cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 19234: Revascularization Improves the Levels and Organization of the Desmin Cytoskeletal System in the Gastrocnemius of Patients With Peripheral Artery Disease

Introduction: Patients with peripheral artery disease (PAD) develop a myopathy in their ischemic limbs which is characterized by myofiber degeneration, mitochondrial dysfunction and impaired leg function. Degenerated myofibers have cytoskeletal abnormalities the best described of which is a disorganized accumulation of desmin filaments. The degree of disruption of the desmin system has been associated with altered myofiber morphology, decreased mitochondrial respiration, reduced calf muscle strength and decreased walking performance. Hypothesis: We hypothesized that the levels and organization of desmin in the myofibers of the gastrocnemius of PAD patients improve after revascularization and correlate with increases in mitochondrial respiration and calf muscle strength. Methods: Gastrocnemius biopsies were collected from 32 PAD patients, before and six months after revascularization. Accumulation and organization of desmin protein in myofibers were determined by quantitative fluorescence microscopy and desmin gene transcripts were quantified by rtPCR of RNA in biopsy homogenates. We evaluated the effects of revascularization on these parameters and their association with ischemic window (a measure of lower limb hemodynamic limitation), mitochondrial function determined by respirometry, and calf muscle strength. Results: Revascularization reduced the abnormal accumulation of disorganized desmin protein and gene transcripts in the PAD gastrocnemius. The ischemic window, myofiber morphology, mitochondrial respiration and calf muscle strength were significantly improved after revascularization. After revascularization, the decreased desmin expression was associated with a more structured appearance of the protein, suggesting a return to the normally filamentous structure. These changes in desmin correlated with improved mitochondrial function and increased calf muscle strength. Conclusions: Revascularization operations improve the levels and organization of the desmin filaments in the gastrocnemius of patients with PAD and these changes correlate with improved mitochondrial function and calf muscle strength.
Magnons in the Linear-Chain Antiferromagnet CsMn Cl 3 ·2 D 2 O

This paper reports the first neutron scattering measurements on spin waves in a linear-chain antiferromagnet. Measurements were made on CsMn${\mathrm{Cl}}_{3}$\ifmmode\cdot\else\textperiodcentered\fi{}2${\mathrm{D}}_{2}$O and clearly indicate a large directional anisotropy of the spin coupling. The dominant exchange occurs along chains extending in the $a$ direction, ${J}_{1}=\ensuremath{-}0.304\ifmmode\pm\else\textpm\fi{}0.003$ meV. The exchange parameters in the $b$ and $c$ directions were measured in the combinative form ${J}_{2}+{J}_{3}=\ensuremath{-}0.0021\ifmmode\pm\else\textpm\fi{}0.0004$ meV. Short-wavelength excitations along the chain direction persist even at $2{T}_{N}$.
Some Restrictions on the Smooth Immersion of Complete Surfaces in E3

Publisher Summary This chapter presents an the idea of Hawley in direction of conjecture that says if S be a complete, umbilic-free surface, C 2 immersed in E 3 , so that the sum of the absolute values of the principal curvatures is bounded away from zero. Then Gauss curvature K on S either changes sign or else vanishes identically. A theorem due to Hawley that says if S be a complete, antiminimal, 2-bounded surface, C 3 imbedded in E 3 with K ≤ 0, then S is a cylinder over an oval. The chapter presents the generalization of Hawley's theorem.
Field methods in the study of toxic cyanobacterial blooms: results and insights from Lake Erie research.

Sound field methodologies are an essential prerequisite in the development of a basic understanding of toxic cyanobacteria blooms. Sample collection, on–site processing, storage and transportation, and subsequent analysis and documentation are all critically dependent on a sound field program that allows the researcher to construct, with minimal uncertainty, linkages between bloom events and cyanotoxin production with the ecology of the studied system. Since 1999, we have collected samples in Lake Erie as part of the MELEE (Microbial Ecology of the Lake Erie Ecosystem) and MERHAB–LGL (Monitoring Event Responses for Harmful Algal Blooms in the Lower Great Lakes) research programs to develop appropriate tools and refine methods necessary to characterize the ecology of the reoccurring cyanobacterial blooms in the systems. Satellite imagery, large ship expeditions, classical and novel molecular tools have been combined to provide insight into both the cyanobacteria responsible for these events as well as into some of the environmental cues that may facilitate the formation of toxic blooms. This information, as well new directions in cyano–specific monitoring will be presented to highlight needs for field program monitoring and/or researching toxic freshwater cyanobacteria.
Aryabhata II and Sripati

Aryabhata II belongs to the tenth century, who wrote his astronomical text “Mahasiddhanta.” Aryabhata II’s contributions to Mathematics given in this chapter are his four lemmas on the “Kuttaka” ax + c = by , areas of rhombus, parallelogram, triangle, square, and isosceles trapezium, area and diagonals of a quadrilateral, length of arc and approximate area of a segment of a circle, volume of sphere, and value of π .
Aspirin-Exacerbated Respiratory Disease

Aspirin-Exacerbated Respiratory Disease About 7% of patients with asthma have mucosal swelling, nasal polyps, and worsening of asthma in response to aspirin and other COX-1 inhibitors. Symptoms may...
Patient preference for receiving information about long-term symptoms.

e21681Background: Maintaining quality of life with minimal symptoms is an important goal of cancer treatment. We surveyed patients undergoing cancer treatment about their preferences for informatio...
Workforce Analysis of Spine Surgeons Involved with Neurological and Orthopedic Surgery Residency Training.

Objective Spinal surgery is taught and practiced within 2 different surgical disciplines: neurological surgery and orthopedic surgery. We have provided a unified analysis of spine-focused faculty at U.S. residency programs. Methods A total of 278 Accreditation Council for Graduate Medical Education training programs were assessed to identify 923 full-time faculty members with a spinal surgery designation, defined by spine fellowship training or surgeon case volume >75% spine surgeries. Faculty were assessed with respect to parent discipline, years of fellowship training, academic rank, gender, and academic productivity (h-index). Results The spine-teaching workforce contains 55% orthopedic surgeons and 45% neurosurgeons with wide gender asymmetry overall and at all faculty ranks. Of the female spine surgeons, those with neurosurgical training (64.44%) nearly doubled the number with orthopedic training (35.56%). Academic productivity increased with academic rank similarly for both genders and subspecialties. Orthopedic spine surgeons had a greater mean fellowship number compared with the neurological spine surgeons. Fellowship time of completion (intraresidency/infolded vs. postresidency) did not significantly affect the h-indexes. Addition of fellowship conferred academic productivity benefit for orthopedic surgeons only. Conclusions Neurological and orthopedic spine surgery showed similar patterns for the spread of faculty across academic ranks and trends in academic productivity. Marked gender disparity was seen in both neurosurgical and orthopedic surgery, with fewer female spine surgeons seen at every academic rank. Orthopedic spine surgeons had a greater mean fellowship number than did their neurosurgical counterparts, and a lack of fellowship correlated with lower academic productivity in orthopedic, but not neurological, spine surgery.
SPECT brain imaging of the dopaminergic system in Parkinsonism using {sup 123}I and {sup 99m}Tc labeled agents

SPECTbrainimaging of the dopaminergic system using I 123 and Tc 99 m labeled agents, especially the simultaneous imaging of both pre- and postsynaptic neurons, promises to provide accurate diagnosis and differentiation of Parkinsonism. However, there are many degrading factors that affect the quality and quantitative accuracy of the SPECTimages. These degrading factors limit the potential clinical applications of brainSPECTimaging. In this work, we studied these degrading factors by developing and validating a Monte Carlo(MC) method that provides accurate SPECT simulation with detailed modeling of the photon interactions inside the collimatordetector system. To compensate for the partial volume effect (PVE) in the SPECTimages caused by finite spatial resolution, we developed a new PVE compensation method that takes into account the effects of nonlinearity in iterative reconstruction-based compensation for image degrading factors, including attenuation, scatter, and collimatordetector response. Compensation using the new method greatly improved the quantitative accuracy of brainSPECTimages. We have also developed model-based method that can accurately estimate the downscatter and crosstalk contamination in the I 123 imaging and the simultaneous I 123 ∕ Tc 99 m dual-isotope imaging. Based on the model-based method, two different approaches to model-based downscatter and crosstalk contamination compensation were proposed. Both methods are based on iterative reconstruction and include compensation for other imaging degrading factors. The model-based downscatter and crosstalk compensation method provided greatly improved accuracy of activity estimates with little effect on the precision. Finally, optimization of energy windows for simultaneous I 123 ∕ Tc 99 m acquisition was performed to find the energy windows with the best trade-off between minimizing the crosstalk and maximizing the detection efficiency for simultaneous acquisitions. In summary, comprehensive methods were developed and evaluated to compensate for image degrading factors in simultaneous dual-isotope brainSPECTimaging. Application of these methods in the imaging of the dopaminergic system has the potential to provide improved accuracy for diagnosis of Parkinsonism.
MODE: automated neural network model debugging via state differential analysis and input selection

Artificial intelligence models are becoming an integral part of modern computing systems. Just like software inevitably has bugs, models have bugs too, leading to poor classification/prediction accuracy. Unlike software bugs, model bugs cannot be easily fixed by directly modifying models. Existing solutions work by providing additional training inputs. However, they have limited effectiveness due to the lack of understanding of model misbehaviors and hence the incapability of selecting proper inputs. Inspired by software debugging, we propose a novel model debugging technique that works by first conducting model state differential analysis to identify the internal features of the model that are responsible for model bugs and then performing training input selection that is similar to program input selection in regression testing. Our evaluation results on 29 different models for 6 different applications show that our technique can fix model bugs effectively and efficiently without introducing new bugs. For simple applications (e.g., digit recognition), MODE improves the test accuracy from 75% to 93% on average whereas the state-of-the-art can only improve to 85% with 11 times more training time. For complex applications and models (e.g., object recognition), MODE is able to improve the accuracy from 75% to over 91% in minutes to a few hours, whereas state-of-the-art fails to fix the bug or even degrades the test accuracy.
On the Factors Controlling the Development of Shallow Convection in Eddy-Diffusivity/Mass-Flux Models

AbstractThis study addresses key aspects of shallow moist convection, as simulated by a multiplume eddy-diffusivity/mass-flux (EDMF) model. Two factors suggested in the literature to be essential f...
Mapping the U.S. Production Network: Identifying Hub Industries

Identifying key suppliers and buyers could help identify the cause of certain economic downturns.
IgE Glycosylation in Health and Disease.

IgE are absolutely required for initiation of allergy reactions, which affect over 20% of the world’s population. IgE are the least prevalent immunoglobulins in circulation with 12-h and 2-day half-lives in mouse and human serum, respectively, but an extended tissue half-life of 3-weeks bound to the surface of mast cells by the high affinity IgE receptor, FceRI (Gould and Sutton 2008). Although the importance of glycosylation to IgG biology is well established, less is known regarding the contribution of IgE glycosylation to allergic inflammation. IgE has seven and nine N-linked glycosylation sites distributed across human and murine constant chains, respectively. Here we discuss studies that have analyzed IgE glycosylation and its function, and how IgE glycosylation contributions to health and disease.
Being There Is Half the Battle: Group Inclusion, Constitution-Writing, and Democracy:

Using an original data set assessing the effect of the 195 new constitutions worldwide over the past 40 years on levels of democracy, this article argues that when popular participation and group i...
Partial Pressures and High-Temperature Thermodynamic Properties for the Germanium-Tellurium System

Our earlier optical density measurements over Ge-Te compositions are reanalyzed. Spectral characteristics of the GeTe(g) spectrum are determined from measurements with a 1 at.% Te sample near 1200 K. Beers law constants for GeTe(g) are established by requiring consistency between spectroscopic results for the dissociation of GeTe(g) into Ge(g) and Te2(g) and our description in terms of the partial pressure of Te2 and the partial optical density of GeTe over Ge saturated GeTe(c). Between 870 and 997 K the partial pressures over Ge saturated GeTe(c) are ln P(Te2,atm) = − 24,800/T + 17.600 and ln P(GeTe,atm) = − 23,900/T + 19.400. The latter pressure is about 2.5 times lower than our earlier result. Between 869 and 997 K the Gibbs energy of dissociation of GeTe(g) to Ge(g) and Te2(g) is $$\Delta {\text{G}}_{\text{D}}^{\rm o} = 281{,}254 - 53.59{\text{T}}$$ J/mol while the Gibbs energy of formation of Ge saturated GeTe(c) from Ge(c) and Te(l) is $$\Delta {\text{G}}_{\rm f}^{\rm o} = - \,44{,}994 + 26.978{\text{T}}$$ J/mol. The partial pressures along and within the three phase curve of GeTe(c) and along the three phase curve for Ge(c) are determined and discussed. Comparisons with other types of data are made.
Critical Experiment Programs at the Los Alamos National Laboratory in Support of the U.S. Department of Energy/National Nuclear Security Administration's Nuclear Criticality Safety Program

Much of the research performed at the Los Alamos Critical Experiments Facility (LACEF) today is in direct support of the U.S. Department of Energy (DOE)/National Nuclear Security Administration 's (NNSA's) Nuclear Criticality Safety Program (NCSP). A key component of this support includes performing high-priority critical and subcritical experiments and then analyzing and documenting those experiments as benchmarks for the International Criticality Safety Benchmark Evaluation Project (ICSBEP). The current complement of five operational critical assemblies is described, and an overview of LACEF support for the DOE/NNSA NCSP and the ICSBEP is presented.
Acquisition of oral microbiota is driven by environment, not host genetics.

The oral microbiota is acquired very early, but the factors shaping its acquisition are not well understood. Previous studies comparing monozygotic (MZ) and dizygotic (DZ) twins have suggested that host genetics plays a role. However, all twins share an equal portion of their parent’s genome, so this model is not informative for studying parent-to-child transmission. We used a novel study design that allowed us to directly examine the genetics of transmission by comparing the oral microbiota of biological versus adoptive mother-child dyads. No difference was observed in how closely oral bacterial community profiles matched for adoptive versus biological mother-child pairs, indicating little if any effect of host genetics on the fidelity of transmission. Both adopted and biologic children more closely resembled their own mother as compared to unrelated women, supporting the role of contact and environment. Mother-child strain similarity increased with the age of the child, ruling out early effects of host genetic influence that are lost over time. No effect on the fidelity of mother-child strain sharing from vaginal birth or breast feeding was seen. Analysis of extended families showed that fathers and mothers were equally similar to their children, and that cohabitating couples showed even greater strain similarity than mother-child pairs. These findings support the role of contact and shared environment, and age, but not genetics, as determinants of microbial transmission, and were consistent at both species and strain level resolutions, and across multiple oral habitats. In addition, analysis of individual species all showed similar results. The host is clearly active in shaping the composition of the oral microbiome, since only a few of the many bacterial species in the larger environment are capable of colonizing the human oral cavity. Our findings suggest that these host mechanisms are universally shared among humans, since no effect of genetic relatedness on fidelity of microbial transmission could be detected. Instead our findings point towards contact and shared environment being the driving factors of microbial transmission, with a unique combination of these factors ultimately shaping the highly personalized human oral microbiome.
Characterization of Yb-doped ZBLAN fiber as a platform for radiation-balanced lasers

Recent advances in power scaling of fiber lasers are hindered by the thermal issues, which deteriorate the beam quality. Anti-Stokes fluorescence cooling has been suggested as a viable method to balance the heat generated by the quantum defect and background absorption. Such radiation-balanced configurations rely on the availability of cooling-grade rare-earth-doped gain materials. Herein, we perform a series of tests on an ytterbium-doped ZrF4–BaF2–LaF3–AlF3–NaF (ZBLAN) optical fiber to extract its laser-cooling-related parameters and show that it is a viable laser-cooling medium for radiation balancing. In particular, a detailed laser-induced modulation spectrum test is performed to highlight the transition of this fiber to the cooling regime as a function of the pump laser wavelength. Numerical simulations support the feasibility of a radiation-balanced laser, but they highlight that practical radiation-balanced designs are more demanding on the fiber material properties, especially on the background absorption, than solid-state laser-cooling experiments.
American Political Architecture: Establishmentarianism, Toleration, Containment

The travails of Jeremiah Moore, a colonial Baptist preacher, set the stage for an exploration into political and religious disputes over the proper intersection and legitimacy of ecclesiastical and governmental regulations of religion in civil society. Establishmentarian justifications are analyzed, including those found in lectures of Puritan and Congregational ministers as well as the Cambridge Platform of Church Discipline and various Acts of Toleration. Warnings of British writers are entertained regarding the growing conflict between advocates of political toleration of religious diversity and proponents of religious liberty in the American colonies, especially as they affected the growing revolutionary blend of political dissidents and religious dissenters. Opinions are examined of founders of the American republic who struggled to identify any formal role of religion in its new Constitution. The chapter’s analysis reveals the path toward the logic underpinning American political architect with its disestablishmentarian preference for religious liberty over religious toleration.
Phase II study of lamivudine in p53 mutant metastatic colorectal cancer (mCRC).

149Background: Non-coding repeat RNAs in cancers are pervasive and “mimic” viruses with activation of pattern recognition receptors and the innate immune response. Many repeat RNAs replicate in can...
What Can We Learn from the Spanish Flu Pandemic of 1918-19 for COVID-19?

As the Spanish flu became more widespread and its dangers apparent, many cities sought to contain the virus by imposing restrictions on social and economic interactions.
Group Training for Psychiatric Residents: Support Group Facilitation and Supervision with Didactics.

Group psychotherapy merits dedicated training during psychiatry residency yet is challenging to implement given competing educational requirements. The authors implemented a voluntary support group training intervention for psychiatry residents consisting of a 6-h didactic series followed by at least 6 months of in vivo group facilitation and supervision. We hypothesized participation would improve residents’ self-reported skill and knowledge in group facilitation. Psychiatry residents (PGY I–IV) voluntarily participated in this novel intervention that included a didactic series followed by experiential group facilitation and supervision. To assess confidence and self-reported skill level in group facilitation, residents completed two brief self-report surveys: before the didactic series (pre-intervention) and after group facilitation for at least 6 months (post-intervention). Surveys included Likert scales and open-ended questions. Quantitative data were analyzed with descriptive statistics and open-ended qualitative data were analyzed using thematic analysis. Twenty-three residents attended 4 to 6 h of didactics between 2016 and 2018. Of these 23 residents, 12 facilitated groups and attended supervision for at least 6 months. Twenty residents responded to pre-intervention surveys and 14 responded to post-intervention surveys. After the intervention, respondents reported a significant increase in knowledge and skills in group facilitation of 88% (15/17) on Likert scale questions. This study implemented a novel educational intervention to train psychiatric residents in group dynamics and group facilitation. Participation increased residents’ self-reported knowledge and skills in group facilitation. Future directions include incorporating feedback about group curriculum, evaluating resident knowledge and skills using assessment measures, recruiting more group participants, and focusing on peer-to-peer mentoring.
It’s a Bad World for Animals: Activism and Sentimental Literature

For some writers, art is a form of advocacy. This chapter examines ways Katherine Applegate’s children’s novel The One and Only Ivan (2012) censures cruelty and models compassion for young readers. It also introduces discussion about sentimentalism in stories promoting welfare themes. Pathos-laden stories are occasionally the target of ridicule. Some distrust appeal to emotions in fiction. It is low-hanging fruit, a literary shortcut to more demanding, reason-based forms of argumentation. Richard Adams is aware of such charges and anticipates the critics’ complaints in his novel The Plague Dogs (1977). This chapter explores ways Adams responds to their concerns while building a compelling case against vivisection.
133 Outcomes of minimally invasive staging for clinical stage I ovarian clear cell carcinoma

Objectives Compare outcomes of open and minimally invasive staging (MIS) for patients with early stage ovarian clear cell carcinoma (OCCC). Methods Patients with clinical stage I OCCC, no history of another tumor and known mode of surgery, diagnosed between 2012–2015 were drawn from the National Cancer Database. Impact of MIS on overall survival (OS) of patients who at least one month of follow-up was assessed with the log-rank test. A Cox model was constructed to control for confounders. Results A total of 1402 patients were identified; 438 (31.2%) had MIS. Conversion rate was 11.6%. Laparotomy and MIS groups were comparable in terms of age, race, insurance, co-morbidities, chemotherapy administration, rate of capsule rupture and final pathologic stage distribution. Patients who had MIS had shorter hospital stay (median 2 vs 4 days, p Conclusions For patients with apparent early stage OCCC, open and MIS staging have similar oncologic outcomes.
Association Between State Medicaid Expansion and Emergency Access to Acute Care Hospitals in the United States.

Importance State decisions not to expand Medicaid under the Patient Protection and Affordable Care Act could reduce emergency access to acute care hospitals. Objective To determine the relationship between state Medicaid expansion and emergency access to acute care hospitals in the United States. Design, Setting, and Participants This cross-sectional study linked hospital-level data from the Centers for Medicare & Medicaid Services from 2007 to 2017 to US Census data for all 50 US states and the District of Columbia. Geospatial analyses and difference-in-differences regression models were used to compare temporal changes in the size of the population without 30-minute access to acute care hospitals between 32 states that expanded Medicaid with the population without access in 19 that did not, before and after expansion. Analyses focused on the total population and those with low incomes; secondary analyses examined emergency access to safety-net hospitals. Exposures State-level Medicaid expansion. Main Outcomes and Measures Population without emergency access to an acute care hospital, defined as living outside a 30-minute drive of any hospital. Results States that did not expand Medicaid experienced an increase in the population without access to hospitals overall (without expansion: 6.76% to 6.79% [0.03%]; vs with expansion: 5.65% to 5.35% [-0.30%]; difference-in-differences, 0.33%; 95% CI, 0.33%-0.34%; P < .001) and for low-income persons (without expansion: 7.43% to 7.39% [-0.04%]; vs with expansion: 6.25% to 6.15% [-0.10%]; difference-in-differences, 0.06%; 95% CI, 0.05%-0.07%; P < .001). If access changes in nonexpansion states were the same as expansion states, an estimated 421 000 more persons overall and 48 000 more low-income persons would have retained access. States that did not expand Medicaid experienced an increase in the population without access to safety-net hospitals overall (46.91% to 47.70% [0.79%] vs 33.94% to 33.07% [-0.87%]; difference-in-differences, 1.66%; 95% CI, 1.64%-1.66%; P < .001) and for low-income persons (45.28% to 46.14% [0.86%] vs 33.00% to 32.23% [-0.77%]; difference-in-differences, 1.63%; 95% CI, 1.63%-1.67%; P < .001). If access changes in nonexpansion states were the same as expansion states, an estimated 2 242 000 more persons overall and 364 000 more low-income persons would have retained access. Conclusions and Relevance States that did not expand Medicaid under the Patient Protection and Affordable Care Act were associated with worse emergency access to acute care hospitals compared with states that expanded Medicaid.
Gottfried Konecny: the ambassador of photogrammetry and remote sensing for 75 years

A 90th birthday would be a milestone celebration for any person, but exceptionally rare if the person is still active after 75 years of working and serving the photogrammetric and remote sensing co...
MaxCut quantum approximate optimization algorithm performance guarantees for p > 1

We obtain worst-case performance guarantees for $p=2$ and 3 QAOA for MaxCut on uniform 3-regular graphs. Previous work by Farhi et al. obtained a lower bound on the approximation ratio of 0.692 for $p=1$. We find a lower bound of 0.7559 for $p=2$, where worst-case graphs are those with no cycles $\ensuremath{\le}5$. This bound holds for any 3-regular graph evaluated at particular fixed parameters. We conjecture a hierarchy for all $p$, where worst-case graphs have with no cycles $\ensuremath{\le}2p+1$. Under this conjecture, the approximation ratio is at least 0.7924 for all 3-regular graphs and $p=3$. In addition, using an indistinguishable argument we find an upper bound on the worst-case approximation ratio for all $p$, which indicates classes of graphs for which there can be no quantum advantage for at least $pl6$.
A review of energy storage technologies for demand-side management in industrial facilities

Abstract Demand-side management (DSM) in industrial facilities provides an opportunity for substantial amounts of energy cost savings, since industrial facilities are the largest energy consuming sectors globally. In this work, energy storage (ES) technologies are critically reviewed and compared with industrial DSM in mind. ES technologies reviewed herein include lithium-ion battery energy storage (BES), sodium-sulfur BES, lead-acid BES, flow BES, supercapacitor ES, superconducting magnetic ES, thermal ES, flywheel ES, pumped hydro ES, and compressed air ES. The fundamentals of these energy storage technologies are reviewed in detail including recent developments, followed by case studies and extensive comparisons. These comparisons include, but are not limited to cost per cycle analyses, levelized cost of energy analyses, and comparisons between performance, transient, and cost characteristics. Some key properties analyzed include the rated power, power density, efficiency, lifetime, discharge time, capital costs, and O&M costs.
Heterogeneity of Hepatic Stellate Cells in Fibrogenesis of the Liver: Insights from Single-Cell Transcriptomic Analysis in Liver Injury

Background & Aims: Liver fibrosis is a pathological healing process resulting from hepatic stellate cell (HSC) activation and the generation of myofibroblasts from activated HSCs. The precise underlying mechanisms of liver fibrogenesis are still largely vague due to lack of understanding the functional heterogeneity of activated HSCs during liver injury. Approach and Results: In this study, to define the mechanism of HSC activation, we performed the transcriptomic analysis at single-cell resolution (scRNA-seq) on HSCs in mice treated with carbon tetrachloride (CCl4). By employing LRAT-Cre:Rosa26mT/mG mice, we were able to isolate an activated GFP-positive HSC lineage derived cell population by fluorescence-activated cell sorter (FACS). A total of 8 HSC subpopulations were identified based on an unsupervised analysis. Each HSC cluster displayed a unique transcriptomic profile, despite all clusters expressing common mouse HSC marker genes. We demonstrated that one of the HSC subpopulations expressed high levels of mitosis regulatory genes, velocity, and monocle analysis indicated that these HSCs are at transitioning and proliferating phases at the beginning of HSCs activation and will eventually give rise to several other HSC subtypes. We also demonstrated cell clusters representing HSC-derived mature myofibroblast populations that express myofibroblasts hallmark genes with unique contractile properties. Most importantly, we found a novel HSC cluster that is likely to be critical in liver regeneration, immune reaction, and vascular remodeling, in which the unique profiles of genes such as Rgs5, Angptl6, and Meg3 are highly expressed. Lastly, we demonstrated that the heterogeneity of HSCs in the injured mouse livers is closely similar to that of cirrhotic human livers. Conclusions: Collectively, our scRNA-seq data provided insight into the landscape of activated HSC populations and the dynamic transitional pathway from HSC to myofibroblasts in response to liver injury.
Multi-Element Stark Broadening for Diagnosing Electron Density in Hed Plasmas

The interpretation of spectral line shapes for plasma characterization is well established as a diagnostic technique for determining number density and electron temperature, essential parameters for predicting radiation dynamics, local thermodynamic equilibrium, and atomic kinetics in laboratory and astrophysical environments. Specifically, Stark broadening is often used to diagnose a plasma's electron density via a tracer element. Weare interested in testing whether Stark broadening models can predict the plasma density from multiple elements within the same plasma, and whether this is done self-consistently. In order to do so, we diagnose transmission spectra through ~0.4-um-thick Mg-NaF foil that is heated and backlit by the Z Pinch Dynamic Hohlraum (ZPDH) at Sandia's Z machine. This foil is tamped on the front and back by incremental amounts of CH, allowing for electron densities between 1x1021 and 1x1022 to be reached. The foil was heated such that He-like charge states were reached for all three elements, allowing for investigation of Stark broadening of those lines. The amount of broadening found from different elements, and different tamper thicknesses will be presented.
A Gravimetric Calibration Procedure for Modern Controls IRD-2 Infrared Water Vapor Diffusometer and Its Correlation with Results from ASTM Method E 96

A brief description of the operating principles of the infrared IRD-2 Water Vapor Diffusometer and a detailed description of the gravimetric calibration procedure for it is given. The calibration is achieved by absorbing and weighing the water transmitted by a film installed in the IRD-2 during a measured time interval. The procedure yielded four replicates near the 0.5 g/100 in. 2 , 24 h rate with 95 percent confidence limits of ′10 percent of the average rate. The data allowed calculation of the background relative humidity in the IRD-2 dry chamber and the increase in relative humidity per cycle. The background humidity varies with the transmission rate of the film being measured, the dry air flow rate, and the efficiency of drying, but relative humidities near 0.2 percent are indicated with flow rates near 2 ft 3 /h and transmission rates near 0.5 g/100 in. 2 , 24 h. The increase in humidity per cycle may vary slightly from instrument to instrument. The instrument used in this study exhibited 0.45, 1.04, and 2.84 percent, respectively, on ranges 5, 4, and 3. The round robin proved the calibration procedure was accurate and that the IRD-2 yields the same results as ASTM Method E 96 with improved precision.
Regional City and Network City: Portland and Seattle in the Twentieth Century

-E n conomic and social interactions in the United States have undergone a massive expansion of scale since the mid-nineteenth century. The change is apparent in the size and scope of business enterprise, government operations, and organized social movements. As Kenneth Boulding pointed out nearly forty years ago, the result has been an "organizational revolution." The relatively isolated and self-contained "island communities" described by Robert Wiebe have been encompassed by a web of national institutions, obligations, and interactions. One result has been the intensification of extra local ties and connections at the ex-
Overview of PARP Inhibitor Design and Optimization

Poly(ADP-ribose) polymerase-1 (PARP-1) is an abundant nuclear enzyme and the founding member of the PARP family of enzymes. Inhibition of PARP-1 has been the focus of drug discovery groups for over three decades in a wide range of therapeutic areas encompassing stroke, cardiac ischemia, inflammation, diabetes and most importantly cancer. Despite the great therapeutic potential for this target and over a decade of clinical studies, only recently have PARP inhibitors made headway in late stage clinical trials. After many tribulations, recent results from several PARP inhibitors in Phase II clinical trials for cancer therapy have reinvigorated the field. This chapter is structured to provide the readers with a brief summary of the rationale for PARP-1 as a therapeutic target for oncology and explain the genesis of the PARP inhibitor pharmacophore. In addition, this chapter will provide the optimization paradigms for each of the PARP inhibitors currently in clinical trials, analyzing some of the differentiating factors for the clinical compounds and a brief mention of the current clinical progress for each inhibitor.
Perifused Fat Cells EFFECT OF LIPOLYTIC AGENTS

Abstract In vitro methods currently utilized for the determination of lipolytic responses in adipose tissue have not allowed for the continuous monitoring of rapid successive changes in rates of lipolysis. The perifused fat cell system utilized in this investigation offers a simple, reproducible method by which minute-to-minute changes in the rate of lipolysis of isolated fat cells may be monitored. In this technique, isolated fat cells are placed in a plastic column and perifused with albumin-containing buffer in the absence and presence of various lipolytic agents. Using this technique, we have been able to observe alterations in the rates of glycerol release during the initiation of hormone-induced lipolysis. In addition, we have been able to observe the decline in glycerol release following the removal of the lipolytic hormone. In the perifused fat cell system, epinephrine, isoproterenol, and norepinephrine elicited a maximal lipolytic response at 10 µm, theophylline at 1 mm, and glucagon at 5 µm. In addition, N6, O2'-dibutyryl cyclic adenosine 3':5'-monophosphate (1 mm), adrenocorticotropic hormone (100 milliunits per ml), and thyroid stimulating hormone (75 milliunits per ml) effectively stimulated lipolysis in the perifused fat cell system, whereas cyclic adenosine 3':5'-monophosphate (1 mm) and serotonin (1 mm) were without effect. Unlike the incubated tissue method, growth hormone (20 µg per ml) was found to be a potent stimulator of lipolysis in this system. The combined administration of theophylline and epinephrine, both at submaximal concentrations, resulted in rates of glycerol release which were significantly greater than the sum of the rates observed during individual administration.
Determining Bonding Quality in Polymer Composites with a Millimeter Wave Sensor

Microwave nondestructive testing (NDT) techniques offer an alternative to other conventional NDT methods. Microwave/millimeter wave techniques (which roughly cover 0.3 to 300 GHz) are particularly useful for examination of dielectric composite materials because their low dielectric losses provide good depth of penetration of electromagnetic radiation in this band [1–4]. Conventional NDT techniques, such as high-frequency ultrasonic testing (UT), are associated with limitations, e.g., large variations in elastic properties of low-density composite materials, that make interpretation of complex UT signals difficult. Furthermore, the criticality of coupling a transducer to a sample surface limits the use of such techniques for on-line applications. High-frequency microwave (millimeter waves, 30–300 GHz) systems, when compared to their low-frequency counterparts, offer higher resolution and sensitivity to variations in dielectric properties of low-loss composites. Moreover, higher frequencies allow utilization of more compact systems, which are often important for practical applications.
Agroecosystems Analysis from the Grass Roots: A Multidimensional Experiential Learning Course

An intensive, experiential travel course in Agroecosystems Analysis was conducted in Iowa, Minnesota, and Nebraska during summers of 1998 and 1999. The intended student audience was advanced undergraduate and beginning graduate students. Pretravel readings and a week-long series of farm visits, which consisted of in-depth interviews with the farmers and their families, prepared student teams to analyze and evaluate the production, economic, environmental, and social sustainability of 10 farms. Students shared their analyses both orally and in written reports. Based on a multifaceted student evaluation process, we found that participants were highly motivated, strongly engaged with the course content and learning activities, and committed to learn from the interviews and group learning processes. They reported that this multidimensional learning experience was more valuable than other traditional courses at their home campuses. Faculty learned how to: (i) allow students the opportunity to assist in developing the learning environment and community; (ii) design an optimum travel schedule to permit adequate time for individual reflection and group process; (iii) deal with challenges in the small group setting; and (iv) design a useful multiphased learning evaluation process. Based on this experience, faculty in Iowa, Minnesota, and Nebraska are highly motivated to continue this course and expand the opportunities for experiential learning.
Resonant-phonon terahertz quantum cascade lasers at long wavelengths

We report a resonant-phonon terahertz quantum cascade laser at a wavelength of /spl lambda/ /spl ap/ 141 /spl mu/m (2.1 THz) that uses a low-loss, high-confinement metal-metal waveguide. Continuous wave operation is obtained up to 40 K.
Spinal muscular atrophy: Development and implementation of potential treatments

In neurodegenerative disorders, effective treatments are urgently needed, along with methods to determine whether treatment worked. In this review, we discuss the rapid progress in the understanding of recessive proximal spinal muscular atrophy and how this is leading to exciting potential treatments of the disease. Spinal muscular atrophy is caused by loss of the survival motor neuron 1 (SMN1) gene and reduced levels of SMN protein. The critical downstream targets of SMN deficiency that result in motor neuron loss are not known. However, increasing SMN levels has a marked impact in mouse models, and these therapeutics are rapidly moving toward clinical trials. Promising preclinical therapies, the varying degree of impact on the mouse models, and potential measures of treatment effect are reviewed. One key issue discussed is the variable outcome of increasing SMN at different stages of disease progression.
Overcurrent protection of pole top distribution transformers that have tank mounted lightning arresters

When protecting distribution transformers, most protection engineers in the utility industry have recognized the importance of placing arresters either on the transformer tank or under oil within the transformer tank. This method greatly reduces arrester lead length and the associated increase in discharge voltage thereby improving transformer failure rates. To obtain the shortest lead lengths possible, utilities have moved from arrester installations on the pole or cross arm to arresters mounted on the transformer tank. By moving the arrester on the tank (or under oil), the lead lengths are shortened as much as possible. Utility experience has proven that this method of arrester protection will decrease the number of transformer failures due to lightning. Another benefit of moving the arrester to the load side of the fuse is that the fuse can also protect the arrester.
New limit on time-reversal violation in beta decay

We report the results of an improved determination of the triple correlation DP{center_dot}(p{sub e}xp{sub v}) that can be used to limit possible time-reversal invariance in the beta decay of polarized neutrons and constrain extensions to the standard model. Our result is D=[-0.96{+-}1.89(stat){+-}1.01(sys)]x10{sup -4}. The corresponding phase between g{sub A} and g{sub V} is {phi}{sub AV}=180.013 deg. {+-}0.028 deg. (68% confidence level). This result represents the most sensitive measurement of D in nuclear {beta} decay.
Blepharospasm and autoimmune diseases

We studied two patients, one with systemic lupus erythematosus and the other with myasthenia gravis, both of whom had coexistent blepharospasm. The blepharospasm occurred during exacerbations of the autoimmune diseases and improved with immunosuppressive therapy. These cases illustrate the possible association of blepharospasm and autoimmune disorders.
Clinical and imaging response in neuroendocrine hepatic metastasis treated with Y-90 radioembolization

Purpose To evaluate both the clinical and imaging response of unresectable hepatic neuroendocrine metastasis after treatment with Y-90 microsphere radioembolization. Materials and Methods This is a single institution retrospective review of 26 patients with neuroendocrine hepatic metastasis treated with Y-90 microsphere radioembolization. Clinical symptoms, biochemical markers and imaging at regular intervals of 1, 3, 6, 12 and 18 months post-procedure were reviewed. The patient's clinical and imaging response were evaluated. Other medical and interventional therapies were recorded. The two largest hepatic lesions were measured and tumor response was determined by RECIST 1.1 criteria. Results There were equal numbers of males and females. The mean patient age was 60, with a range of 26 to 88. Primary neuroendocrine sites were the small bowel (10), pancreas (6), colon and rectum (4), other (4) and unknown (2). Six patients (23%) underwent prior open radiofrequency ablation therapy. Twenty-one patients (81%) also received transarterial chemoembolizations. Most patients (77%) had a single Y-90 treatment. All patients had been treated with octreotide. Partial response was seen in 11 patients (42%), stable disease in 13 patients (50%) and progressive disease in 2 patients (8%). Biochemical marker response was evenly split, half increasing and half decreasing after therapy. Symptomatic improvement was noted in 18 patients (69%). Both patients with progressive disease had symptomatic improvement. Conclusion It has been shown that Y-90 microsphere radioembolization is a safe and effective therapy for hepatic neuroendocrine metastasis. Our data shows that this therapy also improves clinical symptoms. While further evaluation is needed, radioembolization may be able to play a larger role in the management of clinical symptoms.
Thermal properties of rigid polymers. I: Measurement of thermal conductivity and questions concerning contact resistance

Several studies of the influence of contact resistance on the measurement of thermal conductivity of polystyrene using a steady-state device are presented. In each case it is seen that, although this influence can perhaps be minimized, it cannot be eliminated as an experimental complication. A novel technique is then described which does eliminate entirely contact resistance as a variable, and this technique is shown to yield an unequivocal value of thermal conductivity.
Rare-Earth Ions in the Alkali Halides. I. Emission Spectra of Sm 2+ -Vacancy Complex

Measurements have been made of the crystal-field splitting of the $^{7}F_{J}$ energy levels of the $4{f}^{6}$ configuration of the ${\mathrm{Sm}}^{2+}$ ion which is dissolved in a number of alkali-halide lattices. Crystal-field term assignments were made from the results of polarized-emission measurements. Observed crystal-field splittings are compared to those predicted from point-charge models. Contributions to the total crystal field are considered to include that due to the presence of a nearest-neighbor cation vacancy as well as that due to displacements, from normal lattice positions, of the nearest-neighbor halide ions and the ${\mathrm{Sm}}^{2+}$ ion. The splitting is shown to arise in part from a displacement of the ${\mathrm{Sm}}^{2+}$ and the cation vacancy toward each other. The extent of the validity of the use of a point-charge model for this case is discussed.
Quantitative relationships between DNA content and glycolysis or histones of diploid and tetraploid cells.

Abstract The ratio of DNA to the anaerobic glycolysis or the histones of diploid and tetraploid carcinomas and lymphomas was measured. These ratios were observed to be approximately constant for the histologically related cells. The DNA per cell and the ratio of DNA to glycolysis was not changed as a result of the following modifications of the tumor-host environment: (a) the sex of the tumor bearing animal, (b) temperature-stress induced modifications of the host, (c) the time that the tumor cells had grown in the host, and (d) changes of the mouse strain used for tumor cell growth. The ratios of DNA to glycolysis or histones were approx. 30 and 300% greater, respectively, for the carcinoma cells than for the lymphoma cells.