cssi/SciSciGPT-SciSciNet huggingface dataset:
Families With Children With Medical Complexity and Self-Management of Care: A Systematic Review of the Literature

This review analyzes the quantitative literature on children with medical complexity (CMC). Using the Pediatric Self-Management Model, evidence is summarized into facilitators and barriers to self-management. Current quantitative research focuses on the caregiver burden in families with CMC. A model for social work with families with CMC was introduced in response to these findings. A re-envisioned model allows the child with medical complexity to be seen as whole rather than focusing on typically deficit-based areas of medical specialty or service provision.
Cloning and expression of IspDF from Mesorhizobium loti. Characterization of a bifunctional protein that catalyzes non-consecutive steps in the methylerythritol phosphate pathway.

Abstract Gram-negative bacteria, plant chloroplasts, green algae and some Gram-positive bacteria utilize the 2-C-methyl- d -erythritol phosphate (MEP) pathway for the biosynthesis of isoprenoids. IspD, ispE, and ispF encode the enzymes required to convert MEP to 2-C-methyl- d -erythritol 2,4-cyclodiphosphate (cMEDP) during the biosynthesis of isopentenyl diphosphate and dimethylallyl diphosphate in the MEP pathway. Upon analysis of the Mesorhizobium loti genome, ORF mll0395 showed homology to both ispD and ispF and appeared to encode a fusion protein. M. loti ispE was located elsewhere on the chromosome. Purified recombinant IspDF protein was mostly a homodimer, MW ∼46 kDa/subunit. Incubation of IspDF with MEP, CTP, and ATP gave 4-diphosphocytidyl-2-C-methyl- d -erythritol (CDP-ME) as the only product. When Escherichia coli IspE protein was added to the incubation mixture, cMEDP was formed. In addition, M. loti ORF mll0395 complements lethal disruptions in both ispD and ispF in Salmonella typhimurium. These results indicate that IspDF is a bifunctional protein, which catalyzes the first and third steps in the conversion of MEP to cMEDP.
A Nonlinear Total Variation-Based Denoising Method With Two Regularization Parameters

The aim of the present paper is to study the effect of the regularization parameter used in the numerical implementation of the Rudin-Osher-Fatemi denoising model. By using two different regularization parameters in the numerical scheme of the Rudin-Osher-Fatemi model, we will show experimentally that when a particular relationship between the sizes of these parameters holds, the quality of the denoised image and the speed of convergence of the numerical scheme are both much improved in comparison with the classic numerical scheme of the Rudin-Osher-Fatemi model where only one regularization parameter is used.
Transcription Factor FoxO1 Is Essential for Enamel Biomineralization

The Transforming growth factor β (Tgf-β) pathway, by signaling via the activation of Smad transcription factors, induces the expression of many diverse downstream target genes thereby regulating a vast array of cellular events essential for proper development and homeostasis. In order for a specific cell type to properly interpret the Tgf-β signal and elicit a specific cellular response, cell-specific transcriptional co-factors often cooperate with the Smads to activate a discrete set of genes in the appropriate temporal and spatial manner. Here, via a conditional knockout approach, we show that mice mutant for Forkhead Box O transcription factor FoxO1 exhibit an enamel hypomaturation defect which phenocopies that of the Smad3 mutant mice. Furthermore, we determined that both the FoxO1 and Smad3 mutant teeth exhibit changes in the expression of similar cohort of genes encoding enamel matrix proteins required for proper enamel development. These data raise the possibility that FoxO1 and Smad3 act in concert to regulate a common repertoire of genes necessary for complete enamel maturation. This study is the first to define an essential role for the FoxO family of transcription factors in tooth development and provides a new molecular entry point which will allow researchers to delineate novel genetic pathways regulating the process of biomineralization which may also have significance for studies of human tooth diseases such as amelogenesis imperfecta.
Structure, Behavior, and Voter Turnout in the United States

Electoral participation in the United States is examined to provide a clearer account of the effect of the registration requirement on individual voting behavior. Pooling NES data from 1980, 1984, and 1988, I first model, with traditional and selection bias techniques, the full electorate to distinguish among three groups: nonregistrants, registered nonvoters, and voters. Analyses limited to recent movers then reported to understand more fully the forces associated with the actual decision calculi of registering and voting. The influences of many factors commonly accepted as important determinants of voting are disentangled, and their effect at each stage is ascertained. Factors yielding inconsistent effects in previ research or believed to be unimportant—such as race, gender, attitudes toward the candidates, and trust government—are shown to deserve closer scrutiny by electoral scholars.
Primary cutaneous sarcomas showing rhabdomyoblastic differentiation

Rhabdomyosarcoma is a rare soft tissue neoplasm most commonly encountered in childhood and adolescence which has a predilection for the head and neck area, the genito-urinary tract and the extremities. Primary cutaneous presentation is extremely unusual and has been rarely reported in the literature. Herein, we describe two cases of rhabdomyosarcoma arising in the dermis of a 9-year-old girl and an 86-year-old man. Clinically, the tumours presented as solitary plaque-like or nodular lesions confined to the skin of the nose and chest wall, respectively. Histologically, the tumour in the first patient corresponded to an embryonal rhabdomyosarcoma. The tumour recurred locally four times, and in the last recurrence, showed features resembling those of malignant ‘triton’ tumour with fascicles of S-100 protein-positive spindle cells admixed with the rhabdomyoblastic components. The tumour in the second patient corresponded to the solid variant of alveolar rhabdomyosarcoma. Immunohisto-chemical studies in both tumours showed positive labelling for muscle-specific actin, desmin and vimentin. Ultrastructural examination in one case showed clusters of intermediate filaments in the cytoplasm recapitulating abortive sarcomeric structures consistent with rhabdomyoblastic differentiation. Both patients developed repeated recurrences over a period of 2–4 years despite adequate surgical excision, and the second patient had an axillary lymph node metastasis. Primary cutaneous rhabdomyosarcoma should be considered in the evaluation of small ‘blue cell’ tumours or undifferentiated malignant neoplasms of the skin, and appropriate immunohistochemical studies in conjuction with electron microscopy should be employed for proper evaluation of such lesions.
Functional Clustering Algorithm for High-Dimensional Proteomics Data

Clustering proteomics data is a challenging problem for any traditional clustering algorithm. Usually, the number of samples is largely smaller than the number of protein peaks. The use of a clustering algorithm which does not take into consideration the number of features of variables (here the number of peaks) is needed. An innovative hierarchical clustering algorithm may be a good approach. We propose here a new dissimilarity measure for the hierarchical clustering combined with a functional data analysis. We present a specific application of functional data analysis (FDA) to a high-throughput proteomics study. The high performance of the proposed algorithm is compared to two popular dissimilarity measures in the clustering of normal and human T-cell leukemia virus type 1 (HTLV-1)-infected patients samples.
Utilizing the TEOST MHT® to Evaluate Fundamental Oxidation Processes in Low-Phosphorus Engine Oils

The thermo-oxidation engine oil simulation test (TEOST)® MHT protocol was used to generate information on deposits and the formation of polar volatile organic compounds. Fourier transform IR (FTIR) spectroscopy was then used to analyze the level of oxidation in recovered TEOST® used oil as well as in the collected volatiles. Data was generated comparing different antioxidant systems in molybdenum-containing and molybdenum-free low-phosphorus engine oil formulations. The results show a surprising difference in deposits, volatiles, and carbonyl oxidation based on the presence or absence of molybdenum and also based on the type of antioxidant system selected. The amount of volatiles produced in the TEOST® is related to well-established oxidation mechanisms and also explains specific oxidation processes sometimes seen in Sequence III engines. A mathematical definition of antioxidant effectiveness or “robustness” is proposed that combines TEOST® deposits and volatiles measurements with FTIR carbonyl oxidation ...
Fund-Raising and the Articulation of Common Goods:

Nonprofit organizations enable citizens to engage in diverse sorts of public action for the sake of common goods. Nonprofits‘ importance is recognized in political theory but less so in applied ethics. This article examines fund-raising from the perspective of applied ethics through examining Albert Anderson’sEthics for Fundraisers. The article’s concern is not fund-raisers’ day-to-day routine but the relationships they establish. Fund-raisers, it is proposed, emphasize developing relations with donors but not between donors and recipients, thereby creating the danger of donor dominance. Fund-raising, moreover, falls victim to business imagery likening donors with customers or stockholders and uncritically comparing fund-raising with marketing. Through analyzing these analogies, the article concludes that fund-raisers should seek to engage donors with the work, needs, and beneficiaries of their organization and articulate how nonprofits enable donors and beneficiaries to participate together in articulati...
Monte Carlo Simulation of Lignin Pyrolysis: Sensitivity to Kinetic Parameters

The sensitivity of the Monte Carlo simulation of Kraft lignin pyrolysis to one of the model compound rate constants used therein was investigated. Experimental data and an a priori Monte Carlo simulation were compared by summarizing their results into sets of rate constant distributions, obtained by fitting the experimental and simulated data to a simple kinetic scheme. For the limited number of model compound rate constants investigated, the Monte Carlo simulation displayed very little sensitivity towards primary product formation, as its summarizing rate constant distributions were narrow and peaked.
Minimum relative entropy enhancement of FFT spectra

The typical method for obtaining a power spectrum from values of the correlation function is through the FFT (fast Fourier transform). A novel approach to improving the FFT spectrum when it is corrupted by noise is presented. The method minimises a relative entropy functional involving spectral densities and requires knowledge only of the variance of the noise that is corrupting the FFT spectrum.
Cost-Related Health Literacy: A Key Component of High-Quality Cancer Care

Because cancer treatment can result in both short- and long-term financial harm known as financial toxicity; the Institute of Medicine has issued a challenge to improve patients' understanding of cost of cancer care.
Analytical integration formulae for linear isoparametric finite elements

Exact and approximate analytical expressions can be derived for integrals arising in finite element methods, employing isoparametric linear quadrilaterals in two space dimensions with bilinear basis functions. The formulae associated with rectangular elements, arbitrarily oriented in space, can be shown to be a special case. The proposed method provides considerable savings in computational effort, in comparison with a numerical method that employs Gaussian quadrature procedures. In addition, the method, when applied to a quadrilateral inscribable in a circle, can be shown to produce better accuracy than the associated (2 × 2) Gaussian quadrature formulae.
The Human Papillomavirus Type 16 E7 Oncoprotein Activates the Fanconi Anemia (FA) Pathway and Causes Accelerated Chromosomal Instability in FA Cells

Fanconi anemia (FA) patients have an increased risk for squamous cell carcinomas (SCCs) at sites of predilection for infection with high-risk human papillomavirus (HPV) types, including the oral cavity and the anogenital tract. We show here that activation of the FA pathway is a frequent event in cervical SCCs. We found that FA pathway activation is triggered mainly by the HPV type 16 (HPV-16) E7 oncoprotein and is associated with an enhanced formation of large FANCD2 foci and recruitment of FANCD2 as well as FANCD1/BRCA2 to chromatin. Episomal expression of HPV-16 oncoproteins was sufficient to activate the FA pathway. Importantly, the expression of HPV-16 E7 in FA-deficient cells led to accelerated chromosomal instability. Taken together, our findings establish the FA pathway as an early host cell response to high-risk HPV infection and may help to explain the greatly enhanced susceptibility of FA patients to squamous cell carcinogenesis at anatomic sites that are frequently infected by high-risk HPVs.
The role of plasmalemmal-cortical anchoring on the stability of transmembrane electropores

The structure of eukaryotic cells is maintained by a network of filamentous actin anchored subjacently to the plasma membrane. This structure is referred to as the actin cortex. We present a locally constrained surface tension model for electroporation in order to address the influence of plasmalemmal-cortical anchoring on electropore dynamics. This model predicts that stable electropores are possible under certain conditions. The existence of stable electropores has been suggested in several experimental studies. The electropore radius at which stability is achieved is a function of the characteristic radii of locally constrained regions about the plasma membrane. This model opens the possibility of using actin-modifying compounds to physically manipulate cortical density, thereby manipulating electroporation dynamics. It also underscores the need to improve electroporation models further by incorporating the influence of trans-electropore ionic and aqueous flow, cortical flexibility, transmembrane protein mobility, and active cellular wound healing mechanisms.
Population Attributable Fraction Estimation for Established Breast Cancer Risk Factors: Considering the Issues of High Prevalence and Unmodifiability

Established breast cancer risk factors, in addition to being relatively unmodifiable, are highly prevalent among US women. Previous reports of population attributable fraction for the established risk factors have used definitions that resulted in 75-100% of women in the source population labeled exposed. The practical value of such estimates has not been discussed; further, the estimates have frequently been misinterpreted. In the context of examining the interpretation and public health value of such estimates, the authors demonstrate the sensitivity of the population attributable fraction to changes in exposure cutpoints. They use data from the Carolina Breast Cancer Study, a case-control study of breast cancer conducted in North Carolina between 1993 and 1996. For the four established risk factors (menarche before age 14 years, first birth at age 20 years or later/nulliparity, family history of breast cancer, and history of benign breast biopsy), the estimated population attributable fraction was 0.25 (95% confidence interval 0.06-0.48). Over 98% of the source population was exposed to at least one of these risk factors. The population attributable fraction estimate was reduced to 0.15 when more restrictive definitions of early menarche (less than age 12 years) and late age at first full-term pregnancy (30 years or more) were used (proportion exposed, 0.62). Population attributable fractions for established breast cancer risk factors probably have little public health value because of both the high proportions exposed and the relative unmodifiability of the risk factor distributions.
VISIT-TO-VISIT VARIABILITY OF SYSTOLIC BLOOD PRESSURE PREDICTS OUTCOMES MAINLY IN THE ACTIVE TREATMENT GROUP RATHER THAN THE PLACEBO GROUP IN THE SYSTOLIC HYPERTENSION IN THE ELDERLY PROGRAM: PATHOPHYSIOLOGIC IMPLICATIONS

Previous studies of blood pressure visit-to-visit variability (VVV) were of rather short duration and rarely included placebo. We investigated VVV of systolic blood pressure (SBP) in the active and placebo groups of Systolic Hypertension in the Elderly Program (SHEP). SHEP was a placebo-controlled
Not All Negative Words Slow Down Lexical Decision and Naming Speed: Importance of Word Arousal

Previously the authors analyzed sets of words used in emotion Stroop experiments and found little evidence of automatic vigilance, for example, slower lexical decision time (LDT) or naming speed for negative words after controlling for lexical features. If there is a slowdown evoked by word negativity, most studies to date overestimate the effect because word negativity is often confounded with lexical features that promote slower word recognition. Estes and Adelman (this issue) analyze a new set of words, controlling for important lexical features, and find a small but significant effect for word negativity. Moreover, they conclude the effect is categorical. The authors analyze the same data set but include the arousal value of each word. The authors find nonlinear and interaction effects in predicting LDT and naming speed. Not all negative words produce the generic slowdown. Paradoxically, negative words that are moderate to low on arousal produce more LDT slowing than negative words higher on arousal. This finding presents a theoretical and empirical challenge to researchers wishing to understand the boundaries of the automatic vigilance effect.
In vivo Photoacoustic Tomography of Total Blood Flow and Potential Imaging of Cancer Angiogenesis and Hypermetabolism

Blood flow is a key parameter in studying cancer angiogenesis and hypermetabolism. Current photoacoustic blood flow estimation methods focus on either the axial or transverse component of the flow vector. However, the Doppler angle (beam-to-flow angle) is needed to calculate the total flow speed, and it cannot always be estimated accurately in practice, especially when the system's axial and lateral resolutions are different. To overcome this problem, we propose a method to compute the total flow speed and Doppler angle by combining the axial and transverse flow measurements. The method has been verified by flowing bovine blood in a plastic tube at various speeds and Doppler angles. The error was experimentally determined to be less than 0.3 mm/s for total flow speed, and less than 15° for the Doppler angle. In addition, the method was tested in vivo on a mouse ear. We believe that the proposed method has the potential to be used for cancer angiogenesis and hypermetabolism imaging.
IL-22 Is Essential for Lung Epithelial Repair following Influenza Infection

Influenza infection is widespread in the United States and the world. Despite low mortality rates due to infection, morbidity is common and little is known about the molecular events involved in recovery. Influenza infection results in persistent distal lung remodeling, and the mechanism(s) involved are poorly understood. Recently IL-22 has been found to mediate epithelial repair. We propose that IL-22 is critical for recovery of normal lung function and architecture after influenza infection. Wild-type and IL-22(-/-) mice were infected with influenza A PR8/34 H1N1 and were followed up for up to 21 days post infection. IL-22 receptor was localized to the airway epithelium in naive mice but was expressed at the sites of parenchymal lung remodeling induced by influenza infection. IL-22(-/-) mice displayed exacerbated lung injury compared with wild-type mice, which correlated with decreased lung function 21 days post infection. Epithelial metaplasia was observed in wild-type mice but was not evident in IL-22(-/-) animals that were characterized with an increased fibrotic phenotype. Gene expression analysis revealed aberrant expression of epithelial genes involved in repair processes, among changes in several other biological processes. These data indicate that IL-22 is required for normal lung repair after influenza infection. IL-22 represents a novel pathway involved in interstitial lung disease.
Transport and magnetization critical densities in TlBa/sub 2/Ca/sub 2/Cu/sub 3/O/sub x/ tapes

The powder-in-tube process was used to produce silver-sheathed tapes of TlBa/sub 2/Ca/sub 2/Cu/sub 3/O/sub 8+x/ (Tl-1223). The powder was produced by thalliating a precursor powder mixture to produce the Tl-1223 phase and then heating to drive off excess Tl and reach the Tl-2223 stoichiometry. The tapes were rolled and pressed, each step followed by a 3-h sintering. The 200- mu m-thick tapes show little sign of texturing; however, the critical current shows a small ( approximately 50%) dependence on the direction of the applied magnetic field. Both transport and magnetization measurements indicate relatively strong pinning at high temperatures. The 75 K self-field critical current density is 62 MA/m/sup 2/. Transport measurements reveal the presence of weak links at all temperatures, but with a relatively weak field dependence above approximately=0.1 T. >
Watchdog: hardware for safe and secure manual memory management and full memory safety

Languages such as C and C++ use unsafe manual memory management, allowing simple bugs (i.e., accesses to an object after deallocation) to become the root cause of exploitable security vulnerabilities. This paper proposes Watchdog, a hardware-based approach for ensuring safe and secure manual memory management. Inspired by prior software-only proposals, Watchdog generates a unique identifier for each memory allocation, associates these identifiers with pointers, and checks to ensure that the identifier is still valid on every memory access. This use of identifiers and checks enables Watchdog to detect errors even in the presence of reallocations. Watchdog stores these pointer identifiers in a disjoint shadow space to provide comprehensive protection and ensure compatibility with existing code. To streamline the implementation and reduce runtime overhead: Watchdog (1) uses micro-ops to access metadata and perform checks, (2) eliminates metadata copies among registers via modified register renaming, and (3) uses a dedicated metadata cache to reduce checking overhead. Furthermore, this paper extends Watchdog's mechanisms to detect bounds errors, thereby providing full hardware-enforced memory safety at low overheads.
MetaSync: file synchronization across multiple untrusted storage services

Cloud-based file synchronization services, such as Drop-box, are a worldwide resource for many millions of users. However, individual services often have tight resource limits, suffer from temporary outages or even shutdowns, and sometimes silently corrupt or leak user data. We design, implement, and evaluate MetaSync, a secure and reliable file synchronization service that uses multiple cloud synchronization services as untrusted storage providers. To make MetaSync work correctly, we devise a novel variant of Paxos that provides efficient and consistent updates on top of the unmodified APIs exported by existing services. Our system automatically redistributes files upon reconfiguration of providers. Our evaluation shows that MetaSync provides low update latency and high update throughput while being more trustworthy and available. MetaSync outperforms its underlying cloud services by 1.2-10×on three realistic workloads.
Abstract 2751: Cost-effectiveness of Carotid-Artery Stent Placement versus Endarterectomy in Patients with Carotid Stenosis

Introduction: The Stenting versus Endarterectomy for treatment of carotid stenosis trial (CREST) demonstrated that the risk of the composite primary outcome of stroke, myocardial infarction (MI), or death did not differ significantly in the average surgical risk patients undergoing carotid-artery stent placement (CAS) and those undergoing carotid endarterectomy (CEA). However, the cost associated with CAS may limit its broad applicability. Objective: To determine the cost-effectiveness of CAS with emboli-protection device versus CEA in average surgical risk patients with moderate-severe carotid stenosis. Methods: The probability of primary endpoint was obtained from the results of the CREST trial. The quality-adjusted life year (QALYs) associated with each treatment modality were estimated by adjusting for the incidence of each quality adjusted outcome (QALY weights of ipsilateral stroke, MI, death and post-procedure QALYs). Total cost associated with each intervention was derived from hospitalization cost and cost associated with primary endpoints including stroke, MI and death in each group. Costs are expressed in US dollars accounting for inflation up to October 2010. Incremental cost-effectiveness ratios (ICERs) were estimated for the four year period following the procedure. All values are expressed as means and 95% percentile intervals. Results: The estimated net costs for patients after treatment with CAS and CEA after consideration of primary endpoint were $ 18,335 and $ 13,276, respectively from definitive pre-simulation analysis. Post simulation values were $19,210 ($18,264- $ 20,156) and $14,080 ($13,076 - $15,084). Overall QALYs for the CAS and CEA groups were 0.712 and 0.702 respectively (ranging from 0.0 meaning death to 0.815 meaning no adverse events). The estimated ICER for CAS versus CEA treatment was $229,429. Conclusions: Although, the CREST demonstrated equivalent results with CAS (compared with CEA) in average surgical risk patients with severe carotid stenosis, broad applicability of CAS might be limited by the higher cost associated with this procedure.
Multiple Industrializations: Urban Manufacturing Development in the American Midwest, 1880–1925

Recent research in historical and economic geography has documented an interactive agro-industrial dynamic in the American Midwest, which laid the basis for regional mass-production systems often characterized as Fordism. This study examines four Midwestern manufacturing cities during the 'second industrial revolution', reconstructing the pattern and trajectories of leading sectors in bulk, mixed and batch production formats, using detailed, disaggregated census data and other sources. Focusing on value added in manufacturing as a key indicator, the study suggests that Chicago, Cincinnati, Cleveland and Grand Rapids charted quite distinctive pathways to industrial advance and that the significance of non-Fordist, speciality manufacturing to their growth has been undervalued. The Midwestern cases are contrasted with that of Philadelphia, an eastern centrefor batch industries, and thefive cities' situations in 1900 are compared with their industrial positions in 1925. Thefindings indicate a greater diversity in urban industrial structures and histories than is usually appreciated, which limits the reach of both the agro-industrialization model (temporally) and of the Fordism concept more generally, yet opens new venues for research on regional industrialization and its structured variations.
Mechanisms linking high school graduation to health disparities in young adulthood: a longitudinal analysis of the role of health behaviours, psychosocial stressors, and health insurance

OBJECTIVES: This study examined three competing mechanisms in the link between educational attainment and health among young adults: (a) a health behaviour mechanism; (b) a psychosocial stressor mechanism; and (c) a health insurance mechanism. The central research question was the pervasiveness and specificity of these mechanisms in the link between low educational attainment and health outcomes during young adulthood. STUDY DESIGN: A prospective longitudinal study was conducted with 808 men and women followed to age 33 years in the USA. METHODS: Health outcomes included major depressive disorder, obesity, chronic health conditions, and self-rated health. The focal predictor was educational attainment at age 21. The roles of the health behaviour mechanism (heavy episodic drinking, cigarette smoking, and meeting physical activity guidelines), the psychosocial stressor mechanism (stressful life events, perceived financial stress, and lack of control at work), and having health insurance (either through their employer or union or via family members) in the link between education and varying health outcomes were assessed using path analyses. RESULTS: Lack of health insurance emerged as a statistically significant explanatory factor underlying the association of education with depression and self-rated health. Health behaviours, specifically smoking and physical activity, were statistically significant intervening factors for obesity and self-rated health. CONCLUSIONS: The processes linking educational attainment to health inequalities begin unfolding during young adulthood. The salience of different mechanisms is specific to a health outcome rather than pervasive across multiple health outcomes. Public health policies with a broad spectrum of components, particularly focussing on smoking, physical activity, and lack of health insurance, are recommended to promote educational equalities in multiple health outcomes among young adults.Copyright © 2016 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved. Language: en
Abstract 4202: Peptide probes binding to radiation-inducible cell surface GRP78 as a novel targeting strategy for various tumors

Traditional radiation therapy is often associated with significant toxicity to normal cells that could limit the success of cancer therapy. The greater understanding in the molecular differences between cancer cells and normal cells has lead to targeted therapies in cancer treatment. We have discovered novel radiation-inducible antigens in cancer using phage-display peptide libraries. One such inducible-antigen is Glucose regulated protein 78kDa (GRP78) that was shown to bind the hexapeptide GIRLRG. GRP78 is known to regulate cellular stresses, including hypoglycemia, hypoxia and the ER stress response. It is over-expressed in different cancer subtypes and has been correlated to their poor prognosis. In this study, we evaluated the cell surface induction of GRP78 post irradiation (IR) on lung cancer (A549 and LLC), glioma (D54 and GL261) and endothelial (HUVEC and 3B11) cell lines using flow cytometry. Significantly higher surface expression of GRP78 was observed in all cell lines. We determined the specificity of GIRLRG to bind tumors in vivo using nano SPECT technology. GIRLRG was conjugated to a 40KDa PEG (for longer circulation time) and radiolabelled with 111Indium (111In) using diethylene triamine pentaacetic acid (DTPA) as the chelator. The A549 tumor bearing nude mice were irradiated (3Gy x 3 times) or sham irradiated prior to tail vein injections of 111In labeled GIRLRG. The mice were imaged 48h and 96h post injection using nano CT-SPECT imager. The SPECT images revealed that GIRLRG specifically bound to the irradiated A549 tumors while little or no binding was seen in the sham irradiated tumors. The post-SPECT imaging bio-distrubution also revealed maximum uptake in irradiated tumors. We further evaluated tumor binding of GIRLRG in Glioma (D54), esophageal cancer (OE33), cervical cancer (HT3), and pancreatic cancer (BxPC3). The nano-SPECT imaging showed that GIRLRG specifically bound to all the irradiated tumors tested. Phosphor images of the tumor sections showed that GIRLRG specifically bound to the tumors and not to normal tissues. In conclusion, GIRLRG peptide has high affinity to GRP78 in vitro and in vivo. Radiolabeled GIRLRG is a novel tool for imaging tumors and may be developed further as a therapeutic agent to deliver cancer specific drugs or therapeutic radioisotopes. Citation Format: Vaishali Kapoor, David Dadey, Kim Nguyen, Hua Li, Buck Rogers, Dinesh Thotala, Dennis Hallahan. Peptide probes binding to radiation-inducible cell surface GRP78 as a novel targeting strategy for various tumors. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 4202.
Hepatitis C Virus-Host Interactions

Hepatitis C virus (HCV) is an RNA virus with limited genetic content and a specific tropism for the liver. As such, it depends significantly on its host cell to establish a successful infection. Twenty-five years of studying HCV and its relationship with the host hepatocyte have resulted in the identification of hundreds of HCV host cofactors that facilitate and respond to viral infection. Characterization of these cofactors has provided extensive insight into viral replication strategies and gene functions, in addition to expanding our animal and cell culture systems to study HCV replication and pathogenesis. Some of these host cofactors are also targets for therapeutic development. Although it is impossible to critically discuss every putative HCV-host interaction within the allotted space, we attempt to discuss the well-characterized virus-host interactions that function at each stage of the viral life cycle.
Adiabatic quantum computation

The simple act of slowly varying the parameters of a quantum system so that it remains always in its ground state is extremely rich from an information processing point of view. For an ideal, closed system, this adiabatic evolution is equivalent to full quantum computation, and it is convenient for establishing quantum algorithms for optimization. This review presents adiabatic quantum algorithms, proves the closed-system equivalence of the adiabatic and circuit models of quantum computation, reviews the placement of adiabatic quantum computation in the more general classification of computational complexity theory, and discusses the case of ``stoquastic'' quantum evolutions.
Significant Activity of the JAK2 Inhibitor, INCB018424 in Patients with Secondary, Post-Myeloproliferative Disorder (MPD) Acute Myeloid Leukemia (sAML): Results of An Exploratory Phase II Study.

Abstract 631 Background: Mutations of JAK2 gene have been identified in a significant proportion of patients with MPDs with the selective JAK2 inhibitors demonstrating significant activity. Patients with AML following prior MPD (sAML) respond poorly to standard cytotoxic chemotherapy and have a poor outcome. Abnormalities of the Jak-Stat signaling pathway have also been identified in a number of other hematological malignancies; chromosomal translocations resulting in TEL-JAK2 constructs lead to the constitutive activation of STAT5, IL-3-independent cellular proliferation, and leukemogenesis. Similarly, infection with oncogenic viruses such as human T-cell lymphotrophic virus, type I, and Abelson murine leukemia viruses results in enhanced kinase activity of Jaks, possibly accounting for their leukemogenic potential. Furthermore, disrupted Jak-Stat signaling has been reported in a number of leukemias. Aim: To identify potential activity of INCB018424 in patients with advanced hematological cancers. Methods: We are conducting a phase II study of INCB018424 in patients with relapsed/refractory leukemias for which no standard therapies are anticipated to result in a durable remission. Patients with performance status 0,1,and 2 with adequate organ function and no active, uncontrolled intercurrent illness or infection receive INCB018424 orally at 25 mg BID daily for 4 weeks (cycle #1). Response is assessed after 2 cycles of treatment. Responding patients or patients with stable disease are allowed to continue until progression. Predetermined dose modifications to 15 mg or 10 mg BID are allowed for drug related toxicities. Results: Eighteen patients [median age, 68 years; (range, 53-88] with relapsed and refractory leukemias (9 de novo AML, 3 sAML, 2 ALL, 1 MDS, 2 CMML, 1 CML) have been treated. The median number of prior therapies is 2 (range,1 to 6). Five patients (1 with AML, 2 with sAML, and 3 with CMML) had the JAK2 V617F mutation. Cytogenetic abnormalities include diploid in 7, chromosome 5 and 7 in 5, t(2;9) in 1, and the Philadelphia chromosome in 2. Pts have received a median of 1 cycle of therapy (range, 1-5 cycles) with 8 pts having stable disease (3 for 2 cycles, 2 for 3 cycles, 1 for 4 cycles, and 2 for 5 cycles). Three patients (including 2 with sAML and 1 with CMML, all with JAK2 mutation) have had significant declines in their bone marrow blasts (to Conclusion: INCB018424 has significant activity in sAML and CMML associated with JAK2 V617F mutation. Clinical studies combining it with chemotherapy in sAML are warranted. Disclosures: Ravandi: Incyte Corporation: Research Funding. Verstovsek: Incyte: Research Funding. Garrett: Incyte Corporation: Employment. Newton: Incyte Corporation: Employment.
Gluten and non-gluten proteins of wheat as target antigens in autism, Crohn’s and celiac disease

Studies show that patients with celiac disease react not only with gluten wheat proteins but also with non-gluten wheat components. Our goal was to measure IgG or IgA antibodies against wheat proteins or peptides that would provide the most sensitive method for the detection of wheat immune reaction in children with autism spectrum disorder, and patients with Crohn’s and celiac disease (CD). Using ELISA, we measured these antibodies against various gluten and non-gluten wheat proteins. Compared to controls in all three conditions, the strongest reaction was against CXCR3-binding gliadin peptide, followed by a wheat protein mixture, and α-gliadin 33-mer peptide. We determined that a sample that strongly reacted against non-gluten proteins also reacted strongly against gluten proteins. We also found that IgA antibodies against CXCR3-binding gliadin peptide were strongly reactive in a subgroup of 33% in the autism group, 42% in the Crohn’s group, and all tested samples with CD. The results indicate that measuring IgG and IgA antibodies against non-gluten proteins adds nothing to the pathologic relevance of these antibodies. Further research is needed on CXCR3-binding gliadin peptide antibodies as a possible biomarker and as a guide for dietary elimination in CD, Crohn’s disease and a subgroup of children with ASD.
1997–2002 Solar Array String Failures Revisited

In 1997, two commercial geostationary satellites experienced a new phenomenon: sustained solar array arcing. Although arcing on solar arrays in space had been expected from ground tests and space f...
Music: Eros and Embodiment in Renewal Worship

While creational theologies of art often posit that humans worship as an appropriate response to God’s glory and sovereignty, a pneumatological aesthetics sees eros as the necessary dynamism involved in musical worship. As the Spirit beckons the heart of a person, the person too desires closeness to God. This reciprocal relation of desire well describes what happens in renewal worship. This chapter looks at the role of emotion in a holistic spirituality and how it manifests in music. Embodied music comes about as an act of eros, which in turn motivates relational intimacy with God. Discernment is needed in order to avoid the trappings that may arise with emotional and embodied engagements. Nevertheless, rightly directed embodied worship could stimulate some very powerful encounters with God, and aid a person’s relational intimacy with God.
The IL-1 family: The role of IL-1 and IL-18 in inflammation

IL-1 and its related family member IL-18 are primarily proinflammatory cytokines by their ability to stimulate the expression of genes associated with inflammation and autoimmune diseases. The most salient and relevant properties of IL-1 in inflammation are the initiation of cyclooxygenase type 2 (COX-2), type 2 phospholipase A and inducible nitric oxide syntha se (iNOS). This accounts for the large amount of prostaglandin-E2 (PGE2), platelet activating factor, leukotrienes and nitric oxide (NO) produced by cells exposed to IL-1 or in animals or humans injected with IL-1. Another important proinflammatory property of IL-1 is its ability to increase the expression of adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) on mesenchymal cells and vascular-cell adhesion molecule-1 (VCAM-1) on endothelial cells. This latter property promotes the infiltration of inflammatory and immunocompetent cells into the extravascular space. IL-1 is also an angiogenic factor and plays a role in tumor metastasis and blood vessel supply [1]. Mice lacking IL-1 receptors fail to develop proliferative lesions of vascular smooth muscle cells in mechanically injured arteries. In humans with rheumatoid arthritis (RA), the inflammation and joint destructive nature of the disease is reduced with systemic injections of the IL-1 receptor antagonist (IL-1Ra), a member of the IL-1 family that prevents IL-1 activity. However, in addition to these and other proinflammatory properties, IL-1 is also an adjuvant during antibody production and acts on bone marrow stem cells for differentiation in the myeloid series. In fact, unlike TNF, IL-1 is a bone marrow stimulant and was used to treat patients with bone marrow suppression in order to reduce the nadir of thrombocytopenia [2].
Identification of facilitators and barriers to residents' use of a clinical reasoning tool.

Background While there is some experimental evidence to support the use of cognitive forcing strategies to reduce diagnostic error in residents, the potential usability of such strategies in the clinical setting has not been explored. We sought to test the effect of a clinical reasoning tool on diagnostic accuracy and to obtain feedback on its usability and acceptability. Methods We conducted a randomized behavioral experiment testing the effect of this tool on diagnostic accuracy on written cases among post-graduate 3 (PGY-3) residents at a single internal medical residency program in 2014. Residents completed written clinical cases in a proctored setting with and without prompts to use the tool. The tool encouraged reflection on concordant and discordant aspects of each case. We used random effects regression to assess the effect of the tool on diagnostic accuracy of the independent case sets, controlling for case complexity. We then conducted audiotaped structured focus group debriefing sessions and reviewed the tapes for facilitators and barriers to use of the tool. Results Of 51 eligible PGY-3 residents, 34 (67%) participated in the study. The average diagnostic accuracy increased from 52% to 60% with the tool, a difference that just met the test for statistical significance in adjusted analyses (p=0.05). Residents reported that the tool was generally acceptable and understandable but did not recognize its utility for use with simple cases, suggesting the presence of overconfidence bias. Conclusions A clinical reasoning tool improved residents' diagnostic accuracy on written cases. Overconfidence bias is a potential barrier to its use in the clinical setting.
Perception matters: Stressful life events increase breast cancer risk.

Abstract Objective The relationship between psychological stress and breast cancer risk is unclear. The present study sought to understand how stressfulness appraisal of salient Life Events (LEs) influences breast cancer risk. Methods A case-control design was used and included 664 female cases identified through the Cancer Surveillance Program of Orange County, CA and 203 female population-based controls. A LE questionnaire determined if events occurred prior to breast cancer diagnosis and if these events were considered to be stressful or not. Multivariate unconditional logistic regression was used to calculate ORs while adjusting for known breast cancer covariates. Results Cumulative adverse LEs perceived as stressful were associated with increased breast cancer risk in a dose response fashion (OR = 1.63, 95% CI = 1.00–2.66, Ptrend = 0.045). Conversely, events perceived as non-stressful did not have a significant impact on breast cancer risk. Previous personal illness was directly related to increased breast cancer risk, whether perceived as stressful (OR = 2.84, 95% CI = 1.96–4.11) or non-stressful (OR = 3.47, 95% CI = 1.34–8.94). Abortion and relocation were observed to have a protective effect on breast cancer risk only when reported as stressful (OR = 0.54, 95% CI = 0.32–0.92; OR = 0.63, 95% CI = 0.43–0.93, respectively). Pre/Peri-menopausal women who were nulliparous or who had their first child at ≥30 years of age were especially prone to the effects of appraised stress on increased breast cancer risk. Conclusions This study underscores the importance of stressfulness appraisal when determining the effect of major LEs on breast cancer risk. Our results support incorporating assessments of perceived stressfulness in future epidemiological investigation of this topic.
Efficient Estimation of Risk Preferences

Risk and the risk attitude of agents are two fundamental elements of decision making under risk and uncertainty. Recent developments in risk and risk preference analyses have raised questions on conventional approaches to estimating risk preferences. This study proposes an estimation procedure that employs a seminonparametric estimator to estimate the density function of risk without imposing distributional assumptions, as well as a numerical integration method to construct closed-form expressions of conditional moment conditions for efficient estimation. The method achieves a substantial efficiency improvement relative to the conventional GMM approach in Monte Carlo simulations. The proposed approach is general and applies to the estimation of behavioral choice models under risk, or models that require expectation operations and closed-form equations for estimation.
A simplified method for the isolation of glutathione from yeast.

ONE of the difficulties in isolating glutathione from yeast is the extremely slow filtration encountered in removing the yeast residues after extraction. For example, in Pirie's [1930] method, which is probably the simplest thus far proposed, the ifitration requires 4-6 hr. It has now been found that this time can be reduced to 20 min. by liberating the glutathione with acetone, extracting the yeast residue with water, and filtering in the presence of a large quantity of infusorial earth. The details of the method are as follows.
Multifidelity coKriging for High-Dimensional Output Functions with Application to Hypersonic Airloads Computation

An accurate surrogate model is capable of reproducing high-fidelity results at a fraction of the computational cost. coKriging is an efficient method for constructing surrogate models when two leve...