cssi/SciSciGPT-SciSciNet huggingface dataset:
Notch Leads Lymphatics and Links Them to Blood Vessels

Lymphatic vessels sprout from the cardinal vein to form primary lymphatic sacs.1,2 However, molecular mechanisms that guide the formation of a mature functional lymphatic network are still shrouded in mystery. Several molecules that are considered markers of arterial endothelial cells (ECs), such as ephrin B2, Foxc2, and integrin α9, are involved in lymphangiogenesis.1 By using an elegant in vivo approach, Geudens et al3 added another arterial factor to this constellation of molecules. Specifically, they show that Notch (a regulator of cell fate decisions and blood vessel development) is also required for lymphatic network development. By systematically silencing zebra fish orthologues of the Notch family receptors (Notch 1a/b, Notch 5, and Notch 6) and their ligands (jagged 1a/b, jagged-2, delta A-D, and deltalike [Dll] 4) and then tracing blood and lymphatic ECs (LECs) during zebra fish embryogenesis, they reveal the critical role of Notch signaling in the guidance of lymphatics and the formation of a lymphatic network. See accompanying article on page 1695 Notch is known to control endothelial sprouting during angiogenesis.4 During embryogenesis, lymphangiogenesis occurs after angiogenesis, making it difficult to dissect whether and how Notch regulates lymphatic development in mouse models. To this end, Geudens et al3 took advantage of zebra fish as a model organism to study angiogenesis and lymphangiogenesis and …
Isolation of atmospheric effects on rapid polar motion through Wiener filtering

SUMMARY Rapid polar motions are irregular low amplitude fluctuations of the rotation pole of the Earth that occur over timescales of days to months. They have been attributed primarily to variations in atmospheric angular momentum (AAM), with a contribution from oceanic angular momentum as well. Monte Carlo experiments conducted by Stieglitz & Dickman suggest that, given the observed correlations between AAM and rapid polar motion, only two-thirds of the atmospheric excitation is actually being transferred to the solid earth's rotation. Consequently, the traditional procedure for correcting polar motion for atmospheric effects, by simply subtracting the original AAM time-series, is inefficient. Following a suggestion by Stieglitz & Dickman, we have attempted to optimally correct polar motion for atmospheric effects using the technique of Wiener filtering. With the atmospheric excitation as input and geodetic excitation (produced by deconvolving polar motion) as desired output, we use the Wiener filter to produce an atmospheric time-series that relates as meaningfully as possible to the geodetic excitation. The filter can also account for cross-component excitation of rapid polar motion by AAM, such as might result from atmospheric forcing of the oceans or groundwater. We find that the Wiener filter acts to screen non-geodetic power (mostly reddish noise) from AAM across the entire frequency spectrum. The resulting Wiener filtered AAM (WAAM) is reduced in amplitude from the original AAM by at least half and shows higher correlation and coherence with geodetic excitation. Additionally, correcting polar motion data with WAAM reveals the presence of tidal signals not seen in previous studies and allows long-period tide models to be tested.
A required EMC course for computer engineering undergraduates

A required junior-level course on electromagnetic compatibility and signal integrity has been added to our computer engineering curriculum. The goal of the course is to prepare our students for further study in high-speed design and to provide them with a competitive advantage in the marketplace. The course is, of necessity, a compromise between coverage of electromagnetics theory and the breadth of the discussion of EMC practice and techniques. The focus is on those aspects of EMC related to high-speed digital systems and upon EMC laboratory measurements and techniques. This paper reports the course, laboratories; lessons learned and anticipated future directions for the course
Silica Diagenesis, I. Solubility Controls

ABSTRACT The diagenetic sequence of silica is examined in terms of several thermodynamic and kinetic concepts. The relationship between solubility and surface area or particle size is sufficient to explain simple opal-A opal-CT quartz transformations, suggesting that the role of temperature and other physical parameters may not be as critical as previously thought. Complexation and adsorption in an impure system, when added to the model, allow for possibilities of opal-A transformation directly to quartz, of clay and zeolite formation from an opaline silica source, and of variations in silica transformation rates due to presence of impurities in the system.
Duration of volunteer potato (Solanum tuberosum) interference in bulb onion

Abstract Previous research with annual weed species indicates that critical timing of weed removal begins primarily after the two-leaf stage of onion, a time when postemergence (POST) herbicides can first be applied. Volunteer potato is difficult to manage and persists in onion fields of western United States. The purpose of this research was to quantify the duration of volunteer potato interference on yield and market grade of onion as well as potato tuber production. Volunteer potato interference caused a 5% yield loss before onions reached the two-leaf stage, at two of three locations. Relative to weed-free plots, onion bulb diameter was reduced as duration of interference increased, resulting in smaller proportions of marketable bulbs. Volunteer potato produced daughter tubers shortly after emergence, which explains, in part, weed persistence despite removal of shoots with contact herbicides, cultivation, and hand-weeding in onion. Significant losses in onion yield and bulb diameter are likely given c...
Similarities in the Relative Populations of Excited States Produced by Sputtering and by Electron Impact

In both sputtering and medium-energy electron-atom impact, the inelastic energy transfer, ΔEe, should have a similar distribution, dN/d(ΔEe) α 1/(ΔEe)2. This suggests that the relative populations of excited states may be similar for each type of experiment and, in order to test this idea, previously published results for the formation of SiI, SiII, and SiIII in sputtering and for the formation of RbI, RbII, and RbIII in electron-atom impact are compared with theory based on an inverse square distribution of ΔEe. Agreement between experiment and theory is found to be good over the entire 55–60 eV span of excitation energies.
Alterations in Finite Element Results Given Constitutive Models From Tubular and Planar Biaxial Testing of the Same Porcine Coronary Arteries

The biomechanical characterization of tissue offers insight into items such as progression of disease and design parameters for implants1,2. To biomechanically evaluate the properties of blood vessels, biaxial testing is frequently performed because biological samples often exhibit anisotropy, and are most frequently under tension from the applied pressures and stretches3,4. Deciding whether to splay a tubular sample open to test in planar form versus performing pressure-inflation testing is a decision often determined by what testing equipment is available. The purpose of this abstract is to compare pressure-inflation behavior, stress distributions, and fiber architecture in planar versus tubular biaxial testing of the same arteries.Copyright © 2012 by ASME
A Humoral Control of Parathyroid Secretion

SummaryPreliminary investigations involving (a) the intravenous injection of sodium oxalate into normal and parathyroprival dogs and (b) the perfusion of decalcified blood through the thyroid-parathyroid apparatus and injection of the perfusate into normal dogs, indicate a humoral control (low blood calcium) of the parathyroid glands.
Effects of experimental allergic encephalomyelitis on thymus and adrenal: relation to remission and relapse.

AbstractExperimental allergic encephalomyelitis (EAE) was induced by active immunization with neural tissue and adjuvants and by passive transfer of living lymphoid cells. Severe thymolysis occurred along with severe clinical signs and lesions. Thymolysis was preceded and accompanied by a striking rise in serum corticosterone. Clinical signs then remitted, followed by a decline in serum corticosterone and beginning regeneration of the thymus, but histologic EAE lesions persisted. Adrenalectomy performed early in the remission of EAE was followed promptly by disappearance of serum corticosterone and relapses of clinical signs. Relapses occurred in rats of either sex but not until thymic regeneration had begun. All these data support the theory that nonspecific stress and the state of adrenal hyperactivity in response to neurological disability determine patterns of remission and relapse in EAE by way of immunosuppressive effects on lymphoid tissue.
An inexact Gauss-Newton method for inversion of basal sliding and rheology parameters in a nonlinear Stokes ice sheet model

We propose an infinite-dimensional adjoint-based inexact Gauss-Newton method for the solution of inverse problems governed by Stokes models of ice sheet flow with nonlinear rheology and sliding law. The method is applied to infer the basal sliding coefficient and the rheological exponent parameter fields from surface velocities. The inverse problem is formulated as a nonlinear least-squares optimization problem whose cost functional is the misfit between surface velocity observations and model predictions. A Tikhonov regularization term is added to the cost functional to render the problem well-posed and account for observational error. Our findings show that the inexact Newton method is significantly more efficient than the nonlinear conjugate gradient method and that the number of Stokes solutions required to solve the inverse problem is insensitive to the number of inversion parameters. The results also show that the reconstructions of the basal sliding coefficient converge to the exact sliding coefficient as the observation error (here, the noise added to synthetic observations) decreases, and that a nonlinear rheology makes the reconstruction of the basal sliding coefficient more difficult. For the inversion of the rheology exponent field, we find that horizontally constant or smoothly varying parameter fields can be reconstructed satisfactorily from noisy observations.
How I treat diaper dermatitis.

What causes diaper dermatitis? Usually one of these things: Moisture macerates the skin, ammoniacal urine irritates it, plastic or rubber pants sensitize it, or skin diseases—ringworm, psoriasis or candidiasis—afflict it. To treat, find the cause; then eliminate or counteract it.
A comparison of strategies for immortalizing mouse embryonic fibroblasts

The genetically amenable mouse model has led to a large collection of genetically defined lines from which mouse embryonic fibroblasts (MEFs) have been derived. Despite their widespread use, MEFs are time consuming to generate and have a limited lifespan. Immortalizing primary MEFs with the desired genetic manipulations greatly reduces culture maintenance time, enables the generation of near limitless amounts of protein lysate, and facilitates biological replicates during experimentation. In this work, we have evaluated several approaches for MEF immortalization. When cultivated at 3% O2, some primary MEF lines could be proliferated for > 40 passages with a median doubling rate of 45 ± 55 h (n = 8). However, serial passaging at 3% O2 achieved spontaneous immortalization with varying success. If cultures seemed to be reaching their Hayflick limit when cultivated at 3% O2, supplementing the culture media with 5 µM ROCK inhibitor Y-27632 helped to extend proliferation and achieve spontaneous immortalization. MEFs immortalized via SV40 Ta infection reliably produced cell lines with a median doubling rate of 25 ± 9 h (n = 9) and viability greater than 90%. In addition to a discussion of the characteristics of cell lines generated with various immortalization strategies, pros and cons of each strategy are included as are recommendations for generating immortalized MEFs.
Finite element methods of studying mechanical factors in blood flow.

AbstractThis paper reviews some biomechanical analyses of blood flow in large arteries based on a general computer modeling using the finite element method. We study the following question: What is the role played by the interrelated factors of mechanical stress, flow irregularities, and diffusion through the endothelium on the etiology of atherosclerosis or the aggravation of vascular injury. It presents the computational features of the method and stresses the physiological significance of the results, such as the effect of geometric complexities, material nonlinearities, and non-Newtonian rheology of the blood. The specific mechanical and fluid dynamic factors analyzed are wall shear stress, flow profiles, and pressure variations. After simulating tubes of circular cross section, we apply the analysis to a number of physiological situations of significance, including blood flow in the entrance region, at bifurcations, in the annular region between an inserted catheter of varying diameter and the vessel...
Clinical Case #7: Natasha

Natasha is a 42-year-old homemaker and mother of three children, ages 12, 8, and 4. She presents with an 11-month history of lower back pain. Natasha is being referred to this office by her primary care doctor. Natasha’s pain does not radiate into the legs. She denies any numbness, tingling, or burning in the legs. The legs do not feel weak. The pain is described as “sharp” and is centralized around the L5–S1 level. The pain is worse with sitting. She says that going for long car rides is “very difficult” because the pain becomes extremely intense. Standing and walking around makes the pain better. In general, she feels that the more she moves, the better she tends to feel unless she does “too much.”
Teaching Psychiatry to Primary Care Physicians

In another five years, psychiatry will have had approximately a one-hundred year history of trying to reintegrate physical medicine with psychological medicine. If one were to graph the course of this history, one would quickly see the oscillations that Freedman1 called the “to and fro” of trends in psychiatry toward medicalization, demedicalization and remedicalization. In almost a century of persevering efforts, we have come not very far in achieving the objective of teaching nonpsychiatrist physicians to synthesize psyche-medicine and soma-medicine. The first part of this chapter will examine some of the many efforts which have been made over time to overcome the barriers to biopsychosocial practice. The second part will offer some speculative reasons for their degree of success or failure.
Considering Non-Cognitive Factors in the Preparation and Selection of Educators

The effect of non-cognitive factors on the educational process is bi-directional. Its value redounds to both the student and the teacher. One must respect the effectiveness of a teacher who, no matter the obstacle(s) or how long it takes to overcome it, exercises the skill and conviction to successfully instruct the assigned students. Ideally, we seek to develop students who demonstrate the same positive, non-cognitive traits in their work habits in school and in their daily lives.
Dyspnea in Community‐Dwelling Older Persons: A Multifactorial Geriatric Health Condition

Objectives To evaluate the associations between a broad array of cardiorespiratory and noncardiorespiratory impairments and dyspnea in older persons. Design Cross-sectional. Setting Cardiovascular Health Study. Participants Community-dwelling persons (N = 4,413; mean age 72.6, 57.1% female, 4.5% African American, 27.2% <high school education, 54.7% ever-smokers). Measurements Dyspnea severity (moderate to severe defined as American Thoracic Society Grade ≥2) and several impairments, including those established using spirometry (forced expiratory volume in 1 second (FEV1)), maximal inspiratory pressure (respiratory muscle strength), echocardiography, ankle–brachial index, blood pressure, whole-body muscle mass (bioelectrical impedance), single chair stand (lower extremity function), grip strength, serum hemoglobin and creatinine, Center for Epidemiologic Studies Depression Scale (CES-D), Mini-Mental State Examination, medication use, and body mass index (BMI). Results In a multivariable logistic regression model, impairments that had strong associations with moderate to severe dyspnea were FEV1 less than the lower limit of normal (adjusted odds ratio (aOR) = 2.88, 95% confidence interval (CI) = 2.37–3.49), left ventricular ejection fraction less than 45% (aOR = 2.12, 95% CI = 1.43, 3.16), unable to perform a single chair stand (aOR = 2.10, 95% CI = 1.61–2.73), depressive symptoms (CES-D score ≥16; aOR = 2.02, 95% CI = 1.26–3.23), and obesity (BMI ≥30; aOR = 2.07, 95% CI = 1.67–2.55). Impairments with modest but still statistically significant associations with moderate to severe dyspnea included respiratory muscle weakness, diastolic cardiac dysfunction, grip weakness, anxiety symptoms, and use of cardiovascular and psychoactive medications (aORs = 1.31–1.71). Conclusion In community-dwelling older persons, several cardiorespiratory and noncardiorespiratory impairments were significantly associated with moderate to severe dyspnea, akin to a multifactorial geriatric health condition.
LUPU, TUTTLE, AND SINGLING OUT RELIGION

Ira Lupu and Robert Tuttle’s Secular Government, Religious People is one of the very best overviews of the American law of religious liberty in print. Their fundamental claim is that religious liberty in America is founded on a jurisdictional limit upon government competence. A keystone of the book’s argument is its response to the increasingly salient question, “what makes religion special?.” That response has important implications for religious accommodation. This brief review focuses on those issues.
Phase stability, swelling, microstructure and strength of Ti3SiC2-TiC ceramics after low dose neutron irradiation

Abstract Mn+1AXn (MAX) phase Ti3SiC2 materials were neutron irradiated at ∼400, ∼630, and 700 °C to a fluence of ∼2 × 1025 n/m2 (E > 0.1 MeV). After irradiation at ∼400 °C, anisotropic c-axis dilation of ∼1.5% was observed. Room temperature strength was reduced from 445 ± 29 MPa to 315 ± 33 MPa and the fracture surfaces showed flat facets and transgranular cracks instead of typical kink-band deformation and bridging ligaments. XRD phase analysis indicated an increase of 10–15 wt% TiC. After irradiation at ∼700 °C there were no lattice parameter changes, ∼5 wt% decomposition to TiC occurred, and strength was 391 ± 71 MPa and 378 ± 31 MPa. The fracture surfaces indicated kink-band based deformation but with lesser extent of delamination than as-received samples. Ti3SiC2 appears to be radiation tolerant at ∼400 °C, and increasingly radiation resistant at ∼630–700 °C, but a higher temperature may be necessary for full recovery.
Uterine Didelphys with Bilateral Cervical Agenesis in a 15-Year-Old Girl

Abstract Background Isolated uterine didelphys requires no treatment in contrast to cervical agenesis, which requires a hysterectomy. Because of this, correct diagnosis of Mullerian anomalies is paramount for making recommendations for patient care. Case A 15-year-old girl presented to clinic with pelvic pain and primary amenorrhea. Uterine didelphys with bilateral cervical agenesis was diagnosed using imaging. Hysterectomy was recommended and diagnosis was confirmed at surgery and according to anatomic pathology. Summary and Conclusion Our patient with uterine didelphys with bilateral cervical agenesis presented a diagnostic challenge, because, to our knowledge, it has never been reported before in the literature. Her pattern of anomalies had significant implications for future fertility. Radiology exam was vital to confirming this diagnosis in a young, virginal female patient.
HPV literacy and its link to initiation and completion of HPV vaccine among young adults in Minnesota.

Abstract Objectives This study identifies whether, and how, human papillomavirus (HPV) literacy and predisposing, enabling, and need factors are associated with HPV vaccine initiation and completion among young adults in Minnesota. Study design Cross-sectional survey design. Methods Using a sample of 170 young adults (aged 18–26 years), we used logistic regression models to identify factors associated with HPV vaccination initiation and completion, including HPV literacy, adjusting for relevant predisposing, enabling, and need factors. Results Consistent with national estimates, we found relatively low rates of HPV vaccination initiation (46%) and completion (36%). Better HPV literacy was significantly associated with higher rates of both initiation and completion, as was being female and having an annual check-up. Being married/partnered was significantly associated with lower odds of HPV vaccination. Conclusions Public health programs, policy-makers, and healthcare providers can use these results to increase HPV vaccination rates by making concerted efforts to improve HPV vaccination literacy through individual and public education campaigns and by improving access to annual check-ups.
Climate and water resource change impacts and adaptation potential for US power supply

Water-cooled power plants will be affected by changes in water availability and temperature. A system approach examines US thermoelectric power generation and finds whilst individual plants may face constraints, overall the current system can adapt. Power plants that require cooling currently (2015) provide 85% of electricity generation in the United States1,2. These facilities need large volumes of water and sufficiently cool temperatures for optimal operations, and projected climate conditions may lower their potential power output and affect reliability3,4,5,6,7,8,9,10,11. We evaluate the performance of 1,080 thermoelectric plants across the contiguous US under future climates (2035–2064) and their collective performance at 19 North American Electric Reliability Corporation (NERC) sub-regions12. Joint consideration of engineering interactions with climate, hydrology and environmental regulations reveals the region-specific performance of energy systems and the need for regional energy security and climate–water adaptation strategies. Despite climate–water constraints on individual plants, the current power supply infrastructure shows potential for adaptation to future climates by capitalizing on the size of regional power systems, grid configuration and improvements in thermal efficiencies. Without placing climate–water impacts on individual plants in a broader power systems context, vulnerability assessments that aim to support adaptation and resilience strategies misgauge the extent to which regional energy systems are vulnerable. Climate–water impacts can lower thermoelectric reserve margins, a measure of systems-level reliability, highlighting the need to integrate climate–water constraints on thermoelectric power supply into energy planning, risk assessments, and system reliability management.
Tidal Energy Conversion

The gravitational field associated with the sun and moon system results in a variable influence on the sea level of the oceans of the world. Subsequently, ocean tides vary in time and amplitude according to the relative position of the sun, moon, and earth. The experience gained from the world's first industrial tidal scheme at Ranee is of prime importance and proves that all technical problems associated with a large-scale development of tidal power can be overcome. The global amount of tidal energy is big enough to motivate a large program for further development of the techniques necessary for the realization of big tidal schemes. If the economy of tidal plants is not yet fully competitive with other methods of energy production, a combination of public pressure against nuclear power plants and new increases of conventional energy prices lead to a number of governments to reconsider the exploitation of their respective tidal potentials.
Cataract Surgery in the Presence of a Functioning Trabeculectomy Bleb

Performing cataract surgery in an eye with a preexisting trabeculectomy bleb raises unique challenges for the ophthalmic surgeon. Addressing the spectrum of bleb morphologies and the anatomic setting in which the cataract exists requires careful attention to detail and an array of surgical skills. Successful preoperative planning, intraoperative execution, and postoperative care can optimize the functional outcome of the bleb and the shortand long-term visual outcome for the patient. The development of visually significant cataracts in glaucoma patients who have had previous trabeculectomy surgery is common and expected1–8 (Fig. 16.1). Cataracts and glaucoma share many similar pathogenic origins, including well-documented risk factors such as age, diabetes, steroid use, and trauma.9–25 In addition, glaucoma and/or elevated intraocular pressure (IOP) and the treatments for glaucoma—including medications, laser, and surgery—have been shown to increase the development of cataracts.26–29 Conversely, the presence of a cataract can initiate and/or exacerbate ocular hypertension and glaucoma.
Estimation of the Acquisition and Operating Costs for Robotic Surgery.

This study used 1999-2017 financial statements from INTUITIVE, the company that supplies most robotic technology, to establish a hospital cost benchmark to inform future cost-effectiveness evaluations.
Dropping Out and Other Fates of Transmembrane Segments Inserted by the SecA ATPase.

Abstract Type II single-span membrane proteins, such as CadC or RodZ, lacking a signal sequence and having a far-downstream hydrophobic segment, require the SecA secretion motor for insertion into the inner membrane of Escherichia coli. Using two chimeric single-span proteins containing a designed hydrophobic segment H, we have determined the requirements for SecA-mediated secretion, the molecular distinction between TM domains and signal peptides, and the propensity for hydrophobic H-segments to remain embedded within the bilayer after targeting. By means of engineered H-segments and a strategically placed SPase I cleavage site, we determined how targeting and stability of the chimeric proteins are affected by the length and hydrophobicity of the H-segment. Very hydrophobic segments (e.g., 16 Leu) are stably incorporated into the inner membrane, resulting in a C-terminal anchored membrane protein, while a 24L construct was not targeted to the membrane by SecA and remained in the cytoplasm. However, a construct carrying preMalE at the N-terminus led to SecA targeting to SecYEG via the native signal sequence and stable insertion of the downstream 24L H-segment. We show that the RseP intramembrane protease degrades weakly stable H-segments and is a useful tool for investigating the borderline between stable and unstable TM segments. Using RseP− cells, we find that moderately hydrophobic sequences (e.g., 5Leu + 11Ala) are targeted to SecYEG by SecA and inserted, but subsequently drop out of the membrane into the cytoplasm. Therefore, the free energy of transfer from translocon to bilayer is different from the transfer free energy from membrane to water.
Prevalence of COPD among workers with work-related asthma.

Objective: Concurrent asthma and chronic obstructive pulmonary disease (COPD) diagnoses occur in 15%–20% of patients, and have been associated with worse health outcomes than asthma or COPD alone. ...
Evolution of Plant NLRs: From Natural History to Precise Modifications

Nucleotide-binding leucine-rich repeat receptors (NLRs) monitor the plant intracellular environment for signs of pathogen infection. Several mechanisms of NLR-mediated immunity arose independently across multiple species. These include the functional specialization of NLRs into sensors and helpers, the independent emergence of direct and indirect recognition within NLR subfamilies, the regulation of NLRs by small RNAs, and the formation of NLR networks. Understanding the evolutionary history of NLRs can shed light on both the origin of pathogen recognition and the common constraints on the plant immune system. Attempts to engineer disease resistance have been sparse and rarely informed by evolutionary knowledge. In this review, we discuss the evolution of NLRs, give an overview of previous engineering attempts, and propose how to use evolutionary knowledge to advance future research in the generation of novel disease-recognition capabilities.
Structure-function analysis of Arabidopsis TOPLESS reveals conservation of repression mechanisms across eukaryotes

Abstract The corepressor TOPLESS (TPL) is recruited to many promoters, yet the mechanisms by which it inhibits expression of genes is poorly understood. Using a synthetic auxin response circuit in Saccharomyces cerevisiae, we identified two regions of Arabidopsis thaliana TPL that could independently function as repression domains: the LIS1 homology domain (LisH) and the CT11-RanBPM (CRA) domain. The CRA repressor domain required direct interaction with the Mediator subunit MED21 for full function. While corepressor multimerization is highly conserved, we found that multimer formation had minimal influence on TPL repression strength in yeast or in plants. Finally, we showed that the LisH domain may have a conserved role in repression in different proteins, as a LisH domain from the human TBL1 protein could replace TPL in synthetic assays. Our work provides insight into the molecular mechanisms of transcriptional repression, while also characterizing short, autonomous repression domains to augment synthetic biology toolkits.
Abstract 5711: Therapeutic induction of tumor-selective ferroptosis in models of pancreatic cancer

Pancreatic ductal adenocarcinoma (PDA) is an aggressive cancer with few therapeutic options. Oncogenic signaling from mutant Kras, the driving oncogene of PDA, drives ROS production, making PDA cells reliant on ROS detoxification processes. To detoxify ROS, mammalian cells use thiols derived from the semi-essential amino acid cysteine, which is imported from exogenous pools of cystine via the system xC− cystine/glutamate antiporter. We found that cysteine depletion in multiple human PDA lines induced a rapid, oxidative, iron-dependent form of non-apoptotic cell death called ferroptosis. Confirming work in other systems, we found that glutathione depletion was necessary for the induction of ferroptosis in PDA cells. However, depletion of glutathione alone was not sufficient to induce ferroptosis, indicating that modulation of other cysteine-dependent processes must also play a role in ferroptosis. Using carbon-labelled cystine, we determined that extracellular cystine is quickly incorporated into coenzyme A. Furthermore, dual inhibition of both CoA and GSH synthesis combined to induce ferroptosis, and CoA treatment rescued the induction of ferroptosis following cysteine depletion. To assess whether cysteine depletion could be useful for targeting pancreatic tumors in vivo, we utilized both genetic and pharmacological approaches. First, we generated a dual recombinase mouse model in which the system xC- gene Slc7a11 can be acutely, systemically deleted in mice with established K-ras/p53 mutant PDA. Acute deletion of Slc7a11 in mice with established PDA led to tumor stabilizations/regressions and increased overall survival, and this was fully reversed by co-treatment with the membrane-permeable cysteine analog NAC. Second, we treated the well validated KPC genetic model of PDA with cyst(e)inase, an engineered enzyme that breaks down cysteine and cystine in circulation. Tumor-bearing KPC mice treated with cyst(e)inase also exhibited tumor responses. In both the genetic and pharmacological models, we observed tumor-selective necrosis and confirmed the induction of ferroptosis using several orthogonal techniques, including electron microscopy, immunohistochemistry, histopathology, and laser capture microdissection/RNA sequencing. These data demonstrate the potential therapeutic utility of targeting cystine import in pancreatic cancer. Citation Format: Michael Badgley, Kathleen DelGiorno, Geoffrey Wahl, Costas Lyssiotis, Kenneth P. Olive. Therapeutic induction of tumor-selective ferroptosis in models of pancreatic cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5711.
Abstract 2189: Generating Merkel cell polyomavirus-specific T cells from healthy donors for adoptive immunotherapy

Merkel Cell Carcinoma (MCC) is an aggressive neuroendocrine skin cancer that is highly immunogenic. Approximately 80% of MCC tumors are virus positive (VP-MCC) and express Merkel cell polyomavirus (MCPyV) T antigens that drive oncogenesis. As VP-MCC have a low mutation burden with few predicted neoantigens, viral oncogenes are thought to be primary targets for anti-cancer immunity. Immune checkpoint inhibitors improve MCC survival, yet not all patients have durable responses. VP-MCC patients who fail checkpoint inhibition or who have immune dysfunction may benefit from adoptive cellular therapy using virus-specific T cells from HLA-matched donors. As the risk of graft versus host disease is low with virus-specific T cells, this approach is being investigated for other viral diseases. We set out to generate MCPyV-specific T cells from healthy donors for potential adoptive immunotherapy. Naive and memory T cells from donors were magnetically isolated prior to stimulation with autologous monocyte-derived dendritic cells pulsed with 15-mer overlapping peptide libraries of MCPyV T antigens. T cells were serially re-stimulated with peptide-pulsed irradiated, autologous PHA-blasts up to five times. Cultures were maintained in either standard growth cytokines (IL-2, IL-7, and IL-15) or a pro-inflammatory cytokine cocktail. T cell phenotype and reactivity were evaluated by flow cytometry. We found that standard cytokine conditions were unable to promote growth of MCPyV-specific mature T cells. Altering growth conditions to include a cocktail of pro-inflammatory cytokines promoted expansion of polyfunctional Th1 CD4+ T cells specific for MCPyV T antigen peptides. These cells produced TNFα and upregulated the activation markers CD154 and CD137 upon cognate antigen exposure. Cells were generated without bias for particular HLAs. These results suggest that peptide-based expansions may be a suitable platform to generate allogeneic adoptive T cell immunotherapies for patients with VP-MCC. Citation Format: Sarah Davies, John Barrett, Pawel J. Muranski, Isaac Brownell. Generating Merkel cell polyomavirus-specific T cells from healthy donors for adoptive immunotherapy [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2189.
Use of ICD-10 diagnosis codes to identify seropositive and seronegative rheumatoid arthritis when lab results are not available

Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) antibody tests are often measured at the time of rheumatoid arthritis (RA) diagnosis but may not be repeated and therefore not available in electronic health record (EHR) data; lab test results are unavailable in most administrative claims databases. ICD10 coding allows discrimination between rheumatoid factor positive (M05) (“seropositive”) and seronegative (M06) patients, but the validity of these codes has not been examined. Using the ACR’s Rheumatology Informatics System for Effectiveness (RISE) EHR-based registry and U.S. MarketScan data where some patients have lab test results, we assembled two cohorts. Seropositive RA was defined having a M05 diagnosis code on the second rheumatologist encounter, M06 similarly identified seronegative RA, and RF and anti-CCP lab test results were the gold standard. We calculated sensitivity (Se) and positive predicted value (PPV) of the M05/M06 diagnosis codes. We identified 43,581 eligible RA patients (RISE) and 1185 (MarketScan) with RF or anti-CCP lab test results available. Using M05 as the proxy for seropositive RA, sensitivity = 0.76, PPV = 0.82 in RISE, and Se = 0.73, PPV = 0.84 in MarketScan. Results for M06 as a proxy for seronegative RA were comparable in RISE, albeit somewhat lower in MarketScan. Over 3 consecutive visits, approximately 90% of RA patients were coded consistently using either M05 or M06 at each visit. Under ICD10, M05 and M06 diagnosis codes are reasonable proxies to identify seropositive and seronegative RA with high sensitivity and positive predictive values if lab test results are not available.
Mutual fund skill and the performance of corporate acquirers

Abstract We show that the commonly observed correlation between institutional investor ownership and the success of mergers is partly driven by active stock picking. Several mutual fund stock selection skill measures strongly predict the post-merger performance of corporate acquirers even after controlling for possible shareholder monitoring. These findings are stronger for funds with characteristics more indicative of active stock picking. Moreover, firms held by funds with higher stock selection skills are more likely to subsequently become acquirers, suggesting that the mutual fund skill set includes the ability to identify acquirers with value-enhancing acquisition opportunities.
The importance of groundwater in critical zone science

The critical zone (CZ)-from treetops to groundwater-is an increasingly studied part of the earth system, where scientists study interactions between water, air, rock, soil, and life. Groundwater is both a boundary and an essential store in this integrated system, but is often not well considered in part because of the difficulty in accessing it and its slow movement relative to other parts of the system. Here, we describe some fundamental areas where groundwater hydrology is of fundamental importance to CZ science, including sustaining streamflow and vegetation, reacting with minerals to produce dissolved solutes and regolith, and influencing energy fluxes across the land-atmosphere interface. As the timing and type of precipitation change with climate, groundwater may play an even more important role in CZ processes as a sustainable water source for plants and streamflow. Many open questions also exist about the role of CZ processes on groundwater. Many data streams are needed and important to quantifying the integrated response of the CZ to groundwater and vice versa, but long-term data records are often incomplete or discontinued due to limited funding. We argue that the long timescales of processes that involve groundwater necessitate data collection efforts beyond typical federal funding timespans. Sustaining monitoring networks and developing new ones aimed at testing hypotheses related to slow-moving, groundwater-controlled CZ processes should be a scientific priority, and here we outline some open questions that we hope will motivate groundwater scientists to get involved in CZ science.
Polydimethylsiloxane tissue-mimicking phantoms with tunable optical properties.

SIGNIFICANCE The polymer, polydimethylsiloxane (PDMS), has been increasingly used to make tissue simulating phantoms due to its excellent processability, durability, flexibility, and limited tunability of optical, mechanical, and thermal properties. We report on a robust technique to fabricate PDMS-based tissue-mimicking phantoms where the broad range of scattering and absorption properties are independently adjustable in the visible- to near-infrared wavelength range from 500 to 850 nm. We also report on an analysis method to concisely quantify the phantoms' broadband characteristics with four parameters. AIM We report on techniques to manufacture and characterize solid tissue-mimicking phantoms of PDMS polymers. Tunability of the absorption (μa ( λ ) ) and reduced scattering coefficient spectra (μs'(λ)) in the wavelength range of 500 to 850 nm is demonstrated by adjusting the concentrations of light absorbing carbon black powder (CBP) and light scattering titanium dioxide powder (TDP) added into the PDMS base material. APPROACH The μa ( λ ) and μs'(λ) of the phantoms were obtained through measurements with a broadband integrating sphere system and by applying an inverse adding doubling algorithm. Analyses of μa ( λ ) and μs'(λ) of the phantoms, by fitting them to linear and power law functions, respectively, demonstrate that independent control of μa ( λ ) and μs'(λ) is possible by systematically varying the concentrations of CBP and TDP. RESULTS Our technique quantifies the phantoms with four simple fitting parameters enabling a concise tabulation of their broadband optical properties as well as comparisons to the optical properties of biological tissues. We demonstrate that, to a limited extent, the scattering properties of our phantoms mimic those of human tissues of various types. A possible way to overcome this limitation is demonstrated with phantoms that incorporate polystyrene microbead scatterers. CONCLUSIONS Our manufacturing and analysis techniques may further promote the application of PDMS-based tissue-mimicking phantoms and may enable robust quality control and quality checks of the phantoms.
THE LIFE AND TIMES OF PETER BRIGGINS

This article draws attention to a little known and rarely used historical source, the diary of the early eighteenth-centmy London Friend Peter llriggins. Four areas ofllriggins' life are examined: his business, religious, family and leisure activities. It is suggested that the examination of sources such as diaries and personal correspondence can shed new light on the nature of seventeenth and early eighteenth-century Quakerism. In particular, such material can enable the development of a more subtle picture of the relationships that existed between Friends and the communities in which they lived.
A genetic screen to identify interactions between regulators of cell polarity and activation of ErbB2 in human mammary epithelial cells

Proc Amer Assoc Cancer Res, Volume 47, 2006 84 ErbB2 is amplified/overexpressed in about 30% of breast cancers and an antibody against ErbB2, Herceptin, is used to treat breast cancer clinically. We have previously shown that activation of ErbB2 induces transformation of MCF-10A, a human mammary epithelial cell line, when grown on three-dimensional cultures. However, activation of ErbB2 in MCF-10A cells was neither sufficient to induce anchorage-independent growth nor sufficient to induce migration/invasion suggesting that additional events are required for progression of ErbB2 overexpressing tumors. Epithelial cells lining ductal structures in vivo are characterized by asymmetric distribution of proteins along the apical-basal axis, a property referred to as apical-basal polarity. Investigations, in several model systems, have shed light on a class of genes referred to as regulators of epithelial cell polarity and the roles they play during development of cell polarity. It is well acknowledged that epithelial cells in carcinoma lack proper organization and hence a loss of proper cell polarity. Consistent with this notion, recent observations suggest that oncogenic events may cooperate with regulators of polarity to promote epithelial mesenchymal transitions in mouse mammary epithelial cells. In order to investigate whether regulators of cell polarity cooperate with ErbB2, we performed to a genetic screen to identify genes that cooperate with ErbB2 to promote anchorage-independent growth or migration or both. We created a library containing shRNAs against 24 human polarity genes and used it to screen for their ability to cooperate with ErbB2. Our initial results suggest that only a subset of the 24 genes analyzed cooperate with ErbB2 to promote migration and anchorage-independent growth. Further characterization will provide novel insights into genetic events that cooperate with ErbB2 to promote tumor progression.
Impact of a Pre-Course and Real-Time Dissection Demonstrations on Student Learning in Veterinary Gross Anatomy

Currently, no veterinary school in the US requires anatomy as a pre-requisite for admission into the professional program. As curricular changes devote less time to anatomy, instructors have begun ...
ALL SHALL BE WELL: FLOURISHING AND WELL-BEING IN POSITIVE PSYCHOLOGY AND FEMINIST NARRATIVE PASTORAL THEOLOGY

Positive psychology is a recently emergent sub-field within psychology that has grown very quickly. Until recently pastoral theologians have not engaged significantly with this sub-field. The concept of flourishing serves as a lens to explore the intersections and disconnection between positive psychology and a feminist narrative pastoral theology. Martin Seligman’s PERMA model of flourishing provides the framework for a brief review of some of the research in positive psychology. A pastoral theological reflection on each of these dimensions illuminates some of the similarities and differences between these two visions of flourishing. The article concludes with a consideration of the mutual contributions of each perspective to a more robust view of human flourishing.
Critical Comments on Brian Victoria's "Engaged Buddhism: Skeleton in the Closet?"

In "Engaged Buddhism: A Skeleton in the Closet?" (Vol. 2) Brian Daizen Victoria claims, among other things, that Tsunesaburo Makiguchi (1871-1944), founder of the Soka Kyoiku Gakkai (forebear of the Soka Gakkai and Soka Gakkai International), was an active supporter of the Japanese wars of aggression. In this response, Koichi Miyata argues that Victoria's claims rest on the highly selective use of quotes, and ignore key interpretative issues associated with Japanese imperial fascism and its underlying belief structures. Miyata discusses the significance of Makiguchi's arrest and imprisonment under a law specifically aimed at opponents of the war efforts, in his analysis of critical lapses in Victoria's article.
Vacuum ultraviolet radiation from neon implosions

Neon implosions are being studied in order to produce a plasma suitable for photopumping with 11-AA Na X line radiation. The coincidence in wavelength of the Na X 1s/sup 2/-1s2p /sup 1/P (11.0027 AA) transition and the Ne IX 1s/sup 2/-1s4p /sup 1/P (11.0003 AA) transition is being utilized in resonant photopumping experiments directed toward the development of a soft-X-ray laser. A neon gas-puff Z-pinch, driven by a 5-kJ capacitor bank discharge, is being used to determine experimentally the conditions required to produce a neon plasma with ions predominately in the Ne IX ground state. Theoretical calculations for Na/Ne photopumping have indicated that neon temperatures of 50-100 eV and ion densities of 5*10/sup 17/ cm/sup -3/ to 10/sup 19/ cm/sup -3/ are required. A fast Z-pinch model used in the design of this experiment predicts that implosions with mass loadings of 3-9 mu g/cm driven by currents of 120-240 kA should produce such a neon plasma. A 1-m grazing incidence spectrograph is being used to identify the radiation from various ionization states of neon in the pinch. Spatially resolved pinhole-camera images and time-resolved vacuum-diode measurements are used to characterize the pinch. Effects of varying the neon mass loading and the driving-current waveshape are being investigated. >