceome of the ANBL-6 cell line shown by us to best represent the transcriptome of patients newly diagnosed with multiple myeloma. Design: ANBL-6 cells were cultured in RPMI Complete with 2 ng/mL IL-6 and were stained with antibodies directed toward 28 unique cell-surface antigens known to mark myeloma cells, as well as those known to have effects on T cells that are stimulatory, inhibitory, or both. Flow cytometry was employed to assess expression of cell-surface antigens on ANBL-6 cells incubated for 24 hours in and out of the presence of IFNγ, which is expressed by activated T cells, at 100 U/mL. Results: Canonical myeloma markers CD38 and CD138 were expressed. BCMA, BAFF, and the receptor to BAFF (BAFF-R) were not. CD19, CD44, CD56, CD72, CD307, CS1/SLAMF7, GPRC5D, and TACI were expressed. CD19, CD72, CD56, and CS1/SLAMF7 increased with IFNγ. TACI decreased. Stimulatory 4-1BB-L, CD48, CD86, ICOS-L, and OX40-L were present. 4-1BB-L increased with IFNγ. The inhibitory cell-surface antigens CD112, CEACAM, FasL, PD-L1, and PD-L2 were present. CEACAM, FasL, and PD-L1 all increased with IFNγ. Stimulatory and inhibitory CD155 and CD270 were both present and did not change with IFNγ. Inhibitory CD200 and stimulatory CD70 and CD80 were not expressed. Conclusions: ANBL-6 expressed five known T-cell stimulatory antigens and five known inhibitory antigens. One of five stimulatory antigens increased with IFNγ. Three of five inhibitory proteins increased with IFNγ. Thus, stimulated CAR-Ts may cause their own inhibition. These in vitro data in a single cell line offer insight into myeloma tumor dynamics but may not fully reflect in vivo tumor behavior. Characterization of multiple cell lines and primary tumor samples in vitro and in vivo may improve CAR design ranging from having better suited costimulatory domains to switching receptors that transform inhibitory ligands into costimulatory signals.
Detection of Different Bearing Faults in a Permanent Magnet Synchronous Motor using PWT and LVQNN

This paper deals with the detection of bearing-related faults in permanent magnet synchronous motors. First, the motor current was sampled and analyzed using multi-level packet waveform transformation and then based on different features from the transformed signals, which resulting from the primary waveform, the LVQ neural network is trained for doing the classification. The outer-ring, inner-ring, cage, lubricant loss, and imperfect ball fault classes are considered in this paper. The proposed approach for fault detection shows high accuracy for practical cases.
Function Generators and Oscilloscopes

A function generator is an equipment to generate input functions for your circuit. It can generate sinewaves, square waves, triangular waves, modulated signals, and so on. An oscilloscope is an equipment to display the signals in the circuit. It can display multiple signals simultaneously.
Differentiation and characterization of human iPSC-derived vascular endothelial cells under physiological shear stress

Summary Induced pluripotent stem cells (iPSCs) offer a potentially unlimited source to generate endothelial cells (ECs) for numerous applications. Here, we describe a 7-day protocol to differentiate up to 55 million vascular endothelial cells (viECs) from 3.5 million human iPSCs using small molecules to regulate specific transcription factors. We also describe a parallel-plate flow chamber system to study EC behavior under physiological shear stress. For complete details on the use and execution of this protocol, please refer to Atchison et al. (2020) .
Exploring lipid-dependent conformations of membrane-bound α-synuclein with the VDAC nanopore.

Abstract Regulation of VDAC by α-synuclein (αSyn) is a rich and instructive example of protein-protein interactions catalyzed by a lipid membrane surface. αSyn, a peripheral membrane protein involved in Parkinson's disease pathology, is known to bind to membranes in a transient manner. αSyn's negatively charged C-terminal domain is then available to be electromechanically trapped by the VDAC β-barrel, a process that is observed in vitro as the reversible reduction of ion flow through a single voltage-biased VDAC nanopore. Binding of αSyn to the lipid bilayer is a prerequisite of the channel-protein interaction; surprisingly, however, we find that the strength of αSyn binding to the membrane does not correlate in any simple way with its efficiency of blocking VDAC, suggesting that the lipid-dependent conformations of the membrane-bound αSyn control the interaction. Quantitative models of the free energy landscape governing the capture and release processes allow us to discriminate between several αSyn (sub-) conformations on the membrane surface. These results, combined with known structural features of αSyn on anionic lipid membranes, point to a model in which the lipid composition determines the fraction of αSyn molecules for which the charged C terminal domain is constrained to be close, but not tightly bound, to the membrane surface and thus readily captured by the VDAC nanopore. We speculate that changes in the mitochondrial membrane lipid composition may be key regulators of the αSyn-VDAC interaction and consequently of VDAC-facilitated transport of ions and metabolites in and out of mitochondria and, i.e. mitochondrial metabolism.
Enabling antibiotic allergy evaluations and reintroduction of first-line antibiotics for patients with cystic fibrosis.

Abstract Background Patients with cystic fibrosis (CF) often have a history of antibiotic adverse drug reactions (ADRs) that pose a barrier to receiving recommended first-line treatment. Targeted antibiotic allergy evaluations are increasingly recognized as an important strategy for optimization of antimicrobial stewardship. Objective To improve first-line antibiotic use in patients with CF with antibiotic ADRs by streamlining access to antibiotic allergy evaluations and standardizing documentation of plans for antibiotic reintroduction. Methods We incorporated allergy evaluations into a multidisciplinary CF clinic and used telemedicine when allergy evaluations could not be performed during CF clinic. Standard documentation of antibiotic allergy plans was used to enable safe reintroduction of first-line antibiotics by CF providers. Results Strategies used in this study allowed 81.3% (26 of 32) of patients with CF to receive allergy evaluations and antibiotic allergy plans for prioritized antibiotics (penicillin, cephalosporin, sulfonamide), with removal of 41.0% (16 of 39) of prioritized antibiotic ADRs. Only 5.1% (2 of 39) of prioritized antibiotic ADRs evaluated required strict avoidance after evaluation. There were 9 patients who received at least 1 prioritized antibiotic, with 66.6% (6 of 9) of these patients given the antibiotic after only 1 allergy evaluation visit. Furthermore, these strategies allowed allergy evaluations of 23 nonprioritized antibiotics to occur, with removal of the ADR in 39.1% (9 of 23) and use of 77.8% (7 of 9) of nonprioritized antibiotics after removal. Conclusion Incorporating allergy evaluations into a multidisciplinary CF clinic can liberalize first-line antibiotic use in patients with CF. Standard documentation of antibiotic allergy plans allowed antibiotic reintroduction to occur even before complete removal of documented antibiotic ADRs.
Abstract #LB-245: Anthocyanins from black raspberries modulate genes involved in Wnt signaling, inflammation, cell cycle, and angiogenesis in human colon cancer cells

We reported that the short-term (2-to-4 wk) treatment of colorectal cancer patients with freeze-dried black raspberries (BRBs) positively modulated biomarkers of cell proliferation, apoptosis, angiogenesis, and components of the Wnt pathway in colorectal tumor specimens. The present study was conducted to identify additional biomarkers of BRB effects on colon cancer cells. HCT 116 human colon cancer cells were treated with an anthocyanin-rich fraction from BRBs at 5 µg/ml every day for three days. The effects of the berries on gene expression were analyzed using PCR mini-microarrays, targeting 588 cancer-related genes including genes associated with Wnt signaling, angiogenesis, inflammation, apoptosis, cell-cell and cell-matrix adhesion and cell cycle. The results showed that 50 of the 588 genes expressed \#8805; 2.5 fold up/down regulation in anthocyanin-treated vs. non-treated cells; 34 of the 50 genes (68%) were positively modulated. Interestingly, Wnt signaling genes comprised 6 of the 34 genes, and all 6 ( WNT7B, WNT10A, WNT16, FZD2, LRP6, and DVL1 ) were positively down-regulated by anthocyanin treatment. Inflammatory cytokines and their receptors comprised 13 of the 34 genes and these were positively modulated (i.e., IL1F9 , IL10RA , and CCR9 all down-regulated), as were genes associated with angiogenesis (i.e., HGF , ID3 , and CDH5 all down-regulated) and cell cycle control (i.e., ABL1, CCNT2 , and GTSE1 all down-regulated). Notably, three genes were markedly down-regulated by berry anthocyanins; i.e., WNT7B by 53-fold, DVL1 by 39-fold, and ABL1 by 28-fold. These changes in gene expression were validated using Real-time PCR. This study is the first to show that anthocyanins from BRBs modulate genes upstream of the Wnt pathway. It may have also identified additional biomarker genes that will be further investigated in human colon tumor specimens from berry-treated patients. Supported by NCI grant CA103180 and USDA grant 38903-03560. Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr LB-245.
Factor VIII:C concentrate purified from plasma using monoclonal antibodies: human studies

Conventional clotting factor concentrates have, until recently, been "of intermediate purity," containing less than 1% of the coagulation factor, and greater than 99% extraneous plasma proteins such as fibrinogen, fibronectin, gamma globulins, and traces of many others. We report here the results of a new factor VIII concentrate that is purified from human plasma using a mouse monoclonal antibody to factor VIII:vWF in an affinity chromatography system. The resultant concentrate has an activity of between 3,000 and 5,000 U/mg protein before albumin is added as a stabilizer. Seven patients with severe hemophilia A and no inhibitor who were positive for antibody to human immunodeficiency virus (HIV) have been treated solely with this concentrate for over 24 months. Factor usage in these patients has ranged from 611 U/kg/yr to 2,022 U/kg/yr. These patients have infused approximately once per week on the average, most often for joint hemorrhages. The efficacy of the concentrate is excellent. No allergic reactions have occurred and no factor VIII antibodies have developed. In these seven patients mean CD4 counts stabilized (856 +/- 619 at screen v 778 +/- 686 at 24 months) and there was reversal of skin test anergy. In a comparison group on conventional intermediate purity concentrate chosen retrospectively decreases in mean CD4 cell counts similarly did not occur. However, the number of the comparison patients who were anergic increased over the course of the study. These observations indicate the possibility that more highly purified concentrates may stabilize immune function in HIV seropositive patients.
Kill Me If I Have Alzheimer's: Physician-Assisted Suicide and Dementia

To date, the discussion surrounding physician assisted suicide has centered around those succumbing to terminal illnesses such as cancer or ALS. Yet lurking in the background is a far larger population ready to ascend the twin ethical pillars currently justifying physician assisted suicide, death with dignity and the avoidance of great suffering, i.e., sufferers of Dementia. Four and a half million are currently afflicted with Alzheimer Disease, accounting for roughly half the cases of adult dementia, with fourteen million cases projected by mid century. Assessing how society should consider this population literally requires traversing cultural, philosophical, and psychological fault lines as to the nature of personhood. Thus, those in our society characterizing the seriously demented as empty shells are met by those claiming that the capacity of the demented to make meaning and to communicate to the outside has been undermined by what they term malignant positioning, while in the philosophical realm, modern Lockeans locating personhood and personal identity in the cognitive capacity for self reflection and awareness of self over time contend with phenomenologist and those espousing the social construction of meaning in intersubjectivity. At the same time, medical disciplines have entered the fray. In this conflict, cognitive psychologist grapple with proponents of discursive psychology, and even interceptive stances in neurophysiology face off against each other. On top of it all, in the legal regime one encounters a seeming logical paradox as to the capacity of the person to meaningfully choose assisted suicide: when the person is competent, they do not have full information, once they have full information, they are no longer competent. This article analyzes these competing positions, and then using the narrative of the author's mother and her life with Alzheimer Disease as a concrete context, incorporates those analyses into proposals for resolution of what portends a significant societal event.
Integrated web-based architecture for correlative engineering data analysis and decision support

In the dynamic environment of frequently changing technology cycles, semiconductor manufacturing companies strive to optimize processes quickly to increase yields across a myriad of device types being designed and processed simultaneously in a factory. Immense quantities of process and test data are usually collected during silicon processing, and computerized tools are used to extract and analyze the engineering data for decision support. An integrated web-based architecture using Spotfire DecisionSite/spl trade/ framework has been implemented at Kilby Center (KFAB) of Texas Instruments (TI) for engineering data analysis. Rather than merely providing access to the different data sets to the end users, the established infrastructure provides an enormous value by facilitating data merges and correlative analyses across the multiple and complex data warehouses. Ease of employing these correlation techniques has lead to improvements in device designs, process corrections, equipment maintenance, and yields.
Tokamak and RFP ignition requirements

A plasma model is applied to calculate numerically transport-confinement (n tau /sub E/) requirements and steady-state operation points for both the reversed field pinch (RFP) and tokamak. The CIT tokamak and RFP ignition conditions are examined. Physics differences between RFP and tokamaks and their consequences for a DT ignition machine are discussed. The ignition RFP, compared to a tokamak, has many physics advantages. These advantages, coupled with important engineering advantages translate into significant cost reductions for both ignition and power reactor. The primary drawback of the RFP is the uncertainty that the present confinement scaling will extrapolate to reactor regimes. The 4-MA ZTH was expected to extend the n tau /sub E/ transport scaling data three orders of magnitude above ZT-40 M results, and if the present scaling held, to achieve a DT-equivalent scientific energy breakeven, Q=1. A base-case RFP ignition point is identified with a plasma current of 8.1 MA and no auxiliary heating. >
EM algorithms for independent component analysis

This paper presents a new approach to the blind source separation problem. In our approach, each source density is described by a model that is quite general and fully adaptive. Based on this model, we derive and demonstrate unsupervised learning algorithms not only for square noiseless mixing, but also for the general case where the number of sources may differ from the number of observed mixtures and the data are noisy. These algorithms use expectation-maximization to estimate the arbitrary source densities, mixing matrix and noise covariance from the input data. An approximate algorithm, based on the variational framework, is developed for cases where exact learning is intractable.
A learning-based approach to artificial sensory feedback

The planning and control of even simple movements, such as reaching for an object, rely on somatosensory feedback of the state of the limb. Such feedback will be equally important for naturalistic control of neuro-prosthetic devices. For this reason, there has been considerable interest in the development of systems for artificial somatosensory feedback, in particular using electrical microstimulation of the brain. Much of this work has focused on creating “biomimetic” patterns of neural activation, i.e., trying replicate natural sensory-drive activity, however the challenges for this approach remain significant. We have developed a complementary approach, focusing instead on the brain's natural ability to to learn. In particular, we learn to combine somatosensory and visual feedback of the limb in a statistically optimal fashion and to recalibrate the two senses when they come out of alignment. Moreover, computational work from our lab shows that these learning processes can be achieved by simple algorithms, driven only by spatiotemporal correlations between the two sensory signals. We have tested this idea in a demonstration of a novel, learning-based approach to artificial motor feedback. Animals were trained to perform a reaching task under the guidance of visual feedback. They were then exposed to a novel, artificial feedback signal in the form of a non-biomimetic pattern of multielectrode intracortical microstimulation (ICMS). After training with correlated visual and ICMS feedback, the animals were able to perform precise movements with the artificial signal alone. Furthermore, they combine the ICMS signal with vision in a statistically optimal fashion, as would be done for two natural stimuli. This result serves as a proof-of-concept for a learning-based approach to artificial feedback with brain-machine interfaces.
An integrated model for the adoption of information technologies in U.S. colleges and universities

This thesis fulfills the requirements of a Doctor of Liberal Studies degree at Georgetown University. It advances our knowledge of the rationale and mechanisms surrounding the spread, adoption and abandonment of information and communication technologies in tertiary education institutions in the United States. This interdisciplinary thesis approaches the topic from four disciplines: law, communication, economic and technology studies. It also relies heavily on first-hand, experiential accounts of technology adoption initiatives at Georgetown University from 2000 to 2012. U.S. colleges and universities spend considerable resources adopting information and communication technologies. Yet, why has United States tertiary education not adopted information technologies the better to fulfill its mission of preparing the next generation of knowledge workers, and of creating, disseminating and preserving knowledge? This thesis shows the constraints and enablers for this condition, which are rooted in legal, social, economic and technical factors. The thesis proposes an integrated model to improve the adoption of information technologies by higher education faculty, staff, students and administrators leveraging four drivers: legal and policy instruments, diffusion of innovation dynamics, economic incentives, and technical elements. The integrated model helps identify and resolve conflicts among factors and among actors when evaluating, deliberating and executing technology adoption initiatives. Using the
Genetic determinants of susceptibility to estrogen-induced mammary cancer in the rat

Estrogens are inextricably linked to the etiology of breast cancer. We have demonstrated that the ACI rat strain exhibits a unique propensity to develop mammary cancer when treated continuously with 17β-estradiol (E2). Treatment of ovary intact ACI rats with E2 results in virtually a 100% incidence of mammary carcinoma with a median latency of approximately 140 days. These mammary cancers are dependent upon exogenous E2 and exhibit genomic instability, a hallmark of breast cancers in humans. In contrast, the Copenhagen (COP) and Brown Norway (BN) rat strains are resistant to E2-induced mammary carcinogenesis. Susceptibility to E2-induced mammary cancer behaves as an incompletely dominant or dominant trait in crosses between the ACI strain and the COP or BN strains. Genetic linkage analyses of several hundred phenotypically defined F2 progeny from reciprocal crosses between the ACI and COP or BN strains revealed a total of seven genetic determinants of susceptibility to E2-induced mammary cancer on chromosomes 2, 3, 4, 5, 6, 7 and 18. The chromosome 5 locus, designated Emca1, determines susceptibility to E2-induced mammary cancer in reciprocal crosses between the highly susceptible ACI strain and the resistant COP or BN strains. Potential candidate genes residing within the Emca1 locus include Cdkn2a, Cdkn2b and Cdkn2c. Studies on Cdkn2a indicate that expression of the p16Ink4a protein product of the Cdkn2a locus is downregulated at an early stage of E2-induced mammary carcinogenesis in the ACI rat. We are currently evaluating these genes further to determine whether and how they contribute to mammary cancer etiology in this model.