cssi/SciSciGPT-SciSciNet huggingface dataset:
Senescent stromal cell-induced divergence and therapeutic resistance in T cell acute lymphoblastic leukemia/lymphoma

// David M. Habiel 1 , Nicolas Krepostman 2 , Michael Lilly 2 , Karen Cavassani 3 , Ana Lucia Coelho 1 , Takehiko Shibata 2 , Kojo Elenitoba-Johnson 4 , Cory M. Hogaboam 1 1 Division of Pulmonary and Critical Care Medicine, Department of Medicine & Women’s Guild Lung Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA 2 Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109–2200, USA 3 SOCCI Cancer Institute, Urologic Oncology Research Program, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA 4 Department of Pathology and Laboratory medicine, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, 19104, USA Correspondence to: David M. Habiel, email: David.Habiel@cshs.org Keywords: T cell acute lymphoblastic leukemia, senescent fibroblasts, T cell lymphoblastic lymphoma, oncogenesis, cancer microenvironment Received: August 17, 2016 Accepted: October 13, 2016 Published: November 7, 2016 ABSTRACT T cell Acute Lymphoblastic Leukemia/Lymphoma (T-ALL/LBL) is a precursor T cell leukemia/lymphoma that represents approximately 15% of all childhood and 25% of adult acute lymphoblastic leukemia. Although a high cure rate is observed in children, therapy resistance is often observed in adults and mechanisms leading to this resistance remain elusive. Utilizing public gene expression datasets, a fibrotic signature was detected in T-LBL but not T-ALL biopsies. Further, using a T-ALL cell line, CCRF-CEM (CEM) cells, we show that CEM cells induce pulmonary remodeling in immunocompromised mice, suggesting potential interaction between these cells and lung fibroblasts. Co-culture studies suggested that fibroblasts-induced phenotypic and genotypic divergence in co-cultured CEM cells leading to diminished therapeutic responses in vitro . Senescent rather than proliferating stromal cells induced these effects in CEM cells, due, in part, to the enhanced production of oxidative radicals and exosomes containing miRNAs targeting BRCA1 and components of the Mismatch Repair pathway (MMR). Collectively, our studies demonstrate that there may be bidirectional interaction between leukemic cells and stroma, where leukemic cells induce stromal development in vivo and senescent stromal cells generates genomic alterations in the leukemic cells rendering them therapeutic resistant. Thus, targeting senescent stroma might prove beneficial in T-ALL/LBL patients.
Water sustainability of large cities in the United States from the perspectives of population increase, anthropogenic activities, and climate change

Balancing water demand and supply with depleting sources and increasing demand needs a multi-dimensional approach given the pace at which the world is urbanizing. This study selected the contiguous United States (CONUS), 42 specific cities and their river basins to determine: Which basins and cities are more susceptible to increased water shortage? Population, water use, hydrologic model and climate model data from CMIP5 were used. Representative Concentration Pathways scenarios: RCP2.6, RCP4.5, RCP6, and RCP8.5 represented different climate change conditions. Period 1 (1950–2004) showed that more areas are affected by monthly runoff and streamflow than annual averages. In some cases, significant decreasing trends in water availability were observed during the summer (June–July–August) and spring (March–April–May) seasons. The second period (2005–2049) indicated an annual increasing trend (more water available) with higher intensity for the RCP6 scenario. Summer and spring showed areas of decreasing trend (less water available) for RCP4.5 and RCP6. Period 3 (2050–2099) exhibited a decreasing trend for the RCP2.6 (Western and Central CONUS, Great Lakes, and FL), RCP4.5 (Southwest CONUS), RCP6 (Western United States), and Central CONUS (RCP8.5). The Mississippi River has a mixed sensitivity to future climate change. The Central Valley of California, Los Angeles, Phoenix, and Tucson can face further challenges as the Colorado River becomes depleted. Seawater desalination and inter-basin water transfer can be considered in future and present policies and structural developments. The West, Southeastern Coast, and FL may consider desalination, while the West and Central CONUS can use the Mississippi for inter-basin transfer.
MRgFUS for desmoid tumors within the thigh: early clinical experiences

Desmoid tumors are benign but locally aggressive non-malignant tumors derived from fibroblasts. Surgery, chemotherapy, and radiation therapy have been the mainstay of treatment, but recurrence is common and side effects can result in significant morbidity. In this case series, we highlight our experiences performing treatments in the thigh, including strategies for optimizing ablation size and safety. Since December 2014, 14 magnetic resonance-guided focused ultrasound (MRgFUS) treatments for desmoid tumors were performed at our institution in seven patients. Nine of these treatments were completed in three patients with large tumors within the posterior thigh. The first was a 7-year-old boy who had previously been treated with surgical resection, intra-operative radiation, along with courses of vinblastine/methotrexate and sorafenib. Pretreatment tumor volume was 770 cm3 with 75% non-enhancing volume following the initial treatment. The first treatment was complicated by a third-degree far-field skin burn. Enhanced safety measures were developed to protect the far-field skin. The patient had four subsequent treatments over 14 months, without complication, with non-perfused volume of 85% on current imaging. The second patient was a 21-year-old woman who had previously taken sulindac and celecoxib but had no other therapy. Pretreatment tumor volume was 740 cm3. The lateral decubitus position was used to minimize the amount of energy through the sciatic nerve. The first treatment resulted in a relatively low non-perfused volume of 30%. A follow-up treatment resulted in 75–80% ablation of the target. The third patient was a 14-year-old girl with no prior treatment. Pretreatment tumor volume was approximately 440 cm3. The sciatic nerve was encased by the anteromedial portion of the mass. A lateral decubitus position and enhanced safety measures were again used. The first treatment resulted in a relatively low non-perfused volume of 30%, likely related to low energies. The second treatment resulted in 70–80% ablation. MRgFUS is an effective treatment for desmoid tumors of the thigh with a favorable side effect profile, allowing for repeated treatments if necessary. Ablation size and safety can be improved with far-field coupling devices, careful patient positioning, and optimized sonication planning.
A Randomized-Controlled Trial of Social Norm Interventions to Increase Physical Activity

Physical activity confers numerous health benefits, yet few adults meet recommended physical activity guidelines. The impact of brief messages providing descriptive and injunctive social norm feedback on physical activity was tested in this conceptual pilot study. Young adults (N = 111) were randomly assigned to one of three conditions: descriptive norm feedback, descriptive-plus-injunctive norm feedback, or no social feedback (control condition). Participants used pedometers for eight weekdays and recorded their step counts each evening. The descriptive norm group received feedback about the average number of steps taken by group members the previous day. The descriptive-plus-injunctive norm group received feedback about the group average, as well as a sad face if the participant was below the average or a happy face if the participant was above the average. The control group received no feedback throughout the study. By days 7 and 8, the descriptive-plus-injunctive norm group reported significantly more steps relative to the control group, whereas the descriptive norm group showed a trend toward higher step counts relative to the control group. These effects did not differ for participants above versus below the group average at baseline. The combined use of descriptive and injunctive social norms increased physical activity over a short period. This simple feedback strategy has potential for achieving wide reach and dissemination on its own or combined with more comprehensive interventions. This initial evidence can guide larger trials of longer duration. The trial was registered with the ClinicalTrials.gov database (NCT02710201)
Plasmonic nanoantennas for advanced terahertz optoelectronics: (Invited paper)

High-power terahertz radiation sources and high-sensitivity terahertz detectors are highly in demand for various imaging, spectroscopy, and spectrometry applications. This presentation gives an overview of the evolution of plasmonic terahertz optoelectronic devices and their significant role in enhancing the performance of terahertz systems.
The size–luminosity relationship of quasar narrow-line regions

The presence of an active galactic nucleus (AGN) can strongly affect its host. Due to the copious radiative power of the nucleus, the effects of radiative feedback can be detected over the entire host galaxy and sometimes well into the intergalactic space. In this paper we model the observed size-luminosity relationship of the narrow-line regions (NLRs) of AGN. We model the NLR as a collection of clouds in pressure equilibrium with the ionizing radiation, with each cloud producing line emission calculated by Cloudy. The sizes of the NLRs of powerful quasars are reproduced without any free parameters, as long as they contain massive ($10^5 - 10^7 M_\odot$) ionization-bounded clouds. At lower AGN luminosities the observed sizes are larger than the model sizes, likely due to additional unmodeled sources of ionization (e.g., star formation). We find that the observed saturation of sizes at $\sim 10$ kpc which is observed at high AGN luminosities ($L_\text{ion} \simeq 10^{46}$ erg/s) is naturally explained by optically thick clouds absorbing the ionizing radiation and preventing illumination beyond a critical distance. Using our models in combination with observations of the [O III]/IR ratio and the [O III] size -- IR luminosity relationship, we calculate the covering factor of the obscuring torus (and therefore the type 2 fraction within the quasar population) to be $f=0.5$, though this is likely an upper bound. Finally, because the gas behind the ionization front is invisible in ionized gas transitions, emission-based NLR mass calculations underestimate the mass of the NLR and therefore of the energetics of ionized-gas winds.
Clinical Radiobiology and Physics

This chapter will discuss the fundamental concepts and factors important in radiation biology and physics as they apply to radiation therapy.
Aristotle’s Prototype Rule-Based Underlying Logic

This expository paper on Aristotle’s prototype underlying logic is intended for a broad audience that includes non-specialists. It requires as background a discussion of Aristotle’s demonstrative logic. Demonstrative logic or apodictics is the study of demonstration as opposed to persuasion. It is the subject of Aristotle’s two-volume Analytics, as its first sentence says. Many of Aristotle’s examples are geometrical. A typical geometrical demonstration requires a theorem that is to be demonstrated, known premises from which the theorem is to be deduced, and a deductive logic by which the steps of the deduction proceed. Every demonstration produces (or confirms) knowledge of (the truth of) its conclusion for every person who comprehends the demonstration. Aristotle presented a general truth-and-consequence theory of demonstration meant to apply to all demonstrations: a demonstration is an extended argumentation that begins with premises known to be truths and that involves a chain of reasoning showing by deductively evident steps that its conclusion is a consequence of its premises. In short, a demonstration is a deduction whose premises are known to be true. Aristotle’s general theory of demonstration required a prior general theory of deduction presented in the Prior Analytics. His general immediate-deduction-chaining theory of deduction was meant to apply to all deductions: any deduction that is not immediately evident is an extended argumentation that involves a chaining of immediately evident steps that shows its final conclusion to follow logically from its premises. His deductions, both direct and indirect, were rule-based and not tautology-based. The idea of tautology-based deduction, which dominated modern logic in the early years of the 1900s, is nowhere to be found in Analytics. Rule-based (or “natural”) deduction was rediscovered by modern logicians. To illustrate his general theory of deduction, Aristotle presented a prototype: an ingeniously simple and mathematically precise special case traditionally known as the categorical syllogistic. With reference only to propositions of the four so-called categorical forms, he painstakingly worked out exactly what those immediately evident deductive steps are and how they are chained to complete deductions. In his specialized prototype theory, Aristotle explained how to deduce from a given categorical premise set, no matter how large, any categorical conclusion implied by the given set. He did not extend this treatment to non-categorical deductions, thus setting a program for future logicians. The prototype, categorical syllogistic, was seen by Boole as a “first approximation” to a comprehensive logic. Today, however it appears more as the first of the dozens of logics already created and as the first exemplification of a family that continues to expand.
CALCULATION AND MEASUREMENT OF EXPOSURE BUILDUP FACTORS FOR X-RAY RADIOGRAPHY

An x-ray radiographic image is generated by both uncollided and scattered photons. The uncollided flux contribution to the image can be estimated straightforward using the attenuation coefficients of the materials used in the radiography. The scattered flux contribution however, is usually accounted for using Monte Carlo techniques or by solving the Boltzmann transport equation for photons [1]. Both of these approaches are computationally expensive and hence can not be incorporated in radiography simulation models for practical limitations.
Polysomnography in Children

Polysomnography is the gold standard test for the diagnosis of sleep-disordered breathing (SDB) in children. Pediatric polysomnography should be performed in a sleep laboratory equipped for children and staffed by qualified personnel following the American Thoracic Society (ATS) standards for testing. In 2007, the American Academy of Sleep Medicine (AASM) standardized scoring of sleep stages and definitions for sleep-disordered breathing events in children. Controversy remains regarding preoperative screening for SDB in normal children undergoing adenotonsillectomy (T&A). All children with risk factors for respiratory complications postoperatively should have a baseline polysomnogram before T&A. Children requiring positive airway pressure therapy must have a baseline and a titration polysomnogram to evaluate therapeutic effect. Alternative types of sleep studies with variable channels have not been fully validated in children.
Understanding the Pathogenesis of Streptococcus iniae Infection in Fish and Development of an Effective Vaccine for Use in Aquaculture

S. iniae infection has emerged as a serious fish health and economic problem in intensive U.S. aquaculture operations. Current antibiotic options are few and possess severe practical limitations and potential adverse environmental impacts. We believe the major factor contributing to the large burden of S. iniae disease in aquaculture is the lack of fundamental knowledge of S. iniae virulence factors and the fundamental pathogenesis of infection.
How to be Good at Sensing and Responding: The Roles of Three Types of IT Infrastructure

Business agility has been considered as one of the key organizational capabilities in the modern business environment. The current research indicates that information technologies (IT) can help firms develop agility and in turn agility can improve firm performance, but how IT leads to agility and superior performance and under what circumstances is an ongoing consideration. In particular, while current research has examined higher-order latent capacities of IT resources and capabilities, they haven’t clearly specified what IT factors can enable organizational agility and how. In this study, we investigate the distinct values of two key capabilities of agility, i.e., sensing and responding capabilities, under the different levels of market competition. We also identify three types of IT infrastructure and explore the underlying enabling processes between these three infrastructures and sensing and responding capabilities. The model test results using a large-scale field survey data indicate that responding capability becomes more important as the level of market competition increases. The results also reveal that knowledge infrastructure and data service infrastructure are the key enablers of sensing capability and that standard application infrastructure is the key enabler of responding capability. This study helps understand underlying mechanisms of IT-enabled agile processes within a firm.
Observational Data and Relationships

This chapter discusses extended sources. Extended sources are usually associated with bright elliptical galaxies or quasars. Compact sources are typically found in quasars and in the optically bright nuclei of peculiar galaxies often showing strong emission lines compact galaxies. Some compact sources are found in normal spirals and ellipticals. Compact radio sources are typically found in quasistellar objects and in the nuclei of more extended objects: peculiar galaxies such as Seyfert, N-type, compact or elliptical and spiral galaxies with nuclear emission. Some compact sources are found in otherwise normal spiral or elliptical galaxies. To accuracy of the optical position measurement, all those compact structures coincide with a galaxy nucleus or with a quasistellar object. The most compact sources exhibit considerable structure, often similar to, but on much smaller scale than, extended radio sources. The structure is wavelength dependent. Radio galaxies with tails are observed in clusters of galaxies. The sources exhibit double structure of radio tails; higher resolution observations reveal that the tails are made of discrete components increasing in size with increasing distance from the parent object.
A Face Centered Icosahedral Approximant Phase with Local Icosahedral Symmetry

An approximant phase in the Al-Cu-Ru system, isostructural with α—AIMnSi, is described and compared with the face-centered icosahedral phase. The existence of this phase confirms the notion that the structures of simple and face-centered icosahedral alloys are closely related, differing perhaps by the atomic decorations of the quasicrystalline lattice.
TCT-837 Transcatheter Aortic Valve Replacement Outcomes by Procedure Location: Catheterization Laboratory versus Operating Room

The impact of procedure location on clinical outcomes after transcatheter aortic valve replacement (TAVR) remains unclear. The objective of this study was to compare short-term outcomes in patients undergoing TAVR in either the catheterization laboratory (CATH) versus surgical operating room (OR).
The use of bevacizumab in pediatric retinal and choroidal disease: A review

The use of intravitreal bevacizumab in pediatric retinal and uveitic disease has become more widespread over the past decade. This article serves to outline the rationale underlying the use of intr...
Hijacking the ER Membrane: Lessons from Turnip mosaic virus.

Positive-strand (+)RNA viruses account for the majority of plant viruses. Apart from their significant impact on worldwide agriculture, they also inform our understanding of basic virus biology ([Scholthof et al., 2011][1]). Upon entry into the cells of their host, (+)RNA viruses induce drastic
On the medical loss ratio (MLR) and sticky selling general and administrative costs: Evidence from health insurers

Abstract The Patient Protection and Affordable Care Act of 2010 (ACA) imposed an important constraint on health insurers: if the medical loss ratio (MLR), determined as the ratio of claims paid to premiums collected, declined below certain legislative targets, the insurer would be obliged to rebate a portion of the premiums to the customer. It might be expected that this increase in the MLR would result in a decrease in premium dollars available to cover selling, general and administrative costs (SG&A) and a concomitant decrease in profits. However, there is earlier evidence that SG&A “cost stickiness” presents a counter-effect in this instance: namely, that an increase in SG&A costs per each dollar of revenue increase is more than the magnitude of a decrease in SG&A costs per each dollar of revenue decrease. In this context, this paper offers the first preliminary evidence of the impact of the MLR regulatory change on SG&A cost stickiness in the health insurance industry. Applying the Anderson et al. (2003) methodology, our sample of publicly-traded health insurers shows evidence of significant mitigation of the SG&A cost stickiness after the implementation of the ACA medical loss ratio rules and that in periods of revenue declines, SG&A costs decreased more significantly post-ACA than pre-ACA. These results further illustrate the tension created by regulatory policy designed to improve healthcare cost efficiency and its impact on the profit seeking activities of for-profit healthcare enterprises. Thus, this paper contributes to both healthcare and accounting literature by documenting a significant effect of regulatory policy on managerial decisions regarding cost control.
Potential Uses of Naltrexone in Emergency Department Patients With Opioid Use Disorder

Introduction: Despite widespread recognition of the opioid crisis, opioid overdose remains a common reason for Emergency Department (ED) utilization. Treatment for these patients after stabilization often involves the provision of information for outpatient treatment options. Ideally, an ED visit for overdose would present an opportunity to start treatment for opioid use disorder (OUD) immediately. Although widely recognized as effective, opioid agonist therapy with methadone and buprenorphine commonly referred to as "medication-assisted therapy" but more correctly as "medication for addiction treatment" (MAT), can be difficult to access even for motivated individuals due to shortages of prescribers and treatment programs. Moreover, opioid agonist therapy may not be appropriate for all patients, as many patients who present after overdose are not opioid dependent. More treatment options are required to successfully match patients with diverse needs to an optimal treatment plan in order to avoid relapse. Naltrexone, a long-acting opioid antagonist, available orally and as a monthly extended-release intramuscular injection, may represent another treatment option. Methods: We conducted a literature search of MEDLINE and PubMed. We aimed to capture references related to naltrexone and is use as MAT for OUD, as well as manuscripts that discussed naltrexone in comparison toother agents used for MAT, opioid detoxification, and naltrexone metabolism. Our initial search logic returned a total of 618 articles. Following individual evaluation for relevance, we selected 65 for in-depthreview. Manuscripts meeting criteria were examined for citations meriting further review, leading to the addition of 30 manuscripts Conclusions: Here, we review the pharmacology of naltrexone as it relates to OUD, its history of use, and highlight recent studies and new approaches for use of the drug as MAT including its potential initiation after ED visit for opioid overdose.
Significant Enhancements in a New Edition Make a Cell Biology Text Well Worth Considering

The thoroughly revised third edition of Pollard’s Cell Biology is a vastly improved edition in terms of its readability for students and up-to-date information complemented by outstanding illustrat...
Key Issues and Differences in Practical Components of Quality Management in Design-Build Highway Projects

AbstractAssuring quality management is essential for a project’s success for a specific price and within a specific time period. With an increasing number of highway projects being delivered by the...
Analysis of Microsatellites (SSRs) in Processed Olives as a Means of Cultivar Traceability and Authentication

Select cultivars of table olives have more desirable traits and a higher economic value. There are suspected issues with cultivar mislabeling and traceability in the supply chain. Here, we describe a method to identify cultivars by genotyping of processed olives. DNA was extracted from leaves and California-style olives of seven commonly packed cultivars. Processed olive fruits yielded relatively low DNA concentrations (0.04-0.86 μg/g), and extracts had more impurities compared with leaves. From 15 candidate SSRs, five markers showing the highest number of unique allele combinations and discriminatory power were selected. These SSRs were successfully amplified and analyzed in all cultivars of olives except one. When directly comparing any two cultivars, different allele combinations were typically present for at least four of the five SSRs. Microsatellite analysis shows potential as a simple yet robust diagnostic tool. The method can be expanded to include other cultivars, styles of table olives, and potentially other processed plant-based foods.
Root-knot nematodes

The quantity ofMeloidogyne hapla produced on plants depends on the amount of inoculum, the amount of plant present at the moment of root invasion, the plant family, genus, species and variety. Temperature is also a governing factor but this item was not tested in the present experiments. The effect of the nematodes on the host is likewise a complicated interaction.
Repeated Occurrences of Basal Cell Cancer in Patients With Inflammatory Bowel Disease Treated With Immunosuppressive Medications.

Introduction There are limited data on repeated basal cell cancer (BCC) occurrences among patients with inflammatory bowel disease (IBD), especially the impact of continuing immunosuppressive medications. Methods We conducted a retrospective cohort study of 54,919 patients with IBD followed in the Veterans Affairs Healthcare System. We identified patients who had an incident BCC after their IBD diagnosis. We defined patients' exposure based on their IBD medications use as follows: (i) only aminosalicylate (5-ASA) use, (ii) only active thiopurine (TP) use, (iii) past TP use (discontinued >6 months ago) and no antitumor necrosis factor (TNF) use, (iv) anti-TNF use after previous TP use, (v) only anti-TNF use, and (vi) active anti-TNF and TP use. The outcome of interest was the repeated occurrence of BCC. Adjusted and unadjusted hazard ratios with 95% confidence intervals were used to estimate the risk of repeated BCC occurrence. Results A total of 518 patients developed BCC after their IBD diagnosis. The numbers of repeated BCC occurrences per 100 person-years were 12.8 (5-ASA use only), 34.5 (active TP use), 19.3 (past TP use and no anti-TNF use), 25.4 (anti-TNF use after previous TP use), 17.8 (only anti-TNF use), and 22.4 (active anti-TNF and TP use). Compared with 5-ASA use alone, only active TP use was associated with an increased risk for repeated BCC occurrence (adjusted hazard ratio 1.65, 95% confidence interval 1.24-2.19; P = 0.0005). However, the increased risk was no longer present for other exposure categories. Discussion Among IBD patients who developed an incident BCC while taking a TP and continued it, there was an increased risk of repeated BCC occurrences.
State-dependent differences in the frequency of TMS-evoked potentials between resting and active states

Abstract Previous evidence suggests different cortical areas naturally oscillate at distinct frequencies, reflecting tuning properties of each region. The concurrent use of transcranial magnetic stimulation (TMS) and electroencephalography (EEG) has been used to perturb cortical regions, resulting in an observed post-stimulation response that is maximal at the natural frequency of that region. However, little is known about the spatial extent of TMS-induced activation differences in cortical regions when comparing resting state (passive) versus active task performance. Here, we employed TMS-EEG to directly perturb three cortical areas in the right hemisphere while measuring the resultant changes in maximal evoked frequency in healthy human subjects during a resting state (N=12) and during an active sensorimotor task (N=12). Our results revealed that the brain engages a higher dominant frequency mode when actively engaged in a task, such that the frequency evoked during a task is consistently higher across cortical regions, regardless of the region stimulated. These findings suggest that a distinct characteristic of active performance versus resting state is a higher state of natural cortical frequencies.
Time to definitive care among severely injured farmers compared to other work-related injuries in a Midwestern state

Farming is a high risk occupation that predisposes workers to injury, but may also lead to barriers in reaching trauma care. Little is known about emergency and trauma care for patients with farm-related injuries. The purpose of this study was to determine whether severely injured farmers presenting to a statewide trauma system faced delays in reaching definitive care compared to other severely injured workers. A population-based observational study was performed using the Iowa State Trauma Registry from 2005 to 2011. The registry was used to identify a multiply imputed sample of severe occupational injuries. Time to definitive care for farm- and non-farm-related injuries was compared using Kaplan-Meier curves and an extended, stratified Cox model censoring at 4 h. An interaction with time was included in the Cox model to generate hazard ratios for each hour after injury. Seven-hundred forty-eight severe occupational injuries were identified; 21% of these were farm-related. The overall median time to definitive care was nearly an hour longer for farmers compared to other workers (2h46m vs. 1h48m, p < 0.05). When adjusted for confounders, farm status remained a significant predictor of delay in reaching definitive care, but only in the first hour after injury (HR = 0.44, 95%CI = 0.24–0.83). Farm-related injuries accounted for more than 1 of every 5 severe occupational injuries entered into the Iowa trauma system. We found that severely injured farmers had delays in reaching definitive trauma care, even when adjusted for confounding variables such as rurality. This effect was most pronounced in the first hour.
Mechanical failure of fresh nuclear grade iron–chromium–aluminum (FeCrAl) cladding under simulated hot zero power reactivity initiated accident conditions

Abstract The reactivity initiated accident (RIA) is a postulated accident in light water reactors initiated by a rapid increase in reactivity which causes an increase in fission rate and fuel temperature. One potential mode of fuel system failure during RIA is pellet cladding mechanical interaction (PCMI) due to the rapid thermal expansion of the fuel pellet. Simulated PCMI experiments were performed by rapidly pressurizing iron-chromium-aluminum (FeCrAl) cladding tube samples using a hydraulic modified burst test system, causing the specimens to burst under a biaxial loading path. Deformation and rupture of the specimens were tracked with a telecentric lens and high-speed camera system. Outer surface strains were calculated using digital image correlation (DIC) on speckle patterns painted on the specimens’ outer surfaces. Experiments were conducted at approximately 275 °C, representative of hot zero power RIA conditions. The failure hoop strain was DIC-calculated between approximately 1.8–3.4%, corresponding to quasi-static energy depositions of approximately 110–260 calories per gram UO2 assuming initial pellet-cladding contact. These conditions are very similar to the proposed energy deposition limit of 150 calories per gram UO2 for unirradiated zirconium-based cladding in US Nuclear Regulatory Commission (NRC) Draft Regulatory Guide 1327. A very small strain rate dependence was observed in the data, with the magnitude of the failure hoop strain decreasing slightly with increasing strain rate. This observed dependence may be relevant because the FeCrAl cladding strain rate will be approximately 20% higher than in zirconium-based cladding due to the harder neutron spectrum and resultant shorter neutron generation time.
Screening of small molecule inhibitors of the Fanconi Anemia-BRCA pathway

4995 Fanconi anemia (FA) is a cancer-susceptibility syndrome characterized by hypersensitivity to DNA crosslinking agents, such as cisplatin and mitomycin C. All 9 known FA proteins cooperate with breast/ovarian cancer susceptibility gene products (BRCA1 and BRCA2) in a common DNA damage-activated signaling pathway called the Fanconi anemia(FA)-BRCA pathway. Seven FA proteins (FANCA, FANCB, FANCC, FANCE, FANCF, FANCG and FANCL) are components of a multi-subunit ubiquitin ligase complex (FA complex) required for monoubiquitination of FANCD2. After DNA damage, FANCD2 is monoubiquitinated and targeted to BRCA1/BRCA2-containing nuclear foci in an ATR kinase-dependent fashion. Importantly, the pathway is inactivated in a wide variety of human cancers by methylation of the FANCF gene. This inactivation causes cisplatin sensitivity in some ovarian cancer cell lines, suggesting an important role of the pathway in cisplatin sensitivity of human tumors. We hypothesized that inhibitors of the FA-BRCA pathway will sensitize cancer cells to cisplatin and, therefore, may be useful for the treatment of cisplatin-resistant cancer. We developed a high-throughput small molecule screen using cells harboring a Green Fluorescent Protein tagged FANCD2 (GFP-FANCD2) and assaying for GFP-FANCD2 nuclear foci formation as a readout, because FANCD2 foci formation is a surrogate marker of the integrity of the pathway. We plated cells with GFP-FANCD2 onto 384-well plates, added small molecules, gamma-irradiated the cells and scored the GFP-FANCD2 nuclear foci. Wells lacking GFP-FANCD2 nuclear foci were scored as positive. We have screened more than 5000 chemicals so far, and found 30 positive chemicals, including kinase inhibitors (wortmannin, H-9, alsterpaullone), geldanamycin, and curcumin. We also found that wortmannin, H-9, and alsterpaullone inhibit ATR-dependent phosphorylation of Chk1. These results together with our previous finding that ATR is required for the activation of the pathway suggest that these drugs inhibit the pathway through inhibition of ATR. Furthermore, we confirmed that alsterpaullone sensitized an ovarian cancer cell line in an FA-BRCA pathway-dependent manner. These findings support the rationale for further screening for FA-BRCA pathway inhibitors.
Survival of Escherichia coli after isoelectric solubilization and precipitation of fish protein.

Protein recovery for fish processing by-products utilizes extreme pH shifts for isoelectric solubilization and precipitation. The purpose of this study was to determine if Escherichia coli would survive exposure to the extreme pH shifts during the protein recovery process. Fresh rainbow trout were beheaded, gutted, and minced and then inoculated with approximately 109 CFU of E. coli ATCC 25922 per g, homogenized, and brought to the target pH of 2.0, 3.0, 11.5, or 12.5 by the addition of concentrated hydrochloric acid or sodium hydroxide to solubilize muscle proteins. The homogenate was blended and centrifuged to separate the lipid and insoluble components (bones, skin, insoluble protein, etc.) from the protein solution. The protein solution was subjected to a second pH shift (pH 5.5) resulting in protein precipitation that was recovered with centrifugation. Microbial analysis was conducted on each fraction (i.e., lipid, insoluble components, protein, and water) with selective and nonselective media. The s...
h α : An index to quantify an individual’s scientific leadership

The $$\alpha$$ person is the dominant person in a group. We define the $$\alpha$$ -author of a paper as the author of the paper with the highest h-index among all the coauthors, and an $$\alpha$$ -paper of a scientist as a paper authored or coauthored by the scientist where he/she is the $$\alpha$$ -author. For most but not all papers in the literature there is only one $$\alpha$$ -author. We define the $$h_\alpha$$ index of a scientist as the number of papers in the h-core of the scientist (i.e. the set of papers that contribute to the h-index of the scientist) where this scientist is the $$\alpha$$ -author. We also define the $$h'_\alpha$$ index of a scientist as the number of $$\alpha$$ -papers of this scientist that have $$\ge$$ $$h'_\alpha$$ citations. $$h_\alpha$$ and $$h'_\alpha$$ contain similar information, while $$h'_\alpha$$ is conceptually more appealing it is harder to obtain from existing databases, hence of less current practical interest. We propose that the $$h_\alpha$$ and/or $$h'_\alpha$$ indices, or other variants discussed in the paper, are useful complements to the h-index of a scientist to quantify his/her scientific achievement, that rectify an inherent drawback of the h-index, its inability to distinguish between authors with different coauthorships patterns. A high h index in conjunction with a high $$h_\alpha /h$$ ratio is a hallmark of scientific leadership.
Vom »Negersklaven« zum »Sklaven des Kapitals«: Der Topos des schwarzen Amerikaners in der Weimarer Linken

This article explores the debate on »black Americans« among Leftists in the Weimar Republic in the framework of their broader anti-imperialist critique of capitalist modernity. Starting with parallels in the iconographical representation of America in works by Arntz and Heartfield, the article reconstructs this debate through an analysis of the Arbeiter Illustrierte Zeitung, of articles from Pfemfert’s Aktion, and contemporary travelogues and essayistic writings on America. It also shows the importance of Upton Sinclair’s novels for this variety of Americanism. The article shows that the social and political reality of African Americans as well as of Africans in the colonies here becomes an essential part of the codification of blackness. At the same time, the political instrumentalization of racial stereotypes not only in America, but also in the German nationalist »Schwarze Schmach«-Propaganda becomes subject of a political critique. However, the discourse partly displays the same stereotypes which it criticizes when used bynationalists.
Aus der Anfangszeit der Weltmodelle Erinnerungen eines Außenseiters

Der Untertitel meines Beitrags, „Erinnerungen eines Ausenseiters“, weist darauf hin, das ich jene Anfangszeit der Weltmodelle nicht als Fachmann fur Computermodelle und deren Konstruktion erlebte, sondern nur als eine Art von - allerdings sehr interessiertem - Zaungast. Durch irgendwelche Zufalligkeiten in den Strudel der damaligen weltweiten Diskussion um „Limits to Growth“und dann noch der - allerdings schon wesentlich weniger lebhaften - Diskussion um die ersten Nachfolgemodelle geraten, nahm ich an mehreren einschlagigen Tagungen teil, vor allem an jenen des Club of Rome in Philadelphia 1976 und in Berlin 1979, an der Tagung von IIASA (International Institute of Applied Systems Analysis) in Wien-Laxenburg 1978 und an einem mehrwochigen Seminar von Sozialwissenschaftlern und Industriemanagern am Franklin Institute in Philadelphia 1976.
Some Applications of MicroChannel Plates to Electronic Imaging Devices

Publisher Summary This chapter presents some applications of microchannel plates to electronic imaging devices. Microchannel plates have great potential as amplification stages in electronic imaging devices. They combine electron gains of up to 10 7 , resolution limited only by the available channel spacing and a very compact size. The use of a microchannel intensifier stage allows greater flexibility in the application of these devices, as the photon gain at the phosphor output is increased to the point that lens coupling, rather than fiber optic or thin membrane coupling, can be used. The devices can then be used with direct visual observation of the output, as well as with film recording or television readout. The gain of the microchannel stage with subsequent acceleration of the output electrons onto the phosphor screen results in up to lo6 photons per initial photoelectron. It is found that, provided a sufficiently strong electric field is used to pull the emitted photoelectrons through the mesh into the image section of the device, an effective quantum yield of about 40% of an equivalent opaque photocathode is obtained. The extreme ultraviolet microchannel intensifiers are also elaborated.
Terminal Riboadenylate Transferase: a Poly A Polymerase in Purified Vaccinia Virus

Purified vaccinia virus treated with Triton X-100 catalyzes the incorporation of ATP into an acid-insoluble product. The enzymatic activity responsible for the ATP polymerization is demonstrated to be different from vaccinia RNA polymerase in its preferential use of ATP as substrate and on the basis of heat stability, pH optima, and metal ion requirement. The ATP polymerization reaction is stimulated 10-fold by the addition of rA(pA)(5.) In accordance with our earlier terminology, we call this Mn(2+)-dependent enzyme terminal riboadenylate transferase to distinguish it from Mg(2+)-dependent poly A polymerase.
Measurement of the bond strength between VWF A1 domain and clustered platelet glycoprotein Ib-IX using optical tweezers

Adhesion between the A1 domain of the plasma protein von Willebrand factor (VWF) and the platelet glycoprotein (GP) Ib-IX complex is the first stage in thrombus formation and ultimately leads to firm platelet adhesion. Studies have suggested that GP Ib-IX receptor clustering may modulate platelet adhesion and signaling. Therefore, we have investigated the importance of GP Ib-IX clustering in the bond strength between Al and GP Ib-IX. After immobilizing A1 on polystyrene beads, we optically trapped the bead using a laser tuned to 830 nm. The bead was then allowed to adhere for 10 seconds to a transfected Chinese hamster ovary cell which expressed GP Ib-IX receptors that could be conditionally clustered with a small molecule dimerizer. We obtained the force to detach A1 from GP Ib-IX by determining the minimum laser power required to separate the bead from the cell. When pulling the bound bead away from the cell, we found that the lowest strength between GP Ib-IX and A1 effectively doubled when the dimerizer was added. These results indicate that GP Ib-IX clustering can increase the bond strength between the receptor and its cognate ligand, suggesting a role for receptor clustering in thrombus formation.
Psychological Influences on Neuroendocrine and Immune Outcomes

1 Overview of the Immune System 2 Effects of Health Behaviors on Immune Outcomes 3 Stress, Depression, and Inflammation 4 Stress and Wound Healing 5 Stress and Infectious Agents 6 Summary Keywords: stress; depression; inflammation; vaccine; vaccination; antibody response; inflammatory response; intervention; stress reduction; wound healing; latent virus; Epstein-Barr Virus; cytomegalovirus; upper respiratory infection; psychosocial factors; psychoneuroimmunology; cytokines; infectious illness
What's 'Normal': Female Genital Mutilation, Psychology, and Body Image

Despite international efforts to halt the practice of female genital mutilation (FGM), the number of African girls and women undergoing the procedure is not declining as rapidly as international observers had hoped when the World Health Organization began focusing attention on the practice in the 1960s. This article focuses on the psychological effects of FGM through the example of a patient who had undergone the procedure in childhood and now felt that her closed appearance was "normal" and that to be opened would be "abnormal." Western advocates must educate themselves about the various cultural forces that lead to FGM in order to help women who have undergone the procedure heal psychologically, thereby breaking the pattern of abuse from generation to generation.
Adaptive model trust region methods for generalized eigenvalue problems

Computing a few eigenpairs of large-scale matrices is a significant problem in science and engineering applications and a very active area of research. In this paper, two methods that compute extreme eigenpairs of positive-definite matrix pencils are combined into a hybrid scheme that inherits the advantages of both constituents. The hybrid algorithm is developed and analyzed in the framework of model-based methods for trace minimization.
Signaling of High Mobility Group Box 1 (HMGB1) through Toll-like Receptor 4 in Macrophages Requires CD14

High mobility group box 1 (HMGB1) is a DNA-binding protein that possesses cytokinelike, proinflammatory properties when released extracellularly in the C23–C45 disulfide form. HMGB1 also plays a key role as a mediator of acute and chronic inflammation in models of sterile injury. Although HMGB1 interacts with multiple pattern recognition receptors (PRRs), many of its effects in injury models occur through an interaction with toll-like receptor 4 (TLR4). HMGB1 interacts directly with the TLR4/myeloid differentiation protein 2 (MD2) complex, although the nature of this interaction remains unclear. We demonstrate that optimal HMGB1-dependent TLR4 activation in vitro requires the coreceptor CD14. TLR4 and MD2 are recruited into CD14-containing lipid rafts of RAW264.7 macrophages after stimulation with HMGB1, and TLR4 interacts closely with the lipid raft protein GM1. Furthermore, we show that HMGB1 stimulates tumor necrosis factor (TNF)-α release in WT but not in TLR4−/−, CD14−/−, TIR domain-containing adapter-inducing interferon-β (TRIF)−/− or myeloid differentiation primary response protein 88 (MyD88)−/− macrophages. HMGB1 induces the release of monocyte chemotactic protein 1 (MCP-1), interferon gamma-induced protein 10 (IP-10) and macrophage inflammatory protein 1α (MIP-1α) in a TLR4- and CD14-dependent manner. Thus, efficient recognition of HMGB1 by the TLR4/MD2 complex requires CD14.
Derivation of the fast pole-zero (ARMA) recursive least squares algorithm using geometric projections

The Fast Pole-Zero (ARMA) Recursive Least Squares Algorithm is derived using geometric projections. The new algorithm has a reduced number of computations compared to the pole-zero fast Kalman algorithm. In particular, four vector inner products and scalar-times-vector operations are eliminated. This is particularly important in multiprocessor implementations of the algorithm. The geometric approach provides insight and useful interpretations of the various filters and residuals that form the algorithm. Simulations verifying the performance of the algorithm are presented where the poles and zeroes of an IIR filter are estimated.