cssi/SciSciGPT-SciSciNet huggingface dataset:
Effect of Eledoisin on the Systemic Venous Return in Dogs.

SummaryThe effects of eledoisin on the cardiovascular system were studied in anesthetized dogs. It was found that eledoisin decreased MSAP and increased HR, CO, MPAP, and LAP. In addition, when cardiac input was kept constant by means of a Sig-mamotor pump, eledoisin increased the blood level of the venous reservoir, indicating an increase in SVR. The increases in MPAP and LAP observed after eledoisin are most likely due to the increase in SVR.The author wishes to acknowledge the able technical assistance of Mr. G. R. Mercer. Synthetic eledoisin and sodium heparin (Liquaemin and Pan-heparin) were generously supplied, respectively, by Dr. R. Bircher of Sandoz Pharmaceuticals, Dr. H. A. Strade of Organon, Inc. and Dr. H. G. Schoepke of Abbott Laboratories.
The distribution of posterior parietal fibers in the corpus callosum of the rhesus monkey

The distribution of posterior parietal fibers in the corpus callosum of the rhesus monkey was analyzed using autoradiographic techniques. Posterior parietal fibers are located in the posterior half of the body of the corpus callosum. There is some segregation of fibers with respect to their place of origin within the posterior parietal lobe. However, there is also overlap, particularly between fibers coming from the caudal inferior parietal lobule and the medial parietal lobe.
Beta-adrenergic receptors, adenylate cyclase activation, and myofibril enzyme activity in hypothyroid rats

A previous study in intact animals assessed cardiovascular alterations in surgically thyroidectomized rats. Hemodynamic challenge via isoproterenol infusion identified abnormal left ventricular relaxation. Challenge by aortic occlusion revealed a latent deficiency in left ventricular contractility which was not apparent during beta-agonist challenge. The present study utilized left ventricular cardiac tissue obtained from the identical control and thyroidectomized animals from which intact heart hemodynamic information had been obtained. Biochemical systems were selected for evaluation based on demonstrated hemodynamic alterations, i.e., beta-adrenergic receptor number/function and contractile protein enzyme properties. The number of beta-receptors on hypothyroid cardiac membranes was significantly decreased, but receptor agonist affinity was not influenced. Basal adenylate cyclase activity in cardiac membranes from control and thyroidectomized rats was nearly identical; however, isoproterenol activation was diminished in hypothyroid cardiac membrane, particularly at the higher levels of beta-agonist stimulation. Adenylate cyclase enzyme activation by forskolin was not influenced by thyroidectomy; however, activation by sodium fluoride was reduced approximately 30% when compared with preparations from control rats. Cardiac myofibrillar enzyme activity for adenosinetriphosphatase (ATPase) was significantly lower in thyroidectomized rats. Despite reduced ATPase activity, myofibrillar calcium sensitivity was unaltered. Myofibrillar creatine kinase enzyme activity was not influenced by thyroidectomy; therefore, compartmentalized ATP regeneration potential via creatine kinase was enhanced relative to substrate utilization via ATPase. Thus hemodynamically significant cardiac influences of hypothyroidism are mediated, at least in part, via 1) reduced beta-receptor number, 2) diminished catecholamine-induced activation of adenylate cyclase, and 3) reduced myofibrillar ATPase activity.
Cardiac trauma including injury of great vessels.

Two innovations of the past decade — rapid transport of the injured patient and the development of portable machines for circulatory assistance — have extended the salvage possibility of more extensive injuries to the central cardiovascular system. Injuries are classified according to and discussed in terms of their anatomic and functional characteristics, rather than by the nature of the trauma, and emergency management of this type of injury is considered.
Association of Type 1 Blood Group Antigens with Urinary Tract Infections in Children with Genitourinary Structural Abnormalities

AbstractBacterial adherence to carbohydrate receptors on the surface of urothelial cells is important in the pathogenesis of urinary tract infections. Blood group-related antigens, genetically determined carbohydrate structures found on the urothelial cell surface, may influence the availability of these receptors thereby affecting bacterial adherence and the susceptibility to urinary tract infections. Recent evidence indicates that the immunoanatomical distribution of type 1 blood group-related antigens in urothelium is influenced by ABO, Lewis and secretor phenotypes, women with Le(a−b−) and Le(a+b−) blood phenotypes have more than a 3-fold greater risk of recurrent urinary tract infections compared to Le(a−b+) women and epithelial cells from nonsecretors have more bacterial receptors than cells from secretors.To determine the relation between the expression of type 1 blood group-related antigens and urinary tract infections we performed an immunohistochemical analysis using a well characterized panel o...
Early detection of at-risk students in CS1 using teachback/spinoza

In this paper, we provide evidence that analysis of student interaction with web-based pedagogical tools in a large partly-flipped CS1 class can be used for early detection of at-risk students. We used student interaction data to estimate five learning style features: engagement, learning speed, confidence, drive, and persistence. We found a positive correlation between final course grades and two of the features of student learning style: engagement and learning speed. Drive and persistence were not good predictors of student success but did provide lower bounds on overall course performance. Confidence was a poor predictor of overall course performance. This kind of analysis provided a more timely and nuanced view of student learning styles than can be obtained from traditional summative assessments and this data could allow for early detection of at-risk students in an introductory programming course.
PRIMARY EDUCATION: CHANGING MAINSTAY OF URUGUAY

Traditionally one of the countries with highest levels of social and human development in Latin America, Uruguay is a small and eminently urban country, with an extended welfare state and universal education. From the beginnings of the twentieth century, education has been one of its main tools for promoting nationality and citizenship. The region and Uruguay experimented with different economic development models, switching development models from an Import Substitution Model (ISM) to an exportoriented model. As a result, the second half of the twentieth century entailed a series of changes in the social structures of the country. Poverty and inequality indicators grew and the architecture of the welfare state gradually lost its capacity to respond to a changing structure of social risks (Filgueira et al., 2005). Education was not insulated from these changes. In 1995, there is a revolution in the educational public system caused by the reform initiated by the national government. This reform has concentrated most of its strategies on equity in resources (with compensatory emphasis) and has resulted in centralized models that combine focused and universal resources assignment. In primary educational level, Full-Time School model has been its main and more successful tool. 1 Eleven years after the beginning of the reform, the educational system faces, in terms of its organization, a set of tensions between the traditional structure and the emerging model. The challenges are four: Teachers’ stability in schools, degree of autonomy between the school and the central administration, cultural impoverishment of the underprivileged social sectors, and the necessity of basing the expansion of the new model on additional resources. This chapter provides an analysis of the educational system characteristics associated with these four tensions, and a discussion of the most important risks in terms of universalizing the emerging transformation.
Después de Chaos. Auto similaridad en las ciencias sociales

This paper discusses a general cultural mechanism that defines change in sociology and social sciences. To do this, I summarize the exposition that I made of this fractal mechanism in the book Chaos of Disciplines, and then I propose some extensions to locate that mechanism in the more general approach of social scientific knowledge that I have developed in recent years, in an attempt to incorporate it into a broader context.
Developing "whole school" bystander interventions: the role of school-settings in influencing adolescents responses to dating violence and bullying

Abstract Bystander intervention programs have been introduced as innovative strategies to empower teens to intervene proactively when they witness bullying and dating violence (TDV) in their social environments. While there is promising research on the individual-level factors that influence students' willingness to intervene, there has been limited investigation on how teens' school environments encourage proactive responses. Through analysis of focus group data, this study revealed that teens are reluctant to employ bystander behaviors in any capacity. Some of the school-level factors that influenced their willingness to intervene include: trusting relationships with teachers; the perception that school personnel, rather than students, have more expertise to respond effectively; school environments that were tolerant of dating abuse; and ineffective school policies. Implications for creating “whole-school” responses to bullying and TDV will be discussed.
An understanding of Native American entrepreneurship

ABSTRACTNative American entrepreneurship is not just about money, it is about history, tradition, culture and language embedded in time and traditional territory. It is the creation, management and development of entrepreneurial ventures by Native American peoples for the benefit of Native American peoples. With increased recognition of rights come increased opportunities for Native American entrepreneurship and entrepreneurial ventures that focus on social, economic and environment value creation for and by Native American peoples. Native American ventures are more successful when the rights of Native American peoples are addressed and when these initiatives utilize nation-building approaches led by Native American communities. It is a means by which they can assert their rights to design, develop and maintain Native American-centric political, economic and social systems and institutions.
Detecting Privileged Side-Channel Attacks in Shielded Execution with Déjà Vu

Intel Software Guard Extension (SGX) protects the confidentiality and integrity of an unprivileged program running inside a secure enclave from a privileged attacker who has full control of the entire operating system (OS). Program execution inside this enclave is therefore referred to as shielded. Unfortunately, shielded execution does not protect programs from side-channel attacks by a privileged attacker. For instance, it has been shown that by changing page table entries of memory pages used by shielded execution, a malicious OS kernel could observe memory page accesses from the execution and hence infer a wide range of sensitive information about it. In fact, this page-fault side channel is only an instance of a category of side-channel attacks, here called privileged side-channel attacks, in which privileged attackers frequently preempt the shielded execution to obtain fine-grained side-channel observations. In this paper, we present Deja Vu, a software framework that enables a shielded execution to detect such privileged side-channel attacks. Specifically, we build into shielded execution the ability to check program execution time at the granularity of paths in its control-flow graph. To provide a trustworthy source of time measurement, Deja Vu implements a novel software reference clock that is protected by Intel Transactional Synchronization Extensions (TSX), a hardware implementation of transactional memory. Evaluations show that Deja Vu effectively detects side-channel attacks against shielded execution and against the reference clock itself.
The Effects of the Warning Signal on Response Characteristics in Avoidance Learning

Two experiments are reported in which a buzz was used to indicate either the inter-trial interval (ITIBUZZ) or the warning period (WARNBUZZ) in a discriminated avoidance schedule (Experiment 1) or to indicate the beginning only of these periods (FEEDBUZZ and TRACEBUZZ, respectively) (Experiment 2). 11 hooded rats served as Ss. Faster acquisition of the lever press avoidance response was obtained when the buzz was associated with either the beginning or with the entire warning period than when this stimulus was associated with the beginning or with the entire inter-trial interval. The results were related to topographical characteristics of the lever response. During early taining sessions, Ss learned to escape shock and concurrently developed extensive lever holding. It was observed that onset of the buzz interfered with lever holding so that its use as a warning signal, as in WARNBUZZ and TRACEBUZZ conditions, promoted momentary release of the lever and thus favored avoidance acquisition.
Seismic anisotropy beneath the Mississippi Embayment and the New Madrid Seismic Zone: A study of shear wave splitting

Shear wave splitting associated with the Mississippi Embayment (ME) is determined using teleseismic SKS phases recorded by the Northern Embayment Lithosphere Experiment (NELE), the USArray Transportable Array (TA), and the New Madrid seismic network for the period 2005–2016. Our data set consists of ~5900 individual splitting measurements from 257 earthquakes recorded at 151 stations within and outside the ME. Stations outside of the ME exhibit significant shear wave splitting, with average delay times between ~ 0.4 s and ~1.8 s. To the northeast and east of the ME, nearly all observed fast orientations are approximately oriented northeast-southwest, in agreement with absolute plate motion (APM) predicted by HS3-Nuvel-1A. The homogeneity of the fast orientations in this region suggests that the splitting is due to active flow in the asthenosphere. A counterclockwise rotation in the splitting orientation is observed moving northeast to northwest across the study area. Inside the ME, some stations show large and systematic deviations of the measured fast orientations from the APM. The delay times within the entire ME range from ~0.9 s to ~ 2.1 s. Splitting complexity is attributed to relic lithospheric fabrics formed during past tectonic events including passage of a hot spot in mid-Cretaceous time. The anisotropy may also be linked to the presence of a southwest dipping region of low P and S wave velocities below the ME or to deeper flow in the asthenosphere.
New features and capabilities in Arena 15.1

Arena 15.1 was released to the market earlier this year. This latest release of Arena includes a number of advancements designed to enhance ease-of-use, make complex simulations easier and expand the overall simulation capabilities of Arena. This presentation will cover those enhancements and provide demonstrations on how to make the most of these new capabilities.
Standards-based mathematics instruction and sociomathematical norms: Facilitating change in an undergraduate classroom

Research indicates that standards-based mathematics instruction positively supports students’ academic development. Although standards documents identify accepted best practices, they do not speak ...
COMPARISON OF A GENERIC AND A DISEASE-SPECIFIC MEASURE OF PAIN AND PHYSICAL FUNCTION AFTER KNEE REPLACEMENT SURGERY

Generic and disease-specific health status instruments are commonly used to assess patients' outcomes. The hypothesis that they measure distinct but complementary aspects of patients' quality of life was tested using a sample of patients aged 67 to 99 years who had undergone knee replacement surgery 2 to 7 years previously. Patients' scores on a generic health-related quality-of-life (HRQOL) measure, the SF-36, were compared to those of the Western Ontario and McMaster Universities (WOMAC) Osteoarthritis Index; the WOMAC was developed specifically for patients with lower extremity arthritis, whereas the SF-36 is aimed at all conditions. A stratified sample of 1,750 Medicare beneficiaries was surveyed and an overall response rate of 80.3% achieved, resulting in 1,193 usable surveys (after adjustment for ineligible, incapacitated, and deceased individuals). The distribution of scores on the three dimensions common to both instruments (i.e., pain, physical function, and overall score) showed consistently higher scores on the WOMAC, on a scale of 0 (worst) to 100 (best), than on the SF-36, indicating less disability from arthritis than from other conditions after knee surgery in this elderly population. Statistically significant differences in the number of people with perfectly healthy scores were detected between the instruments; with regard to pain, 32.2% of the sample reported no pain due to arthritis on the WOMAC, compared with only 13.6% reporting no pain due to any conditions on the SF-36. The figures for physical function and overall score were 9.6% versus 1.4%, and 6.9% versus 0.2%, respectively. Examination for discriminant validity showed that the scores on the two scales followed hypothesized patterns: the WOMAC discriminated better among subjects with varying severity of knee problems, whereas the SF-36 discriminated better among subjects with varying levels of self-reported health status and comorbidity. The results of this study support the inclusion of both a generic and a disease-specific HRQOL measure to assess patient outcomes fully.
Sleep Apnea in the Bariatric Surgery Patient

Obstructive sleep apnea hypopnea (OSAH) is a chronic medical condition characterized by repetitive episodes of breathing disturbance, characterized by upper airway obstruction, occurring during sleep. It is extremely common in patients undergoing bariatric surgery and may impact perioperative complications. It is also one of the medical comorbidities of obesity that may be cured after the weight loss resulting from bariatric surgery. This chapter reviews the pathophysiology and clinical aspects of OSAH, emphasizing the relationship with obesity, bariatric preoperative workup and management, and the perioperative implications of OSAH.
Structure of glycoproteins of human erythrocytes. Alkali-stable oligosaccharides.

Studies have been made on the oligosaccharide residues of the alkali-stable carbohydrate–protein linkage of sialoglycopeptides derived from human erythrocytes. Four glycopeptides were isolated after alkaline borohydride treatment and Pronase digestion of MN-active sialoglycopeptides. The structure of one of these glycopeptides (GPIV) has been studied by sequential hydrolysis with specific glycosidases. Glycopeptide GPIV contained (per mol): 1mol of fucose, 1mol of sialic acid, 3mol of galactose, 3mol of mannose, 4mol of acetylglucosamine, 1mol of aspartic acid and fractional amounts of threonine, serine and glycine. The molecular weight of the glycopeptide was estimated to be 2330 by gel filtration. On the basis of glycosidase-digestion results, a tentative structure is proposed for the oligosaccharide moiety of glycopeptide GPIV.
Evaluation of sanitizer penetration and its effect on destruction of Escherichia coli O157:H7 in Golden Delicious apples.

This study was conducted to determine the penetration of 5% trisodium phosphate solution at various depths within punctures and calyces of apples spot inoculated with Escherichia coli O157:H7 and the effect of solution agitation on destruction of the pathogen. Sanitizer solutions containing radiolabeled disodium phosphate (DSP 32 ) were able to penetrate apple tissues through punctures and calyx cavities. However, agitation of the solutions did not result in significantly greater penetration in these areas (P > 0.05). Overall, there were 1.57- and 1.11-log reductions of pathogen cells within 4-h-old punctures treated with and without trisodium phosphate solution agitation, respectively. Sanitizer solutions were effective in destroying pathogen cells residing within the upper 4.2-mm region of the punctures. Destruction of pathogen cells within open and closed calyces occurred mainly within the basin and the upper 3 mm of the calyx cavity. Treatment with agitated sanitizer solution resulted in a 0.67-log reduction in pathogen concentration within open calyces. In contrast, treatment of closed calyces resulted in a 1.37-log reduction, mainly within the basin. Washing with water alone appeared to result in further penetration of the cells within calyces without significantly reducing the number of pathogen cells (P > 0.05). To develop more effective methods for reducing contamination on produce, it is important to know the extent of sanitizer penetration and its effect on destruction of pathogens.
Neuroendocrine Regulation in Sex-changing Fishes

Publisher Summary This chapter discusses the neuroendocrine regulation of sex reversal in teleost fishes. Sex reversal is a complex integrative, multilevel phenomenon that covers multiple aspects of multiple endocrine axes. It also discusses various types of sex reversal, social control, and evolutionary aspects, and most importantly the neuroendocrine control mechanisms of sex reversal in fishes. Sex change in fishes is one of the most fascinating aspects in the field of vertebrate reproduction. Sex change can be from female to male (protogyny) or male to female (protandry). Social cues mediate the change process, but these cues trigger a cascade of events in the hypothalamic–pituitary–gonadal axis. The end result is a total reconfiguration of the gonad and behavior. Chemical signals ranging from classical neurotransmitters to neuropeptides to steroids are involved.
Psychotherapeutic interventions for chronic pain: Evidence, rationale, and advantages.

BackgroundLong-term use of opioids to treat chronic pain incurs serious risks for the individual—including misuse, abuse, addiction, overdose and death—as well as creating economic, social, and cul...
Abstract 4702: Upgrading cancer immunotherapy: Checkpoint blockade mAb-ODN conjugate

Programmed death 1 (PD-1) and its ligand PD-L1 provide inhibitory signals that affect the balance of T cell activation, playing major roles in tumor immune escape. Inhibition of negative regulators of T cell activation effectively remove signals that restrain T cell proliferation and gain of effector function. Hence, disruption of the PD-1/PD-L1 signaling pathway by the use of monoclonal antibodies (mAbs) can improve tumor control by enhancement of the endogenous antitumor immune responses. Toll-like receptors (TLR) are a specialized set of pathogen recognition receptors found in innate and adaptive immune system cells. Activation of these receptors by danger-associated molecules such as bacterial DNA or RNA, initiate signaling cascades leading to protective immune responses. Synthetic oligodeoxynucleotides (ODNs) containing unmethylated CpG motifs can mimic bacterial DNA and therefore function as ligands for intracellular TLR9, prompting consequential activation of immune responses. The purpose of this study was to assess the feasibility of using PD-1/PD-L1 mAbs conjugated to TLR9 agonists (ODNs) as a novel strategy for tumor-targeting immune checkpoint signaling and activation of immune cells. Antibodies recognizing PD-1 and PDL-1 were covalently modified with a 21mer ssDNA oligonucleotide linker sequence that served as an anchor site for the ODNs synthesized with a 39 extension. Annealing of complementary strands formed mAb-ODN conjugates. Quantification of ODNs per PD-1 or PDL-1 mAbs was verified by flow cytometry. Functionality of PD-1 and PDL-1-ODN conjugates was analyzed in vitro using splenocyte cultures and cell proliferation was evaluated by incorporation of radiolabeled H3 Thymidine. In vivo experiments were carried out using Balb/c mice bearing 4T1 subcutaneous tumors. Flow cytometry analysis confirmed each modified mAb had 5 linker sequences available to bind ODNs, and also defined the binding capability of mAb portion of the conjugate to epitope target. Splenocytes proliferation at day 5 after treatment revealed that PD-1 and PDL-1 conjugated to ODNs have significantly increased proliferation in comparison to non-conjugated mAb and ODN controls. These results indicate that conjugation of mAb-ODN is feasible and that conjugation does not affect PD-1 and PDL-1 antibody functionality. Interestingly, in vivo experiments demonstrated PDL-1-ODN but not PD1-ODN conjugate affects 4T1 tumor growth. Use of this approach to improve the therapeutic index of immunotherapeutic mAbs requires further study and validation in different murine tumor models. Citation Format: Ana Paula Benaduce, Tal Gefen, Sergio Rodriguez, Brian Marples, Eli Gilboa, Adrian Ishkanian. Upgrading cancer immunotherapy: Checkpoint blockade mAb-ODN conjugate [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4702.
Fasting versus Non-fasting Lipid profile in the clinical practice

There are pros and cons doing fasting and random non-fasting lipid profile test. However, when we consider cardio vascular risk, non-fasting lipid test more reliable than fasting test. In current practice, using fasting lipid profile was challenged in 2007 by two studies that showed that random non-fasting triglyceride (TG) could be superior than fasting TG in predicting risk of cardiovascular risk. Postprandial concentrations of triglyceride were higher than fasting. However, levels of non-fasting triglycerides are better at predicting future cardiovascular events than levels of fasting triglycerides. Random non-fasting lipid test is not a new phenomenon, it already practicing in Denmark since 2009. Moreover, NICE guidelines have recommended non-fasting test in the primary prevention setting since 2014. As the major shift in newer guidelines reflects the changing focus of risk assessment from LDL to non-HDL cholesterol (apolipoprotein B) as a better predictor of cardiovascular risk, indirectly tell us non-fasting lipid level superior than fasting lipid. The aim of the review is to compare both fasting and non-fasting measurements in our clinical practice.
On the statistical distribution of primary and secondary dendrite arm spacing in cast metals

Statistical distributions of dendrite arm spacing have not been addressed in the literature. Two histograms for primary dendrite arm spacing in a cast nickel-based superalloy, and four histograms f...
Realizing highly coordinated, rapid and sustainable nucleate boiling in microchannels on HFE-7100

Abstract Flow boiling in microchannels using dielectric fluids is one of the most desirable cooling solutions for high power electronics. However, it is challenging to promote the flow boiling performances, particularly critical heat flux (CHF), due to their unfavorable thermophysical properties. Flow boiling in parallel and isolated microchannels has been extensively studied. In this study, five parallel microchannels (W = 200 µm, H = 250 µm, L = 10 mm) are interconnected by 4 × 28 micro-slots (20 µm wide and 250 µm deep) starting from the middle section to the channel outlet. Our visualization study shows that these micro-slots designed as artificial nucleation sites can enable high frequency nucleate boiling by drastically reducing the bubble waiting time and remaining fully activated, simultaneously. More importantly, such rapid switch on–off harmonically coordinated nucleate boiling in the neighboring channels creates a highly desirable periodic rewetting mechanism to substantially delay CHF conditions and enhance heat transfer rate. Flow boiling in this innovative microchannel configuration has been systematically characterized with mass flux ranging from 462 kg/m2∙s to 1617 kg/m2∙s. Compared to plain-wall microchannels with inlet restrictors (IRs), flow boiling heat transfer coefficient (HTC) is enhanced up to ∼172% at a mass flux of 462 kg/m2·s primarily owing to the enhanced latent heat transfer including nucleate boiling and thin film evaporation. The peak value of effective HTC is ~60 kW/m2·K in the fully developed boiling regime. Moreover, CHF is substantially enhanced by ∼76% at a mass flux of 1155 kg/m2·s owing to the rapid and periodic rewetting enabled by these micro-slots. Such drastic enhancements have been achieved without compromising two-phase pressure drop.
Site Specific X‐Ray Anomalous Dispersion of the Geometrically Frustrated Kagome Magnet, Herbertsmithite, ZnCu3(OH)6Cl2.

A single crystal of (Zn0.85Cu0.15)Cu3 (OH)6Cl2 is obtained from a mixture of CuO, ZnCl2, and H2O (185 °C, 2 d) followed by recrystallization of the microcrystalline product.
Abstract 2608: EGF signaling activates a TAZ-driven oncogenic program in glioblastoma

Glioblastoma multiforme (GBM) is the most aggressive and lethal primary brain tumor in humans. Hyperactivation of the signaling pathway driven by the epidermal growth factor (EGF) and its receptor (EGFR) are commonly occurring in GBM. The oncogenic transcriptional program driven by EGF signaling is still incompletely understood in GBM. Here, we found that EGF induces the upregulation and nuclear translocation of TAZ, an oncogenic transcriptional co-activator. TAZ and its paralog gene YAP are commonly known as downstream mediators of the Hippo signaling pathway. TAZ has been found as a driver of mesenchymal transition in GBM cells and promotes GBM radioresistance. Our results support that EGF induces TAZ transcription and the activation of TAZ gene targets, through the signaling axis including EGFR, STAT3 and ERK. EGFRvIII is the most frequently occurring EGFR mutation in GBM causing constitutively active EGFR. We found that EGFRvIII causes EGF-independent activation of TAZ and its downstream oncogenic targets. Next, we used next-generation sequencing to establish a genome-wide map of TAZ gene targets in GBM cells after EGF stimulation. The results suggest that EGF signaling activates a TAZ-driven oncogenic program including autocrine and paracrine factors that promote GBM growth, angiogenesis, stemness and immunoescape. Moreover, we found that TAZ targeting by shRNAs or the FDA-approved drug Verteporfin effectively inhibits the TAZ-driven oncogenic program activated by EGF stimulation or the EGFRvIII mutant. TAZ targeting also inhibits GBM cell growth and xenograft formation. In contrast, enforced TAZ induces the TAZ-driven oncogenic program and promotes GBM cell growth and xenograft formation. In conclusion, our results reveal a novel TAZ-driven oncogenic program that is activated by EGF signaling in GBM. Our discoveries strongly support TAZ as a therapeutic target for GBM and likely other human cancer with hyperactivation of EGF signaling. Our preclinical studies also provide a clinically translatable strategy for GBM therapy based on using the FDA-approved drug Verteporfin. Citation Format: Minling Gao, Yi Fu, Laterra John, Mingyao Ying. EGF signaling activates a TAZ-driven oncogenic program in glioblastoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 2608.
INTEGRATION AND THE CHANGING ROLE OF COMPUTING IN ACADEMIC HEALTH CENTERS.

Abstract Integration is emerging as a key concept in managing information resources for the academic health center (AHC) environment, with its multiple functions. The changing role of computing is characterized by a growing symbiosis with the health sciences library, which is increasingly automated. Academic health centers have moved to bring information resources under the control of top level policy officers and to restructure computing resources into an information utility. With an infrastructure capable of supporting a distributed networked system, outreach is critical. Outreach services and programs range from support services provided by the information utility, informatics programs within the schools, and technology assisted learning centers.
Chapter 17: Global Public Health Disaster Management and Technology

Disasters can dismantle the lives of entire populations in unimaginable ways. Minimizing the impact of these disasters, and helping people to recover from their aftermath, are major areas of concern in the global public health field. Increasingly so, largely because of innovations, decreasing cost, and increasing accessibility, is the ability of technology to both mitigate and assist with the response to disasters. Some of the specific methods by which technology can assist in the field of disaster response investigated in this chapter include virtual reality simulations, modeling and simulation of disasters, the use of mobile technology and phones for civilians, social media, early warning systems, mapping, and information dissemination. The next steps necessary to optimize the use of technology in disaster preparedness, as well as a specific case study outlining the workflow in the face of a disaster, are also included.
Hybrid and Total Endovascular Approaches to Tandem Carotid Artery Lesions Have Similar Short- and Long-Term Outcomes

BACKGROUND Addition of ipsilateral proximal endovascular intervention (PEI, common carotid/innominate) increases the risk of perioperative stroke/death for both carotid endarterectomy (CEA) and carotid stenting (CAS). However, these approaches have not been directly compared and is the subject of this study. METHODS VQI (2005-2020) was queried for CEA and CAS with PEI, excluding emergent, bilateral, and repeat procedures, patients with prior ipsilateral CAS, ICA lesions with stenosis 70%. Long-term outcomes were compared with Kaplan-Meier Analysis. RESULTS There were 1,433 patients (795 endovascular;638 hybrid); mean age 69.8±9.4 years. Patients undergoing hybrid procedures were more likely to be female (49.4% vs. 37.5%; P 70% stenosis (77.3% vs. 95.6%%; P < 0.001). Perioperative stroke/death was 3.6% for hybrid and 3.9% for endovascular approaches (P = 0.77). In the multivariable model, hybrid operative approach (compared to the total endovascular approach) was not significantly associated with stroke/death (OR 1.29; 95%CI: 0.55-3.07; P = 0.56). For the 981 patients with long-term follow-up (556 endovascular; 425 hybrid), 1-year freedom from stroke/reintervention/death was 94.0% (95%CI: 90.9%-96.0%) for hybrid approach vs. 92.3% (95%CI: 89.5%-94.4%) for endovascular approach (P = 0.27). CONCLUSION Although simultaneous repair of tandem carotid lesions portends worse outcomes when compared to CEA or CAS alone, there was no difference in short or long-term stroke and death rates with a hybrid or totally endovascular approach. Therefore, it is reasonable to use either approach in the select patients who require simultaneous repair of both lesions.
Incarceration of transplanted kidney through incisional hernia.

Transplanted allograft kidney herniation through an incisional hernia resulting in incarceration is a rare condition with only one other similar case reported in the literature. The primary imaging modalities used to diagnose kidney herniation are graft ultrasound, abdominal computed tomography and abdominal magnetic resonance imaging [Sugi et al. (Imaging of renal transplant complications throughout the life of the allograft: comprehensive multimodality review. Radiographics 2019;39:1327-1355)]. Treatment should be based on patient's symptoms. This case report highlights the initial presentation of hematuria in a 57-year-old male that eventually led to the diagnosis of a right-sided incarcerated grafted kidney through an incisional hernia. Subsequently, the patient underwent transplant nephrectomy.
The ASK1-Signalosome regulates p38 MAPK activity in response to levels of endogenous oxidative stress in the Klotho mouse models of aging

Reactive oxygen species (ROS) and elevated levels of p38 MAPK activity accelerate physiological aging. This emphasizes the importance of understanding the molecular mechanism(s) that link ROS production to activation of the p38 mediated promotion of aging, longevity, and resistance to oxidative stress. We examinedKlotho(-/-) (elevated ROS) and Klotho overexpressing mice (low ROS and resistance to ROS) to determine whether the ROS-sensitive apoptosis signal-regulating kinase (ASK1)-signalosome → p38 MAPK pathway plays a role in the accelerated aging of Klotho(-/-), and resistance to oxidative stress and extended lifespan in the Klotho overexpressing models. Our results suggest that increased endogenous ROS generated by Klotho(-/-) and resistance to oxidative stress in Klotho overexpression are linked to the regulation of ASK1-signalosome → p38 activity. We propose that (a) the ASK1-signalosome → p38 MAPK pathway is activated by oxidative stress due to ablation of the Klotho gene; (b) increased longevity by Klotho overexpression is linked to to suppression of the ASK1-signalosome-p38 MAPK activity; (c) the ROS-responsive ASK1-signalosome regulates physiological aging via its regulation of p38 MAPK, through a mechanism that balances the levels of inhibitory vs. activating ASK1-signalosomes. We conclude that the Klotho suppressor-of-aging activity is linked to the ASK1-signalsome, a physiological ROS-sensitive signaling center.
Extended operational space formulation for serial-to-parallel chain (branching) manipulators

This paper extends the operational space formulation to the important class of serial-to-parallel chain (branching) manipulators. The various models and concepts developed in operational space, such as dynamically consistent force/torque decomposition for control of redundant manipulators and the augmented object model for cooperative manipulator systems, are shown to extend directly. Dynamic modeling and experimental results for a free-flying, two-arm space robot are presented to validate this extension.
Constant Cost Industry

Constant cost industries are defined. Keywords: Cobb–Douglass production function; economies of scale; diseconomies of scale
Dressed Atom Picture of High Intensity Gas Laser

When an atom is placed in a strong optical field, its energy levels are effectively split by the field. This phenomenon may be interpreted as an ac Stark effect and the atom which has been modified by the strong field can be termed a "dressed atom" [I]. It is then of interest to examine the interaction of this dressed atom with additional fields (usually weak) that can serve to probe the dressed atom's structure. However, this type of approach breaks down when one considers the interaction of atoms or molecules with two strong fields If both fields are strong, the concept of one being the dressing field and one the probe field is not particularly useful. Nevertheless, it is still possible to interpret the interaction of two strong fields with atoms or molecules using a "dressed atom" approach. To illustrate this technique, we consider the interaction of a twolevel system with a strong standing wave field (equivalent to two strong traveling wave fields) such as is encountered in the theory of a high intensity single-mode gas laser [2]. To apply the dressed atom approach, we somewhat arbitrarily break up the atom-field interaction into a dressing field plus probe field interaction. The "dressed atoms" consist of atoms interacting with the oppositely directed traveling waves in the rate equation approximation (neglect of coupling between the fields except insofar as they share the same available population of atoms) while the "probe" interaction is represented by the difference between the true atom-field interaction and that of the rate equation approximation. With this approach, we can semiquantitatively predict which velocity subsets of atoms will experience saturation resonances. This resonance structure has been previously discovered in numerical solutions to the high intensity laser problem [2], and our predictions are in very good agreement with the actual position of the resonances. As such, the dressed atom approach is a useful method for obtaining some physical intu±tion in problems involving the interaction of two strong fields with atoms or molecules. The resonances discussed above are not directly measurable in the laser output. However, the resonances can be investigated by subjecting the atoms in this standing wave field to an additional probe field [3]. Alternatively, one can study the resonances by considering the mathematically equivalent problem of a single traveling wave inter. acting with an atom, but without using the rotating-wave or resonance approximation. In that case the resonances mentioned above can be viewed as representing multiphoton interactions of the field with the atoms.
Modifiable risk factors for coronary heart disease in women

Research in human coronary heart disease has been conducted primarily on males; however, investigators have begun to focus research efforts on female subjects as well. A literature review that identified studies on women and coronary heart disease was done to describe modifiable risk factors for coronary heart disease in women. Several modifiable risk factors such as smoking, hypertension, and disorders of lipid metabolism previously identified for men are also risk factors for women. However, the mechanisms by which some of these risk factors work in women are different from those in men. Moreover, women have additional risk factors related to menopause and, in some cases, the use of oral contraceptives. Significant initial information has been gained concerning women and coronary heart disease risk factors. However, gaps persist in information regarding the individual and synergistic effects of risk factors for CHD in women.
Gα13 Switch Region 2 Binds to the Talin Head Domain and Activates αIIbβ3 Integrin in Human Platelets

Even though GPCR signaling in human platelets is directly involved in hemostasis and thrombus formation, the sequence of events by which G protein activation leads to αIIbβ3 integrin activation (inside-out signaling) is not clearly defined. We previously demonstrated that a conformationally sensitive domain of one G protein, i.e. Gα13 switch region 1 (Gα13SR1), can directly participate in the platelet inside-out signaling process. Interestingly however, the dependence on Gα13SR1 signaling was limited to PAR1 receptors, and did not involve signaling through other important platelet GPCRs. Based on the limited scope of this involvement, and the known importance of G13 in hemostasis and thrombosis, the present study examined whether signaling through another switch region of G13, i.e. Gα13 switch region 2 (Gα13SR2) may represent a more global mechanism of platelet activation. Using multiple experimental approaches, our results demonstrate that Gα13SR2 forms a bi-molecular complex with the head domain of talin and thereby promotes β3 integrin activation. Moreover, additional studies provided evidence that Gα13SR2 is not constitutively associated with talin in unactivated platelets, but becomes bound to talin in response to elevated intraplatelet calcium levels. Collectively, these findings provide evidence for a novel paradigm of inside-out signaling in platelets, whereby β3 integrin activation involves the direct binding of the talin head domain to the switch region 2 sequence of the Gα13 subunit.
MRI measurements of intracranial pressure in the upright posture: The effect of the hydrostatic pressure gradient

Purpose To add the hydrostatic component of the cerebrospinal fluid (CSF) pressure to magnetic resonance imaging (MRI)-derived intracranial pressure (ICP) measurements in the upright posture for derivation of pressure value in a central cranial location often used in invasive ICP measurements. Materials and Methods Additional analyses were performed using data previously collected from 10 healthy subjects scanned in supine and sitting positions with a 0.5T vertical gap MRI scanner (GE Medical). Pulsatile blood and CSF flows to and from the brain were quantified using cine phase-contrast. Intracranial compliance and pressure were calculated using a previously described method. The vertical distance between the location of the CSF flow measurement and a central cranial location was measured manually in the mid-sagittal T1-weighted image obtained in the upright posture. The hydrostatic pressure gradient of a CSF column with similar height was then added to the MR-ICP value. Results After adjustment for the hydrostatic component, the mean ICP value was reduced by 7.6 mmHg. Mean ICP referenced to the central cranial level was −3.4 ± 1.7 mmHg compared to the unadjusted value of +4.3 ± 1.8 mmHg. Conclusion In the upright posture, the hydrostatic pressure component needs to be added to the MRI-derived ICP values for compatibility with invasive ICP at a central cranial location. J. Magn. Reson. Imaging 2015;42:1158–1163.
Differential Presentation of the Same MHC Class I Epitopes by Fibroblasts and Dendritic Cells

Ag is presented to CTL as peptide associated with MHC class I molecules, which are present on most types of cells. We have investigated the presentation of Db-restricted lymphocytic choriomeningitis virus (LCMV) peptides by a fibroblast line (MC57) and a dendritic cell line (JawsII) to splenocytes from LCMV-immune C57BL/6 mice. We found that when LCMV-infected MC57 were used to restimulate the spleen cells, the resulting CTL line lost its ability to respond to the two dominant epitopes of the immune response to LCMV glycoprotein (gp)33 and nucleoprotein (np)396 but remained strongly lytic for targets coated with the subdominant gp276 epitope. In contrast, when LCMV-infected JawsII cells were used to restimulate the splenocytes, the resulting line continued to target gp33 and np396 but lost reactivity to gp276. When uninfected JawsII or MC57 cells were coated with peptides and used as stimulators, the resulting CTL lines continued to recognize all three epitopes, indicating that costimulatory or other potential innate differences in Ag presentation between the two cell lines are unlikely to account for the selective expansion of CTL specificities. When infected, both cell types produce similar levels of infectious LCMV, have similar levels of the NP and GP proteins from which np396 and gp33 are derived, and can be recognized by CTL specific for each of the three epitopes. These data indicate that in the generation of peptides for MHC-I binding and presentation to CTL, MC57 and JawsII process the same set of virus proteins in quantitatively different ways.
MutS Preferentially Recognizes Cisplatin- over Oxaliplatin-modified DNA

Loss of mismatch repair leads to tumor resistance by desensitizing cells to specific DNA-damaging agents, including the anticancer drug cisplatin. Cisplatin analogs with a diamminocyclohexane (DACH) carrier ligand, such as oxaliplatin and Pt(DACH)Cl(2), do not elicit resistance in mismatch repair-deficient cells and therefore present promising therapeutic agents. This study compared the interactions of the purified Escherichia coli mismatch repair protein MutS with DNA modified to contain cisplatin and DACH adducts. MutS recognized the cisplatin-modified DNA with 2-fold higher affinity in comparison to the DACH-modified DNA. ADP stimulated the binding of MutS to cisplatin-modified DNA, whereas it had no effect on the MutS interaction with DNA modified by DACH or EN adducts. In parallel cytotoxicity experiments, methylation-deficient E. coli dam mutants were 2-fold more sensitive to cisplatin than DACH compounds. A panel of recombination-deficient mutants showed striking sensitivity to both compounds, indicating that both types of adducts are strong replication blocks. The differential affinity of MutS for DNA modified with the different platinum analogs could provide the molecular basis for the distinctive cellular responses to cisplatin and oxaliplatin.