cssi/SciSciGPT-SciSciNet huggingface dataset:
Women and Public Administration in a Comparative Perspective: The Case of Representation in Brazilian Local Governments

This article explores two questions related to whether passive representation leads to active representation using Brazilian municipal data: Does electing women to public office increase the proportion of women in public administration? Does the representation of women in elected office and public administration lead to better representation of women’s interests? Results suggest that women elected leaders increase the probability that women will be appointed to head public agencies, and through these agency heads they indirectly affect representation in other administrative positions. In addition, women elected officials and public administrators are also associated with the adoption of more women-friendly policies.
On Higher Order Hydrodynamic Theories of Shock Structure

The Burnett equations for shock structure in a Maxwell gas (inverse fifth power repulsion) are not amenable to numerical integration by the usual methods (fourth order Runge-Kutta) above a Mach number of 1.9. The super-Burnett equations are not amenable to numerical integration by the usual methods for any Mach number. It is not yet clear whether these negative results indicate a fundamental difficulty in the Chapman-Enskog solution of the Boltzmann equation.
The evolving field of cardio-oncology: beyond anthracyclines and heart failure.

Dr Michael Fradley discusses the cardiac implications beyond anthracyclines and heart failure Over the last several decades, the survival rates for many cancers have increased dramatically, largely driven by improved screening modalities and the development of novel cancer treatments including targeted and immunologic therapies. Despite these advancements, cardiovascular toxicity is a commonly observed complication of many of these treatments. As a result, the field of cardio-oncology has developed at a rapid pace. Cardio-oncology is a multidisciplinary specialty aimed at managing and preventing cardiovascular disease in cancer patients and survivors.1 Initially, cardio-oncology was focused on cardiomyopathy and congestive heart failure associated with anthracyclines, a class of chemotherapeutics used to treat a variety of cancers including breast, sarcoma, leukaemia, and lymphoma.2 As the field of cardio-oncology has grown, there is increased recognition that cardiotoxicity is not limited to just anthracyclines and heart failure; instead novel cancer therapeutics are associated with a variety of cardiac complications including vascular disease, accelerated hypertension, and arrhythmias. It is important for the cardio-oncologist to possess a broad knowledge of these agents and their toxicities in order to provide optimal care to patients. With improved understanding of cancer biology, the landscape of cancer therapeutics has changed dramatically. For example, abnormal cell signalling pathways have been implicated in many different cancers, often due to overexpressed or mutated protein kinases impacting the amino acid tyrosine.3 There is also data demonstrating that certain cancers are particularly dependent on proteasomes (multienzyme complexes that play a key role in protein degradation and homeostasis) for survival and proliferation.4 As such, the development of tyrosine kinase inhibitors (TKIs) and proteasome inhibitors (PIs), have led to significant improvements in the treatment of many liquid and solid tumours. More recently, immunomodulatory drugs (IMiDs) and other immunotherapies that harness the body’s own immune …
Burden of Cardiac Arrhythmias in Patients With Anthracycline-Related Cardiomyopathy.

Abstract Objectives The objective of this study was to determine the incidence of arrhythmias and device (internal cardiac defibrillator/cardiac resynchronization therapy defibrillator) therapies in patients with a diagnosis of cardiomyopathy and anthracycline exposure. Background The burden of arrhythmias in adult cancer survivors with anthracycline-related cardiomyopathy has not been studied, but might have important implications for clinical management and outcomes. Methods Retrospective cohort study of all patients with left ventricular dysfunction (LVD) who underwent internal cardiac defibrillator/cardiac resynchronization therapy defibrillator implantation at the Mayo Clinic from 1990 to 2012. Ninety-five patients were cancer survivors (on average, 5 years), 23 of which had anthracycline-related cardiomyopathy (CA-ACM) and 72 of which had non–anthracycline-related cardiomyopathy (CA-NACM). A second control group of 68 noncancer patients with ischemic heart disease-related LVD or dilated cardiomyopathy (ischemic heart disease [IHD]/DCM) was age- and gender-matched to patients with CA-ACM. All patients were followed for arrhythmias and appropriate ICD therapies, total mortality, heart transplantation, and left ventricular ejection fraction. Results More than 5.5 ± 3.0 years after device implantation, nonsustained ventricular tachycardia was the most common arrhythmia in patients with CA-ACM followed by atrial fibrillation and sustained ventricular tachycardia or fibrillation (73.9%, 56.6%, and 30.4%, respectively), which was not significantly different from CA-NACM and IHD/DCM. The 5-year rate of ICD therapies was 19.9% in the CA-ACM group versus 22.1% in the CA-NACM group and 32.6% in the IHD/DCM group (p = NS for both). Device therapy–free, heart transplantation–free, and/or overall survival as well as cardiac function dynamics over time were not different in patients with CA-ACM than in patients with CA-NACM and IHD/DCM. Conclusions This study indicates that the burden of arrhythmia in patients with anthracycline-related cardiomyopathy is not different from cancer and non-cancer patients with IHD-related LVD or DCM.
Differential equations in music and dance

AbstractThis is the second paper in a series that connects ideas from differential equations to relevant and interesting material from the arts and humanities. In this article, we investigate a variety of works in music and dance. We present applications to musical composition, to performance techniques in classical guitar and to choreographing dance.
Enduring biographic heritage - Medical numismatics

The most enduring archive of medical biography is that composed of coins and medals. More than 20,000 commemorative and tribute medals comprise the domain of medical numismatics. Several thousand of these portray individual doctors whose lives and work are thus recorded in gold, silver, bronze and the alloys of medallic art. Such enduring records range from the names and images of the most famous and significant of doctors in international perspective, to those held in local or parochial esteem by their peers. The medical numismatic archive includes medals and coins which portray the gods of medicine; founders of the profession such as Hippocrates and Galen; and those who have been held in local esteem, all such that the record of their service to medicine might not be forgotten.
Canine Cancer Genomics: Lessons for Canine and Human Health.

Dogs are second only to humans in medical surveillance and preventative health care, leading to a recent perception of increased cancer incidence. Scientific priorities in veterinary oncology have ...
Prone positioning reduces perineal infections when performing the miles procedure

Abstract Background Abdominoperineal resection (APR) remains the cornerstone treatment for rectal cancers less than 5 cm from the anal verge. The perineal portion of an APR can be done with the patient in lithotomy or repositioned to prone jack-knife position, which influences accessibility, visualization and ability to close the wound. This paper analyses the effect of patient positioning on perineal wound dehiscence and infections. Methods A retrospective review of all rectal cancer patients who underwent an APR at Massachusetts General Hospital between 2004 and 2014 (n = 149). Patients were divided into supine (n = 91) or prone (n = 58) positioning as documented in operative reports. Results Twenty-two percent of supine positioned patients developed a perineal wound infection, versus 3.4% of the prone patients (P = 0.002). Perineal wound dehiscence rate was also higher in the supine positioned group (14.3% vs. prone 3.4%; P = 0.032). Multivariable analysis showed OR = 9.2 of developing a perineal wound infection for supine positioned patients, compared to prone, corrected for obesity and smoking history. Conclusion Repositioning patients into prone position for the perineal portion of an APR was associated with significantly lower perineal wound infection and dehiscence rates compared to supine positioned patients.
And Who Will Review the Review(er)s

Peer review maintains an implacable presence in the collaborative enterprise of scholarly production. Widely viewed as the “gold standard,” it is considered a requirement for affirming validity and quality, as well as for codifying disciplinary boundaries. As journal editor Richard Smith vividly recalled: “It is the method by which grants are allocated, papers published, academics promoted, and Nobel prizes won. … When something is peer reviewed it is in some sense blessed.”
Air source integrated heat pump simulation model for EnergyPlus

Abstract Air source integrated heat pump (ASIHP) is an air source, multi-functional space-conditioning unit with water heating function (WH), which can lead to significant energy savings by recovering condensing waste heat in the cooling season and providing dedicated or desuperheating heat pump water heating in the remaining months. This paper summarizes development of the EnergyPlus ASIHP model. It introduces the physics, sub-models, working modes, and control logic. Based on the model, building energy simulations were conducted to demonstrate greater than 50% annual energy savings, in comparison to a baseline heat pump with electric water heater, over 10 US cities, using the EnergyPlus quick-service restaurant template building. We assessed water heating energy saving potentials using ASIHP versus gas heating, and identified the climate zones where ASIHPs are promising. In addition, a grid integration strategy was investigated to reveal further energy saving and electricity cost reduction potentials, via increasing the water heating set-point temperature during off-peak hours and using larger water tanks.
Effects of Enrichment Presentation and Other Factors on Behavioral Welfare of Pantropical Spotted Dolphin (Stenella attenuata)

Environmental enrichment is a crucial element of promoting welfare for animals in captivity. However, enrichment programs are not always formally evaluated for their efficacy. Furthermore, there is little empirical evidence of enrichment evaluation for species of small cetaceans in zoological settings. A wide range of variables may potentially influence enrichment efficacy and how it in turn affects behavior. The purpose of this study was to determine the most preferred environmental enrichment, and method of presentation, for a species that has not been well studied in captivity, the pantropical spotted dolphin (Stenella attenuata). In order to determine which enrichment items and method of presentation were most effective at eliciting enrichment interaction, we systematically examined how several variables of enrichment influenced enrichment interaction. The results suggested that presenting enrichment after training sessions influenced interaction with the enrichment. The results also indicated preference for enrichment type and a specific enrichment device. Finally, factors that influenced interaction were also found to influence aberrant behavior. The results support the premise that enrichment be "redefined" for each species and each individual.
Maternal-Fetal rejection reactions are unconstrained in preeclamptic women.

The risk factors for preeclampsia, extremes of maternal age, changing paternity, concomitant maternal autoimmunity, and/or birth intervals greater than 5 years, suggest an underlying immunopathology. We used peripheral blood and lymphocytes from the UteroPlacental Interface (UPI) of 3rd trimester healthy pregnant women in multicolor flow cytometry-and in vitro suppression assays. The major end-point was the characterization of activation markers, and potential effector functions of different CD4-and CD8 subsets as well as T regulatory cells (Treg). We observed a significant shift of peripheral CD4 -and CD8- T cells from naive to memory phenotype in preeclamptic women compared to healthy pregnant women consistent with long-standing immune activation. While the proportions of the highly suppressive Cytokine and Activated Treg were increased in preeclampsia, Treg tolerance toward fetal antigens was dysfunctional. Thus, our observations indicate a long-standing inflammatory derangement driving immune activation in preeclampsia; in how far the Treg dysfunction is caused by/causes this immune activation in preeclampsia will be the object of future studies.
Application sentinel-1 SAR data for ocean research and operation

The European Space Agency (ESA) launched Sentinel-1A and −1B synthetic aperture radar (SAR) satellites in 2014 and 2016, respectively. This is the first set of a constellation mission of two identical SAR satellites providing continuity of SAR data from earlier ESA's ERS-1/2 and Envisat missions for oceans and ice, land changes and emergency responses applications. The Sentinel-1A and −1B SAR data were made freely and openly available to registered users through ESA's Sentinel-1 internet data hub. The data have been utilized in both research including hurricane/typhoon and atmospheric boundary layer phenomena studies and operational generation of ocean surface wind and oil spill maps. In this study, we present the preliminary studies of the Sentinel-1 SAR-derived surface wind products and validation results. Examples of applications of SAR for atmospheric boundary layer phenomena and oil spill detection are also given.
Clinical Features and Prognosis of Type 2 Myocardial Infarction in Acutely Decompensated Diabetic Patients.

Abstract Background After the introduction of the universal definition of myocardial infarction, the incidence and diagnosis of type 2 myocardial infarction have risen dramatically, yet there are no clear guidelines on clinical management. Diabetic patients are at high risk for developing type 2 myocardial infarction when admitted in a decompensated state, and they are also at high risk for future cardiovascular events. Methods We performed a retrospective analysis of 1058 patients admitted with diabetic ketoacidosis or hyperosmolar hyperglycemic state between 2011 and 2016. Patients were included if they had cardiac troponin I measured within 24 hours of admission, were older than 18 years of age, and had no evidence of acute coronary syndrome on admission. Baseline characteristics, admission laboratory test results, major adverse cardiovascular events, cardiac stress testing, and coronary angiography data up to 1 year after admission were reviewed. Patients were categorized into 2 groups: those with and those without type 2 myocardial infarction. The study had 2 endpoints: mortality and major adverse cardiac events (MACE) at 1 year and an abnormal result on stress test or coronary angiography at 1 year. Results Of the 845 patients who met the inclusion criteria, 133 patients (15%) had type 2 myocardial infarction on admission. Patients with type 2 myocardial infarction were at a significantly higher risk for mortality and MACE at 1 year than those without. Patients with type 2 myocardial infarction were also at higher risk for developing an abnormal result on stress test or coronary angiography within 1 year of admission as compared with those without type 2 myocardial infarction (40% vs 24%; odds ratio 2; P = .0699). Conclusion Acutely decompensated diabetic patients with type 2 myocardial infarction are at increased risk for death and MACE. These patients may also be at risk for undiagnosed coronary artery disease.
Adapting design patterns across learning environments

Pedagogical design patterns offer high-quality solutions to known educational problems. Design patterns are meant to guide teachers' pedagogical decisions to improve student learning in varied learning contexts such as intelligent tutoring systems, traditional classrooms, online learning systems, and so forth. In theory, design patterns are written so that they are applicable to multiple learning contexts, but, in practice, we wonder if pedagogical design patterns intended specifically for one learning environment can be used in other learning environments. We explore this theoretical question for practical reasons. Over the past three years, we applied existing pedagogical design patterns and wrote new pedagogical patterns to enhance student feedback for math problems in an intelligent tutoring system (ITS) called ASSISTments. It was more difficult than expected for two reasons: there are few pedagogical design patterns specifically for ITSs and contextual features for design patterns developed for other learning environments make them either too general or too specific to apply to an ITS. For example, feedback design patterns that involve interpreting learners' misconceptions may be easy for teachers to apply in traditional classroom settings, but difficult for ITSs because current algorithms poorly predict student misconceptions. In this paper, we explore the adaptability of design patterns to different learning environments using guide questions and contextual design pattern features we developed from our experience of adapting design patterns to ITSs.
Plug-and-Play Approach for Preparing Chromatin Containing Site-Specific DNA Modifications: The Influence of Chromatin Structure on Base Excision Repair

The genomic DNA of eukaryotic cells exists in the form of chromatin, the structure of which controls the biochemical accessibility of the underlying DNA to effector proteins. In order to gain an in depth molecular understanding of how chromatin structure regulates DNA repair, detailed in vitro biochemical and biophysical studies are required. However, because of challenges associated with reconstituting nucleosome arrays containing site-specifically positioned DNA modifications, such studies have been limited to the use of mono- and dinucleosomes as model in vitro substrates, which are incapable of folding into native chromatin structures. To address this issue, we developed a straightforward and general approach for assembling chemically defined oligonucleosome arrays (i.e., designer chromatin) containing site-specifically modified DNA. Our method takes advantage of nicking endonucleases to excise short fragments of unmodified DNA, which are subsequently replaced with synthetic oligonucleotides containin...
Bioequivalence study of stressed and nonstressed hard gelatin capsules using amoxicillin as a drug marker and gamma scintigraphy to confirm time and GI location of in vivo capsule rupture.

Purpose: Evaluate if crosslinked hard gelatin capsules (HGCs) havingdifferent in vitro dissolution profiles changed in vivo release times oraltered bioavailability of a drug marker; assess if a two-tier dissolutiontest (with and without enzyme) predicted in vivo performance.
CTPPL: a continuous time probabilistic programming language

Probabilistic programming languages allow a modeler to build probabilistic models using complex data structures with all the power of a programming language. We present CTPPL, an expressive probabilistic programming language for dynamic processes that models processes using continuous time. Time is a first class element in our language; the amount of time taken by a subprocess can be specified using the full power of the language. We show through examples that CTPPL can easily represent existing continuous time frameworks and makes it easy to represent new ones. We present semantics for CTPPL in terms of a probability measure over trajectories. We present a particle filtering algorithm for the language that works for a large and useful class of CTPPL programs.
Resilient Agent for Power System Operations and Protection

During a power system event, a system operator needs to conservatively reduce operating limits in real time as the changing system conditions are analyzed. The time it takes operators or their tools to develop new operating limits could affect millions of transmission system users, especially events classified as NERC Category D type events (extreme events resulting in the loss of two or more bulk electric system elements). Controls for the future evolution of the grid must be able to perform distributed real-time analysis, identify new reliability risks, and set new System Operating Limit's (SOLs) for real-time operations. In this paper we are developing requirements for distributed resilient agents that measure how systems able to operate at acceptable levels of normalcy despite disturbances or threats and define measures to determine how far the system is from boundary conditions and manage coordination between agent to achieve optimal global resiliency in the power system during the event.
Bandits with Global Convex Constraints and Objective

Multiarmed bandit (MAB) is a classic model for capturing the exploration–exploitation trade-off inherent in many sequential decision-making problems. The classic MAB framework, however, only allows...
Population prevalence of individuals meeting criteria for hereditary breast and ovarian cancer testing.

BACKGROUND Personal cancer diagnosis and family cancer history factor into which individuals should undergo genetic testing for hereditary breast and ovarian cancer (HBOC) syndrome. Family history is often determined in the research setting through kindreds with disease clusters, or clinically from self-report. The population prevalence of individuals with diagnostic characteristics and/or family cancer history meeting criteria for HBOC testing is unknown. METHODS Utilizing Surveillance, Epidemiology, and End Results (SEER) cancer registry data and a research resource linking registry records to genealogies, the Utah Population Database, the population-based prevalence of diagnostic and family history characteristics meeting National Comprehensive Cancer Network (NCCN) criteria for HBOC testing was objectively assessed. RESULTS Among Utah residents with an incident breast cancer diagnosis 2010-2015 and evaluable for family history, 21.6% met criteria for testing based on diagnostic characteristics, but the proportion increased to 62.9% when family history was evaluated. The proportion of cases meeting testing criteria at diagnosis was 94% for ovarian cancer, 23% for prostate cancer, and 51.1% for pancreatic cancer. Among an unaffected Utah population of approximately 1.7 million evaluable for family history, 197,601 or 11.6% met testing criteria based on family history. CONCLUSIONS This study quantifies the population-based prevalence of HBOC criteria using objectively determined genealogy and cancer incidence data. Sporadic breast cancer likely represents a portion of the high prevalence of family cancer history seen in this study. These results underline the importance of establishing presence of a deleterious mutation in an affected family member, per NCCN guidelines, before testing unaffected relatives.
Effect of Delayed vs Immediate Umbilical Cord Clamping on Maternal Blood Loss in Term Cesarean Delivery: A Randomized Clinical Trial.

Importance The American College of Obstetricians and Gynecologists recommends a delay in umbilical cord clamping in term neonates for at least 30 to 60 seconds after birth. Most literature supporting this practice is from low-risk vaginal deliveries. There are no published data specific to cesarean delivery. Objective To compare maternal blood loss with immediate cord clamping vs delayed cord clamping in scheduled cesarean deliveries at term (≥37 weeks). Design, Setting, and Participants Randomized clinical trial performed at 2 hospitals within a tertiary academic medical center in New York City from October 2017 to February 2018 (follow-up completed March 15, 2018). A total of 113 women undergoing scheduled cesarean delivery of term singleton gestations were included. Interventions In the immediate cord clamping group (n = 56), cord clamping was within 15 seconds after birth. In the delayed cord clamping group (n = 57), cord clamping was at 60 seconds after birth. Main Outcomes and Measures The primary outcome was change in maternal hemoglobin level from preoperative to postoperative day 1, which was used as a proxy for maternal blood loss. Secondary outcomes included neonatal hemoglobin level at 24 to 72 hours of life. Results All of the 113 women who were randomized (mean [SD] age, 32.6 [5.2] years) completed the trial. The mean preoperative hemoglobin level was 12.0 g/dL in the delayed and 11.6 g/dL in the immediate cord clamping group. The mean postoperative day 1 hemoglobin level was 10.1 g/dL in the delayed group and 9.8 g/dL in the immediate group. There was no significant difference in the primary outcome, with a mean hemoglobin change of −1.90 g/dL (95% CI, −2.14 to −1.66) and −1.78 g/dL (95% CI, −2.03 to −1.54) in the delayed and immediate cord clamping groups, respectively (mean difference, 0.12 g/dL [95% CI, −0.22 to 0.46];P = .49). Of 19 prespecified secondary outcomes analyzed, 15 showed no significant difference. The mean neonatal hemoglobin level, available for 90 neonates (79.6%), was significantly higher with delayed (18.1 g/dL [95% CI, 17.4 to 18.8]) compared with immediate (16.4 g/dL [95% CI, 15.9 to 17.0]) cord clamping (mean difference, 1.67 g/dL [95% CI, 0.75 to 2.59];P Conclusions and Relevance Among women undergoing scheduled cesarean delivery of term singleton pregnancies, delayed umbilical cord clamping, compared with immediate cord clamping, resulted in no significant difference in the change in maternal hemoglobin level at postoperative day 1. Trial Registration ClinicalTrials.gov Identifier:NCT03150641
A note on the accuracy of the generalized-$\alpha$ scheme for the incompressible Navier-Stokes equations.

We investigate the temporal accuracy of two generalized-$\alpha$ schemes for the incompressible Navier-Stokes equations. The conventional approach treats the pressure with the backward Euler method while discretizing the remainder of the Navier-Stokes equations with the generalized-$\alpha$ method. We developed a suite of numerical codes using inf-sup stable higher-order non-uniform rational B-spline (NURBS) elements for spatial discretization. In doing so, we are able to achieve very high spatial accuracy and, furthermore, to perform temporal refinement without consideration of the stabilization terms, which can degenerate for small time steps. Numerical experiments suggest that only first-order accuracy is achieved, at least for the pressure, in this aforesaid approach. Evaluating the pressure at the intermediate time step recovers second-order accuracy, and the numerical implementation, in fact, becomes simpler. Therefore, although the pressure can be viewed as a Lagrange multiplier enforcing the incompressibility constraint, its temporal discretization is not independent and should be subject to the generalized-$\alpha$ method in order to maintain second-order accuracy of the overall algorithm.
Psychological Attachment Orientations of Surrogate Decision-Makers and Goals-of-Care Decisions for Brain Injury Patients in ICUs.

To determine whether ICU surrogates with "insecure" psychologic attachment orientations are more prone to requesting tracheostomy and gastrostomy (i.e., life-sustaining therapy) for severe acute brain injury patients with poor prognosis compared to surrogates with "secure" orientations. Design Cross-sectional survey from November 2017 to August 2018. Setting Single neuroscience ICU at an academic medical center. Subjects Consecutive sample of surrogates of patients admitted to the ICU with a minimum length of stay of 24 hours. Interventions None. Measurements and Main Results We identified surrogates' psychologic attachment orientation via a standard tool, the Relationship Questionnaire, and collected other surrogate and patient demographics. We also presented surrogates with a hypothetical scenario of an intubated severe acute brain injury patient with poor prognosis and asked each surrogate whether he or she would request life-sustaining therapy or comfort measures only. Fisher exact test was used to compare frequency of life-sustaining therapy selection between secure and insecure surrogates. Additionally, we conducted univariate and multivariate analyses to determine other independent predictors of life-sustaining therapy selection. Two-hundred seventy-five of 713 (38.6%) eligible respondents participated; 153 (55.6%) surrogates were secure, and 122 (44.4%) insecure. There was no significant difference in the proportion of secure respondents selecting life-sustaining therapy compared to insecure (18.3% vs 20.5%; p = 0.38). Although still nonsignificant, the observed difference was slightly greater for those with a specific "anxious" insecure subtype versus "nonanxious" (18.2% vs 23.0%; p = 0.41). Overall, a higher proportion of respondents selecting life-sustaining therapy (vs comfort measures only) reported feeling uncertain or very uncertain about the hypothetical decision (45.3% vs 9.5%; p < 0.001). In a multivariate model, nonwhite race and high religiosity were significant predictors of life-sustaining therapy selection. Conclusions Although surrogate attachment orientation is not predictive of life-sustaining therapy selection, nonwhite race and high religiosity are. Future interventions designed to support severe acute brain injury surrogates could focus on surrogates prone to selecting life-sustaining therapy with high degrees of uncertainty.
Thalidomide for refractory gastrointestinal bleeding from vascular malformations in patients with significant comorbidities

Thalidomide for refractory gastrointestinal bleeding from vascular malformations in patients with significant comorbidities
Emerging Gene-Editing Modalities for Osteoarthritis

Osteoarthritis (OA) is a pathological degenerative condition of the joints that is widely prevalent worldwide, resulting in significant pain, disability, and impaired quality of life. The diverse etiology and pathogenesis of OA can explain the paucity of viable preventive and disease-modifying strategies to counter it. Advances in genome-editing techniques may improve disease-modifying solutions by addressing inherited predisposing risk factors and the activity of inflammatory modulators. Recent progress on technologies such as CRISPR/Cas9 and cell-based genome-editing therapies targeting the genetic and epigenetic alternations in OA offer promising avenues for early diagnosis and the development of personalized therapies. The purpose of this literature review was to concisely summarize the genome-editing options against chronic degenerative joint conditions such as OA with a focus on the more recently emerging modalities, especially CRISPR/Cas9. Future advancements in novel genome-editing therapies may improve the efficacy of such targeted treatments.
Thermal Swing Evaluation of Thermal Barrier Coatings for Diesel Engines

“Thermal swing” coatings have recently been of great interest to automotive researchers for their potential to insulate internal combustion engines, reduce cooling requirements, and increase their efficiency. Plasma-sprayed yttria-stabilized zirconia, ceramics in the MgO-Al2O3-SiO2 system (cordierite, mullite, and steatite), and silicate-yttria-stabilized zirconia composite thermal barriers have been investigated in this context with thermophysical properties measured using a thermal flash method and further screened by thermal swing using a custom laboratory developed functional test. Correlations between microstructure and thermal properties are developed and their combined impact on thermal swing assessed. The coatings thermal effusivity dominates these considerations for coatings above the characteristic thermal diffusion length of periodic exposure, with substrate thermal properties quickly becoming important below this thickness. Plasma-sprayed cordierite and its composites are determined to be the most promising materials for this application, exhibiting the highest thermal swing and effusivities as low as 373 Ws1/2/m2K. Performance testing in a heavy-duty single-cylinder diesel engine is ongoing with preliminary data suggesting that thermal swing alone may not provide efficiency benefits. Coating thickness, roughness, and dynamic interactions in the engine may play a role in this, highlighting that many potential nuances need consideration for the successful applications of these coatings.
766 Novel bioluminescent bioassays for the discovery and development of T cell redirecting cancer therapies

Background Two main approaches for T cell-based therapies involve molecular T cell redirection by CD3 bispecific molecules such as bispecific T-cell engagers (BiTE) and cellular T cell redirection by genetic modification of T cells with chimeric antigen receptors (CAR) or transgenic T cell receptors (TCR). BiTEs redirect the cytotoxic activity of endogenous polyclonal T cells by simultaneously engaging CD3 on T cells and tumor antigens on target cells. BiTE potency studies have relied on primary cells, which measure target cell killing through redirected T cell cytotoxicity (RTCC) or cytokine release. However, these primary cell-based assays suffer from high donor-to-donor variability, as well as lengthy and hard to implement protocols Methods We have recently developed a new RTCC assay and cytokine immunoassays that are simple, sensitive and can quantitatively measure the potency of BiTEs and similar biologics. In this assay, preactivated cytotoxic T cells and target cells (both in cryopreserved thaw-and-use format) stably expressing a HaloTag-HiBiT fusion protein are co-incubated with a BiTE, which results in lysis of the target cells and subsequent release of the Halotag-HiBiT protein. These HiBiT proteins then bind to extracellular LgBiT provided in the detection reagent and form functional NanoLuc Luciferase to generate luminescence. Results The assay is homogenous, highly sensitive, and has a robust assay window. Use of CAR-T has demonstrated promising results in treating leukemia, while the development of TCR-engineered T cells that can recognize intracellular tumor antigens, is still in early stages. To facilitate the screening and characterization of new transgenic TCRs, we used CRISPR/Cas9 to develop two TCRas-null reporter T cell lines, which are CD4+ or CD8+. Reintroduction of peptide-specific TCR a and s chains into TCRas-null reporter T cell lines results in peptide-dependent TCR activation and luciferase reporter expression. The select expression of CD4 or CD8 in the TCRas-null reporter T cell lines can enable the development of transgenic TCRs for both MHCI- and MHCII-restricted tumor antigen targets. Conclusions Together, these bioluminescent bioassays represent a new set of tools for the discovery and development of T cell-based immunotherapies.
Improvisation Within the Range of Implication: Cora Diamond, Henry James, and the Space of Moral Reflection

We, or at least many of us, are the inheritors of a deeply-embedded picture of ethical thought, of moral psychology, that is clear, stable in its conceptual architecture, straightforwardly articulated, of exceptionally distinguished intellectual heritage, and – because blind to the nuances of our moral psychology – as misleading as it is schematically oversimplified. As a depiction of moral life, it is a picture that in Wordsworth’s sense murders to dissect.
Frequency Sensitivity of Integrated Oscillators to Nearby Conductors

A measurement setup including a metal plate probe mounted on a micrometer-controlled positioner is used to quantify the effects of surrounding to voltage-controlled oscillator (VCO) characteristics. Including a metal ring shield around the inductor of LC-VCO and placing components underneath the inductor to reduce the circuit area lower the sensitivity of VCO performance to surroundings. It should be possible to incorporate a metal plate on top of the oscillator as part of packaging to shield the VCO from the surrounding with tolerable impact to the oscillator performance.
Pattern Filtering for Detection of Replayed Patterns in HVc Sleep Activity

Consolidation of memories during sleep may involve neuronal replay of daytime activity patterns. A precise replay phenomenon was observed in the song system nucleus RA. We developed statistical pattern filtering to investigate replay in HVc, where spiking activity is more variable. Long spike sequences during sleep were convolved with filters constructed from exemplar auditory spike sequences. Examining peaks in the filter responses, we found many examples of HVc spike trains with temporal patterns similar to the exemplars, confirming a replay phenomenon for HVc. Statistical pattern filtering has general utility for finding spike patterns when a referent pattern is known.
Liposomal encapsulation of polysaccharides (LEPS) as an effective vaccine strategy to protect aged hosts against S. pneumoniae infection

Despite the availability of licensed vaccines, pneumococcal disease caused by the bacteria Streptococcus pneumoniae (pneumococcus), remains a serious infectious disease threat globally. Disease manifestations include pneumonia, bacteremia, and meningitis, resulting in over a million deaths annually. Pneumococcal disease disproportionally impacts elderly individuals [≥]65 years old. Interventions are complicated through a combination of complex disease progression and 100 different bacterial capsular polysaccharide serotypes. This has made it challenging to develop a broad vaccine against S. pneumoniae, with current options utilizing capsular polysaccharides as the primary antigenic content. However, current vaccines are substantially less effective in protecting the elderly. We previously developed a Liposomal Encapsulation of Polysaccharides (LEPS) vaccine platform, designed around limitations of current pneumococcal vaccines, that allowed the non-covalent coupling of polysaccharide and protein antigen content and protected young hosts against pneumococcal infection in murine models. In this study, we modified the formulation to make it more economical and tested the novel LEPS vaccine in aged hosts. We found that in young mice (2-3 months), LEPS elicited comparable responses to the pneumococcal conjugate vaccine Prevnar-13. Further, LEPS immunization of old mice (20-22 months) induced comparable antibody levels and improved antibody function compared to Prevnar-13. Importantly, LEPS protected old mice against both invasive and lung localized pneumococcal infections. In summary, LEPS is an alternative and effective vaccine strategy that protects aged hosts against different manifestations of pneumococcal disease.
The Effect of Legal Rules on the Value of Economic and Non-Economic Damages and the Decision to File

This study focuses on the economic consequences of tort reform. In particular, we address two issues. First, we test the relationship between tort reforms and claim severity for an automobile liability incident while controlling for a variety of cost drivers including the presence of no-fault rules, and the impact of a plaintiff's attorney. In addition to examining the effect of tort reforms on total claim severity, we also test their effect on economic and non-economic damages separately. Second, we test the proposition that tort reforms, by reducing the damages available at trial, have reduced the likelihood that an injured party will seek legal remedy. Both aspects of this study are examined with individual data from a large sample of insurance claims from 61 insurers. Our results suggest that many of the reforms have had a statistically significantly effect on total damages, non-economic damages and economic damages. Caps on non-economic damages, collateral source rule reforms, and minor reforms impacting prejudgment interest, frivolous suits, and provisions for periodic payments are negatively related to the value of non-economic claims, while joint and several reform is positively related to the value of non-economic claims. We find collateral source rule reforms and minor reforms are negatively related to the value of economic claims. We find that caps on non-economic damages and minor reforms are associated with a decreased probability to file. We do not find any evidence that joint and several or collateral source rule reform is associated with the decision to file.
Variability-Aware Training and Self-Tuning of Highly Quantized DNNs for Analog PIM.

DNNs deployed on analog processing in memory (PIM) architectures are subject to fabrication-time variability. We developed a new joint variability- and quantization-aware DNN training algorithm for highly quantized analog PIM-based models that is significantly more effective than prior work. It outperforms variability-oblivious and post-training quantized models on multiple computer vision datasets/models. For low-bitwidth models and high variation, the gain in accuracy is up to 35.7% for ResNet-18 over the best alternative. We demonstrate that, under a realistic pattern of within- and between-chip components of variability, training alone is unable to prevent large DNN accuracy loss (of up to 54% on CIFAR-100/ResNet-18). We introduce a self-tuning DNN architecture that dynamically adjusts layer-wise activations during inference and is effective in reducing accuracy loss to below 10%.
Order Flow, Trading Volume, and Short-Term Stock Returns

This paper tests whether net order flow (or signed trading volume, the difference between public buy order volume and public sell order volume) helps predict short term future returns. It finds that net order flow does not explain daily and weekly return autocovariances. Thus, short term return reversals or continuations are not likely to be due to information asymmetry or public liquidity shocks as modeled in Llorente, Michaely, Saar, Wang (2000) and similar previous studies. I also compare my results to those of similar empirical studies that test these models by using trading volume.
Computational soundness for standard assumptions of formal cryptography

The Dolev-Yao model is a useful and well-known framework in which to analyze security protocols. However, it models the messages of the protocol at a very high level and makes extremely strong assumptions about the power of the adversary. The computational model of cryptography, on the other hand, takes a much lower-level view of messages and uses much weaker assumptions. Despite the large differences between these two models, we have been able to show that there exists a relationship between them. Previous results of ours demonstrate that certain kinds of computational cryptography can result in an equivalence of sorts between the formal and computational adversary. Specifically: (1) We gave an interpretation to the messages of the Dolev-Yao model in terms of computational cryptography, (2) We defined a computational security condition, called weak Dolev-Yao non-malleability, that translates the main assumptions of the Dolev-Yao model into the computational setting, and (3) We demonstrated that this condition is satisfied by a standard definition of computational encryption security called plaintext awareness. In this work, we consider this result and strengthen it in four ways: (1) Firstly, we propose a stronger definition of Dolev-Yao non-malleability which ensures security against a more adaptive adversary. (2) Secondly, the definition of plaintext awareness is considered suspect because it relies on a trusted third party called the random oracle . Thus, we show that our new notion of Dolev-Yao non-malleability is satisfied by a weaker and less troublesome definition for computational encryption called chosen-ciphertext security. (3) Thirdly, we propose a new definition of plaintext-awareness that does not use random oracles, and an implementation. This implementation is conceptually simple, and relies only on general assumptions. Specifically, it can be thought of as a ‘self-referential’ variation on a well-known encryption scheme. (4) Lastly, we show how the computational soundness of the Dolev-Yao model can be maintained even as it is extended to include new operators. In particular, we show how the Diffie-Hellman key-agreement scheme and the computational Diffie-Hellman assumption can be added to the Dolev-Yao model in a computationally sound way. (Copies available exclusively from MIT Libraries, Rm. 14-0551, Cambridge, MA 02139-4307. Ph. 617-253-5668; Fax 617-253-1690.)
Propagating Integrity Information among Interrelated Databases

Data integrity policies often require that quality and integrity metadata be generated and communicated to potential users. However, in data warehouses, federations, and other multi-tier databases, administrators at different tiers use different schemas. Data at the upper tier is derived from the lower, so we consider the upper tier’s tables to be views, derived by SQL-like expressions. Unfortunately, an assertion about some granule in the sources (a table, column, or cell) is often meaningless to view users, and vice versa. An understanding of the SQL view gives intuitive guidance for propagating such metadata, but not explicit semantics.
Metatheoretic plan summarization and comparison

We describe a domain-independent framework for plan summarization and comparison that can help a human understand both key strategic elements of an individual plan and important differences among plans. Our approach is grounded in a domain metatheory, which specifies important semantic properties of tasks, instances and planning methods. The metatheory provides a semantic framework for guiding the choice and description of concepts used in summarizing and comparing plans, thus avoiding syntactic constructs whose meaning or import is unclear. We define three capabilities grounded in the metatheoretic approach: (a) summarization of an individual plan, (b) comparison of pairs of plans, and (c) analysis of a collection of plans. Application of these capabilities within a rich application domain shows their value in facilitating user understandability of complex plans.
The (g92)2 residual interaction from 87Sr(d, t)86Sr

Abstract Differential cross sections for 87 Sr(d, t) 86 Sr transitions to the (1 g 9 2 ) −2 states of 86 Sr were obtained with the Pittsburgh 18 MeV deuteron beam and the Enge split-pole spectrograph. States of 86 Sr up to 3.82 MeV in excitation were studied with a total resolution of 12 keV. Successful distorted-wave Born approximation (DWBA) predictions for 87 Sr(d, t) 86 Sr angular distributions permitted the extraction of l -values and spectroscopic strengths. The sum-rule value agrees with the observed value for the (1 g 9 2 ) −2 configuration. The observed g 9 2 strength is spread over 13 states. Contrary to an earlier interpretation, the 0 + ground state is found to contain only 65% of the ( g 9 2 ) 2 0 + strength. Similarly, the full 4 + strength is not located in a single state. The new data change the interpretation of the ( g 9 2 ) −2 spectrum of 86 Sr. They significantly alter the deduced low-spin matrix elements and bring them into much closer agreement with those derived from 88 Y. Several new negative-parity states dominated by l = 1 orbital angular momentum transfer have also been identified.