cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract A05: Coordinated control of protein synthesis by mTORC1 and RSKs in triple-negative breast cancer (TNBC)

Triple-negative breast cancer (TNBC) is a heterogeneous group of tumors that do not express ER, PR or HER2 receptors. These tumors respond to conventional chemotherapy but have a significantly higher probability of relapse and poorer overall survival in the first few years after diagnosis compared with other breast cancer subtypes. Unfortunately, unlike ER+ and HER2+ subtypes, targeted therapies have not been validated to treat TNBC yet. For these reasons, our goal is to identify molecular drivers of TNBC that could be therapeutically targeted to improve patient outcome. Two major signaling pathways PI3K/AKT/mTOR and Raf/MEK/ERK are frequently up-regulated in TNBC. Targeting these pathways with specific inhibitors reduces proliferation of TNBC cell lines in preclinical studies, although combined treatment is required to prevent the activation of compensatory mechanisms between pathways and, therefore, the development of resistance. Interestingly, the ERK substrates p90 Ribosomal S6 Kinases (RSKs) regulate mTORC1 activity and/or mTORC1 downstream targets implicated in the control of translation initiation complex eIF4F and, in turn, protein synthesis. Therefore, these proteins integrate PI3K/AKT/mTOR and Raf/MEK/ERK pathways to regulate protein synthesis. Based on these data, we have investigated the contribution of mTORC1 and RSKs to the control of eIF4F activity and protein synthesis in MDA-MB-231 cells, TNBC cells with constitutively up-regulated ERK pathway. Here we show that mTORC1 and RSKs activate the translation initiation factor eIF4B and promote the degradation of the tumor suppressor PDCD4, which results in increased helicase activity of eIF4A, a component of eIF4F initiation complex, in MDA-MB-231 cells. However, regulation of eIF4A activity through eIF4B and PDCD4 relies on mTORC1 in ER-positive MCF7 cells with constitutively up-regulated PI3K/AKT/mTOR pathway. Additionally, we observe RSK-dependent increase in the translation of mRNAs with highly structured 5′UTR that encode factors involved in cell proliferation and survival in MDA-MB-231 cells. The contribution of mTORC1 and individual RSK isoforms (RSK1-4) to these processes is being evaluated upon specific stimulation of each pathway in TNBC cells. We are also investigating the role of the translational control by mTORC1 and RSKs in cellular proliferation, survival, migration and invasion. In summary, our results indicate that both mTORC1 and RSKs translationally regulate the expression of key factors involved in cell transformation and tumorigenesis in TNBC MDA-MB-231 cells, while these regulatory mechanisms rely on mTORC1 in ER-positive MCF7 cells. Citation Format: Rafael Cuesta, Marina K. Holz. Coordinated control of protein synthesis by mTORC1 and RSKs in triple-negative breast cancer (TNBC). [abstract]. In: Proceedings of the AACR Special Conference: Targeting the PI3K-mTOR Network in Cancer; Sep 14-17, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Mol Cancer Ther 2015;14(7 Suppl):Abstract nr A05.
Further Evolution of Metronomic Therapy Extended to 28 Days (Metro28) for Relapsed Refractory Multiple Myeloma (RRMM)

Despite the increasing availability of novel agents for RRMM, many patients run out of treatment options due to disease refractoriness and/or progressive toxicities, both hematological (cytopenia) and non-hematological (cachexia, asthenia, renal and cardiopulmonary).Patients who are refractory to both proteasome inhibitors and immunomodulatory agents (IMIDs) carry an ominous prognosis with a median overall survival (OS) of 9 months (Leukemia, Kumar 2013). We previously reported on the efficacy and toxicity profiles of a metronomically scheduled chemotherapy regimen administered over the course of 16 days (Haematologica, Papanikolaou 2014). Encouraged by the results of that treatment, we have since modified metronomic chemotherapy to cover a 28-day period (metro28). The regimen consisted largely of bortezomib 1.0mg/m2 on days 1, 4, 7, 10, 13,16,19, 22,25,28; along with dexamethasone 12mg on days 1-4, 7-10, 13-16, 19-22, 25-28; thalidomide 100mg days 1-28, continuous 28 day infusion of doxorubicin 1.0mg/m2 (0.5mg/m2 for Ejection Fraction 2mg/dL), with the addition of arsenic trioxide (ATO) at 0.1mg/kg on each day after bortezomib; and lately vincristine (VCR) at 0.07mg daily dose by continuous infusion for 28 days. Patient characteristics included age >65yr, 46%; female, 33%; cytogenetic abnormalities at any time prior to therapy (CA), 86%; Gene Expression Profile (GEP) 70-defined high risk, 44%. The median number of prior therapies was 8 (1-64), prior transplants, 83% (1, 2, >=3), 20%, 32%, 31%; prior exposure to novel agents including Carfilzomib/Pomalidomide was 81%. Thrombocytopenia prior to treatment was present in 75% including thrombocytopenia Disclosures Zangari:Norvartis: Membership on an entity9s Board of Directors or advisory committees; Onyx: Research Funding; Millennium: Research Funding. van Rhee:Janssen: Membership on an entity9s Board of Directors or advisory committees; Celgene: Membership on an entity9s Board of Directors or advisory committees; Millenium: Membership on an entity9s Board of Directors or advisory committees; Sanofi: Membership on an entity9s Board of Directors or advisory committees. Morgan:Celgene Corp: Membership on an entity9s Board of Directors or advisory committees; Novartis: Membership on an entity9s Board of Directors or advisory committees; Janssen: Membership on an entity9s Board of Directors or advisory committees; Myeloma UK: Membership on an entity9s Board of Directors or advisory committees; International Myeloma Foundation: Membership on an entity9s Board of Directors or advisory committees; The Binding Site: Membership on an entity9s Board of Directors or advisory committees; MMRF: Membership on an entity9s Board of Directors or advisory committees.
735. Functional Restoration of Dystrophin Protein in HiPSC-Derived Skeletal Myotubes and Cardiomyocytes After CRISPR/Cas9-Mediated Deletion of 530-725kb of DMD

Duchenne muscular dystrophy (DMD) is typically due to frameshifting mutations in the DMD gene encoding dystrophin. Loss of dystrophin protein results in progressive muscle degeneration and premature death. Approximately 60% of DMD patients have frameshifting mutations in a hotspot region within exons 45-55 in the rod domain of dystrophin. Genotype/phenotype assessments have revealed that in-frame deletion of exons 45-55 leads to the milder, allelic disease, Becker muscular dystrophy. This finding suggests that restoration of the reading frame by targeting exons 45-55 could treat ~60% of DMD patients to greatly reduce disease severity. We have developed a platform using clustered regularly interspaced short palindromic repeats (CRISPR) and- associated protein (Cas9) gene editing to achieve this purpose. We have utilized CRISPR/Cas9-mediated deletion and rejoining of up to 725kb to restore the reading frame in DMD human induced pluripotent stem cells (hiPSCs). This is the largest deletion shown to date in DMD. Clonal hiPSC lines containing the exon 45-55 deletion were differentiated to disease relevant types, such as cardiomyocytes and skeletal muscle myotubes, which had restored dystrophin protein. We demonstrated, for the first time, that the internally deleted dystrophin generated by CRISPR/Cas9 was functional and improved membrane integrity, reduced miR31 expression, and restored the dystrophin glycoprotein complex in vitro and after engraftment of skeletal muscle cells in vivo. This gene editing platform restores the reading frame for the majority of DMD patients and offers potential as an ex vivo correction for stem cell therapy or for use in vivo.
Mass Spectrometry Approaches for Identification and Quantitation of Therapeutic Monoclonal Antibodies in the Clinical Laboratory

Therapeutic monoclonal antibodies (MAbs) are an important class of drugs used to treat diseases ranging from autoimmune disorders to B cell lymphomas to other rare conditions thought to be untreatable in the past. Many advances have been made in the characterization of immunoglobulins as a result of pharmaceutical companies investing in technologies that allow them to better understand MAbs during the development phase. Mass spectrometry is one of the new advancements utilized extensively by pharma to analyze MAbs and is now beginning to be applied in the clinical laboratory setting. The rise in the use of therapeutic MAbs has opened up new challenges for the development of assays for monitoring this class of drugs. MAbs are larger and more complex than typical small-molecule therapeutic drugs routinely analyzed by mass spectrometry. In addition, they must be quantified in samples that contain endogenous immunoglobulins with nearly identical structures. In contrast to an enzyme-linked immunosorbent assay (ELISA) for quantifying MAbs, mass spectrometry-based assays do not rely on MAb-specific reagents such as recombinant antigens and/or anti-idiotypic antibodies, and time for development is usually shorter. Furthermore, using molecular mass as a measurement tool provides increased specificity since it is a first-order principle unique to each MAb. This enables rapid quantification of MAbs and multiplexing. This review describes how mass spectrometry can become an important tool for clinical chemists and especially immunologists, who are starting to develop assays for MAbs in the clinical laboratory and are considering mass spectrometry as a versatile platform for the task.
Nano Sensing Devices – Future Directions

Nanotechnology offers tremendous opportunities for developing sensing and monitoring devices that are small and inexpensive with rapid response time of multiple analyte detection. In addition, there is the potential for these sensors to have “smart” or active capabilities embedded in them. These devices can help meet critical challenges identified in the environmental, occupational, biological and national security areas.
First Coastal Californians: Edited by Lynn H. Gamble. School for Advanced Research Press, Santa Fe. 2015. ISBN 978-1-938645-19-8 (Paperback US $24.95), 144 pp, 24 color plates, 13 color illustrations, 3 drawings, 135 halftones, 5 maps, 3 charts.

To those of us who pursue it, we know that California archaeology is spectacular and immensely interesting, but we should face it, this is not generally well known by the public. Indeed, as far as ...
Microring Weight Banks for Neuromorphic Silicon Photonics

Research in photonic information processing has experienced a recent resurgence. Microring weight banks enable reconfigurable neural network approaches on silicon photonics. We discuss the latest results in neuromorphic silicon photonic networks and microring weight banks.
Field Observations and Modeling of Surfzone Sensible Heat Flux

AbstractSurf zone sensible heat flux (HS,SZ) obtained through direct eddy-covariance estimates was measured at four different sandy beach sites along Monterey Bay, CA, USA. The HS,SZ source region is estimated from a footprint probability distribution function (pdf) model and is only considered when at least 70% of the footprint pdf occupies the surf zone. HS,SZ measured are two times larger than modeled interfacial sensible heat (HS,int) using COARE3.5. A formulation for estimating sensible heat flux from spray droplets (HS,spray) generated during depth-limited wave breaking is developed. The sea-spray generation function for droplet radii ranging 0.1<ro<1000μm is based on self-similar spectra of spray droplets measured from the surf zone forced by the average depth-limited breaking wave dissipation across the surf zone. However, it is shown that the size of the spume droplets that contribute to HS,spray is limited owing to the relatively short residence time in air as the droplets fall to the sea surfac...
Wave prediction using wave rider position measurements and NARX network in wave energy conversion

Abstract Several control methods of wave energy converters (WECs) need prediction in the future of wave surface elevation. Prediction of wave surface elevation can be performed using measurements of surface elevation at a location ahead of the controlled WEC in the upcoming wave. Artificial neural network (ANN) is a robust data-learning tool, and is proposed in this study to predict the surface elevation at the WEC location using measurements of wave elevation at ahead located sensor (a wave rider buoy). The nonlinear autoregressive with exogenous input network (NARX NN) is utilized in this study as the prediction method. Simulations show promising results for predicting the wave surface elevation. Challenges of using real measurements data are also discussed in this paper.
Support for and interest in alternative models of medication abortion provision among a national probability sample of U.S. women.

Abstract Objective The objective was to assess women's personal interest in and support for three alternative models of medication abortion (MA) provision. Study design Using an online survey of a U.S. national, probability-based representative sample of women ages 18–49, we gauged personal interest in and general support for three alternative models for accessing abortion pills: (1) in advance from a doctor for future use, (2) over-the-counter (OTC) from a drugstore and (3) online without a prescription. We conducted multivariable analyses to identify characteristics associated with support for these provision models. Results Fifty percent (n=7022) of eligible women invited completed the survey. Nearly half (49%) supported and 30% were personally interested in one or more of the three access models; 44% supported advance provision, 37% supported OTC access, and 29% supported online access. Common advantages reported for advance provision, OTC and online access included privacy (49%, 29% and 46%, respectively), convenience (38%, 44% and 38%) and being able to end the pregnancy earlier (48%, 40% and 29%). Common disadvantages included concern that women might take the pills incorrectly (55%, 53% and 57%), not seeing a clinician before the abortion (52%, 54% and 53%) and safety (42%, 43% and 60%). History of abortion and experiencing barriers accessing reproductive health services were associated with greater support for the alternative models. Conclusion Women are interested in and support alternative models of MA provision, in particular, advance provision. However, they also reported concerns about incorrect pill use and not seeing a clinician beforehand. Implications Offering women more choices in how they access medication abortion, including options where they can safely self-manage their own care, has the potential to expand access to care.
Abstract TP157: Ethnic Difference in Stroke Recurrence for Patients With Intracranial Atherosclerotic Stenosis

Background: Intracranial atherosclerotic stenosis (ICAS), one of most common stroke subtypes worldwide, carries high risk of stroke recurrence despite maximal medical treatment. ICAS more commonly ...
Antidepressant use in elderly medical inpatients: lessons from an attempted clinical trial.

The authors conducted a clinical trial to examine the efficacy and safety of nortriptyline in the treatment of major depression in elderly medical inpatients. The diagnosis of major depression was made by a psychiatrist in 41 of 680 patients 65 years of age or older. The study was halted at the midpoint because of inadequate patient recruitment, primarily a consequence of medical illnesses that prevented more than 80% of eligible patients from participating in or completing the clinical trial. Major or minor medical contraindications to the use of antidepressants were present in over 90% of depressed patients. Short-term follow-up was cnducted on untreated depressed patients, those receiving antidepressants at the time of assessment, and those in whom antidepressant treatment was initiated after assessment. Non-randomized exposure to antide-pressants did not predict remission of depression at follow-up due to spontaneous remission in the untreated group. Given the prevalence of medical contraindications to antidepressant use among depressed elderly patients and the problems with side effects in treated patients, there were few depressed, elderly hospitalized patients who were candidates for antidepressant therapy.
A Parallel Graph Algorithm for Detecting Mesh Singularities in Distributed Memory Ice Sheet Simulations

We present a new, distributed-memory parallel algorithm for detection of degenerate mesh features that can cause singularities in ice sheet mesh simulations. Identifying and removing mesh features such as disconnected components (icebergs) or hinge vertices (peninsulas of ice detached from the land) can significantly improve the convergence of iterative solvers. Because the ice sheet evolves during the course of a simulation, it is important that the detection algorithm can run in situ with the simulation --- running in parallel and taking a negligible amount of computation time --- so that degenerate features (e.g., calving icebergs) can be detected as they develop. We present a distributed memory, BFS-based label-propagation approach to degenerate feature detection that is efficient enough to be called at each step of an ice sheet simulation, while correctly identifying all degenerate features of an ice sheet mesh. Our method finds all degenerate features in a mesh with 13 million vertices in 0.0561 seconds on 1536 cores in the MPAS Albany Land Ice (MALI) model. Compared to the previously used serial pre-processing approach, we observe a 46,000x speedup for our algorithm, and provide additional capability to do dynamic detection of degenerate features in the simulation.
Deck Tennis: A Prerequisite to Net Sports

Deck tennis is an educational game that builds confidence and serves as a helpful introductory unit to net sports. This article discusses the history and rules of deck tennis and how it serves as a...
Investigating Neurogenic Differentiation of Dental Pulp Stem Cells Using PLA and Graphene Thin-Film and Electrospun Fiber Scaffolds in Vitro

Dental pulp derived cells are pluripotent stem cells which can be differentiated along odontogenic, osteogenic, adipogenic, or neurogenic lineages. Odontogenic and osteogenic differentiation, in the absence of dexamethasone, have been shown to be highly dependent on substrate morphology and mechanics. Here we focus on neurogenic differentiation, using the protocol described by A. Arthur et al., and its dependence on substrate nature. DPSCs were cultured on PLA, a biodegradable polymer approved for internal use. The upregulation of genetic markers was compared with that of cells plated on standard TCP. The role of substrate morphology was investigated by plating on electrospun fibers approximately 2.0 ± 1.0 μm in diameter and on spin-cast thin films. The influence of graphene was investigated through the addition of 3% and 10% graphene nanoparticles to the films and fibers respectively. The aspect ratio of the cells was measured using confocal microscopy. Cells grown on graphene containing substrates had larger aspect ratios than their non-graphene counterparts, and cells grown on microfibers were longer than their counterparts on the flat films. But the cell aspect ratio did not necessarily correlate with genetic differentiation. The results after 21 days of incubation indicated that early markers (TBP, β-III tubulin), decreased uniformly on all substrates relative to day 0, with the largest decrease occurring on the PLA flat film with graphene. The late stage marker, NEFM, which indicates differentiation, was upregulated to a significantly larger extent on all PLA substrates. No difference was observed between the fibers and the flat film in the absence of graphene, thus morphology did not play a significant role on this polymer. Addition of graphene did not affect the outcome on the fibers, but significantly suppressed the gene expression on the flat films. These results indicate that PLA is a promising scaffold material for neurogenic differentiation.
Risk and Vulnerability on the Campanian Plain: The Vesuvius Eruption of A.D. 472

The projects of social history, disaster studies, and archaeology deliberately tend to eschew consideration of events, focusing instead on processes and structures that unfold gradually over time. ...
Teaching NeuroImages: MRI abnormalities in frontal lobe seizures due to nonketotic hyperglycemia.

A 56-year-old woman presented with electroclinical focal seizures in the setting of hyperglycemia (808 mg/dL) and elevated HbA1c of 14.7%. She had varying seizure semiology, consisting of early forced head turn to the left, speech arrest, left facial twitching, and impaired awareness. Her seizures arose from the right frontotemporal area on EEG (figure 1). MRI showed hypointensities in the right prefrontal lobe that resolved after 6 months (figure 2).
Obesity is a predictor of increased morbidity after tracheostomy.

Abstract Objective The purpose of this study was to analyze the relationship between body mass index (BMI) and 30-day morbidity and mortality risk in patients undergoing tracheostomy using the American College of Surgeons National Quality Improvement Program (ACS-NSQIP). Study design This is a retrospective, cross-sectional, cohort study. Setting Patients were identified with Current Procedural Terminology codes in the ACS-NSQIP database. Subjects and methods Patients who underwent tracheostomy from 2005 to 2018 were queried. They were stratified into four BMI classes and matched to normal BMI cohorts. Multivariate logistic regression was used to identify independent predictors for complications, readmissions, and unplanned reoperations within 30 days. Results Among 3784 patients meeting inclusion and exclusion criteria, obesity was shown to be a significant independent risk factor for overall complications (OR 1.439, 95% CI 1.226–1.689, p Conclusions Obesity was found to be independently associated with an increased risk of overall complication, developing acute renal failure, and having an unplanned 30-day readmission following tracheostomy. The risk of postoperative transfusion appears to be lower in obese patients. Level of evidence 4.
The Present and Future of Consultation Scholarship: Reflections on Seven Years as Editor of Journal of Educational and Psychological Consultation

This article provides the perspective of the outgoing Editor of this journal. Reflecting on this editor’s seven years in this role, suggestions for future directions in consultation scholarship are...
Toxic Effects of Polychlorinated Biphenyl Congeners and Aroclors on Embryonic Growth and Development

Polychlorinated biphenyls (PCBs) cause significant health and reproductive problems in many vertebrates. Exposure during embryogenesis likely leads to defects in organ development, compromising survival and growth through adulthood. The present study identifies the impact of PCBs on the embryonic development of key organs and resulting consequences on survival and growth. Zebrafish embryos were treated with individual PCB congeners (126 or 104) or one of 4 Aroclor mixtures (1016, 1242, 1254, or 1260) and analyzed for changes in gross embryonic morphology. Specific organs were assessed for defects during embryonic development, using a variety of transgenic zebrafish to improve organ visualization. Resulting larvae were grown to adulthood while survival and growth were assayed. Embryonic gross development on PCB treatment was abnormal, with defects presenting in a concentration-dependent manner in the liver, pancreas, heart, and blood vessel organization. Polychlorinated biphenyl 126 treatment resulted in the most consistently severe and fatal phenotypes, whereas treatments with PCB 104 and Aroclors resulted in a range of more subtle organ defects. Survival of fish was highly variable although the growth rates of surviving fish were relatively normal, suggesting that maturing PCB-treated fish that survive develop compensatory strategies needed to reach adulthood. Life span analyses of fish from embryogenesis through adulthood, as in the present study, are scarce but important for the field because they help identify foci for further studies. Environ Toxicol Chem 2021;40:187-201. © 2020 SETAC.
The Cultural Revolution: A People’s History, 1962–1976: by Frank Dikötter, New York: Bloomsbury, 2016; paperback ed. 2019, $20.00

One of the most horrific major events of human history only ended in the mid-1970s; to say that it is within living memory is to profoundly understate its ongoing social reality. Huge numbers of cu...
Toward an Open IoT Implementation for Urban Environments: The Architecture of the DBL SmartCity Platform

Smart cities collect and utilize various types of geo-referenced data in order to enhance the performance and quality of urban services, such as governance, transportation, energy use, and air quality monitoring. Information and communication technologies (ICT), including Internet of Things (IoT) systems and networks, constitute an essential component of smart city initiatives. In this chapter, we describe the architectural considerations behind our recently introduced, open DBL SmartCity platform for managing geo-referenced IoT data typically generated in urban environments. One of the principal requirements selected for the platform involved the utilization of open data standards, open data transfer protocols, and open data formats in order to facilitate interoperability and data exchange. Another requirement concerned platform scalability, which was achieved through the adoption of open-sourced “big data” and streaming computing frameworks, libraries, and technologies. The platform also fulfills the modularity requirement as it is able to exchange its parts and modules with alternative, functionally equivalent technologies.
Are H I Supershells the Remnants of Gamma-Ray Bursts?

Gamma-ray bursts (GRBs) are thought to originate at cosmological distances from the most powerful explosions in the universe. If GRBs are not beamed, then the distribution of their number as a function of ?-ray flux implies that they occur once per ~(0.3-40) million years per bright galaxy and that they deposit 1053 ergs into their surrounding interstellar medium. The blast wave generated by a GRB explosion would be washed out by interstellar turbulence only after tens of millions of years when it finally slows down to a velocity of ~10 km s-1. This rather long lifetime implies that there could be up to several tens of active GRB remnants in each galaxy at any given time. For many years, radio observations have revealed the enigmatic presence of expanding neutral-hydrogen (H I) supershells of near-kiloparsec radius in the Milky Way and in other nearby galaxies. The properties of some supershells cannot be easily explained in terms of conventional sources such as stellar winds or supernova explosions. However, the inferred energy and frequency of the explosions required to produce most of the observed supershells agree with the above GRB parameters. More careful observations and analysis might reveal which fraction of these supershells are GRB remnants. We show that if this link is established, the data on H I supershells can be used to constrain the energy output, the rate per galaxy, the beaming factor, and the environment of GRB sources in the universe.
Consumer-Based Brand Equity and Consumer-Based Brand Performance: Evidence From Smartphone Brands in the USA

Consumer-based brand equity (CBBE) has attracted academic endeavor and strategic emphasis in practice to examine its role for brand success. Despite its diagnostic power for brands, prior studies fail to: reach consensus on conceptualization and operationalization, consider prospective consumers and competing brands, and identify linkages with brand performance. Our study therefore proposes an integrative model of consumer-based brand performance (CBBP) to address its relationship with CBBE. Within this aim, we intend to achieve two objectives. First, we prove that the key components of CBBE, that is, brand attributes, associations and judgments, all play significant roles in determining CBBP. Second, we demonstrate the detailed relationship among the three components of CBBE. Accordingly, we test hypotheses based on the structural equation modeling of 1670 valid questionnaire responses from young consumers (aged 18–35) in the USA and comparative analysis of two competing smartphone brands (iPhone vs. Samsung). As a result, we contribute to theoretical and empirical understanding concerning the relationship between CBBE and CBBP. We also enrich brand empirical understanding by addressing two main competing brands in the US smartphone industry. The combined SEM and comparative analysis add both breadth and depth to current understandings. The results provide implications for practitioners to devise brand strategies which consider the varied impact of consumers, as a key stakeholder, for success.
Multiscale model of the physiological control of myocardial perfusion to delineate putative metabolic feedback mechanisms

Abstract Coronary blood flow is tightly regulated to ensure that myocardial oxygen delivery meets local metabolic demand via the concurrent action of myogenic, neural, and metabolic mechanisms. While several competing hypotheses exist, the specific nature of the local metabolic mechanism(s) remains poorly defined. To gain insights into the viability of putative metabolic feedback mechanisms and into the coordinated action of parallel regulatory mechanisms, we applied a multi-scale modeling framework to analyze experimental data on coronary pressure, flow, and myocardial oxygen delivery in the porcine heart in vivo. The modeling framework integrates a previously established lumped-parameter model of myocardial perfusion used to account for transmural hemodynamic variations and a simple vessel mechanics model used to simulate the vascular tone in each of three myocardial layers. Vascular tone in the resistance vessel mechanics model is governed by input stimuli from the myogenic, metabolic, and autonomic control mechanisms. Seven competing formulations of the metabolic feedback mechanism are implemented in the modeling framework, and associated model simulations are compared to experimental data on coronary pressures and flows under a range of experimental conditions designed to interrogate the governing control mechanisms. Analysis identifies a maximally likely metabolic mechanism among the seven tested models, in which production of a metabolic signaling factor is proportional to MVO2 and delivery proportional to flow. Finally, the identified model is validated based on comparisons of simulations to data on the myocardial perfusion response to conscious exercise that were not used for model identification.
Bio-Tile: An Intelligent Hybrid-Infrastructure

Bio-tile is a multipurpose artifact designed for protecting the coastline from erosion while creating a landscape element and an architectural experience for visitors. Bio-tile performs as a mitigation strategy to slow down erosion while promoting biodiversity. This paper describes the methodology used to develop the bio-tile as the nexus between digital and environmental for resolving coastline challenges through material tectonics. A non-linear algorithm and nature’s inherent code are used to develop the Bio-tile, a nature-based hybrid infrastructure. This approach aims to generate a performance-oriented design by using emergence theory to construct shoreline elements adaptive to climatic conditions.
Effect of Antibodies to Somatostatin on Acid Secretion and Gastrin Release by the Isolated Perfused Rat Stomach

The present studies were directed toward examining the effect of somatostatin on gastrin release and acid secretion by the isolated vascularly perf used rat stomach. Rat stomachs were perf used in situ with Krebs-Ringer bicarbonate buffer containing 10% ovine erythrocytes and gassed with 95% O 2 –5% CO 2 . Inclusion of pentagastrin in the perfusion buffer increased acid output from 2.2 ± 0.4 μEq H + /h during control perfusion to 18.8 ± 1.8 μEq H + /h (p + /h (p
Misoprostol for second trimester pregnancy termination in women with prior caesarean: a systematic review.

Background Second trimester pregnancy induction with misoprostol in women with prior caesarean delivery is not well studied. Objective To estimate the risk of uterine rupture using misoprostol as an induction agent for pregnancy termination in the second trimester of pregnancy in women with prior caesarean delivery. Search strategy Cases of women with a history of prior caesarean delivery and subsequent misoprostol induction for pregnancy termination in the second trimester (16–28 weeks) were obtained from two main data sources. First, a retrospective chart analysis was performed at Thomas Jefferson University Hospital and Christiana Hospital between 1998 and 2004. Second, multiple Medline, Scopus and POPLINE literature searches were performed. Selection criteria Case series and cohort studies of women with one or more prior caesarean delivery (of any type), and with a subsequent pregnancy with induction of labour for pregnancy termination at 16–28 weeks using misoprostol as the initial primary agent were included. Case reports were analysed separately. Data collection and analysis Total cases were analysed by type and number of prior caesarean delivery, for the primary outcome of uterine rupture. Main results The incidence of uterine rupture associated with second trimester misoprostol termination was 0.4% (2/461) in women with one prior low transverse, 0% (0/46) in those with two prior low transverse and 50% (1/2) in those with a prior classical caesarean delivery. One of the cases of uterine rupture in a woman with a prior low transverse caesarean required transfusion. None of the total eight cases (including case reports) of uterine rupture was associated with hysterectomy. Conclusions Second trimester misoprostol termination appears safe among women with one prior low transverse caesarean birth, as it is associated with incidences of uterine rupture of 0.4% (95% confidence interval 0.08–1.67%), of hysterectomy of 0% and of transfusion of 0.2%. There are insufficient data on risk with more than one prior caesarean birth or with prior classical caesarean birth.
Alginate production by plant-pathogenic pseudomonads.

Abstract Eighteen plant-pathogenic and three non-plant-pathogenic pseudomonads were tested for the ability to produce alginic acid as an exopolysaccharide in vitro. Alginate production was demonstrated for 10 of 13 fluorescent plant-pathogenic pseudomonads tested with glucose or gluconate as the carbon source, but not for all 5 nonfluorescent plant pathogens and all 3 non-plant pathogens tested. With sucrose as the carbon source, some strains produced alginate while others produced both polyfructan (levan) and alginate. Alginates ranged from <1 to 28% guluronic acid, were acetylated, and had number-average molecular weights of 11.3 × 103 to 47.1 × 103. Polyfructans and alginates were not elicitors of the soybean phytoalexin glyceollin when applied to wounded cotyledon surfaces and did not induce prolonged water soaking of soybean leaf tissues. All or most pseudomonads in rRNA-DNA homology group I may be capable of synthesizing alginate as an exopolysaccharide.
A Client-Server Architecture for Document Image Recognition

We propose a client-server architecture for deploying document image recognition applications, especially graphics recognition applications, in large organizations. An example of such an application is presented. We discuss advantages of client-server techniques over the currently available stand-alone tools for document image recognition.
Restriction of expression of an integrated recombinant retrovirus in primary but not immortalized murine hematopoietic stem cells.

A recombinant retrovirus (DHFR*-SVADA) in which human adenosine deaminase (ADA) cDNA is transcribed from an internal SV40 promoter was used to infect murine hematopoietic stem and progenitor cells. Human ADA enzyme was not expressed in infected primary murine pluripotent stem cell-derived spleen or progenitor colonies (CFU-GM, CFU-Mix, BFU- E). In contrast, human ADA enzyme activity was readily detected in progenitor colonies derived from immortalized multipotent factor- dependent cells. The level of human enzyme was near endogenous murine enzyme levels and was equivalent in undifferentiated stem cells and differentiated myeloid, erythroid, and mixed colonies. These results indicate that cellular properties other than the stage of differentiation are important in determining the expression of foreign sequences introduced by retroviruses. Cell lines that are immortalized but still capable of induced differentiation may contain factors that abrogate blocks to expression that are manifested in primary hematopoietic stem cells.
Scaled accumulation FETs for ultra-low power logic

Ultra-low power systems require very low standby power and operate at moderate speeds. Traditionally, the normal surface channel inversion (SCI) FET would be considered better for such applications when compared to the buried channel (BC) FET, since the BC FET has always shown more short channel effects in past research. However, past comparisons between the two FETs have been done with the highest frequency in mind and the same conclusion need not hold true for moderate speed, ultra-low power applications. Due to a better subthreshold slope and negligible band to band tunneling leakage at the drain-halo and drain-channel region, the BC FET is better suited for such applications.
The genomic instability associated with integrated simian virus 40 DNA is dependent on the origin of replication and early control region.

Abstract DNA rearrangements in the form of deletions and duplications are found within and near integrated simian virus 40 (SV40) DNA in nonpermissive cell lines. We have found that rearrangements also occur frequently with integrated pSV2neo plasmid DNA. pSV2neo contains the entire SV40 control region, including the origin of replication, both promoters, and the enhancer sequences. Linearized plasmid DNA was electroporated into X1, an SV40-transformed mouse cell line that expresses SV40 large T antigen (T Ag) and shows very frequent rearrangements at the SV40 locus, and into LMtk-, a spontaneously transformed mouse cell line that contains no SV40 DNA. Stability was analyzed by subcloning G-418-resistant clones and examining specific DNA fragments for alterations in size. Five independent X1 clones containing pSV2neo DNA were unstable at both the neo locus and the T Ag locus. By contrast, four X1 clones containing mutants of pSV2neo with small deletions in the SV40 core origin and three X1 clones containing a different neo plasmid lacking SV40 sequences were stable at the neo locus, although they were still unstable at the T Ag locus. Surprisingly, five independent LMtk- clones containing pSV2neo DNA were unstable at the neo locus. LMtk- clones containing origin deletion mutants were more stable but were not as stable as the X1 clones containing the same plasmid DNA. We conclude that the SV40 origin of replication and early control region are sufficient viral components for the genomic instability at sites of SV40 integration and that SV40 T Ag is not required.
Shame and the Social Bond

This article proposes that shame may be the hidden key to understanding our civilization, in the sense that shame or its anticipation is virtually ubiquitous, yet, at the same time, usually invisible. C.H. Cooley's idea of the looking glass self implies that shame and pride can be seen as signals of the state of the social bond. Theoretical work by Cooley and Erving Goffman imply ubiquity, and empirical studies by Norbert Elias and Helen Lewis provide support. The findings of Elias and Lewis also suggest that shame is usually invisible; Elias stated this proposition explicitly. Like other emotions, such as fear, shame can be recursive, acting back on itself (shame about shame). In unusual circumstances, limitless recursion of shame may explain extreme cases of silence or violence.
Physics of Cometary Magnetospheres

This tutorial summarizes our present, pre-Rosetta understanding of the basic physical processes operating in cometary environments with particular attention to cometary magnetotails. Ionization of cometary gases is responsible for most plasma processes in the magnetospheres of active comets. The interaction between the superalfvenic, magnetized solar wind and cometary ions forms a number of plasma boundaries starting with the weak bow shock and continuing with the contact surface (diamagnetic cavity boundary), the recombination layer and the inner shock. The plasma tail is sensitive to changes in the solar wind and to varying cometary activity. These processes will be explored in detail.
Interaction of the bacteriophage T4 gene 59 helicase loading protein and gene 41 helicase with each other and with fork, flap, and cruciform DNA.

Abstract Bacteriophage T4 gene 59 helicase loading protein accelerates the loading of T4 gene 41 DNA helicase and is required for recombination-dependent DNA replication late in T4 phage infection. The crystal structure of 59 protein revealed a two-domain α-helical protein, whose N-terminal domain has strong structural similarity to the DNA binding domain of high mobility group family proteins (Mueser, T. C., Jones, C. E., Nossal, N. G., and Hyde, C. C. (2000) J. Mol. Biol. 296, 597–612). We have previously shown that 59 protein binds preferentially to fork DNA. Here we show that 59 protein binds to completely duplex forks but cannot load the helicase unless there is a single-stranded gap of more than 5 nucleotides on the fork arm corresponding to the lagging strand template. Consistent with the roles of these proteins in recombination, we find that 59 protein binds to and stimulates 41 helicase activity on Holliday junction DNA, and on a substrate that resembles a strand invasion structure. 59 protein forms a stable complex with wild type 41 helicase and fork DNA in the presence of adenosine 5′-O-(thiotriphosphate). The unwinding activity of 41 helicase missing 20 C-terminal amino acids is not stimulated by 59 protein, and it does not form a complex with 59 protein on fork DNA.
Specifying differential cyclical response in economic time series: Capacity utilization and demand for imports

Abstract This paper begins with a discussion of several techniques currently employed to specify non-reversible relationships and shows that many of the more popular techniques lead to biased slope and intercept estimates when the data have a natural order and the purpose is to estimate differential response over a series of cycles. Next a general specification of a non-reversible relationships is proposed. This variable partitioning procedure has two advantages over currently employed techniques: (1) It allows unbiased estimation of slope and intercept parameters; (2) It implies a set of joint hypotheses which can be tested to deduce the appropriate adjustment path. The suggested procedure is then applied to an investigation of the effect of capacity utilization on US import demand. Employing a model posited by Gregory [5] but correcting his inappropriate specification of capacity utilization's ratchet effect, we find a significant, non-reversible relationship between capacity utilization and import demand. This result is precisely the opposite of that originally inferred by Gregory. We conclude that inappropriate specification of non-reversible relationships can lead to incorrect forecasts and policy decisions and that these problems can be corrected if our specification procedure is employed.
Nonhydrostatic nested climate modeling: A case study of the 2010 summer season over the western United States

[1] The potential importance of local-scale climate phenomena motivates development of approaches to enable computationally feasible nonhydrostatic climate simulations. To that end, we evaluate the potential viability of nested nonhydrostatic model approaches, using the summer climate of the western United States (WUSA) as a case study. We use the Weather Research and Forecast (WRF) model to carry out five simulations of summer 2010. This suite allows us to test differences between nonhydrostatic and hydrostatic resolutions, single and multiple nesting approaches, and high- and low-resolution reanalysis boundary conditions. WRF simulations were evaluated against station observations, gridded observations, and reanalysis data over domains that cover the 11 WUSA states at nonhydrostatic grid spacing of 4 km and hydrostatic grid spacing of 25 km and 50 km. Results show that the nonhydrostatic simulations more accurately resolve the heterogeneity of surface temperature, precipitation, and wind speed features associated with the topography and orography of the WUSA region. In addition, we find that the simulation in which the nonhydrostatic grid is nested directly within the regional reanalysis exhibits the greatest overall agreement with observational data. Results therefore indicate that further development of nonhydrostatic nesting approaches is likely to yield important insights into the response of local-scale climate phenomena to increases in global greenhouse gas concentrations. However, the biases in regional precipitation, atmospheric circulation, and moisture flux identified in a subset of the nonhydrostatic simulations suggest that alternative nonhydrostatic modeling approaches such as superparameterization and variable-resolution global nonhydrostatic modeling will provide important complements to the nested approaches tested here.
The Cambridge Companion to the Arthurian Legend

Reviewed Medium: book Year: 2009 Pages: 286 Publisher: Cambridge University Press ISBN: 978-0-521-86059-8 (hard cover).
Carbon Isotopic Fractionation in Fischer-Tropsch Type Reactions and Relevance to Meteorite Organics

Fischer-Tropsch-Type (FTT) reactions have been hypothesized to contribute to the formation of organic compounds in the early solar system, but it has been difficult to identify a signature of such reactions in meteoritic organics. The work reported here examined whether temperature-dependent carbon isotopic fractionation of FTT reactions might provide such a signature. Analyses of bulk organic deposits resulting from FTT experiments show a slight trend towards lighter carbon isotopic ratios with increasing temperature. It is unlikely, however, that these carbon isotopic signatures could provide definitive provenance for organic compounds in solar system materials produced through FTT reactions, because of the small scale of the observed fractionations and the possibility that signatures from many different temperatures may be present in any specific grain.