cssi/SciSciGPT-SciSciNet huggingface dataset:
Gene Therapy of a Rat Follicular Thyroid Carcinoma Model with Adenoviral Vectors Transducing Murine Interleukin-12

Interleukin-12 (IL12) is a heterodimeric cytokine that plays an important role in the development of cellular immunity. We previously reported the antitumor activity of mouse IL12 (mIL12) transduced by adenovirus in a medullary thyroid carcinoma model. In this study, a rat thyroid follicular cancer cell line (RTC-R2) was employed to develop tumors after sc injection in Wistar rats. In five of five animals, RTC-R2 cells infected with mIL12 transducing adenovirus (AdCMVmIL12) in vitro failed to be tumorigenic in vivo in syngenic rats, whereas four of five animals developed tumors after injection of luciferase transducing adenovirus (AdCMVLuc)-infected cells. After intratumoral treatment with AdCMVmIL12 at 1 x 10(9) plaque-forming units per rat, 90% (26/29) of animals bearing small (<100 mm(3)) tumors were apparently cured. Larger tumors treated by injection of AdCMVmIL12 became significantly smaller than AdCMVLuc-treated animals, and growth stabilized. Challenge studies showed that only 3 of 28 animals previously treated and cured with AdCMVmIL12 developed a tumor after sc reinjection of RTC-R2 cells, whereas all animals developed tumors in naive animals. Thus, AdCMVmIL12-treated animals developed long-term antitumor immunity. We also studied animals with two tumors, injecting virus in one. Tumors regressed at both sites in five of six animals after treatment of one tumor with AdCMVmIL12, and in the sixth animal one site tumor regressed and another tumor continued to grow. In AdCMVLuc-treated animals, both tumors regressed in only one animal, and the reminder continued to grow. To detect toxicity to liver and other tissues after administration of AdCMVmIL2, the vector was administrated intratumorally or iv at the dose of 2 x 10(9) plaque-forming units per rat. No change in behavior was observed in any of the treated animals. Rats were killed at different time after virus administration. An overt increase of spleen size was observed 7 d after infection in all animals treated with AdCMVmIL12. All animals given virus IV had some lymphocyte infiltration in the sinusoids and triads of the liver, whereas AdCMVmIL12 injected intratumorally did not cause this effect. Spleens of some virus-treated animals showed decreased white pulp, with apparently increased hematopoiesis. No specific changes were found in lungs and kidneys. Iv administration of AdCMVmIL12 induced a moderate increase of glutamic-oxalacetic transaminase and glutamic-pyruvic transaminase, whereas AdCMVmIL12 injected intratumorally did not. This study confirms the efficient antitumor activity of an adenovirus expressing mIL12 after in vivo delivery in an animal model and indicates the possibility of application to patients because of the low toxicity.
Agency Political Ideology and Reform Implementation: Performance Management in the Bush Administration

A central purpose of performance management reforms such as the Bush administration’s Program Assessment Rating Tool (PART) is to promote the use of performance information in federal agencies. But reforms initiated by partisan political actors may be pursued differently, and may face relatively more obstacles, in agencies whose programs or personnel are associated with divergent political ideologies. Using data from a survey of federal agency managers, our analysis indicates that the impact of PART on managers’ use of performance information is largely contingent on the political ideology of the agencies in which managers work. Managers involved with the PART review process report greater performance information use than those not involved if they work in politically moderate and, especially, conservative agencies. However, there is no such difference in liberal agencies between those involved and those not involved with PART reviews. Supplementary analyses provide some evidence that these results are attributable to the PART review process itself, as opposed to inherent differences in the extent to which programs administered by liberal and conservative agencies lend themselves to performance management.
High-flow gas insufflation to facilitate MIDCABG: effects on coronary endothelium

Abstract Background . During less invasive coronary bypass operations on the beating heart, as well as conventional operations using continuous warm cardioplegia, a precise anastomosis is facilitated by a bloodless field. To maintain a clear field, many surgeons use high-flow gas insufflation. However, the potentially damaging effects of gas insufflation on coronary endothelium have not been elucidated. Methods . Seven pigs underwent median sternotomy. Between two coronary occluders, an arteriotomy in the mid left anterior descending coronary artery (LAD) was performed. In the experimental group (n = 5), the operative field was kept clear by exposing the arteriotomy to a catheter-directed stream of carbon dioxide at 15 L/min. In the control group (n = 2), the arteriotomy was left open to room air. After 20 minutes, the segments of LAD exposed to carbon dioxide or room air, and the unexposed proximal LAD and right coronary artery, were processed, sectioned, and stained together. A murine anti-human tie-2 monoclonal antibody was used to identify endothelium. Results . All unexposed LAD and right coronary artery segments and all LAD segments exposed only to room air demonstrated normal, contiguous staining of endothelium with the murine anti-human tie-2 monoclonal antibody. In contrast, all LAD segments exposed to high-flow carbon dioxide gas insufflation demonstrated near-complete loss of endothelium. Conclusions . These data demonstrate that high-flow carbon dioxide gas insufflation denudes the coronary artery of its endothelium. This exposes blood elements to the subendothelium and promotes clotting, and endothelial loss may promote smooth muscle cell migration and proliferation. These events set the stage for early and late graft failure.
Plastin polymorphisms predict gender- and stage-specific colon cancer recurrence after adjuvant chemotherapy

Tumor recurrence after curative resection remains a major problem in patients with locally advanced colorectal cancer treated with adjuvant chemotherapy. Genetic single-nucleotide polymorphisms (SNP) may serve as useful molecular markers to predict clinical outcomes in these patients and identify targets for future drug development. Recent in vitro and in vivo studies have demonstrated that the plastin genes PLS3 and LCP1 are overexpressed in colon cancer cells and play an important role in tumor cell invasion, adhesion, and migration. Hence, we hypothesized that functional genetic variations of plastin may have direct effects on the progression and prognosis of locally advanced colorectal cancer. We tested whether functional tagging polymorphisms of PLS3 and LCP1 predict time to tumor recurrence (TTR) in 732 patients (training set, 234; validation set, 498) with stage II/III colorectal cancer. The PLS3 rs11342 and LCP1 rs4941543 polymorphisms were associated with a significantly increased risk for recurrence in the training set. PLS3 rs6643869 showed a consistent association with TTR in the training and validation set, when stratified by gender and tumor location. Female patients with the PLS3 rs6643869 AA genotype had the shortest median TTR compared with those with any G allele in the training set [1.7 vs. 9.4 years; HR, 2.84; 95% confidence interval (CI), 1.32–6.1; P = 0.005] and validation set (3.3 vs. 13.7 years; HR, 2.07; 95% CI, 1.09–3.91; P = 0.021). Our findings suggest that several SNPs of the PLS3 and LCP1 genes could serve as gender- and/or stage-specific molecular predictors of tumor recurrence in stage II/III patients with colorectal cancer as well as potential therapeutic targets. Mol Cancer Ther; 13(2); 528–39. ©2013 AACR .
Designing an adaptive path execution system

The goal of this research was to develop a fully functional robot in a dynamic environment. The approach to this problem is to plan a path for the robot to move from a starting point using a map that may not have all the current information on the environment. The controller then dynamically reacts in an intelligent fashion to unplanned obstacles along the path. This system attempts to follow the path, adapting its course to the obstacles and shortcuts it perceives along the way. The key element of the approach is in using fuzzy logic to express and manipulate concepts needed for intelligent control. The robot only uses information gathered from the sensors, and avoids dynamically placed obstacles near and along the path. >
Research and development in the molecular genetics of pituitary adenomas and related tumors

Interview by Rona Williamson Constantine A Stratakis received his MD and Doctor of Medical Sciences degrees from the University of Athens (Greece) in 1989 and 1994, respectively; he did predoctoral work at the Unit of Endocrinology, Department of Experimental Pharmacology of the same University and at Hospital Cochin (Paris, France), before joining the Developmental Endocrinology Branch of the then National Institute of Child Health & Human Development (NICHD) at the NIH (MD, USA). He continued his postgraduate medical education at Georgetown University Medical School (DC, USA), where he finished a residency in Pediatrics and two fellowships, in Pediatric Endocrinology, followed by Medical Genetics and Clinical Dysmorphology (in a joint program with the then newly founded National Center for Genomic Research, now NHGRI). Dr Stratakis is Board-certified in Pediatrics, Pediatric Endocrinology and Medical Genetics; after a brief stint as faculty at Georgetown University Department of Pediatrics and the Fairfax Children's Hospital, he joined the Developmental Endocrinology Branch, NICHD, NIH as a Unit Chief in 1996; he continued there as a Senior Investigator and Chief of the Section on Genetics & Endocrinology. Since 2002, he is the Director of the Pediatric Endocrinology Training Fellowship and from 2007 to 2011, he served as Branch Chief and then Head of the Program on Developmental Endocrinology & Genetics (PDEGEN), the largest Department of the Intramural Clinical Research program of NICHD at the NIH Clinical Center. He is the author of more than 400 publications, and has served as a regular Reviewer in more than 100 journals, including Science, Nature Genetics, New England Journal of Medicine and others; he was Editor-in-Chief of the Journal of Endocrine Genetics (2000-2005) and is currently serving on the Editorial Boards of several journals; as of 1 January 2010, Dr Stratakis is a Deputy Editor of the Journal of Clinical Endocrinology & Metabolism, the leading journal in endocrinology. Dr Stratakis has been the recipient of the 1999 Pharmacia-Endocrine Society Award for Excellence in Published Clinical Research, three NIH Merit Awards and other honors, and has been named Visiting Professor in academic centers around the world. He was awarded the 2009 Ernst Oppenheimer Award of the Endocrine Society. Dr Stratakis has been the Scientific Director of the Eunice Kennedy Shriver National Institute of Child Health & Human Development since 2011.
Phosphorylation at the Nuclear Localization Signal of Ca2+/Calmodulin-dependent Protein Kinase II Blocks Its Nuclear Targeting

Translocation of protein kinases with broad substrate specificities between different subcellular compartments by activation of signaling pathways is an established mechanism to direct the activity of these enzymes toward particular substrates. Recently, we identified two isoforms of Ca2+/calmodulin-dependent protein kinase II (CaM kinase II), which are targeted to the nucleus by an alternatively spliced nuclear localization signal (NLS). Here we report that cotransfection with constitutively active mutants of CaM kinase I or CaM kinase IV specifically blocks nuclear targeting of CaM kinase II as a result of phosphorylation of a Ser immediately adjacent to the NLS of CaM kinase II. Both CaM kinase I and CaM kinase IV are able to phosphorylate this Ser residue in vitro, and mutagenesis studies suggest that this phosphorylation is both necessary and sufficient to block nuclear targeting. Furthermore, we provide experimental evidence that introduction of a negatively charged residue at this phosphorylation site reduces binding of the kinase to an NLS receptor in vitro, thus providing a mechanism that may explain the blockade of nuclear targeting that we have observed in situ.
Product Innovation Incentives: Monopoly vs. Competition

In contrast to Arrow's result for process innovations, we show that the gain from a product innovation can be larger to a secure monopolist than to a rivalrous firm that would face competition from independent sellers of the old product. A monopolist incurs profit diversion from its old good but may gain more than a rivalrous firm on the new good by coordinating the prices. In a Hotelling framework, we find simple conditions for the monopolist's gain to be larger. We also explain why the ranking of innovation incentives differs under vertical product differentiation.
An implementation of the Buzacott algorithm for network global-reliability

This study presents an implementation of the Buzacott algorithm (1980), and is based on a sequence-generating algorithm that lends itself to a simple computational procedure to locate probability values at any computation. A comparison made with the polychain algorithm on various network-sizes shows that polychain outperformed the algorithm presented by J.A. Buzacott (1980) by several orders of magnitude on sparse networks. The Buzacott algorithm outperformed polychain on fully connected and on dense, but less than fully connected, networks. A complexity model of the implementation is given. >
Clinical Reasoning: A 34-year-old man with recurrent limb weakness

A 34-year-old healthy man presented with 3 weeks of progressive bilateral arm weakness. He first noticed weakness while combing his hair and getting dressed. His symptoms were preceded by transient paresthesia in all 5 fingertips of both hands. Over the next 2 weeks, his weakness progressed slowly and spread to his forearms and hands. He never felt numbness or tingling in the feet. There was no visual disturbance, dysphagia, dysarthria, or bladder or bowel disturbance. There was no prodromal illness or vaccination. He took no medications and did not drink, smoke, or use drugs. Familial history was unremarkable. His general examination, including supine and erect blood pressure and pulse, was normal. The cranial nerves were intact. Strength was 3/5 in both deltoids and 4/5 in remaining muscles of both upper extremities. Neck flexor, extensor, and bilateral lower extremity muscles demonstrated normal muscle strength. Tendon reflexes were all absent apart from reduced bilateral brachioradialis and left triceps reflexes. Sensory tests with pin, cold, vibration, and proprioception had normal results. The rest of his examination, including gait, was normal. ### Question for consideration: 1. What is your differential diagnosis at this stage? This patient presented with progressive bilateral arm weakness. The sensory symptoms were subjective, minimal, and resolved eventually prior to treatment. Although the pattern of weakness suggests a myopathy, the clinical examination is more consistent with a motor neuropathy. The absence of the reflexes, in particular in the legs which were strong, makes the diagnosis of myopathy unlikely. Patients with Lambert-Eaton myasthenic syndrome (LEMS) can have absent reflexes which may reappear after exercise, but frequently have autonomic symptoms with weakness mainly in the legs. The differential diagnosis of an acute motor neuropathy includes the following1: 1. Idiopathic inflammatory causes such as Guillain-Barre syndrome (GBS), multifocal motor neuropathy (MMN), acute onset chronic inflammatory demyelinating polyneuropathy (CIDP), …
Robustness of Multiplicative Processes in Auditory Spatial Tuning

Auditory space-specific neurons in the owl's inferior colliculus selectively respond to the direction of sound propagation, which is defined by combinations of interaural time (ITD) and level (ILD) differences. Mathematical analyses show that the amplitude of postsynaptic potentials in these neurons is a product of two components that vary with either ITD or ILD. Temporal correlation in the fine structure of signals between the ears is essential for detection of ITD. By varying the degree of binaural correlation, we could accurately change the amplitude of the ITD component of postsynaptic potentials in the space-specific neurons. Multiplication worked for the entire range of postsynaptic potentials created by manipulation of ITD.
Contractual and regulatory compliance challenges in grid computing environments

Grid computing has been touted as an emerging revolution that transforms the enterprise information technology landscape by enabling organizations to share access to computing systems and data across organizational boundaries. The promised benefits include increased utilization of otherwise idle computing systems, and sharing data between organizations in a seamless but secure fashion. If these promises are fulfilled, grids can enable business partners to create virtual organizations with unique competitive advantages that are difficult to imitate. However, there are a number of technical and business challenges that must be overcome before the benefits of grid computing can be realized. In particular, this paper analyzes how contractual issues and government regulations can impact grid computing projects.
Hepatitis B Virus HBx Protein Localizes to Mitochondria in Primary Rat Hepatocytes and Modulates Mitochondrial Membrane Potential

Over 350 million people are chronically infected with hepatitis B virus (HBV), and a significant number of chronically infected individuals develop primary liver cancer. HBV encodes seven viral proteins, including the nonstructural X (HBx) protein. The results of studies with immortalized or transformed cells and with HBx-transgenic mice demonstrated that HBx can interact with mitochondria. However, no studies with normal hepatocytes have characterized the precise mitochondrial localization of HBx or the effect of HBx on mitochondrial physiology. We have used cultured primary rat hepatocytes as a model system to characterize the mitochondrial localization of HBx and the effect of HBx expression on mitochondrial physiology. We now show that a fraction of HBx colocalizes with density-gradient-purified mitochondria and associates with the outer mitochondrial membrane. We also demonstrate that HBx regulates mitochondrial membrane potential in hepatocytes and that this function of HBx varies depending on the status of NF-kappaB activity. In primary rat hepatocytes, HBx activation of NF-kappaB prevented mitochondrial membrane depolarization; however, when NF-kappaB activity was inhibited, HBx induced membrane depolarization through modulation of the mitochondrial permeability transition pore. Collectively, these results define potential pathways through which HBx may act in order to modulate mitochondrial physiology, thereby altering many cellular activities and ultimately contributing to the development of HBV-associated liver cancer.
The affinity of MOG specific CD4 + T cells does not predict cross-recognition to NFM in demyelinating autoimmune disease (BA2P.127)

TCRs can recognize and cross-react to multiple antigens, but little is known of how cross-reactivity might contribute to the etiology of demyelinating autoimmune disease. Here we extend the analysis of monoclonal 2D2 TCR cross-reactivity for MOG38-49 (myelin oligodendrocyte glycoprotein) and NFM18-30 (neurofilament medium protein) to polyclonal T cells. Utilization of the 2D micropipette adhesion frequency assay allows definition of antigen specificity and affinity of individual T cells for peptide:MHC ex vivo. We show that the frequency of CD4+ T cells from the CNS recognizing MOG, NFM, or both fluctuate during the course of MOG35-55 induced experimental autoimmune encephalomyelitis. Higher affinity T cells are maintained as a rare population within the repertoire yet the frequency of higher affinity, MOG specific T cells increase to a greater extent than NFM specific T cells during disease and MOG specific T cells exhibit higher affinities (10-4 to 10-3) than NFM specific T cells (<10-4). Importantly, cross-recognition is not limited to higher or lower affinity clones. We have cloned an encephalitogenic T cell that is high affinity for MOG and low affinity for NFM, which contrasts the 2D2 TCR exhibiting a medium affinity for NFM and a very low MOG affinity. On a population level, TCR recognition of one or more CNS antigens is dynamic within the chronic autoimmune repertoire warranting future research to understand their individual contributions to disease.
Parent attitudes about pediatricians addressing parental smoking.

Objective.— Pediatricians have a great opportunity to intervene in parental smoking, but few do so consistently. Pediatricians consistently cite concern about negative parental reaction as one barrier to addressing parental smoking. This study investigated parent attitudes about pediatricians addressing parental smoking at pediatric visits. Methods.— Parents (N = 341) were interviewed immediately after a pediatric visit about their attitudes toward pediatricians addressing parental smoking. Chi-square analyses identified relevant factors in parents' responses. Results.— Most parents (99%; n=337) said that asking about smoking is a very important part of a pediatrician's job (89%; n=302) or felt that it did not matter one way or the other (10%; n=35). There was no difference between attitudes of smoking and nonsmoking parents on this variable (χ 2 = 5.9, df = 1, P > .05). Very few nonsmokers (1%; n=2) or smokers (5%; n=2) believed that pediatricians have no business asking about parental smoking. The results support recent reports from adult practice that patient satisfaction ratings are improved when physicians ask about tobacco use and advise about quitting. Conclusions.— Both smoking and nonsmoking parents strongly believe that pediatricians should address parental smoking in the context of pediatric visits.
Size effect on structural strength: a review

The article attempts a broad review of the problem of size effect or scaling of failure, which has recently come to the forefront of attention because of its importance for concrete and geotechnical engineering, geomechanics, arctic ice engineering, as well as for designing large load-bearing parts made of advanced ceramics and composites, e.g. for aircraft or ships. First, the main results of Weibull statistical theory of random strength are briefly summarized, and its applicability and limitations described. In this theory as well as plasticity, elasticity with a strength limit, and linear elastic fracture mechanics (LEFM), the size effect is a simple power law, because no characteristic size or length is present. Attention is then focused on the deterministic size effect in quasibrittle materials which, because of the existence of a nonnegligible material length characterizing the size of the fracture process zone, represents the bridging between the simple power-law size effects of plasticity and of LEFM. The energetic theory of quasibrittle size effect in the bridging region is explained, and then a host of recent refinements, extensions and ramifications are discussed. Comments on other types of size effect, including that which might be associated with the fractal geometry of fracture, are also made. The historical development of the size-effect theories is outlined, and the recent trends of research are emphasized.
A hidden Markov model combined with climate indices for multidecadal streamflow simulation

Hydroclimate time series often exhibit very low year-to-year autocorrelation while showing prolonged wet and dry epochs reminiscent of regime-shifting behavior. Traditional stochastic time series models cannot capture the regime-shifting features thereby misrepresenting the risk of prolonged wet and dry periods, consequently impacting management and planning efforts. Upper Colorado River Basin (UCRB) annual flow series highlights this clearly. To address this, a simulation framework is developed using a hidden Markov (HM) model in combination with large-scale climate indices that drive multidecadal variability. We demonstrate this on the UCRB flows and show that the simulations are able to capture the regime features by reproducing the multidecadal spectral features present in the data where a basic HM model without climate information cannot.
Failure of Colorectal Surgical Site Infection Predictive Models Applied to an Independent Dataset: Do They Add Value or Just Confusion?

Background Colorectal surgical site infections (C-SSIs) are a major source of postoperative morbidity. Institutional C-SSI rates are modeled and scrutinized, and there is increasing movement in the direction of public reporting. External validation of C-SSI risk prediction models is lacking. Factors governing C-SSI occurrence are complicated and multifactorial. We hypothesized that existing C-SSI prediction models have limited ability to accurately predict C-SSI in independent data. Study Design Colorectal resections identified from our institutional ACS-NSQIP dataset (2006 to 2014) were reviewed. The primary outcome was any C-SSI according to the ACS-NSQIP definition. Emergency cases were excluded. Published C-SSI risk scores: the National Nosocomial Infection Surveillance (NNIS), Contamination, Obesity, Laparotomy, and American Society of Anesthesiologists (ASA) class (COLA), Preventie Ziekenhuisinfecties door Surveillance (PREZIES), and NSQIP-based models were compared with receiver operating characteristic (ROC) analysis to evaluate discriminatory quality. Results There were 2,376 cases included, with an overall C-SSI rate of 9% (213 cases). None of the models produced reliable and high quality C-SSI predictions. For any C-SSI, the NNIS c-index was 0.57 vs 0.61 for COLA, 0.58 for PREZIES, and 0.62 for NSQIP: all well below the minimum "reasonably" predictive c-index of 0.7. Predictions for superficial, deep, and organ space SSI were similarly poor. Conclusions Published C-SSI risk prediction models do not accurately predict C-SSI in our independent institutional dataset. Application of externally developed prediction models to any individual practice must be validated or modified to account for institution and case-mix specific factors. This questions the validity of using externally or nationally developed models for "expected" outcomes and interhospital comparisons.
Low voltage blue phase liquid crystal for spatial light modulators

We demonstrated a low-voltage polymer-stabilized blue phase liquid crystal (BPLC) for phase-only modulation with a liquid-crystal-on-silicon (LCoS). A new device configuration was developed, which allows the incident laser beam to traverse the BPLC layer four times before exiting the LCoS. As a result, the 2π phase change voltage is reduced to below 24 V in the visible region. The response time remains relatively fast (∼3 ms). The proposed device configuration enables widespread applications of BPLC spatial light modulators.
Leaving the Ballpark

Justice Stevens’s Sammy Sosa "leaving the ballpark" metaphor in City of Chicago v. Morales is used as a reminder that words may have multiple meanings.
On the nature of HNO2 and UV damages in T-even bacteriophages.

The interpretation of experiments with HNO2-inactivated phage T4 published byHarm (1960) and of similar experiments with UV inactivated phages T2 and T4 (Dulbecco 1952,Harm 1956, andEpstein 1958) is discussed. Two alternative theories are used as possible interpretations of the HNO2 experiments: (1) The “injection damage” theory holding that a fractionJ of the damages caused in a phage by HNO2 treatment prevent participation of the phage in the infectious process. (2) The “finite damage” theory holding that the damages produced by HNO2 in the genetic material are much larger (have a greater target length) than UV damages, and otherways applying to HNO2 damages the same theory earlier applied to UV-damages (Barricelli 1956 and 1960). Experimental methods to decide between the two theories are indicated. In the conclusion it is shown that the injection damage theory is not valid for UV damages in T2 and T4. In this case the theory is ruled out by the results ofDulbecco's (1952),Harm's (1956) andEpstein's (1958) MR experiments.
Economic Factors to Consider in Choosing Hatching Versus Table Eggs

Abstract INTRODUCTION ALTHOUGH production of hatching eggs was a sizable industry thirty years ago, it has reached greater importance since the development of the broiler industry to its present size. In spite of the importance of hatching egg production, there is little in the literature (including popular trade magazines) concerning the way in which an egg producer decides whether to produce hatching or table eggs. Yet this may be a problem of paramount importance to an egg producer. An egg producer has at his disposal a given amount of resources such as housing, equipment, labor, and managerial know-how which can be used in egg production. He is interested in maximizing returns to these resources and has at least two alternative uses for them: 1. Production of table eggs 2. Production of hatching eggs Within the category of hatching egg production, he can produce hatching eggs for laying flock replacement chicks or …
Bleeding during pregnancy.

The usual causes of bleeding at various periods of gestation are described in some detail. The rationale for the use of the steroid sex hormones in the treatment of threatened abortion is outlined. The treatment of the more serious complications of pregnancy, such as placenta previa, premature separation of the placenta and hydatidiform mole, is described.
SLX4-SLX1 Protein-independent Down-regulation of MUS81-EME1 Protein by HIV-1 Viral Protein R (Vpr)

Evolutionarily conserved structure-selective endonuclease MUS81 forms a complex with EME1 and further associates with another endonuclease SLX4-SLX1 to form a four-subunit complex of MUS81-EME1-SLX4-SLX1, coordinating distinctive biochemical activities of both endonucleases in DNA repair. Viral protein R (Vpr), a highly conserved accessory protein in primate lentiviruses, was previously reported to bind SLX4 to mediate down-regulation of MUS81. However, the detailed mechanism underlying MUS81 down-regulation is unclear. Here, we report that HIV-1 Vpr down-regulates both MUS81 and its cofactor EME1 by hijacking the host CRL4-DCAF1 E3 ubiquitin ligase. Multiple Vpr variants, from HIV-1 and SIV, down-regulate both MUS81 and EME1. Furthermore, a C-terminally truncated Vpr mutant and point mutants R80A and Q65R, all of which lack G2 arrest activity, are able to down-regulate MUS81-EME1, suggesting that Vpr-induced G2 arrest is not correlated with MUS81-EME1 down-regulation. We also show that neither the interaction of MUS81-EME1 with Vpr nor their down-regulation is dependent on SLX4-SLX1. Together, these data provide new insight on a conserved function of Vpr in a host endonuclease down-regulation.
Mapping of leu-enkephalin-containing axons and cell bodies of the rat forebrain

The suggestion that the enkephalin peptides represent natural ligands for the opiate receptors (Hughes et al., 1975) has resulted in several recent reports on the distribution of the enkephalin pentapeptides by immunohistochemical methods (Elde et al., 1976, Hokfelt et al., 1977, Simantov et al., 1977; Watson et al., 1977; Sar and Stumpf, 1977; Uhl et al., in this volume). These studies have focused attention on small varicose endings reminiscent of catecholamine-containing terminals. Furthermore, cell bodies were observed to contain the immunoreactive peptides following treatment with colchicine (Hokfelt et al., 1977).
Reflection on Assumptions from Designing Female-Centric Educational Games

In this paper we present a detailed analysis of the design and implementation of an educational game targeting young women entrepreneurs by a predominantly male team. During the process, we arrived at assumptions based on intrinsic and extrinsic influences that effected the design of the game. After creating a prototype, the game was provided to the target audience during a usability test. Our observations reveal that even after following a rigorous and agile development model that included stakeholders at several time frames, we were not successful in delivering the desired experience to our target audience. We conclude by presenting a strategy for changing the agile development model to be inclusive of the target audience.
Radiofrequency ablation of the sacral lateral branches

Abstract The objective of this article is to recommend an approach to radiofrequency ablation (RFA) of the sacral lateral branches that is safe, effective, and simple to perform. To do so, one must identify the proper patient, perform a diagnostic block to confirm the sacroiliac joint as the pain generator, and then, after 2 successful blocks, move to RFA of the sacral lateral branches as the next step in treatment. The choice of an RFA technique is controversial. Here, an argument is made for moving to bipolar RFA of the lateral branches of S1-S3. If pain is refractory, then cooled RFA may be an appropriate next step in care.
Combining finger vision and optical tactile sensing: Reducing and handling errors while cutting vegetables

We develop an optical multimodal-sensing skin for fingers of a robotic gripper. This sensor consists of a transparent skin made with a marked soft elastic outer layer on a hard layer, and internal RGB cameras. The cameras can see the external scene through the skin. This sensor provides a contact force field estimated by tracking markers in the skin, and visual information of close or grasped objects. This sensor uses off-the-shelf materials, is easy to manufacture, and is robust against an external force as the force is not applied to the sensing devices (cameras). We install a prototype of this sensor on fingers of a Baxter robot, and demonstrate its usefulness with a cutting vegetable task. The sensor gave us force information to control cutting vegetables and avoiding slippage of the knife. Accompanying video: https://youtu.be/ifOwQdy9gDg.
Ecotone response to climatic variability depends on stress gradient interactions

Variability added to directional climate change could have consequences for ecotone community responses, or positive and negative variations could balance. The response will depend on interactions among individuals along environmental gradients, further affected by stress gradient effects. Two instantiations of the stress gradient hypothesis, simple stress and a size-mediated model, are represented in a spatially explicit agent based simulation of an ecotone derived from observations of Abies lasiocarpa, Picea engelmannii, and Pinus albicaulis in the northern Rocky Mountains. The simple model has two hierarchically competitive species on a single environmental gradient. The environment undergoes progressive climate change and increases in variability. Because the size model includes system memory, it is expected to buffer the effects of extreme events. The interactions included in both models of the stress gradient hypothesis similarly reduce the effects of increasing climatic variability. With climate amelioration, the spatial pattern at the ecotone shows an advance of both species into what had been a higher stress area, but with less density when variation increases. In the size-mediated model the competitive species advances farther along the stress gradient at the expense of the second species. The memory embedded in the size-mediated model does not appear to buffer extreme events because the interactions between the two species within their shifting ecotone determine the outcomes. Ecotone responses are determined by the differences in slopes of the species response to the environment near their point of intersection and further changed by whether neighbor interactions are competitive. Interactions are more diverse and more interwoven than previously conceived, and their quantification will be necessary to move beyond simplistic species distribution models.
Public archaeology is citizen science in Arkansas

The Arkansas Archeological Survey (ARAS) is a unit of the University of Arkansas tasked with working with the public to research and preserve the state’s archaeological heritage. As the first forma...
Visual strategies for co-design with a community partner

Deficient financial literacy is an important international problem, and research suggests the potential effectiveness of narrative visualizations. This paper presents a case study: a collaboration between a class of design students and a community-based financial-counseling organization to develop financial-literacy comic strips for use with the organization’s low-income clients. We describe and examine the communication challenges between a community partner and an academic institution, detailing the several communication modes employed. These modes include questionnaire and surveys of the counsellors; emails directly between students and counsellors; and most successfully, a hands-on visualization workshop with counsellors. The visualizations engaged counsellors with generated (based) design practices, which resulted in superior communication with design students. Lessons from this experience may be broadly useful for any collaborative efforts among academic institutions, design students and community partners.
On the use of Laplace's equation for global predictions of internuclear separation and dissociation energy

Properties of target species can be estimated by various means including interpolations in periodic charts. Interpolation is equivalent to numerical solution of the Laplace equation. A test of this equivalence, within some confidence level, for any N-atomic molecule surrounded by 4N nearest neighbors: the sum of the second differences of the data in all directions must be zero. Since very few molecules have 4N neighbors with known data, the test becomes: the sum of the averages of the second differences must be zero. The validity of these tests is explored. For radii of main-group atoms, and for internuclear separations of their diatomic combinations, the averages are different from zero and the sums of the averages are zero to within one σ if second-nearest neighbors are used. Dissociation potentials pass the tests but with larger scatter. Predictions for dissociation potentials, using iterative interpolation within boundaries on which there are known data, are reviewed.
High Resolution Interferometric Observations of Eclipsing Binary Stars

Eclipsing binary stars are of great importance in astronomy. Now, high angular resolution measurements of eclipsing stars with the Mark III Stellar Interferometer ( Shao 1988) can determine not only all of the orbital parameters, but also the luminosities and color indices of the two components, and can yield precise information for the study of the stellar evolution models. Particularly, the combination of interferometric and photometric results provide a direct measurement of stellar effective temperature. In the case where the primary component can be resolved, the results from the optical interferometer then provide a reliable determination of the absolute system parameters. In addition, eclipsing binary stars are good candidates for comparison of different techniques, i.e., interferometric, photometric, astrometric, and spectroscopic, and for checking whether systematic uncertainties exist with certain techniques.
Hill-Climbing Theories of Learning

Abstract Much human learning appears to be gradual and unconscious, suggesting a very limited form of search through the space of hypotheses. We propose hill climbing as a framework for such learning and consider a number of systems that learn in this manner. We focus on CLASSIT, a model of concept formation that incrementally acquires a conceptual hierarchy, and MAGGIE, a model of skill improvement that alters motor schemas in response to errors. Both models integrate the processes of learning and performance.
Efficacy and safety of examethasone, high dose cytarabine, and carboplatin (DHAC) with and without rituximab (R) as a salvage regimen for relapsed/refractory (R/R) lymphoma.

e19023Background: Adequate cytoreduction with cisplatin-based chemotherapy is commonly used prior to high dose chemotherapy and autologous stem cell support (HDC-ASCS) among R/R aggressive lymphoma...
Public School Principals: Agents of Bridging and Buffering

This article focuses on the leadership practices that four public school principals in two Northern California large urban school districts used during the process of implementing the state-mandate...
Tropical and extratropical general circulation with a meridional reversed temperature gradient as expected in a high obliquity planet

Abstract Planets with high obliquity receive more radiation in the polar regions than at low latitudes, and thus, assuming an ocean-covered surface with sufficiently high heat capacity, their meridional temperature gradient was shown to be reversed for the entire year. The objective of this work is to investigate the drastically different general circulations of such planets, with an emphasis on the tropical Hadley circulation and the mid-latitude baroclinic eddy structure. We use a 3D dry dynamic core model, accompanied by an eddy-free configuration and a generalized 2D Eady model. When the meridional temperature gradient is reversed, the Hadley cell becomes much weaker, shallower and thermally indirect, as seen in other studies, though not in the context of high obliquity planets. Regardless of whether the temperature is decreasing (normal) or increasing (reverse) poleward, surface friction and eddy momentum transport are shown to be the primary drivers of the Hadley cell. Because mid-latitude baroclinic eddies concentrate westerly momentum toward the mid-latitude baroclinic zone, the surface wind pattern is easterly-westerly-easterly from the equator to the pole in both normal and reverse cases. As a result, low-latitude air parcels near the surface gain westerly momentum through friction, and are redirected equatorward by the Coriolis force, forming thermally indirect (direct) circulation in the reverse (normal) case. The Hadley cell under a reverse temperature gradient configuration is shallow and weak, even when the magnitude of the gradient is the same as in the normal case. This shallow structure is a result of the bottom-heavy structure of the baroclinic eddies in the reverse case, and relatively weak wave activity. We propose a new mechanism to explain the mid-latitude eddy structure for both cases, and verify it using the generalized Eady model. With seasonal variations included, the annual mean circulation resembles that under perpetual annual mean setup. Approaching the solstices, a strong cross-equator Hadley cell forms in both cases, and about 2/3 of the Hadley circulation is driven by eddies, as shown by eddy-free simulations and using a decomposition of the Hadley cell.
Sensitization of Vascular Endothelial Cells to Ionizing Radiation Promotes the Development of Delayed Intestinal Injury in Mice

Exposure of the gastrointestinal (GI) tract to ionizing radiation can cause acute and delayed injury. However, critical cellular targets that regulate the development of radiation-induced GI injury remain incompletely understood. Here, we investigated the role of vascular endothelial cells in controlling acute and delayed GI injury after total-abdominal irradiation (TAI). To address this, we used genetically engineered mice in which endothelial cells are sensitized to radiation due to the deletion of the tumor suppressor p53. Remarkably, we found that VE-cadherin-Cre; p53FL/FL mice, in which both alleles of p53 are deleted in endothelial cells, were not sensitized to the acute GI radiation syndrome, but these mice were highly susceptible to delayed radiation enteropathy. Histological examination indicated that VE-cadherin-Cre; p53FL/FL mice that developed delayed radiation enteropathy had severe vascular injury in the small intestine, which was manifested by hemorrhage, loss of microvessels and tissue hypoxia. In addition, using dual-energy CT imaging, we showed that VE-cadherin-Cre; p53FL/FL mice had a significant increase in vascular permeability of the small intestine in vivo 28 days after TAI. Together, these findings demonstrate that while sensitization of endothelial cells to radiation does not exacerbate the acute GI radiation syndrome, it is sufficient to promote the development of late radiation enteropathy.
Towards Soft Exact Computation (Invited Talk)

Exact geometric computation (EGC) is a general approach for achieving robust numerical algorithms that satisfy geometric constraints. At the heart of EGC are various Zero Problems, some of which are not-known to be decidable and others have high computational complexity. Our current goal is to introduce notions of “soft- Open image in new window correctness” in order to avoid Zero Problems. We give a bird’s eye view of our recent work with collaborators in two principle areas: computing zero sets and robot path planning. They share a common Subdivision Framework. Such algorithms (a) have adaptive complexity, (b) are practical, and (c) are effective. Here, “effective algorithm” means it is easily and correctly implementable from standardized algorithmic components. Our goals are to outline these components and to suggest new components to be developed. We discuss a systematic pathway to go from the abstract algorithmic description to an effective algorithm in the subdivision framework.
Septal Versus Lateral Mitral Isthmus Ablation for Treatment of Mitral Annular Flutter

Abstract Objectives This study sought to compare efficacy and safety of the septal mitral isthmus line (SMIL) with that of the lateral mitral isthmus line (LMIL) for treatment of mitral annular flutter (MAF). Background MAF is the most common left atrial macro-re-entrant organized atrial tachycardia (OAT) occurring after catheter ablation of atrial fibrillation. The 2 most common lesion sets for treating MAF include linear ablation from the anteroseptal mitral annulus to the right superior pulmonary vein (SMIL) and from the lateral mitral annulus to left inferior pulmonary vein (LMIL). Methods The study included all mitral isthmus ablations performed at the Hospital of the University of Pennsylvania in 2016 and 2017. Acute procedural results and long-term arrhythmia-free survival were compared between groups. Results Of 114 total MILs, conduction block was achieved across 73 (93.6%) SMILs compared with 29 (80.6%) LMILs (p = 0.05). Although the length of the SMIL was longer (48.9 ± 12.8 cm vs. 38.7 ± 12.8 cm; p = 0.001), time required to achieve block was shorter (25.2 ± 15.9 min vs. 36.6 ± 21.3 min; p = 0.03). Coronary sinus ablation was required in 58.3% of LMILs due to inability to achieve conduction block with left atrial ablation alone. In multivariate analysis, only failure to achieve acute MIL block remained significantly associated with subsequent OAT recurrence (hazard ratio: 6.39; 95% confidence interval: 1.37 to 29.9; p = 0.02). Conclusions The SMIL requires less time to complete and more frequently results in acute MIL block than the LMIL. Additionally, ablation is rarely required outside the left atrium. Failure to achieve acute MIL block is strongly associated with subsequent OAT recurrence.