cssi/SciSciGPT-SciSciNet huggingface dataset:
In utero nanoparticle delivery for site-specific genome editing

Genetic diseases can be diagnosed early during pregnancy, but many monogenic disorders continue to cause considerable neonatal and pediatric morbidity and mortality. Early intervention through intrauterine gene editing, however, could correct the genetic defect, potentially allowing for normal organ development, functional disease improvement, or cure. Here we demonstrate safe intravenous and intra-amniotic administration of polymeric nanoparticles to fetal mouse tissues at selected gestational ages with no effect on survival or postnatal growth. In utero introduction of nanoparticles containing peptide nucleic acids (PNAs) and donor DNAs corrects a disease-causing mutation in the β-globin gene in a mouse model of human β-thalassemia, yielding sustained postnatal elevation of blood hemoglobin levels into the normal range, reduced reticulocyte counts, reversal of splenomegaly, and improved survival, with no detected off-target mutations in partially homologous loci. This work may provide the basis for a safe and versatile method of fetal gene editing for human monogenic disorders.
Emerging investigator series: sunlight photolysis of 2,4-D herbicides in systems simulating leaf surfaces

Pesticides are commonly applied on foliage, forming dry deposits on the leaf cuticular wax. However, their photochemical transformation in this lipophilic environment is much less understood compared with that in surface water. In this work, sunlight photolysis of six chlorinated phenoxyacetic acid herbicides (i.e., 2,4-D and structural analogues) was evaluated in four organic solvents, on quartz, and on paraffin wax. In solvents of low polarity (i.e., n-heptane and 2-propanol), direct photolysis of 2,4-D herbicides was enhanced due to the relatively high quantum yields in these solvents. Photolysis on paraffin wax was slower than photolysis on quartz by a factor of 3-9, but was comparable with that in solvents of low polarity. With environmentally relevant irradiation and surface loading, the half-lives of 2,4-D herbicides on paraffin wax were 27-159 h, which are within the same range reported for biodegradation, the dominant dissipation pathway in the current 2,4-D fate model. Product analyses showed that photoreductive dechlorination is the dominant pathway in organic solvents, accounting for 68-100% of parent compound decay. On quartz and paraffin wax surfaces, however, photoreductive dechlorination products accounted for <60% of parent compound decay. Combining kinetic modeling and product analyses, it was shown that neither could the two additional putative pathways (photosubstitution of chlorine by hydroxyl group and cleavage of the ether bond) fully account for the total phototransformation on surfaces. These results suggest that rapid photolysis on surfaces can be attributed to unique pathways that are absent in the organic solvent phase.
A Bayesian way to make stopping rules matter

Disputes between advocates of Bayesians and more orthodox approaches to statistical inference presuppose that Bayesians must regard must regard stopping rules, which play an important role in orthodox statistical methods, as evidentially irrelevant. In this essay, I show that this is not the case and that the stopping rule is evidentially relevant given some Bayesian confirmation measures that have been seriously proposed. However, I show that accepting a confirmation measure of this sort comes at the cost of rejecting two useful ancillary Bayesian principles.
Motor Output Variability

Motor-output variability refers to the involuntary inconsistency in the output of voluntary muscle contractions. Numerous factors can influence the amplitude of motor-output variability. The functional significance of motor-output variability is that it can impair the ability of humans to perform accurate movements.
Mixed mode I and II fracture of carbon black filled natural rubber

The J-integral was used to characterize initiation and rapid fracture under mixed mode loading conditions in carbon black filled natural rubber. The total critical J was geometry dependent, but the J analysis partitions the energy into that needed locally in the crack tip region and in the bulk. The critical conditions for pure mode II loading could not be determined because of buckling of the specimen; however, values obtained by extrapolation show J IIc to be about twice J Ic. The relation % MathType!MTEF!2!1!+-% feaafiart1ev1aaatCvAUfeBSjuyZL2yd9gzLbvyNv2CaerbuLwBLn% hiov2DGi1BTfMBaeXafv3ySLgzGmvETj2BSbqef0uAJj3BZ9Mz0bYu% H52CGmvzYLMzaerbd9wDYLwzYbItLDharqqr1ngBPrgifHhDYfgasa% acOqpw0xe9v8qqaqFD0xXdHaVhbbf9v8qqaqFr0xc9pk0xbba9q8Wq% Ffea0-yr0RYxir-Jbba9q8aq0-yq-He9q8qqQ8frFve9Fve9Ff0dme% aabiqaaiGacaGaamqadaabaeaafiaakeaadaWcaaqaaiaadQeadaWg% aaWcbaGaamysaaqabaaakeaacaWGkbWaaSbaaSqaaiaadMeacaWGJb% aabeaaaaGccaqGGaGaae4kaiaabccadaWcaaqaaiaadQeadaWgaaWc% baGaamysaiaadMeaaeqaaaGcbaGaamOsamaaBaaaleaacaWGjbGaam% ysaiaadogaaeqaaaaakiaabccacaqG9aGaaeiiaiaabgdaaaa!5355!\[\frac{{J_I }}{{J_{Ic} }}{\text{ + }}\frac{{J_{II} }}{{J_{IIc} }}{\text{ = 1}}\]
Mechanisms of synaptic pathology in Alzheimer's disease

Neurodegenerative disorders are characterized by damage to selective neuronal populations that could be followed or preceded by synaptic injury. Therefore, specific mutations in and other alterations of synaptic proteins might lead to particular neurodegenerative diseases. The predominant hypothesis is that these mutations result in an increased production of amyloid β-protein 1–42 which acts as a neurotoxin. However, it could also be postulated that amyloid precursor protein might play an important role in synaptic function and neuronal maintenance, and that its abnormal activity may lead to neurodegeneration. Recent studies have shown that amyloid precursor protein has an important role in regulating glutamate levels at the synaptic site by modulating the activity of glutamate transporters. The objectives of this manuscript are to highlight recent data supporting the hypothesis that neurodegeneration in Alzheimer’s disease might be the combined result of abnormal protective activity of amyloid precursor protein and amyloid β-protein toxicity.
Management of the Difficult Aspects of the Antiphospholipid Syndrome

Publisher Summary This chapter focuses on the various challenging aspects of antiphospholipid syndrome (APS) therapy, such as recurrent events despite optimal anticoagulation, long-term management of anticoagulation, the management of some rare nonthrombotic manifestations, the perioperative medical management of the APS patients. The chapter presents a case study of a 20-year old woman with the diagnosis of primary APS with new liver left lobe infarct. Four years prior to admission, the lady had developed right lower extremity arterial thrombosis, which was treated with thrombectomy followed by intravenous (IV) heparin and warfarin. In such cases, patients should be advised to stop smoking, have well-controlled blood pressure, and the women should be counseled against the use of estrogen-containing oral contraceptive pills. Patients should also introduce lifestyle changes to achieve and maintain ideal weight, cholesterol level, and physical activity. The APS patients who are undergoing renal transplant should be anticoagulated aggressively during the perioperative period. Recommended standard antithrombotic regimens for the high-risk patients should be the minimum administered dose in the APS patients. Timing of the anticoagulation is also crucial in APS patients to keep periods without anticoagulation to an absolute minimum.
Intracellular signalling in salt-secreting cells - recent advances in the avian nasal gland model

The avian nasal gland has had an important role as a model system in studies of ion secretion for almost forty years, ever since the discovery of its role as an extrarenal salt-secreting organ by Schmidt-Nielsen and colleagues (Fange et al. 1958). Less widely appreciated is the fact that this tissue also played a critical role in the earliest studies of the intracellular signalling pathways involved in the stimulation of cell activity. Some of the original studies demonstrating for the first time that the muscarinic stimulation of secretory activity in cells was associated with an increased turnover of membrane phosphoinositides were performed on the avian nasal gland (Hokin and Hokin 1964). Unfortunately, the key connection between this turnover of phosphoinositides and increases in cytosolic Ca2+ concentrations ([Ca]j) was not appreciated until more than ten years later (Michell 1975), and the role of inositol 1,4,5-trisphosphate in providing the critical link between these two processes was not revealed for a further eight years (Streb et al. 1983).
Technik und Ergebnisse bei kruromalleolären Bypassoperationen

Obwohl im Terminalstadium der AVK eine langstreckige, femorokrurale Verschlusausdehnung uberwiegt, findet sich bei Diabetikern mitunter eine oft nur kurze, weit peripher gelegene Verschlusstrecke. Bei freiem Einstrom in die mfragenuale A. poplitea kommt es hierbei zu einer sogenannten Querschnittsunterbrechung der Unterschenkelarterien, wahrend im Fusbereich wieder anschlusfahige Arteriensegmente vorhanden sind. Patienten mit diesem Verschlustyp, die eine Gangran im Fusbereich entwickeln, sprechen nach unseren Erfahrungen nicht auf eine konservative Behandlung an und waren somit Kandidaten fur eine primare Unterschenkelamputation.
Development of Therapeutic Genes for Breast Cancer Treatment

This chapter describes preclinical development of therapeutic genes in breast cancer treatment. Beginning from targeting HER-2/neu-overexpressing breast cancer cells by adenovirus E1A, we found E1A expression had profound effects on tumor cells including growth suppression, apoptosis, and sensitization to chemo-drugs and radiation. The mechanisms of the antitumor activities as well as the preliminary results obtained from multiple E1A clinical trials are discussed. Also identified are the antitumor activity of interferon inducible genes, p202 and IFIX, and a proapoptotic gene, bik. The mechanism of action and the therapeutic potential of these genes in breast cancer models are also discussed.
The Diversity Ideal: History and Values (Chapter 3)

This chapter is divided into two main sections. The first is a brief intellectual history of diversity-as-ideal, beginning with the Biblical texts and continuing up to the present. I emphasize the novelty of diversity-as-ideal, its cultural antecedents in America, and its efflorescence in the late 1960s when the civil rights movement and a new immigration system provided ideological and demographic energy to this nascent ideal. The second section identifies the values and dis-values of diversity by considering how a liberal, a communitarian, a utilitarian, and a social functionalist would understand and assess diversity.
Interactive Tweaking of Text Analytics Dashboards

With the increasing importance of text analytics in all disciplines, e.g., science, business, and social media analytics, it has become important to extract actionable insights from text in a timely manner. Insights from text analytics are conventionally presented as visualizations and dashboards to the analyst. While these insights are intended to be set up as a one-time task and observed in a passive manner, most use cases in the real world require constant tweaking of these dashboards in order to adapt to new data analysis settings. Current systems supporting such analysis have grown from simplistic chains of aggregations to complex pipelines with a range of implicit (or latent) and explicit parametric knobs. The re-execution of such pipelines can be computationally expensive, and the increased query-response time at each step may significantly delay the analysis task. Enabling the analyst to interactively tweak and explore the space allows the analyst to get a better hold on the data and insights. We propose a novel interactive framework that allows social media analysts to tweak the text mining dashboards not just during its development stage, but also during the analytics process itself. Our framework leverages opportunities unique to text pipelines to ensure fast response times, allowing for a smooth, rich and usable exploration of an entire analytics space.
Some Remarks on Good, Simple, and Optimal Quadrature Formulas

Publisher Summary This chapter presents some remarks on good, simple, and optimal quadrature formulas. The construction of a whole family of quadrature formulas of that order which are simple and whose error bound, while not quite minimal, is asymptotically equal to the minimal error bound is described. The problem of finding the optimal quadrature formula can be reduced to solving linear equations in unknowns, and solved some special cases. The chapter discusses the construction of a large class of simple schemes whose error bounds have asymptotic expressions with the same first term as that of the optimal scheme. The somewhat more general problem of tabulating the indefinite integral is considered in such a way that when a prescribed interpolation scheme is applied to the tabulated values, one obtains a good approximation in norm to this indefinite integral. These limiting values are precisely what one obtains for the optimal approximation. The corresponding formulas were discovered and called semicardinal spline quadrature formulas.
Genetics of central nervous system developmental disorders.

Genetic and environmental factors regulate the development of the central nervous system. This article highlights some of the important molecules and genes that are necessary for early stages of brain development. A number of disorders are caused when disruptions occur in the normal developmental process. The molecular basis for some of these disorders is reviewed.
Physical activity and common tasks of California farm workers: California Heat Illness Prevention Study (CHIPS)

AbstractFarm workers are at risk of heat related illness (HRI), but their work rates that contribute to HRI have not been objectively assessed. The CHIPS study collected accelerometer data and characterized the physical activity of major farm tasks. Demographic information, work characteristics, and accelerometer data were collected from 575 farm workers in California. Each participating worker contributed measurements over one work shift. An Actical accelerometer was attached securely to a belt worn at the hip. Data were collected at one-minute intervals throughout the work shift. A total of 13 major work-task categories were defined. The mean physical activity counts per minute (cpm) and percentage of the shift spent at moderate and/or vigorous levels of activity were described for each task. Multiple linear regression models were constructed to determine the worker and environmental characteristics contributing to the physical activity level. Mean levels of physical activity ranged from 700 cpm (worker...
The impact of skin allograft on inpatient outcomes in the treatment of major burns 20–50% total body surface area — A propensity score matched analysis using the nationwide inpatient sample

Abstract Background Human cadaveric skin (allograft) is used in treating major burns both as temporizing wound coverage and a means of testing wound bed viability following burn excision. There is limited information on outcomes, and clinicians disagree on indications for application in intermediate-sized burns. This study aims to improve understanding of allograft use in 20–50% total body surface burns by assessing current utilization and evaluating inpatient outcomes. Methods Discharge data from the Nationwide Inpatient Sample (NIS), Healthcare Cost and Utilization Project (HCUP), Agency for Healthcare Research and Quality assessed 3557 major burn patients (>second degree depth and 20–50% TBSA) undergoing operative treatment. Outcomes were evaluated with propensity score matching. The primary outcome was mortality with secondary outcomes including complications, length of stay, total burn operations, and charges. Results After matching, 771 allografted patients were paired with 1774 controls. Covariate mean standard differences were all Conclusions Allograft use in major burns 20–50% TBSA was associated with a significant increase in inpatient mortality. There was a notable correlation with increased inpatient complications, longer length of stay, more burn operations, and greater total charges. Better studies are needed to justify the use of this costly and limited resource in the intermediate sized major burn population.
In vitro security of 3 surgical knots placed by novice veterinary students.

OBJECTIVE: To determine the most secure knot when tied by veterinary students in a ligation model. STUDY DESIGN: Prospective study. SAMPLE POPULATION: Sixteen first‐year veterinary students. METHODS: Veterinary students were taught 3 knots: surgeon's, Miller's, and strangle. After having demonstrated competence, students tied each knot twice in a vascular ligation model at physiologic pressure. The system was tested for completeness of occlusion and volume of fluid lost over 10 seconds. Time, reattempts, repositioning, correctness, and difficulty score were documented. Students were surveyed before and after training regarding their experience. RESULTS: Students correctly tied 75% of all knots and achieved complete occlusion of the model with 56% of knots. No difference was identified among knot types in correctness, difficulty, complete occlusion, or time to construct the knot. The first surgeon's knot placed by students had more fluid loss than the Miller's knot, but this was not true of the second knot. CONCLUSION: Incomplete occlusion was common among all knot types, but students generally achieved similar knot security when placing surgeon's, Miller's, and strangle knots on a model. More surgeon's knots failed catastrophically during the first attempt, evidenced by a greater volume of fluid loss. CLINICAL SIGNIFICANCE: This study does not provide evidence to recommend any of the 3 tested knots as superior to the others to improve the security of ligatures during surgeries performed by students. The prevalence of incomplete occlusion among student knots illustrates the requirement for education regarding knot security and vigilant monitoring of students performing live animal surgeries.
Differences in adult and adolescent listeners' ratings of valence and arousal in emotional prosody.

ABSTRACTJudgments of emotional stimuli’s valence and arousal can differ based on the perceiver’s age. With most of the existing literature on age-related changes in such ratings based on perception...
Factoring civil society actors into health policy processes in low- and middle-income countries: a review of research articles, 2007–16

Civil society actors have substantially increased their participation in global and national health policymaking processes since the 1970s. Civil society roles in shaping such significant global health milestones as the Doha Declaration on Intellectual Property Rights, the Framework Convention on Tobacco Control and the recently adopted United Nations Sustainable Development Goals are well documented, but knowledge of civil society actor influence on health policy processes in low- and middle-income countries remains fragmented. This study analyses 24 peer-reviewed research articles published between 2007 and 2016 to identify factors affecting civil society influence in the pre-implementation stages of the policy process. The articles reviewed span 13 health issues and more than 50 countries in four regions of the world. This body of work focuses on civil society as represented by formal groups, primarily domestic and to some extent international non-governmental organizations, but also social movements, professional associations and faith-based organizations, among others. The studies document several actor-centred and contextual factors that affect civil society actor power, commonly across stages of the policy process. Crucially, civil society actors were challenged to impact the process in countries that lacked participative norms and governing structures. When repressive conditions existed, regime changes and donors sometimes helped to open doors to participation. The power of civil society actors was enhanced when they joined strong epistemic networks and broader coalitions of stakeholders, were resourced, and framed issues in ways that resonated with national policies and political priorities. The synthesis offers guidance to practitioners on factors to consider in strategy development and points to several issues for further investigation by health policy analysis scholars, including the implications of issue (non)adoption by civil society actors and contestation dynamics among those with differing perspectives.
Stepwise methodology for processing marrow products from matched siblings for possible T-cell depletion in patients with fanconi anemia

Background & Aim Post-transplant GvHD risk is increased in patients with aplastic anemia and Fanconi anemia (FA). T-cell depletion (TCD) is considered the most efficient GvHD prophylaxis. in hematopoietic stem cell transplantation (HCT). Overall risk of GvHD is less than 10% at our center using grafts from unrelated or mismatched, related donors for HCT to treat FA. Grafts with higher cell numbers (e.g. adults to children) are often used, providing increased cell numbers. For HCT in HLA matched siblings, most centers use unmodified grafts since TCD is problematic in young, comparably sized donors. Red blood cell (RBC) depletion due to ABO mismatch results in further loss. We studied the feasibility of TCD in a stepwise manner for the processing of marrow products from matched siblings in 2 patients with Fanconi anemia and aplastic anemia, both with a minor ABO mismatch requiring RBC depletion. Methods, Results & Conclusion At HCT, the first patient was 10.5 years old (22.1kg ( 90th%tile for age)). The second patient was 8.7 years old (24.4kg (10th%tile for age)). His sibling was 9.9 years of age (55kg (>90th %tile for age)). Volumes after collection, heparin addition, and stepwise processing are provided in table 1. Initial cell doses were above the threshold for proceeding to TCD (≥5.2 × 106). Products were RBC depleted (CD34+ recovery in table 1). The decision to proceed to TCD was made at this point with the aim for final doses of 2-4 × 106 CD34 cells/kg likely to occur post CD34 selection, even with moderate recovery using a threshold of ≥4.3 × 108 TNC/Kg. We would have proceeded to added GvHD prophylaxis and unmodified grafts should the CD34 cell doses have been lower post RBC depletion. TCD was performed using CliniMACS columns (Miltenyi) (table 1 shows CD34 recovery). The final CD3 cell doses of the two grafts were 3.6 and 0.9 × 103 CD3 cell doses/kg respectively (4.2 and 4.7 log reductions). Both patients engrafted with neutrophil engraftment (day +13), and platelet count of 50,000 (day +32). Patients are alive and disease free approx. 1 yr. post-transplant with complete hematologic and immune reconstitution and chimerism showing 100% myeloid donor engraftment. Careful, stepwise processing can be done in TCD of marrow for HCT in patients using HLA matched sibling donors. (1) Adequate and safe volume must be collected from donors. (2) Cell doses post RBC depletion must be assessed prior to proceeding with unmodified or TCD grafts.
Graph convolutional networks for exploring authorship hypotheses

This work considers a task from traditional literary criticism: annotating a structured, composite document with information about its sources. We take the Documentary Hypothesis, a prominent theory regarding the composition of the first five books of the Hebrew bible, extract stylistic features designed to avoid bias or overfitting, and train several classification models. Our main result is that the recently-introduced graph convolutional network architecture outperforms structurally-uninformed models. We also find that including information about the granularity of text spans is a crucial ingredient when employing hidden layers, in contrast to simple logistic regression. We perform error analysis at several levels, noting how some characteristic limitations of the models and simple features lead to misclassifications, and conclude with an overview of future work.
Help Seeking in the Perinatal Period: A Review of Barriers and Facilitators

ABSTRACTPerinatal depression affects approximately 10 to 20 percent of women during pregnancy or the first 12 months postpartum. Increased attention has been given to the prevalence of and screenin...
All-metal Dual Frequency RHCP High Gain Antenna for the Extreme Environments of a Potential Europa Lander

A new all-metal dual-frequency RHCP high gain antenna is under development at NASA's Jet Propulsion Laboratory for a potential Europa Lander. The antenna is mainly made of metal so it could survive the harsh environment conditions (i.e. very low temperature and high radiation and ESD levels). The antenna is also flat to meet drastic volume constraints and has efficiencies higher than 80% at both the uplink and downlink X-band Deep Space frequency bands. This antenna is a key component for the potential mission enabling Direct Link to Earth (DTE) from and Direct-from-Earth (DFE) to the lander without any relay.
Concussion, sensation-seeking and substance use among US adolescents

Background: No large-scale epidemiological survey of adolescents in the US has assessed the association between lifetime history of concussion, propensity toward sensation-seeking, and recent substance use. Methods: This study assesses the association between lifetime history of diagnosed concussions, sensation-seeking, and recent substance use (i.e., cigarette use, binge drinking, marijuana use, illicit drug use, and nonmedical prescription drug use) using the 2016 and 2017 Monitoring the Future study of 25,408 8th, 10th, and 12th graders. Results: Lifetime diagnosis of concussion was associated with greater odds of past 30-day/2-week substance use. Adolescents who indicated multiple diagnosed concussions (versus none) had two times greater odds of all types of recent substance use, after adjusting for potential confounding factors. Adolescents indicating multiple diagnosed concussions also had higher adjusted odds of cigarette use, binge drinking, and marijuana use) when compared to adolescents who only indicated one diagnosed concussion. Accounting for adolescents' propensity toward sensation-seeking did not significantly change the association between substance use and multiple diagnosed concussions. Conclusions: This study provides needed epidemiological data regarding concussion and substance use among US adolescents. Exposure to a single diagnosed concussion is associated with a modest increase in the risk of substance use and this association increases with the accumulation of multiple diagnosed concussions. These associations hold when controlling for sensation-seeking. Substance use prevention efforts should be directed toward adolescents who have a history of multiple concussions.
18F-FDG PET Imaging Features of Patients With Autoimmune Lymphoproliferative Syndrome.

Introduction Autoimmune lymphoproliferative syndrome (ALPS) is a rare immune dysregulatory condition, usually presenting in childhood with massive lymphadenopathy, splenomegaly, and an increased incidence of lymphoma. Methods to differentiate between benign ALPS adenopathy and lymphoma are needed. To this end, we evaluated the usefulness of FDG PET. Methods We prospectively evaluated 76 ALPS/ALPS-like patients including FS-7-associated surface antigen (FAS) germline mutation with (n = 4) and without lymphoma (n = 50), FAS-somatic (n = 6), ALPS-unknown (n = 6), and others (n = 10) who underwent FDG PET. Uptakes in 14 nodal sites, liver, and spleen were determined. Results In 76 ALPS patients, FDG PET showed uptake in multiple nodal sites in all but 1 patient. The highest SUVmax values in FAS mutation without lymphoma, FAS mutation with lymphoma, FAS somatic, ALPS-unknown, and other genetic mutations were a median (range) 9.2 (4.3-25), 16.2 (10.7-37.2), 7.6 (4.6-18.1), 11.5 (4.8-17.2), and 5.5 (0-15.3), respectively. Differences between uptake in the FAS group with and without lymphoma were statistically significant, but overlapped, making discrimination between individuals with/without lymphoma impossible. The spleen:liver uptake ratio was greater than 1 in 82% of patients. Conclusions While statistically significant differences were observed in FAS mutation ALPS with and without lymphoma, the significant overlap in FDG uptake and visual appearance in many patients prevents discrimination between patients with and without lymphoma. Similar patterns of FDG biodistribution were noted between the various ALPS subgroups.
Unraveling Chiral Selection in the Self-assembly of Chiral Fullerene Macroions: Effects of Small Chiral Components Including Counterions, Co-ions, or Neutral Molecules.

Lactic acid-functionalized chiral fullerene (C60) molecules are used as models to understand chiral selection in macroionic solutions involving chiral macroions, chiral counterions, and/or chiral c...
Freeform based focusing attachment for fixed focus thermal LWIR objectives (Conference Presentation)

Many fixed focus lenses for uncooled state of the art LWIR cameras are frequently factory set at large distance and therefore produce blurred thermal imagery when targets are closer than 80 m. To solve this issue, we propose a freeform based varifocal attachment that consists of two thin Germanium plates and is derived from Alvarez-Lohmann concept. When implemented together with our low-cost f/1.1 65 mm LWIR lens, the varifocal attachment enables sharp thermal imagery from 2 m to infinity. Extensive tolerancing study supports feasibility of this freeform device for future manufacturing.
Abstract PO015: Tumor-cell-intrinsic epigenetic factors underlie the heterogeneity of immune infiltration and response to immunotherapy in pancreatic cancer

Intertumoral heterogeneity—the biologic and functional differences among different individual tumors—poses a challenge for immunotherapy. To understand the tumor cell-intrinsic factors underlying the heterogeneity of tumor immunity and sensitivity to immunotherapy, we established a new experimental system by generating a library of congenic pancreatic tumor cell clones from a genetic mouse model driven by mutant Kras and p53. These tumor cell clones robustly formed implanted tumors that recapitulated the T cell-inflamed and non-T cell-inflamed tumor microenvironments in human patients, associated with distinct patterns of infiltration by T cells and myeloid cells. We found that the non-T cell-inflamed phenotype was dominant over the T cell-inflamed phenotype in the local tumor microenvironment. Both quantitative and qualitative features, specifically expression of markers of prior TCR activation, of intratumoral CD8+ T cells predicted the response to immunotherapies. An integrated transcriptomic and epigenetic analysis revealed that tumor cell-intrinsic expression of the chemokine CXCL1 as a major determinant of the non-T cell-inflamed microenvironment, and ablation of tumor cell-intrinsic CXCL1, promoted T-cell infiltration and sensitivity to a combination of chemotherapies, CD40 agonist, and checkpoint blockades. These results demonstrated that heterogeneity of tumor immune phenotypes is driven by tumor cell-intrinsic factors that can be manipulated to influence the outcome of immunotherapies. The observation that non-T cell-inflamed phenotype is dominant emphasized the importance of targeting mechanisms driving T-cell low phenotype for improving immunotherapy response. This experimental system will provide opportunities for understanding other aspects of tumor heterogeneity as well. This abstract is also being presented as Poster A45. Citation Format: Jinyang Li, Katelyn T. Byrne, Fangxue Yan, Taiji Yamazoe, Zeyu Chen, Timour Baslan, Lee P. Richman, Jeffrey Lin, Yu H. Sun, Shannon M. Liudahl, John W. Tobias, Scott Lowe, Lisa M. Coussens, John E Wherry, Robert H. Vonderheide, Ben Z. Stanger. Tumor cell-intrinsic factors underlie the heterogeneity of immune infiltration and response to immunotherapy in pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2018 Nov 27-30; Miami Beach, FL. Philadelphia (PA): AACR; Cancer Immunol Res 2020;8(4 Suppl):Abstract nr PR11.
Fiber-coupled microsphere laser.

We demonstrate a 1.5-mm-wavelength fiber laser formed by placement of glass microsphere resonators along a fiber taper. The fiber taper serves the dual purpose of transporting optical pump power into the spheres and extracting the resulting laser emission. A highly doped erbium:ytterbium phosphate glass was used to form microsphere resonant cavities with large gain at 1.5 mm. Laser threshold pump powers of 60 mW and fiber-coupled output powers as high as 3 mW with single-mode operation were obtained. A bisphere laser system consisting of two microspheres attached to a single fiber taper is also demonstrated. © 2000 Optical Society of America
A model of collaboration network formation with heterogeneous skills

Collaboration networks provide a method for examining the highly heterogeneous structure of collaborative communities. However, we still have limited theoretical understanding of how individual heterogeneity relates to network heterogeneity. The model presented here provides a framework linking an individual's skill set to her position in the collaboration network, and the distribution of skills in the population to the structure of the collaboration network as a whole. This model suggests that there is a non-trivial relationship between skills and network position: individuals with a useful combination of skills will have a disproportionate number of links in the network. Indeed, in some cases, an individual's degree is non-monotonic in the number of skills she has—an individual with very few skills may outperform an individual with many. Special cases of the model suggest that the degree distribution of the network will be skewed, even when the distribution of skills is uniform in the population. The degree distribution becomes more skewed as problems become more difficult, leading to a community dominated by a few high-degree superstars. This has striking implications for labor market outcomes in industries where production is largely the result of collaborative effort.
HRV-Spark: Computing Heart Rate Variability Measures Using Apache Spark

Heart rate variability (HRV) analysis has been serving as a significant promising marker in clinical research over the last few decades. The rapidly growing heart rate data generated from various devices, particularly the electrocardiograph (ECG), need to be stored properly and processed timely. There is a pressing need to develop efficient approaches for performing HRV analyses based on ECG signals. In this paper, we introduce a cloud computing approach (called HRV-Spark) to compute HRV measures in parallel by leveraging Apache Spark and a QRS detection algorithm in [1]. We ran HRV-Spark on Amazon Web Services (AWS) clusters using large-scale datasets in the National Sleep Research Resource. We evaluated the performance and scalability of HRV-Spark in terms of the number of computing nodes in the AWS cluster, the size of the input datasets, and the hardware configuration of the computing nodes. The results show that HRV-Spark is an efficient and scalable approach for computing HRV measures.
Living in Boston during COVID-19: Economic Strains

In the Summer of 2020, the Boston Area Research Initiative (BARI) at Northeastern University, the Center for Survey Research (CSR) at University of Massachusetts Boston, and the Boston Public Health Commission (BPHC) conducted a survey that captures the experiences of 1626 Bostonians during the first months of the COVID-19 pandemic. The survey provides unique insights into how experiences and challenges varied across the populations and neighborhoods of a single city—something not currently available from any other source, in Boston or otherwise. This third report in a series describes how the pandemic has affected the employment trajectories and economic resources of Boston’s residents. By examining how these impacts were distributed by race and ethnicity, socioeconomic status, and family composition, we reveal a range of inequities in how different populations have experienced financial disadvantage due to the pandemic.
Asyut in Modern Times: The Problem of Invisibility

If a major city, the major administrative capital of the south and an integral part of how the system reproduces itself, is invisible beyond an occasional passing reference in the familiar narrative of the history of a country, something has gone amiss. Such is the situation of Asyut, a city so invisible that even the English spelling of its name is elusive—variably Asyut, Assuit, Assiut, Siout, or even Essiout—sometimes appearing to be a deliberate attempt to retain an ancient pharaonic or biblical rendering. So why is there this invisibility and how can it be overcome?
Gibbs entropy from entanglement in electric quenches

In quantum electrodynamics with charged chiral fermions, a background electric field is the source of the chiral anomaly which creates a chirally imbalanced state of fermions. This chiral state is realized through the production of entangled pairs of right-moving fermions and left-moving antifermions (or vice versa, depending on the orientation of the electric field). Here we show that the statistical Gibbs entropy associated with these pairs is equal to the entropy of entanglement between the right-moving particles and left-moving antiparticles. We then derive an asymptotic expansion for the entanglement entropy in terms of the cumulants of the multiplicity distribution of produced particles and explain how to re-sum this asymptotic expansion. Finally, we study the time dependence of the entanglement entropy in a specific time-dependent pulsed background electric field, the so-called "Sauter pulse", and illustrate how our re-summation method works in this specific case. We also find that short pulses (such as the ones created by high energy collisions) result in an approximately thermal distribution for the produced particles.
Non-audit Services and Shareholder Ratification of Auditors

The SEC changed its rules recently and required companies to disclose information about audit and non-audit fees. The Commission asserted that such data would be useful for shareholders in making their investment and voting decisions. An analysis of shareholder votes at 172 of the Fortune 1,000 companies indicates that the proportion of shareholders voting against or abstaining from ratification of the external auditor is positively associated with the level of the non-audit fee ratio. The change in shareholder votes (from the period before the required disclosure) also is positively associated with the relative magnitude of non-audit fees. These results provide empirical support to the SEC's assertion that disclosure of fees paid to the auditor can influence shareholders' voting decisions. However, even in companies with non-audit fee ratios exceeding four, the average shareholder ratification rate was about 97 percent. This suggests that a large majority of shareholders do not perceive auditor independence to be impaired, even in the presence of relatively high non-audit fees.
Experimental observation of a suspended single layer graphene film on Cu foil grown via chemical vapor deposition method

The authors present the blue-shift of Raman 2D and G peak of a single layer graphene film, which is fabricated via chemical vapor deposition, on the relatively even Cu foil domain with nearly uniform thickness. This can be interpreted that rather mechanically compressive strain is exerted between graphene and the even Cu domain compared to the uneven. We observe that relaxing compressive strain to minimize the perturbation from Cu surface to the graphene film by virtue of the uneven Cu domain has a critical role in forming a suspended graphene. Furthermore, mechanical strain influence derived from the underlying substrate morphology can be suggested as one of the crucial elements in evaluating high quality graphene film considering suspended shape.
Chromatographic fractionation of crystallized rennin

It was shown that a specimen of crystallized rennin was inhomogeneous, and that a homogeneous rennin could be separated by means of the diethylaminoethyl cellulose ion exchange chromatography. The pure enzyme was characterized by determining its terminal amino acids, and by spectropolarimetry. Rennin behaved abnormally with respect to optical rotatory dispersion, an indication of peculiar structure and configuration of this protein. Es wurde gezeigt, das kristalline Labferment (Rennin) nicht einheitlich ist. Einheitliches Rennin kann durch chromatographische Trennung auf Diathylaminoathylcellulose hergestellt werden. Das reine Ferment wurde durch die Bestimmung der endstandigen Aminosauren und spektropolarimetrisch charakterisiert. Hinsichtlich der Rotationsdispersion zeigt einheitliches Rennin ein abnormales Verhalten, was auf eine strukturelle Eigenart des Ferments hinweist.
Geometry of a Class of Generalized Cubic Polynomials

This paper studies a class of generalized complex cubic polynomials of the form p(z)=(z-1)(z-r_1)^k(z-r_2)^k where r_1 and r_2 lie on the unit circle and k is a natural number. We completely characterize where the nontrivial critical points of p can lie, and to what extent they determine the polynomial. The main results include (1) a nontrivial critical point of such a polynomial almost always determines the polynomial uniquely, and (2) there is a `desert' in the unit disk in which critical points cannot occur.
Geometric relationships of pristine Martian complex impact craters, and their implications to Mars geologic history

[1] Based on the depths of pristine complex craters on Mars, we have estimated the final, post-modification phase depth (dr) to diameter (D) function of Martian complex craters. We suggest that the dr/D function determined here holds globally for complex craters >∼12 km diameter. The global nature of this function may be due to the stability of slopes in the highly fractured rock that makes up the steep interior walls of post-modification phase craters. The stability of such slopes should be controlled mainly by such factors as the nature of the fractures and not target strength. This function is an essential benchmark for studies that utilize crater geometry as their basis. For example, the function can be used in gradation history of Mars to predict the magnitude of degradation. For instance, an example 20-km-diameter, Middle/Early Noachian-age crater that initially formed in the mid-latitudes of Mars with a depth of 1800 m (instead of 1404 m as predicted by the fresh craters function) has lost ∼1450 m of its depth over its history, ∼350 m in the Noachian, ∼400 m during an intense episode of degradation at the end of the Noachian, and ∼700 m thereafter. No evidence of the period of intense degradation is found in the high-latitudes, although those regions appear to have been affected by a process that reduced crater depth soon after they form.
Characteristic Study on the Optimization of Micro PinFin Heat Sink with Staggered Arrangement

The effect of the Pinfin shapes on the overall per formance of the micro Pinfin heat sink with staggered arrangement is studied in this paper. Six different shapes of micro Pinfins, square, rectangle, circle, rhombus, triangle and ellipse are subjected to study in this paper. The optimization processes are carried out using computer simulations performed using COVE*TORWARE™. The study is carried out over a range of Reynolds number ranging from 50 to 500 and a figure of merit term (FOM) consisting of both the thermal resistance and the pumping power is developed for the overall performance evaluation of different models. A weighted average scheme is used for developing the FOM term. The results of the study revealed that at low values of Reynolds numbers (Re 200) rectangle showed the best performance. *omenclature C = specific heat capacity (J/kg K) h = total height of the heat sink (m) k = thermal conductivity (W/K m) L = length of the heat sink (m) n = constant P = pressure (N/m 2 )
Solid-State Hydriding Mechanism in the LiBH4 + MgH2 System

The LiBH4 + MgH2 system has great potential in reversible hydrogen storage for fuel cell vehicles. However, it has always been dehydrogenated and rehydrogenated in the liquid state until recently. ...
The Identity of Dexamonica and Prinassus

[Die Genera Prinassus Hansen (1887) und Dexamonica Barnard (1957) sind synonym. Prinassus ist ein Subgenus von Guernea Chevreux (1887). Die Mundteile von Prinassus sind ahnlich denen von Guernea, jedoch hat Prinassus einen Ruckzahn auf dem 4. Pleonite. Die Familien Anatylidae, Atylidae, Lepechinellidae und Prophliantidae werden mit den Dexaminidae vereint. Die folgenden Charakteristika sind veranderlich und haben keine Bedeutung als Familienmerkmale: die Abwesenheit oder das Vorhandensein des Mandibular Palpus; die Grosse des Kauhockers am Kiefer; die Grosse der Zahne an Kopf oder Segmenten; die Verschmelzung des 1. und 2. bis 3. Segments der Urosome. Die Prophliantidae sind eine Subfamilie der Dexaminidae, die sich von den Dexaminidae durch die Verschiedenheit der 5. bis 7. Pereopoden unterscheiden. Sie enthalten die Genera Prophlias, Haustoriopsis und Guernea ( = Prinassus, = Dexamonica)., Die Genera Prinassus Hansen (1887) und Dexamonica Barnard (1957) sind synonym. Prinassus ist ein Subgenus von Guernea Chevreux (1887). Die Mundteile von Prinassus sind ahnlich denen von Guernea, jedoch hat Prinassus einen Ruckzahn auf dem 4. Pleonite. Die Familien Anatylidae, Atylidae, Lepechinellidae und Prophliantidae werden mit den Dexaminidae vereint. Die folgenden Charakteristika sind veranderlich und haben keine Bedeutung als Familienmerkmale: die Abwesenheit oder das Vorhandensein des Mandibular Palpus; die Grosse des Kauhockers am Kiefer; die Grosse der Zahne an Kopf oder Segmenten; die Verschmelzung des 1. und 2. bis 3. Segments der Urosome. Die Prophliantidae sind eine Subfamilie der Dexaminidae, die sich von den Dexaminidae durch die Verschiedenheit der 5. bis 7. Pereopoden unterscheiden. Sie enthalten die Genera Prophlias, Haustoriopsis und Guernea ( = Prinassus, = Dexamonica).]
The Distribution of Mormon Wealth and Income in 1857

In February 183 1, slightly less than 1 year after Joseph Smith founded his new religion in New York State, the Mormon prophet announced to his followers a program of economic reform which has since been known as the “Law of Consecration and Stewardship.” One purpose of the far-reaching design was to bring about parity of incomes at levels recognizing the “circumstances, . . . wants and needs” of individual families. Joseph Smith’s subsequent revelations pertaining to economic affairs fairly bristle with strong injunctions to achieve economic equality among the “Saints,” as his followers called themselves.’ Consecration and stewardship was later replaced by tithing, but with the promise that one day faithful Mormons would be asked to live under it again. The economic idealism of the “higher law,” as it was sometimes called by Mormons, remained with Smith’s followers, arising at various times to reshape their economic lives. In the 1850s the faithful were asked to “consecrate” or deed their property, real and personal, to the church, with probably half of the heads of family in Utah responding; in the 1860s an extensive system of consumer’s and producer’s cooperatives was founded under church leadership; in the 1870s for a brief time, the entire Mormon population, embracing more than 80,000 persons, was organized under the “United Order,” Brigham Young’s vision of a self-sufficient, egalitarian commonwealth of village communes; and in 1936 the Church Welfare Program was initiated, a network of cooperatives owned by diocesan-level church units, which collectively produce goods sufficent to stock central and local warehouses with most commodities needed to provide relief for the Mormon poor and aid for disaster victims.2