cssi/SciSciGPT-SciSciNet huggingface dataset:
One step at a time: endoplasmic reticulum-associated degradation

Protein folding in the endoplasmic reticulum (ER) is monitored by ER quality control (ERQC) mechanisms. Proteins that pass ERQC criteria traffic to their final destinations through the secretory pathway, whereas non-native and unassembled subunits of multimeric proteins are degraded by the ER-associated degradation (ERAD) pathway. During ERAD, molecular chaperones and associated factors recognize and target substrates for retrotranslocation to the cytoplasm, where they are degraded by the ubiquitin-proteasome machinery. The discovery of diseases that are associated with ERAD substrates highlights the importance of this pathway. Here, we summarize our current understanding of each step during ERAD, with emphasis on the factors that catalyse distinct activities.
A Concentration-Dependent Mechanism by which Serum Albumin Inactivates Replacement Lung Surfactants

Endogenous lung surfactant, and lung surfactant replacements used to treat respiratory distress syndrome, can be inactivated during lung edema, most likely by serum proteins. Serum albumin shows a concentration-dependent surface pressure that can exceed the respreading pressure of collapsed monolayers in vitro. Under these conditions, the collapsed surfactant monolayer can not respread to cover the interface, leading to higher minimum surface tensions and alterations in isotherms and morphology. This is an unusual example of a blocked phase transition (collapsed to monolayer form) inhibiting bioactivity. The concentration-dependent surface activity of other common surfactant inhibitors including fibrinogen and lysolipids correlates well with their effectiveness as inhibitors. These results show that respreading pressure may be as important as the minimum surface tension in the design of replacement surfactants for respiratory distress syndrome.
BIOCHEMICAL IDENTITY AND CHARACTERIZATION OF THE MOUSE INTERLEUKIN-2 RECEPTOR BETA AND GAMMA C SUBUNITS

Although the mouse IL-2 receptor (IL-2R) β and γc subunits have been identified by molecular cloning, the biochemical identity of these subunits has not yet been established. In the present study, ...
The traumatized tooth: a synthesis.

Abstract This paper is a compilation, correlation, and summarization of the views of the participants in the Workshop on the Biologic Basis for Modern Endodontic Practice. It represents a synthesis of three input sources: the position and review papers presented at the Workshop, the consensus of the Workshop participants, and the particular expertise of the author in the subject area.
MonkEllipse: Visualizing the History of Information Visualization

In this paper, we describe the process and result of creating a visualization to capture the past 10 years of history in the field of Information Visualization, as part of the annual InfoVis Conference Contest. We began with an XML file containing data provided by the contest organizers, scrubbed and augmented the data, and created a database to hold the information. We designed a visualization and implemented it using Flash MX 2004 Professional with ActionScript 2.0, PHP, and PostgreSQL. The resulting visualization provides an overview of the field of Information Visualization, and allows users to see the connections between areas of the field, particular researchers, and documents.
BRAF Mutation and Microsatellite Instability Status in Colonic and Rectal Carcinoma: Context Really Does Matter

References 1. Gomez SL, Noone A-M, Lichtensztajn, DY, et al. Cancer incidence trends among Asian-American populations in the United States, 1990-2008 J Natl Cancer Inst. 2013;105(15):1096–1110. 2. Liu L, Noone A-M, Gomez SL, et al. Cancer incidence trends among Native Hawaiians and other Pacific Islanders in the United States, 19902008 J Natl Cancer Inst. 2013;105(15):1086–1095. 3. Buell P, Dunn JE. Cancer mortality among Japanese Issei and Nisei of California. Cancer. 1965;18(5):656–664. 4. Kolonel L, Hinds MW and Hankin JH. 1980. Cancer patterns among migrant and native-born Japanese in Hawaii in relation to smoking drinking and dietary habits. In: Gelboin HV, MacMahon B, Matsushima T, Sugimura T, Takayama S, Takebe H, ed. Genetic and Environmental Factors in Experimental and Human Cancer. Tokyo: Japan Scientific Societies Press; 1980: 327–340. 5. Kolonel L, Wilkens LR. Migrant Studies. In: Schottenfeld D, Fraumeni JF Jr, eds. Cancer Epidemiology and Prevention. 3rd ed. New York: Oxford University Press; 2006:189–201. 6. Ziegler RG, Hoover RN, Pike MC, et al. 1993. Migration patterns and breast cancer risk in Asian-American women. J Natl Cancer Inst. 1993;85(22):1819–1827. 7. Center for Immigration Studies. Immigration Policy at the Edges: International Migration to and Through the U.S. Island Territories, 2003. http:www.cis.org/USIslandTerratories-IntrnationalMigration.html. Accessed June 10, 2013. 8. Countries and their Cultures. Polynesians History and Cultural Relations. http://www.everyculture.com/North-America/Polynesians-History-andCulture-Relations.html. Accessed June 10, 2013. 9. Wikipedia. History of Asian American Immigration. http://en.wikipedia.org/ wiki/History_of_Asian_American_immigration. Accessed June 10, 2013. 10. Wikipedia. Japanese American. http://www.en.wikipedia.org/wiki/Japanese_ American. Acccessed June 10, 2013. 11. US Census Bureau. An Older and More Diverse Nation by Midcentury. http:// www.census.gov/newsroom/releases/archives/population/cb08-123.html. Accessed June 27, 2013. 12. US Department of Health and Human Services. Hepatitis and Asian Americans. http://minorityhealth.hhs.gov/templates/content.aspx?lvl=3& lvlid=541I40(1):43–68.
The Complementary/Substitution Effects of the Code of Best Corporate Practices in Mexico with Firm Specific Characteristics on the Improvements in the Quality of Earnings

In this study, we investigate whether or not the Code of Best Corporate Practices (Code) in Mexico is complementary to or a substitute for other corporate governance mechanisms (auditor quality, firm size and board independence). We find that the Code complements high auditor quality and substitutes for high board independence. In tests of the interactions among the firm characteristics, we find that auditor quality results in the most persistent increases in earnings quality. Although we find that size can partially substitute for auditor quality, the largest improvements in earnings quality occurs in firms with high quality auditors. This study contributes to the existing international literature on corporate governance and earnings quality by investigating the differential impact of firm specific characteristics on earnings quality. This study also contributes to the auditing literature by indicating that while auditor quality is an important corporate governance mechanism, size is a viable substitute.
Inhibition of secretion by 1,3-Cyclohexanebis(methylamine), a dibasic compound that interferes with coatomer function.

We noted previously that certain aminoglycoside antibiotics inhibit the binding of coatomer to Golgi membranes in vitro. The inhibition is mediated in part by two primary amino groups present at the 1 and 3 positions of the 2-deoxystreptamine moiety of the antibiotics. These two amines appear to mimic the e-amino groups present in the two lysine residues of the KKXX motif that is known to bind coatomer. Here we report the effects of 1,3-cyclohexanebis(methylamine) (CBM) on secretion in vivo, a compound chosen for study because it contains primary amino groups that resemble those in 2-deoxystreptamine and it should penetrate lipid bilayers more readily than antibiotics. CBM inhibited coatomer binding to Golgi membranes in vitro and in vivo and inhibited secretion by intact cells. Despite depressed binding of coatomer in vivo, the Golgi complex retained its characteristic perinuclear location in the presence of CBM and did not fuse with the endoplasmic reticulum (ER). Transport from the ER to the Golgi was also not blocked by CBM. These data suggest that a full complement of coat protein I (COPI) on membranes is not critical for maintenance of Golgi integrity or for traffic from the ER to the Golgi but is necessary for transport through the Golgi to the plasma membrane.
Cytosolic Selection Systems To Study Protein Stability

Here we describe biosensors that provide readouts for protein stability in the cytosolic compartment of prokaryotes. These biosensors consist of tripartite sandwich fusions that link the in vitro stability or aggregation susceptibility of guest proteins to the in vivo resistance of host cells to the antibiotics kanamycin, spectinomycin, and nourseothricin. These selectable markers confer antibiotic resistance in a wide range of hosts and are easily quantifiable. We show that mutations within guest proteins that affect their stability alter the antibiotic resistances of the cells expressing the biosensors in a manner that is related to the in vitro stabilities of the mutant guest proteins. In addition, we find that polyglutamine tracts of increasing length are associated with an increased tendency to form amyloids in vivo and, in our sandwich fusion system, with decreased resistance to aminoglycoside antibiotics. We demonstrate that our approach allows the in vivo analysis of protein stability in the cytosolic compartment without the need for prior structural and functional knowledge.
Affibody‐Functionalized Gold–Silica Nanoparticles for Raman Molecular Imaging of the Epidermal Growth Factor Receptor

The affibody functionalization of fluorescent surface-enhanced Raman scattering gold–silica nanoparticles as multimodal contrast agents for molecular imaging specific to epidermal growth factor receptor (EGFR) is reported. This nanoparticle bioconjugate reports EGFR-positive A431 tumors with a signal nearly 35-fold higher than EGFR-negative MDA-435S tumors. The low-level EGFR expression in adjacent healthy tissue is 7-fold lower than in the positive tumors. Validation via competitive inhibition reduces the signal by a factor of six, and independent measurement of EGFR via flow cytometry correlates at R2 = 0.92.
Physical activity social support and middle- and older-aged minority women: results from a US survey

Abstract Background: Many American adults remain sedentary despite many known health benefits. Research on the determinants of physical activity have indicated that social support is one of the strongest correlates, but little is known about this relation in important subgroups of middle and older-aged women. Objective: The purpose of this study was to assess the association of physical activity-related social support on several measures of physical activity in a national sample of minority women. A unique aspect of these measures is the inclusion of vigorous household tasks and occupational physical activities. Methods: The US Women's Determinants Study was conducted in 1996–1997. The survey was a modified-random sample, telephone survey of 2912 Black, Hispanic, American Indian/Alaskan Native, and White women age 40 and older. A composite score of physical activity social support (PASS) was analyzed as the independent variable in logistic regression analyses. Four measures of physical activity levels served as the dependent variables. A separate analysis was done to distinguish PASS from friends versus PASS from relatives. The potential confounding effect of race/ethnicity, marital status, age, income and education were evaluated and adjusted in the models. Results: Hispanic women were more likely to have high PASS scores than the other racial/ethnic groups. Odds ratios indicate that subjects with high levels of PASS were significantly less likely to be sedentary than those with low support, even after adjusting for race/ethnicity. While there were significant associations among levels of social support and physical activity, this was not true for the measure of “regular exercise.” There was no significant difference between the contribution of “friend” support versus “family” support on all four measures on physical activity. Discussion: Based on our results, enhancing social support may be an important aspect of interventions aimed at increasing physical activity in a population of sedentary women of various racial/ethnic backgrounds. Also, “regular exercisers” in this population appear to be less reliant social support to maintain their behavior.
Adaptive AIMD rate control for smooth multimedia streaming

Internet applications use rate control algorithms, such as the additive-increase/multiplicative-decrease (AIMD) mechanism of the TCP protocol, to adjust transmission rates. An important design factor of rate control algorithms is the tradeoff between responsiveness and smoothness. In general, responding aggressively to changes in network conditions causes wide fluctuations in sending rates. In this paper, we address this tradeoff and develop an adaptive AIMD (ADAIMD) model that adjusts AIMD parameters dynamically. When the network condition is stable, an ADAIMD flow changes its sending rate in small steps to avoid rate fluctuations. When the network condition is changing significantly, the flow adjusts the additive and multiplicative coefficients of AIMD to accelerate rate changes. We will show that these goals can be achieved by applying the additive increase and multiplicative decrease rules to the additive coefficient of AIMD. Our simulation studies show that ADAIMD produces near constant bit rate (CBR), TCP-friendly flows with good responsiveness. Such a rate-control model forms the foundation of realtime transport protocols that provide exceedingly smooth streaming services to Internet multimedia applications.
Early detection and longitudinal changes in amyotrophic lateral sclerosis by 1H MRSI

Objective: To determine 1) the reproducibility of metabolite measurements by 1 H MRS in the motor cortex; 2) the extent to which 1 H MRS imaging (MRSI) detects abnormal concentrations of N -acetylaspartate (NAA)-, choline (Cho)-, and creatine (Cre)-containing compounds in early stages of ALS; and 3) the metabolite changes over time in ALS. Methods: Sixteen patients with definite or probable ALS, 12 with possible or suspected ALS, and 12 healthy controls underwent structural MRI and multislice 1 H MRSI. 1 H MRSI data were coregistered with tissue-segmented MRI data to obtain concentrations of NAA, Cre, and Cho in the left and right motor cortex and in gray matter and white matter of nonmotor regions in the brain. Results: The interclass correlation coefficient of NAA was 0.53 in the motor cortex tissue and 0.83 in nonmotor cortex tissue. When cross-sectional data for patients were compared with those for controls, the NAA/(Cre + Cho) ratio in the motor cortex region was significantly reduced, primarily due to increases in Cre and Cho and a decrease in NAA concentrations. A similar, although not significant, trend of increased Cho and Cre and reduced NAA levels was also observed for patients with possible or suspected ALS. Furthermore, in longitudinal studies, decreases in NAA, Cre, and Cho concentrations were detected in motor cortex but not in nonmotor regions in ALS. Conclusion: Metabolite changes measured by 1 H MRSI may provide a surrogate marker of ALS that can aid detection of early disease and monitor progression and treatment response.
Use of Drosophila S2 Cells as a Model for Studying Ehrlichia chaffeensis Infections

Ehrlichia chaffeensis is an obligate intracellular bacterium and the causative agent of human monocytic ehrlichiosis. Although this pathogen grows in several mammalian cell lines, no general model for eukaryotic cellular requirements for bacteria replication has yet been proposed. We found that Drosophila S2 cells are permissive for the growth of E. chaffeensis. We saw morulae (aggregates of bacteria) by microscopy, detected the E. chaffeensis 16S rRNA gene by reverse transcriptase PCR, and used immunocytochemistry to detect E. chaffeensis in S2 and mammalian cells. Bacteria grown in S2 cells reinfected mammalian macrophages. S2 cells were made nonpermissive for E. chaffeensis through incubation with lipopolysaccharide. Our results demonstrate that S2 cells are an appropriate system for studying the pathogenesis of E. chaffeensis. The use of a Drosophila system has the potential to serve as a model system for studying Ehrlichia due to its completed genome, ease of genetic manipulation, and the availability of mutants.
Science Data Products for Public Health Decision Support

The Public Health Applications in Remote Sensing (PHAiRS) project is engineering an enhanced syndromic surveillance system for dust-related respiratory diseases in the southwestern United States based on assimilating Earth observation (EO) data from NASA experimental satellites. There is a rich literature describing the roles and benefits of using EO data in public health, but most of the documentation is based on anecdotal inferences derived from traditional image interpretation. For several reasons, public health communities cannot rely on evidence of this type because: (1) they need science results that verify, validate, and benchmark the statistical and economic benefits from these exotic inputs; and, (2) they lack the systems that can deliver such reliable information economically and swiftly. In PHAiRS, several data sets are being assimilated as replacement parameters in the Dust Regional Atmospheric Model (DREAM) to improve simulations of particulate matter entrainment, timing of entrainment, concentrations, and subsequent movement as governed by hourly weather variables available in a regional version of the National Centers for Environmental Prediction (NCEP/Eta) model. On-going simulations from DREAM measure hourly, daily and weekly model improvements from individual EO data replacements that are refreshed on a weekly, seasonal, or inter-annual basis. The overall aims are to: (a) combine the measured improvements from several EO data series that optimize dust forecast scenarios for public health authorities; (b) benchmark each step in the process to document the benefits of EO data inputs into respiratory health care; and (c) develop retrospective and forecast statistics from model runs that boost system reliability and user confidence. Ultimately, the goal is to develop a reliable respiratory public health syndromic surveillance system that can be translated into routine uses of EO data from future NPOESS sensors.
Two-Stage Reactive Polymer Network Forming Systems

There are distinct advantages to designing polymer systems that afford two distinct sets of material properties– an intermediate polymer that would enable optimum handling and processing of the material, while maintaining the ability to tune in different, fi nal polymer properties that enable the optimal functioning of the material. In this study, by designing a series of non-stoichiometric thiol-acrylate systems, a polymer network is initially formed via a base catalyzed Michael addition reaction that proceeds stoichiometrically via the thiol-acrylate “click” reaction. This self-limiting reaction results in a polymer with excess acrylic functional groups within the network. At a later point in time, the photoinitiated, free radical polymerization of the excess acrylic functional groups results in a highly crosslinked, robust material system. These two stage reactive thiol-acrylate networks that have intermediate stage rubbery moduli and glass transition temperatures that range from 0.5 MPa and − 10 ° C to 22 MPa and 22 ° C, respectively, are formulated and characterized. The same polymer networks can then attain glass transition temperatures that range from 5 ° C to 195 ° C and rubbery moduli of up to 200 MPa after the subsequent photocuring stage. The two stage reactive networks formed by varying the stoichiometric ratios of the thiol and acrylate monomers were shown to perform as substrates for three specifi c applications: shape memory polymers, impression materials, and as optical materials for writing refractive index patterns.
A new calibrant for matrix-assisted laser desorption/ionization time-of-flight-time-of-flight post-source decay tandem mass spectrometry of non-digested proteins for top-down proteomic analysis.

RATIONALE Matrix-assisted laser desorption/ionization (MALDI) time-of-flight-time-of-flight (TOF-TOF) post-source decay (PSD) tandem mass spectrometry (MS/MS) has seen increasing use for analysis of non-digested protein ions for top-down proteomic identification. However, there is no commonly accepted calibrant for this purpose beyond the use of peptide calibrants whose fragment ions span a lower mass-to-charge (m/z) range. METHODS We have used the PSD-generated fragment ions of disulfide-reduced/alkylated thioredoxin (AlkTrx) for TOF-TOF calibration in reflectron mode for the purpose of PSD-MS/MS analysis. The average m/z values of AlkTrx fragment ions were used for calibration. The quality of the calibration was assessed from the observed fragment ion mass error of MS/MS of the YahO protein from an unfractionated bacterial cell lysate of Escherichia coli O157:H7 as well as from MS/MS of bovine ubiquitin. The fragment ion mass errors of these two analytes were also used to assess instrument calibration using the monoisotopic fragment ions of [Glu1]-fibrinopeptide B (GluFib). RESULTS A general improvement in fragment ion mass accuracy was observed using the AlkTrx calibration compared to the GluFib calibration which resulted in a more significant top-down proteomic identification of these analyte proteins. CONCLUSIONS Our results suggest that AlkTrx may be useful as a calibrant for MALDI-TOF-TOF-PSD-MS/MS of small and modest-sized protein ions. The uniform fragmentation efficiency of YahO across its sequence suggests that it may be useful as a post-calibration standard to assess PSD-MS/MS instrument performance as well as establishing appropriate top-down proteomic fragment ion tolerances. Published 2012. This article is a US Government work and is in the public domain in the USA.
Distressed family caregivers of lung cancer patients: an examination of psychosocial and practical challenges

Purpose Lung cancer and its treatment impose many demands on family caregivers, which may increase their risk for distress. However, little research has documented aspects of the caregiving experience that are especially challenging for distressed caregivers of lung cancer patients. This study aimed to explore caregivers’ key challenges in coping with their family member’s lung cancer.
The Post-merger Performance Puzzle

While the bulk of the research on the financial performance of mergers and acquisitions has focused on stock returns around the merger announcement, a surprisingly, large set of papers has also examined long-run stock returns following acquisitions. We review this literature, concluding that long-run performance is negative following mergers, though performance is non-negative (and perhaps even positive) following tender offers. However, the effects of both methodology (see Lyon, Barber & Tsai, 1999) and chance (see Fama, 1998) may modify this conclusion. Two explanations of under performance (speed of price-adjustment and EPS myopia) are not supported by the data, while two other explanations (method of payment and performance extrapolation) receive greater support.
Identification of Novel GRM1 Mutations and Single Nucleotide Polymorphisms in Prostate Cancer Cell Lines and Tissues

Metabotropic glutamate receptor 1 (GRM1) signaling has been implicated in benign and malignant disorders including prostate cancer (PCa). To further explore the role of genetic alterations of GRM1 in PCa, we screened the entire human GRM1 gene including coding sequence, exon-intron junctions, and flanking untranslated regions (UTRs) for the presence of mutations and single nucleotide polymorphisms (SNPs) in several PCa cell lines and matched tumor-normal tissues from Caucasian Americans (CAs) and African Americans (AAs). We used bidirectional sequencing, allele-specific PCR, and bioinformatics to identify the genetic changes in GRM1 and to predict their functional role. A novel missense mutation identified at C1744T (582 Pro > Ser) position of GRM1 gene in a primary AA-PCa cell line (E006AA) was predicted to affect the protein stability and functions. Another novel mutation identified at exon-intron junction of exon-8 in C4-2B cell line resulted in alteration of the GRM1 splicing donor site. In addition, we found missense SNP at T2977C (993 Ser > Pro) position and multiple non-coding mutations and SNPs in 3′-UTR of GRM1 gene in PCa cell lines and tissues. These novel mutations may contribute to the disease by alterations in GRM1 gene splicing, receptor activation, and post-receptor downstream signaling.
Utilisation of a trauma meeting handover proforma to improve trauma patient pathway

Abstract Decision making within orthopaedic centres predominantly occurs at the trauma meeting, where all decisions are made as a part of the multidisciplinary process. This is an essential handover process. Difficulties occur when teaching and detailed case discussions detract from the actual decision making process, leading to failure in documentation and implementing treatment plans. An audit was carried out in a busy district general hospital (DGH), assessing the quality of trauma meeting documentation in patient records, and assessing whether the introduction of a proforma document would improve this. Prospective clinical reviews were performed on all patients discussed in the trauma meeting over a one month period. Following the initial audit cycle a proforma was introduced, and the audit process was repeated at a two month and six month interval. The quality of the entries were assessed and compared to the Academy of Medical Royal Colleges Standards for the clinical structure and content of patient records, and The Royal College of Surgeons (RCS) of England Guidelines for Clinicians on Medical Records and Notes. Sixty three patient records during a one month period from 1 August 2014 found that only 16% had any documentation of the trauma meeting, none of which met the standard set at the beginning of the audit. Following the introduction of the proforma, 102 patient records were reviewed from October 2014, showing 70% had documentation of the trauma meeting. This improved further to 84% in February 2015. The proforma has provided an effective means of documenting and communicating management plans, and in turn also improved the trauma patient pathway to theatre or discharge.
An experimental investigation of domain wall motion in polycrystalline Ni during high-rate compressive loading

This paper describes experimental data on a polycrystalline nickel subjected to compressive loads induced in a split Hopkinson pressure bar test. A perpendicular bias magnetic field with respect to the loading direction is used to orient the domains and a pick-up coil measures the magnetic response of the sample during loading. Utilizing this experimental configuration, this study investigated the coupled effects of the magnetic and mechanical fields on domain wall motion in a polycrystalline magnetostrictive material (Ni) during the high-rate elastic loading. The experimental measurements reveal that the magnitude of the stress-induced magnetization change is dependent upon bias magnetic field.
UMTRI Experimental Techniques in Head Injury Research

Discussion des techniques pour la mesure du mouvement de la tete dans les trois dimensions, des contraintes crâniennes, de la pression epidurale, du mouvement du cerveau interne de cadavres repressurises et de singes Rhesus lors des chocs de la tete. Description de l'appareillage
Aerothermoelastic Reduced-Order Model of a Hypersonic Vehicle

Model reduction techniques are applied to a hypersonic vehicle on terminal trajectories to capture the aerodynamic, thermodynamic, and structural dynamic system evolution and couplings. The General Pseudospectral Optimization Software (GPOPS-II) was used to determine a set of terminal trajectories which maximized impact velocity. Shock, Prandtl-Meyer expansion, and piston theory were combined to create an approximate flow solution over the outer mold line which was then compared to Fully Unstructured Navier-Stokes 3-Dimensional (FUN3D) computational fluid dynamics solutions. Proper orthogonal decomposition of the thermal state of the vehicle was conducted leading to 33 thermal degrees of freedom rather than approximately 28,000 contained by a representative finite element model, while sacrificing negligible system energy. Free vibration mode shapes are derived and used to generalize the structural dynamics equations of motion reducing the number of structural degrees of freedom to 8 from the original 130,000. Finally, the combination of these reduced order models is discussed in the context of future work toward a full vehicle simulation.
Current concepts in the management of the adult respiratory distress syndrome.

The adult respiratory distress syndrome is the most severe pulmonary complication that can follow multiple trauma and critical illness. It is caused by an insult to the pulmonary circulation which results in an increased capillary permeability and subsequent interstitial edema. An increased venoarterial shunt occurs resulting in arterial hypoxemia. The mortality rate is at least 50% if treatment is not begun before profound hypoxemia occurs. Recognition of abnormal cardiopulmonary function before overt hypoxemia develops is important. This is best accomplished by attentive monitoring of arterial blood gases. Sequential arterial oxygen tensions obtained on 40% and 100% inspired oxygen concentration are the best guides to selecting patients who have a high probability of pulmonary deterioration. Aggressive cardiovascular monitoring and early treatment with low levels of positive-end expiratory pressure offer this group of patients an improved change of survival.
Extraction of Combustion Instability Mechanisms from Detailed Computational Simulations

Previous unsteady computational studies have demonstrated combustion instability for a single-element rocket engine, matching experimental instability trends. The current paper seeks to better understand the mechanisms of combustion instability by demonstrating and evaluating possible diagnostics using computational data. Specifically, the following types of diagnostics are evaluated: point measurements, power spectral density analysis, instantaneous flow plots, Rayleigh index, signal filtering, phase difference analysis, mode shape analysis, and time-averaged flow-field plots. Used together, these various types of diagnostics proved to be effective in better understanding the mechanisms causing combustion instability for the particular configurations. Concerning the instability mechanism, the results suggest that axial velocity fluctuations at the driving frequency (induced by the acoustic field) cause oscillations in the oxidizer post vorticity, which then affect the pulsing of the combustion. For the current configuration, the propagation of these vorticity oscillations into the combustor, along with the subsequent combustion, occurs sufficiently in-phase with the pressure oscillations to permit instability to occur. For the experimental configuration where combustor step height was varied, the stronger instability of the smaller step-height combustor is likely due to the increased mixing and combustion that occurs as the vortices interact more strongly with the combustor wall, providing a greater unsteady heat source for driving instability.
Correction: 3D printed nervous system on a chip

Correction for '3D printed nervous system on a chip' by Blake N. Johnson et al., Lab Chip, 2016, 16, 1393-1400.
The Duration of an Exposure Response Gradient between Incident Obstructive Airways Disease and Work at the World Trade Center Site: 2001-2011

Background Adverse respiratory effects of World Trade Center (WTC) exposure have been widely documented, but the length of time that exposure remains associated with disease is uncertain. We estimate the incidence of new cases of physician-diagnosed obstructive airway disease (OAD) as a function of time since 9/11/2001 in WTC-exposed firefighters. Methods Exposure was categorized by first WTC arrival time: high (9/11/2001 AM); moderate (9/11/2001 PM or 9/12/2001); or low (9/13-24/2001). We modeled relative rates (RR) and 95% confidence intervals (CI) of OAD incidence by exposure over the first 10 years post-9/11/2001, estimating the time(s) of change in the RR with change point models. We further examined the relationship between self-reported lower respiratory symptoms and physician diagnoses. Results Change points were observed at 15 and 84 months post-9/11/2001, with relative incidence rates for the high versus low exposure group of 4.02 (95% CI 2.62-6.16) prior to 15 months, 1.90 (95% CI 1.49-2.44) from months 16 to 84, and 1.20 (95% CI 0.92-1.56) thereafter. Incidence in all exposure groups increased after the WTC health program began to offer free coverage of OAD medications in month 63. Self-reported lower respiratory symptoms in the first 15 months had 80.6% sensitivity, but only 35.9% specificity, for eventual OAD diagnoses. Conclusions New OAD diagnoses are associated with WTC exposure for at least seven years. Some portion of the extended duration of that association may be due to delayed diagnoses. Nevertheless, our results support recognizing OAD among rescue workers as WTC-related even when diagnosed years after exposure.
p53 interacts with the spliceosomal protein SAP145 and affects pre-mRNA processing

4599 The tumor suppressor protein p53 functions to maintain cellular homeostasis and to prevent tumorigenesis by mediating cell cycle arrest and/or apoptosis in response to cellular stress and DNA damage. p53 primarily acts as a transcription factor, but it has become clear that p53 uses additional mechanisms of action to affect cellular processes. Through a p53 dissociator screen in yeast, we uncovered a set of new p53-interacting proteins, including the spliceosome associated protein 145kDa (SAP145). SAP145 is a core component of the U2 small nuclear ribonucleoprotein subunit of the spliceosome complex. The discovery of a splicing protein from the screen is interesting because it suggests a novel role for p53 in splicing which could have direct implications for p53’s functions in cancer biology. We have established that p53 interacts with SAP145 by coimmunoprecipitation of over-expressed p53 and FLAG-tagged SAP145. We have also determined that the N-terminus of p53 and the N-terminus of SAP145 are important for their physical interaction. Furthermore, activated p53 can affect the stability of SAP145 by decreasing protein levels of both full-length SAP145 and the N-terminus of SAP145, as shown by Western Blotting. However, p53 does not decrease protein levels of the C-terminus of SAP145. These results indicate that the interaction between p53 and SAP145, in particular the N-terminus of SAP145, affects SAP145 protein stability and may consequently affect pre-mRNA processing. To study the functional roles of p53 in pre-mRNA splicing, we performed RT-PCR analysis to examine the alternative splicing patterns of two different minigenes: survival motor neuron 2 (SMN2) and alpha-globin fibronectin (alpha-glob FN). p53 was shown to affect the alternative splicing pattern of exon 7 of SMN2 and the EDI exon of alpha-glob FN transcripts. Activated p53 also affects alternative splicing of endogenous p53-inducible gene 3 (PIG3) transcripts. We are currently examining p53’s effects on splicing of other endogenous p53 target genes involved in cell cycle arrest and apoptosis. Continued RT-PCR analyses will focus on how the interaction of p53 and SAP145 (and its consequences on SAP145 stability) affect p53-mediated alternative splicing of these gene products. The connection of the splicing factor SAP145 to p53 biology is intriguing in that it implicates a novel role for p53 in pre-mRNA splicing which may be linked to p53-mediated cellular outcomes of cell cycle arrest and apoptosis. Our data demonstrate not only a physical interaction between p53 and SAP145 but also show that p53 can affect SAP145 protein stability. We propose that p53 interacts with SAP145 to affect pre-mRNA splicing. By studying this interaction and its functional consequences, we will better understand how the tumor suppressor protein p53 regulates gene expression at the post-transcriptional level.
Widefield fluorescence microscopy with sensor-based conjugate adaptive optics using oblique back illumination

We describe a wavefront sensor strategy for the implementation of adaptive optics (AO) in microscope applications involving thick, scattering media. The strategy is based on the exploitation of multiple scattering to provide oblique back illumination of the wavefront-sensor focal plane, enabling a simple and direct measurement of the flux-density tilt angles caused by aberrations at this plane. Advantages of the sensor are that it provides a large measurement field of view (FOV) while requiring no guide star, making it particularly adapted to a type of AO called conjugate AO, which provides a large correction FOV in cases when sample-induced aberrations arise from a single dominant plane (e.g., the sample surface). We apply conjugate AO here to widefield (i.e., nonscanning) fluorescence microscopy for the first time and demonstrate dynamic wavefront correction in a closed-loop implementation.
Financial Analysts’ Long-Term Growth Forecasts and Market Efficiency with Respect to Firms’ Innovative Efficiency

This paper investigates the role of financial analysts’ long-term growth (LTG) forecasts in stock market efficiency with respect to information about firms’ innovative efficiency (IE). Hirshleifer, Hsu, and Li (2013) attribute evidence of market inefficiency with respect to IE information to investor limited attention constraints. We predict and find that innovatively efficient firms attract analyst publication of long-term growth (LTG) forecasts. Further evidence suggests that these forecasts proxy for analyst attention to long-term prospects, thus mitigating investor inattention and market underreaction to IE information. Our results also indicate that analysts publishing LTG forecasts bring more private information to bear on firms whose prospects depend on IE. Furthermore, we find that forecasted LTG rates increase with firms’ IE. Finally, analysts’ LTG forecasting experience and expertise in analyzing the implications of technological innovation further attenuate analyst and market inefficiency with respect to IE information. When attracted to research-intensive firms, analyst publication of LTG forecasts apparently corresponds to a long-term perspective that mitigates investor inattention and market underreaction to IE information.
Initiation and Development of a Toxic and Persistent Pseudo-nitzschia Bloom off the Oregon Coast in Spring/Summer 2015

In spring/summer 2015, a toxic bloom by the diatom Pseudo-nitzschia (PN) occurred along the west coast of the United States which led to closures of the harvest of razor clams and Dungeness crabs. Twice monthly observations of temperature, salinity, nutrients, chlorophyll and phytoplankton species composition allowed us to track oceanographic conditions preceding and during the development of the bloom. PN cells were first detected during late winter 2015. A PN bloom was initiated following the onset of coastal upwelling in mid-April; subsequent peaks in May and June were sustained by episodic upwelling events and reached magnitudes of 105 cells/L and 106 cells/L, 40% and 90% of the total diatom abundance, respectively. The bloom temporarily crashed in July due to a lack of upwelling, but PN cells increased again in August due to a resumption of upwelling, albeit with lower magnitude. Macronutrient conditions prior to this bloom likely played a critical role in triggering the bloom and its toxicity (particularly silicic acid limitation stress). Nutrient stress preceding the toxic bloom was related to two oceanographic events: an anomalously warm and thick water mass that occupied the northern North Pacific from September 2014 through 2015 leading to a highly-stratified water column, and the drawdown of nitrate and silicic acid during an unusually intense winter phytoplankton bloom in February and early March 2015.
Real-time, ultrasound-based control of a virtual hand by a trans-radial amputee

Advancements in multiarticulate upper-limb prosthetics have outpaced the development of intuitive, non-invasive control mechanisms for implementing them. Surface electromyography is currently the most popular non-invasive control method, but presents a number of drawbacks including poor deep-muscle specificity. Previous research established the viability of ultrasound imaging as an alternative means of decoding movement intent, and demonstrated the ability to distinguish between complex grasps in able-bodied subjects via imaging of the anterior forearm musculature. In order to translate this work to clinical viability, able-bodied testing is insufficient. Amputation-induced changes in muscular geometry, dynamics, and imaging characteristics are all likely to influence the effectiveness of our existing techniques. In this work, we conducted preliminary trials with a transradial amputee participant to assess these effects, and potentially elucidate necessary refinements to our approach. Two trials were performed, the first using a set of three motion types, and the second using four. After a brief training period in each trial, the participant was able to control a virtual prosthetic hand in real-time; attempted grasps were successfully classified with a rate of 77% in trial 1, and 71% in trial 2. While the results are sub-optimal compared to our previous able-bodied testing, they are a promising step forward. More importantly, the data collected during these trials can provide valuable information for refining our image processing methods, especially via comparison to previously acquired data from able-bodied individuals. Ultimately, further work with amputees is a necessity for translation towards clinical application.
Abstract 108: Women and Minorities Have Lower Patient-reported Functional Status 3 Months Post-stroke

Background: Functional outcomes after stroke are important to patients but not found in administrative data. Using a hospital quality improvement program to assess outcomes 3 months after discharge, we examined the relationship between outcome measured with the Stroke Impact Scale-16 (SIS-16) and sex, comorbidities, depression, and risk factors. Methods: We enrolled patients with ischemic/hemorrhagic stroke or TIA in an ongoing hospital-supported quality improvement program focused on transitional care and outcomes (TRAnsition Coaching for Stroke or TRACS). SIS-16 assesses self-reported mobility, arm strength, and basic/instrumental ADLs. Transformed scores range from 0 (worst) to 100 (best). Questionnaires were mailed 3 months post-discharge or collected by phone if no mailed response. Bivariate associations between baseline covariates and SIS-16 were analyzed, followed by stepwise linear regression modeling to assess independent predictors of SIS-16, adjusted for NIHSS. Results: We captured 90-day outcomes on 129 patients from 9/2011 to 4/2015; mean age was 66.0 y -(+12.3), 45.7% women, 73% white, and mean NIHSS 4.0 + 5.2. Twenty-eight percent had diabetes, 82% hypertension, 15.6% CAD, 35% prior stroke/TIA, 7% pre-stroke depression. Therapy types included 37% with none, 14.7% inpatient, 24% home health, and 23.2% outpatient. Overall SIS-16 was 81.1 (+21.01). Women, non-white race, and NIHSS were associated with lower SIS-16 (table). In a stepwise linear regression model adjusted for NIHSS (p Conclusion: Controlling for stroke severity, women, minorities, and those with prior stroke had lower functional status 3 months after stroke. Future quality improvement projects could target improving outcomes in these groups specifically.
Survivin Is Required for Proliferation, but Not Polyploidization of Megakaryocytes.

Abstract Survivin is a member of chromosome passenger complex, which plays an important role in chromosome alignment, separation and cytokinesis. We recently reported that survivin is necessary for the proliferation and survival of hematopoietic stem and progenitor cells. Furthermore, we previously showed that reduced levels of survivin expression facilitates megakaryocyte development, whereas elevated levels of survivin inhibit their maturation and polyploidization. However, the extent to which survivin is necessary for polyploidization and terminal differentiation of committed megakaryocytes remains unclear. To determine whether survivin is required for megakaryocyte and platelet biogenesis, we mated mice with floxed alleles of survivin (sur fl/fl) to mice that express Cre recombinase under the control of the PF4 promoter. Compound mutant animals appeared grossly normal and harbored normal platelet counts. Furthermore, survivin deleted and control littermates displayed similar expression of CD41 and CD42, as well as similar DNA content within the CD41+ population. The only significant difference detected was an increase in annexin V staining of CD41+ cells within the bone marrow of the mice with survivin deletion. Analysis of DNA extracted from these bone marrows showed no evidence of the survivin deletion, indicating that the surviving cells all escaped excision. These in vivo findings are consistent with a requirement for survivin in the survival or proliferation of megakaryocyte progenitors. Next, to induce megakaryocyte development ex vivo, we cultured bone marrow from surv fl/fl mice in vitro in the presence of TPO. Using this approach, we were able to induce survivin deletion in 75% of the cells as evidenced by PCR. Despite the deletion of survivin, polyploidization of the ex vivo generated megakaryocytes was unaffected. Finally, we induced deletion of survivin by retroviral infection of surv fl/fl progenitors with MSCV-Cre and found that megakaryocyte polyploidization was actually increased in the excised population. Taken together, our results suggest that survivin is not required for polyploidization, but is necessary for proliferation of megakaryocyte progenitors.
Digital Data Monitoring Display and Logging -An Approach to Intelligent Data Display and Control

A digital data acquisition system for monitoring plant variables has been designed and implemented at the University of Michigan’s Ford Nuclear Reactor (FNR), a 2 Megawatt, open-pool, research reactor.
Some trends in metal productions and processing

This paper is concerned with identifying the trends that have emerged and which still are emerging in the metallurgical technology. An examination of the current practices will enable us to evaluate the new trends. The practical information and thermodynamic analysis will enable us to predict future emerging directions in technology development. The principal avenues in the development of production of both ferrous and non–ferrous metals include smelting reduction, near–net–shape casting integrated with rolling, and implementation of continuous processes. The production and refining of molten metals will be carried out at the sequence of interconnected sealed reactors, fed by fine concentrates, coal and fluxes, and oxygen, air, inert gases, and electricity. It is expected that new developments in metallurgical technology will improve production and aid the industry's environmental conservation efforts.