cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract B39: Multidrug resistant ovarian cancer cells are less susceptible to orlistat-induced cell death

In the United States, there will be over 21,000 new cases and more than 15,000 deaths from ovarian cancer in 2008. With a 70% death rate within one year of diagnosis, ovarian cancer is righteously coined the ‘silent killer.’ Multidrug resistance (MDR) and the lack of effective alternate drug treatments pose further serious dilemmas to ovarian cancer patients. Orlistat, an anti-obesity drug, functions by inhibiting fatty acid synthase (FASN), an enzyme up-regulated in approximately 50% of cancers. Current research indicates that orlistat preferentially destroys cancer cells via an apoptotic mechanism; however, the exact pathway of orlistat-induced tumor cell death is unclear. Our objective is to elucidate the basic mechanism of orlistatinduced cell death so that an emerging class of new drugs (FASN inhibitors) can be better tailored to treat ovarian cancer patients. The ovarian cancer lines OVCAR-8 and NCI/ADR (OVCAR-8 drug-resistant) were treated with increasing concentrations of orlistat over a period of 96 hrs. We hypothesized that the MDR cells will undergo less cell death compared to the sensitive ovarian cancer cells with orlistat. Using a combination of three different cell proliferation/death assays, it was determined that MDR cells are more robust and have increased proliferative capacity compared to the OVCAR-8 cells under equivalent conditions of orlistat treatment. In contrast, additional results by immunoblotting show that orlistat can more effectively reduce FASN protein expression over time. Furthermore, orlistat can induce an endoplasmic reticulum stress-response by up-regulating GRP78/BiP. Taken together, our data demonstrates that MDR ovarian cancer cells are not as susceptible to orlistat-induced cell death despite increased FASN reduction and this suggests that alternative stress-response or survival pathways may be active.
Teaching Children with Language-Learning Disabilities to Plan and Revise Compare-Contrast Texts.

This study used a multiple-probe, multiple-baseline single-case design to investigate the efficacy of planning, and then revising strategy instruction using self-regulated strategy development on the compare–contrast writing performance of three late elementary students with language-learning disabilities. After receiving the planning instruction, all three students spent more time planning and generated quality written plans. Their essays were longer, included more text structure elements, and demonstrated better overall quality. After receiving the subsequent revising instruction, further increases in writing accuracy were found, but planning time, quality of written plans, text length, and text structure elements somewhat decreased. Also, overall essay quality did not further improve following revising instruction. Positive gains were maintained for 4 weeks and generalized to writing explanatory essays.
Cancer donor preferences for disposition of their biospecimens after biobank closure

BACKGROUND Biobank funding is unstable and biobank administrators are concerned about loss of funding and subsequent biobank closure. Nevertheless, only a minority of biobanks have policies regarding the distribution or destruction of tissue if the biobank were to close. To the authors' knowledge, the current study is the first to report on the preferences of oncology biospecimen donors regarding the handling of their biospecimens in the event of biobank closure. METHODS A total of 98 biospecimen donors who were diagnosed with cancer at the Georgia Cancer Center for Excellence at Grady Memorial Hospital or the Winship Cancer Institute were interviewed concerning their preferences for the handling of their biospecimens in the event of biobank closure. RESULTS The majority of biospecimen donors who expressed a preference (62 of 83 donors; 75%) wanted their biological materials transferred to another biobank, specifically an academic bank or a national bank. The most unacceptable options for the handling of tissue were transfer to a for-profit/pharmaceutical biobank (39 of 98 donors; 40%) or a biobank based outside of the United States (31 of 98 donors; 32%). Nonwhite participants were more likely to view the transfer of their tissue to a for-profit/pharmaceutical tissue bank, international tissue bank, or a national tissue bank as unacceptable compared with white participants. CONCLUSIONS According to these biospecimen donors, the most acceptable options for the handling of biospecimens after biobank closure were transfer to an academic or national bank. The most objectionable options were transfer to a for-profit/pharmaceutical biobank or a biobank based outside of the United States. These findings can be used as the basis for educational interventions directed at the public and can inform the policies of biobanks that serve oncology research. Cancer 2017. © 2017 American Cancer Society.
From Entry Barriers to Survival Barriers: Entry Into the Biotechnology Industry

A qualitative grounded theory building approach has been taken to deeply understand incumbent biotechnology firms’ behaviors in cases of different entrants. The research shows that the unique chara...
Expanding Our Understanding of Forest Structural Restoration Needs in the Pacific Northwest

Ecological departure, or how much landscapes have changed from a natural range of variation (NRV), has become a key metric in forest planning and restoration efforts. In this study we define forest restoration need as the specific change in structural stage abundance necessary to move landscapes into the NRV. While most restoration projects in the forested ecosystems of the Pacific Northwest, USA (Oregon and Washington) have embraced this paradigm, our understanding of what treatments to apply where, when, and at what magnitude is evolving and continues to be refined. We build on a body of existing LANDFIRE/Fire Regime Condition Class (FRCC) work on ecological departure to assess the ecological departure of all forested landscapes in the region. Moreover, we assess departure in moister forests west of the Cascade crest, and compare them with fire-dependent forests east of the crest and in southwest Oregon. These “moister Westside” forests have received relatively less attention in a fire ecology context, and we hypothesize restoration needs there are quite different. We show a substantial need for disturbance-related treatments in the drier fire-dependent portion of this region (east of the Cascade crest plus southwest Oregon), with over half of this treatment type falling on Federally-administered land. On the Westside the need for succession is more pronounced. The lack of pronounced disturbance need west of the Cascade crest suggests restoration there may require strategies more nuanced than in the fire-dependent zone.
Design and Testing of a Carbon-Fiber-Wrapped Synchronous Reluctance Traction Motor

Synchronous reluctance machines are very appealing for high-speed traction applications due to their robustness, simple structure, absence of magnets, and simple control. The absence of magnets means that synchronous reluctance machines are not susceptible to price variability and sustainability of rare-earth materials. Also, there are no concerns about demagnetization or uncontrolled generation mode. However, the challenge of achieving a good constant power to speed ratio is dependent on the mechanical aspects of the design. Conventional synchronous reluctance designs perform poorly compared to permanent magnet machines due to the presence of bridges and/or center posts that provide a path for performance-robbing leakage flux and the absence of permanent magnets that help saturate the bridges and/or center posts. Elimination or reduction of these features presents a challenge for rotor mechanical retention due to the reduction in radial stiffness that these members provide mainly for high-speed applications. A carbon-fiber sleeve on the rotor will provide the needed mechanical strength to enable a reduction of bridges and/or center posts. This paper will present the design details, analysis, manufacturing, and test results of a proof-of-concept carbon-fiber-wrapped synchronous reluctance machine targeting traction applications.
Direct and Indirect Staining of Bacteria with Fluorescein-Labeled Antibodies

The two most frequently used fluorescent procedures for the localization of antigens in different preparations are the direct and indirect methods. In direct staining, the antibody which has been produced in experimental animals or isolated from human serum is directly labeled with fluorescein. In the indirect method, the antibody which will react with the antigen present in the preparation is not labeled with any tracers. To make the antigen-antibody complex visible, antibodies have been produced in another animal species against the antibodies participating in the antigen-antibody reaction. These anti-immunoglobulin antibodies are labeled with fluorescein dyes. The latter procedure is not only convenient but also it gives a more intensive fluorescent staining. The use of fluorescein-labeled antibodies has recently been made extremely easy, since several fluorescein-labeled antirabbit or antihuman immunoglobulins are commercially available.
Genomics of Erwinia amylovora and Related Erwinia Species Associated with Pome Fruit Trees

Erwinia amylovora, the causal agent of fire blight disease of apples and pears, is one of the most important plant bacterial pathogens with worldwide economic significance. In this chapter, the author describes up-to-date information about the genomes of E. amylovora and related Erwinia species primarily associated with pome fruit trees, provides recent developments in genome-enabled understanding of E. amylovora virulence, and highlights latest comparative and functional genomic studies of E. amylovora, including proteomics and transcriptomics, in understanding the biology, population diversity, and evolution of this important group of pathogens. The chapter also summarizes the current progress in understanding of the pathogen and its virulence mechanism from genome sequencing data, as well as the potential evolutionary origin of these Erwinia species. In the introduction part, the chapter contains comprehensive information about the distribution, economic losses, and spread of the fire blight disease, the characteristics of the pathogen as well as its key features associated with virulence factors and regulatory systems, including type III secretion systems and the exopolysaccharide amylovoran. Future perspectives and research directions from systems biology to host–pathogen interactions are also suggested.
Anchoring Temporal Expressions in Scheduling-related Emails

In this paper we adopt a constraint-based representation of time, Time Calculus (TC), for anchoring temporal expressions in a novel genre, emails. Email is sufficiently different from the most studied genre - newswire texts, and its highly under-specified nature fits well with our representation. The evaluation of our anchoring system shows that it performs significantly better than the baseline, and the result compares favorably with some of the closest related work.
DETECTION OF AUTOANTIBODIES USING PROTEIN ARRAYS

ABSTRACT In the 21st century, protein arrays have emerged as a useful tool for measuring multiple autoantibodies in serum and other clinical samples. Antigen arrays may use affinity-purified proteins, recombinant proteins or cell lysates as targets. The arrays can be prepared on nitrocellulose, glass or plastic (planar arrays), or they can utilize polymeric beads or bar-coded microparticles in solution. Preparation and optimal use of these arrays requires proper execution of a number of common steps, which are critical to reproducibility and specificity. Diagnostic methods range from simple strip techniques to fully automated multiplex analyzers. The ability to search for previously unrecognized antibodies against targets has stimulated recent research and is a complementary approach to the discovery of new biomarkers via proteomics. The importance of multiple antibody detection will increase with our understanding of new markers and may represent the primary approach to autoantibody detection in the future.
Dynamic Control of Ca2+ Binding in the C2 Domains of Synaptotagmin 1

Synaptotagmin senses fluctuations in the Ca 2+ environment of neurons near active zones and transduces a signal to the SNARE complex to initiate exocytosis at the presynaptic terminus. The 3D structures of the two tandem C2 domains of synaptotagmin have been determined to high resolution; however, it is currently unclear how each domain dynamically interacts with Ca 2+ at the atomic level. To study the mechanistic consequences of the lethal mutations at the AD3 locus, we introduced tyrosine to asparagine point mutations in both the C2A and C2B domains of synaptotagmin 1, and we have constructed a model that describes the relationship between Ca 2+ -binding and the structural changes within each C2 domain. We show that the mobility of loop 3 in the Ca 2+ binding pocket increases markedly in C2A, while the mobility of loop 1 changes in C2B with the AD3 mutation. This increase in loop mobility results in an increase in the average volume and variance of the Ca 2+ -binding pockets of C2A and C2B. The volume of the unbound Ca 2+ -binding pocket in C2A is usually restrained by intra-domain interactions between the tyrosine residue at the AD3 locus and residues on loop 3; however, the AD3 mutation decouples the restraint and results in a larger, more variable Ca 2+ -binding pocket in C2A. C2B maintains a more compact Ca 2+ -binding pocket; however, its volume also fluctuates significantly with the AD3 mutation. Changes in binding pocket volume that involve more variable Ca 2+ binding loops would likely affect Ca 2+ affinity in the neurons of the affected organism. Using molecular-dynamics simulations, we show that mutations at the AD3 locus alter the mobility of the Ca 2+ -binding loops by removing a key stabilization mechanism that is normally present in C2 domains. The lack of loop stabilization results in a net increase in the volume of the Ca 2+ -binding pocket and provides an explanation for the observed lethal phenotype.
The role of fetal growth restriction in the association between Down syndrome and perinatal mortality.

Objective: Down syndrome (DS) is associated with significant risk of perinatal mortality. We hypothesize that this association is primarily mediated through the effects of fetal growth restriction ...
Durability Data for Bioprosthetic Surgical Aortic Valve: A Systematic Review.

Importance Although several studies have reported data on surgical aortic valve durability, variability in study methodologies and definitions as well as inadequate follow-up make the interpretation of data from these studies difficult to interpret. Objective To review available data on structural valve deterioration (SVD) of surgical bioprosthetic aortic valves by examining the published literature as well as data reported to the US Food and Drug Administration (FDA). Evidence Review A systematic review using Preferred Reporting Items for Systematic Review and Meta-Analysis reporting guidelines to obtain all available data from preexisting literature on the actuarial freedom from SVD and outcomes of SVD. Data were collected from database inception to November 2016. Additionally, data reported to the FDA were obtained. Findings In total, 167 studies and 12 FDA reports including 101 650 patients and 17 different valve types were analyzed. There were 11 different definitions of SVD used in the studies. Core laboratory data were available for 11 studies. Mean follow-up ranged from less than 1 year to 14 years. Kaplan-Meier estimates were reported for up to 30 years of follow-up, with 0% to 37% of patients remaining at risk at maximum follow-up. Food and Drug Administration–reported data are similarly variable in duration (mean follow-up range, 1.2 to 7 years) and completeness of follow-up, with final follow-up of 0.1% to 95%. Conclusions and Relevance There is considerable variability in reporting SVD of surgical aortic valves, with different definitions and inadequate long-term systematically collected core laboratory data. Rigorously collected long-term data with standardized definitions for surgical valves are needed to provide a benchmark for the durability of rapidly evolving transcatheter valves.
Seismic velocity structure across the 2013 Craig, Alaska rupture from aftershock tomography: Implications for seismogenic conditions

Abstract The 2013 Craig, Alaska MW 7.5 earthquake ruptured along ∼150 km of the Queen Charlotte Fault (QCF), a right-lateral strike-slip plate boundary fault separating the Pacific and North American plates. Regional shear wave analyses suggest that the Craig earthquake rupture propagated in the northward direction faster than the S-wave (supershear). Theoretical studies suggest that a bimaterial interface, such as that along the QCF, which separates oceanic and continental crust with differing elastic properties, can promote supershear rupture propagation. We deployed short-period ocean-bottom seismometers (OBS) as a part of a rapid-response effort less than four months after the Craig earthquake mainshock. During a 21-day period, 1,133 aftershocks were recorded by 8 OBS instruments. Aftershock spatial distribution indicates that the base of the seismogenic zone along the QCF approaches ∼25 km depth, consistent with a thermally-controlled fault rheology expected for igneous rocks at oceanic transform faults. The spatial distribution also provides supporting evidence for a previously hypothesized active strand of the QCF system within the Pacific Plate. Tomographic traveltime inversion for velocity structure indicates a low-velocity (VP and VS) zone on the Pacific side of the plate boundary at 5–20 km depths, where Neogene Pacific crust and upper mantle seismic velocities average ∼3–11% slower than the North American side, where the Paleozoic North American crust is seismically faster. Our results suggest that elastic properties along the studied portion of the QCF are different than those of a simple oceanic–continental plate boundary fault. In our study region, velocity structure across the QCF, while bimaterial, does not support faster material on the west side of the fault, which has been proposed as one possible explanation for northward supershear propagation during the Craig earthquake. Instead, we image low-velocity material on the west side of the fault. Explanations could include that part of the rupture was subshear, or that fault damage zone properties or fault smoothness are more important controls on supershear rupture than a bimaterial contrast.
Cardiac dysfunction during Francisella novicida bacterial infection; an instructive sepsis model to study heart function

Francisella novicida ( Ft.n ) is a gram negative intracellular pathogen that causes severe sepsis syndrome. Sepsis patients with cardiac dysfunction have significantly higher mortality. Although several pathways have been associated with myocardial damage in sepsis, the precise cause(s) remains unclear and treatment options are limited. We have shown that Ft.n infection causes rapid dissemination, inflammation and sepsis in the mouse model, however, the basis for cardiac dysfunction during Ft.n infection is unknown. In our Ft.n sepsis model we have observed ECG abnormalities such as R’ wave formation, prolonged QRS and PR intervals, left ventricular wall thickening and increased cardiac output, similar to sepsis patients. Notably, we detected microlesions in the myocardium, and also seen in nosocomial Streptococcu s infection and in sepsis patients. We have also determined that Ft.n -mediated microlesions are due to cardiomyocyte apoptosis due to increased infiltration of leukocytes and expression of inflammatory mediators (TNFα, IL-1β, IL-8 and SOD2). Finally we have found increased expression of miR155 and rapid degradation of HSF-1 in the heart suggesting that these processes regulate myocaridal inflammation and apoptosis. In conclusion, we have developed and used an Ft.n infection model to study the pathogenesis of heart dysfunction during sepsis.
米国ロースクール教員の現場レポート(5)(6) (A Field Report from a Japanese Professor at an American Law School (5)(6))

Japanese Abstract: 筆者は,2013年11月以来,日本の法律雑誌NBLに,UC Hastingsとアメリカの法学教育に関する連載を行ってきた。これらは,その第5回と第6回である。English Abstract: The author has been writing a series of essays on UC Hastings and American legal education in a Japanese law journal, NBL (New Business Law), since November 2013. These are his fifth and sixth essays.
Unique objects attract attention even when faint.

Abstract Locally contrasting objects, e.g. a red apple surrounded by green apples, attract attention. Does this generalize to differences in feature space? That is, do unique objects-regardless of their location-stand out from a collection of objects that are similar to one another, even when the unique object has lower local contrast with the background than the other objects? Behavioral data show indeed a preference for unique items but previous experiments enabled viewers to anticipate what response they were “supposed” to give. We developed a new experimental paradigm that minimizes such top-down effects. Pitting local contrast against global uniqueness, we show that unique stimuli attract attention even in not-anticipated, never-seen images, and even when the unique stimuli are faint (low contrast). A computational model explains how competition between objects in feature space favors dissimilar objects over those with similar features. The model explains how humans select unique objects, without a loss of performance on natural scenes.
Mucosal Vaccines for Genital Herpes

Abstract Genital herpes is caused by infection with herpes simplex virus type 2 (HSV-2) and more recently by HSV type 1 (HSV-1). The viruses infect and replicate in the genital mucosal epithelium and infect innervating sensory neurons. HSV-2 and HSV-1 can become latent in the sensory neurons of the dorsal root ganglia, leading to lifelong infection. Stress and other triggers can lead to the reactivation of latent viruses, eventually leading to viral emergence from neurons. The virus can then infect the skin epithelium around the genitalia. In addition to causing painful ulcers, genital herpes is a risk factor for HIV transmission. Antiviral drugs can relieve the symptoms of genital herpes, but these drugs are not sufficient to control asymptomatic shedding and potential transmission. Although many attempts have been made to develop vaccines for genital herpes, none of them showed successful outcomes in clinical trials. While traditional vaccines have focused on generating systemic immunity, evidence indicates that local immune responses against HSV in the genital mucosa are needed to block infection and disease. This chapter outlines current understanding of the pathogenesis of HSV-2 and the host immune responses, with a focus on mucosal immunity. Further, the chapter discusses previous and ongoing efforts to develop mucosal vaccines and future strategies ahead.
A Wholistic View of Black Women on Scripted TV: A Content Analysis:

Existing analyses of Black women on TV have tended to focus on their general prevalence or employment/family status. As such, less is known about the extent to which they reflect broader attributes...
Using qualitative data to examine disparities in cancer outcomes: Results from interviews with African American (AA) and white (W) patients regarding health beliefs and perceptions of chemotherapy

16016 Background: Prior data indicate African Americans are less likely to receive appropriate and timely therapy for breast, colon, and lung cancers. The reasons for this may involve differences i...
A LUTI microsimulation framework to evaluate long-term impacts of automated mobility on the choice of housing-mobility bundles:

Land use–transportation interaction models can be useful planning support systems to assess the long-term implications of emerging transportation technologies like mobility-on-demand and automated ...
Disease control after surgery for chronic rhinosinusitis: prospective, multi-institutional validation of the Sinus Control Test

BACKGROUND The Sinus Control Test (SCT) is a 4-question, patient-reported questionnaire that assesses disease control in chronic rhinosinusitis (CRS). This prospective, multicenter study examines SCT outcomes following endoscopic sinus surgery (ESS), further validating its use as a control instrument for CRS. METHODS Adults with CRS undergoing ESS were prospectively enrolled from 5 centers across North America. The SCT was administered at baseline and once 6 months after surgery. Quality of life and disease burden were evaluated using the 22-item Sino-Nasal Outcome Test (SNOT-22) and Lund-Kennedy endoscopy scores. Linear regression was used to determine whether specific demographic, comorbidity, or disease severity measures were independently associated with changes in SCT scores postoperatively. RESULTS A total of 218 patients, 111 females (50.9%) and 107 males (49.1%), were enrolled, with mean ± standard deviation age of 50.1 ± 15.6 years. Mean SCT score improved from 8.9 ± 3.5 to 4.3 ± 3.7 postoperatively (p < 0.001). Preoperatively, 21.6% were uncontrolled, 71.5% partially controlled, and 6.9% controlled. Postoperatively, 6.0% were uncontrolled, 42.6% partially controlled, and 51.4% controlled (p < 0.001). Change in SCT score correlated independently with change in SNOT-22 (r = 0.500, p < 0.001) and endoscopy scores (r = 0.310, p < 0.001). Endoscopy scores did not correlate with control status among patients with CRS without nasal polyposis (CRSsNP) nor between uncontrolled and partially controlled patients. Demographics and comorbidities were not associated with changes in SCT. CONCLUSION Improvement in disease control following ESS as measured by the SCT correlated with improvements in SNOT-22 and endoscopy scores. The SCT is an easily administered instrument that provides information complementary to existing patient-reported and objective measures of disease severity.
A Novel Interaction of Translocator Protein 18 kDa (TSPO) with NADPH Oxidase in Microglia

In the brain neuropil, translocator protein 18 kDa (TSPO) is a stress response protein that is upregulated in microglia and astrocytes in diverse central nervous system pathologies. TSPO is widely used as a biomarker of neuroinflammation in preclinical and clinical neuroimaging studies. However, there is a paucity of knowledge on the function(s) of TSPO in glial cells. In this study, we explored a putative interaction between TSPO and NADPH oxidase 2 (NOX2) in microglia. We found that TSPO associates with gp91phox and p22phox, the principal subunits of NOX2 in primary murine microglia. The association of TSPO with gp91phox and p22phox was observed using co-immunoprecipitation, confocal immunofluorescence imaging, and proximity ligation assay. We found that besides gp91phox and p22phox, voltage-dependent anion channel (VDAC) also co-immunoprecipitated with TSPO consistent with previous reports. When we compared lipopolysaccharide (LPS) stimulated microglia to vehicle control, we found that a lower amount of gp91phox and p22phox protein co-immunoprecipitated with TSPO suggesting a disruption of the TSPO-NOX2 subunits association. TSPO immuno-gold electron microscopy confirmed that TSPO is present in the outer mitochondrial membrane but it is also found in the endoplasmic reticulum (ER), mitochondria-associated ER membrane (MAM), and in the plasma membrane. TSPO localization at the MAM may represent a subcellular site where TSPO interacts with gp91phox and p22phox since the MAM is a point of communication between outer mitochondria membrane proteins (TSPO) and ER proteins (gp91phox and p22phox) where they mature and form the cytochrome b558 (Cytb558) heterodimer. We also found that an acute burst of reactive oxygen species (ROS) increased TSPO levels on the surface of microglia and this effect was abrogated by a ROS scavenger. These results suggest that ROS production may alter the subcellular distribution of TSPO. Collectively, our findings suggest that in microglia, TSPO is associated with the major NOX2 subunits gp91phox and p22phox. We hypothesize that this interaction may regulate Cytb558 formation and modulate NOX2 levels, ROS production, and redox homeostasis in microglia.
Variation in immunosuppression practices among pediatric liver transplant centers—Society of Pediatric Liver Transplantation survey results

Background Variation in IS exists among pediatric liver transplant centers. While individual centers may publish their practice paradigms, current data on practices as a whole are lacking. This study sought to ascertain the IS protocols of pediatric liver transplant centers within the SPLIT to better understand variability and similarities among peer institutions. Methods A 27-item questionnaire was developed within the SPLIT Quality Improvement and Clinical Care Committee. The survey collected data regarding center demographics, IS practices, and treatment of acute cellular rejection. Results Twenty-eight (64%) SPLIT centers responded with 22 (79%) centers performing more than 10 transplants per year and 17 (61%) following more than 100 post-transplant recipients. All centers use a written protocol, and 25 (89%) have a dedicated transplant pharmacist/PharmD. Twenty-five (89%) centers use steroids for induction alone or in combination with thymoglobulin/interleukin-2 antibodies. All centers use tacrolimus for initial maintenance therapy. Most centers have specialized protocols for ABO-incompatible transplants, recipients with renal dysfunction, autoimmune liver diseases, and liver tumors. Treatment of rejection varied but was associated with escalation in IS. Conclusion IS practices among pediatric liver transplant centers are similar including the use of written protocols, pharmacy involvement, steroids for induction, tacrolimus as initial IS, tacrolimus reduction/delay for renal dysfunction, and escalation of IS with rejection severity. However, other IS practices show wide variability including treatment for ABO-incompatible grafts and presumed rejection. This study serves as a foundation to guide prospective research linking IS practice to outcomes to determine best practice.
A pro-metastatic tRNA fragment drives Nucleolin oligomerization and stabilization of bound metabolic mRNAs

Stress-induced cleavage of transfer RNAs (tRNAs) into tRNA-derived fragments (tRFs) occurs across organisms from yeast to human, yet its mechanistic bases and pathological consequences remain poorly defined. By performing genome-wide small RNA profiling, we detected increased abundance of a Cysteine tRNA fragment (59-tRFCys) during breast cancer metastatic progression. 59-tRFCys is required for efficient breast cancer metastatic lung colonization and metastatic cell survival. We identified Nucleolin as the direct binding partner of 59-tRFCys. 59-tRFCys binding enhanced the stability of Nucleolin9s associated pro-metastatic transcripts encoding metabolic enzymes Mthfd1l and Pafah1b1. 59-tRFCys stabilized these transcripts by promoting Nucleolin oligomerization and the assembly of Nucleolin and its bound transcripts into a higher-order ribonucleoprotein complex. Our findings reveal that a tRF can promote oligomerization of an RNA binding protein into a stabilizing ribonucleoprotein complex containing specific target transcripts, thereby driving specific metabolic pathways underlying cancer progression.
Is Optimism a Protective Factor for Cardiovascular Disease

Purpose of review Does optimism contribute to superior cardiovascular health? We examined prospective studies investigating the connections between optimism and cardiovascular health and examining the biological and behavioral mechanisms that may mediate such connections. Recent findings Optimism, independent of sociodemographic, medical, and negative psychological factors, has been prospectively associated with a lower risk of cardiovascular disease and lower rates of cardiac and all-cause mortality. The mechanisms by which optimism may prevent cardiovascular disease remain unclear, but one mechanism may be through health behaviors. Indeed, optimism has been linked with physical activity, healthy diet, and smoking cessation, all of which are associated with better cardiovascular health. Additional studies are needed to: (1) understand the relationships between more dynamic measures of optimism and health outcomes, (2) delineate the mechanisms underlying the relationships between optimism and cardiovascular health, and (3) assess the potential for interventions to modify optimism.
WE‐D‐BRA‐07: Analysis of ArcCHECK Diode Array Performance for ViewRay Quality Assurance

Purpose: Discrepancies in absolute dose values have been detected between the ViewRay treatment planning system and ArcCHECK readings when performing delivery quality assurance on the ViewRay system with the ArcCHECK-MR diode array (SunNuclear Corporation). In this work, we investigate whether these discrepancies are due to errors in the ViewRay planning and/or delivery system or due to errors in the ArcCHECK’s readings. Methods: Gamma analysis was performed on 19 ViewRay patient plans using the ArcCHECK. Frequency analysis on the dose differences was performed. To investigate whether discrepancies were due to measurement or delivery error, 10 diodes in low-gradient dose regions were chosen to compare with ion chamber measurements in a PMMA phantom with the same size and shape as the ArcCHECK, provided by SunNuclear. The diodes chosen all had significant discrepancies in absolute dose values compared to the ViewRay TPS. Absolute doses to PMMA were compared between the ViewRay TPS calculations, ArcCHECK measurements, and measurements in the PMMA phantom. Results: Three of the 19 patient plans had 3%/3mm gamma passing rates less than 95%, and ten of the 19 plans had 2%/2mm passing rates less than 95%. Frequency analysis implied a non-random error process. Out of the 10 diode locations measured, ion chamber measurements were all within 2.2% error relative to the TPS and had a mean error of 1.2%. ArcCHECK measurements ranged from 4.5% to over 15% error relative to the TPS and had a mean error of 8.0%. Conclusion: The ArcCHECK performs well for quality assurance on the ViewRay under most circumstances. However, under certain conditions the absolute dose readings are significantly higher compared to the planned doses. As the ion chamber measurements consistently agree with the TPS, it can be concluded that the discrepancies are due to ArcCHECK measurement error and not TPS or delivery system error. This work was funded by the Bhudatt Paliwal Professorship and the University of Wisconsin Medical Radiation Research Center.
Constitutional Necessity and Presidential Prerogative: Does Presidential Discretion Undergird or Undermine the Constitution?

For those with freedom of action and a corresponding disposition, crises whether real or contrived reflect opportunities. Few better examples of this exist than in the constitutional station of President of the United States. Duty bound to "take Care that the Laws be faithfully executed,"' presidents throughout constitutional history have acted in times of crisis to interpret, bend, circumvent, and even disregard the law based on appeals to supposedly higher values. It will little surprise that these actions trend toward enrichment of executive power. In aggregate, they amply support Edward Corwin's summary in the last century that "[tlaken by and large, the history of the Presidency is a history of aggrandizement." 2 In the quarter century since this observation, the platform for unilateral executive action has only expanded, perhaps markedly so. The reasons are multiple and diverse, but significant among them are the ever-increasing significance of foreign affairs for the United States, the lethality of modem terrorism, and broad societal and technological trends that increasingly empower expeditious, unilateral decision making (e.g., access to information, communications, travel). With this greatly enhanced freedom of action, advocates of unilateral executive power found their true champion in a president with an appropriate disposition, George W. Bush. Propelled by the events of September 11, 2001, and the resultant national security concerns, President Bush advanced claims of unilateral executive power that were extravagant even against the high bar set by some of his most aggressive predecessors. The lines of legitimate argumentation were then further distorted by unserious government lawyers willing to sew cloaks of legality to fit expected conclusions. These developments provide the material for two recent books that make valuable
Statistical methods for gene expression analysis

Microarray technology makes it possible to simultaneously study the expression levels from thousands of genes and is widely used in functional genomics research. The analysis of microarray data provides a challenge to researchers because of its high dimensionality and complexity. Extensive research has been devoted recently to address the statistical issues raised from the analysis of the microarray data, and a comprehensive review is not possible here given space limitations and the proliferation of new papers. Instead, this chapter reviews some of the more basic statistical methods used for microarray gene expression data analysis. We divide the methods into three major areas: differential expression, classification, and clustering. Keywords: microarray; gene expression; differential expression; classification; clustering; transcriptomics
Building Webcorpora of Academic Prose with BootCaT

A procedure is described to gather corpora of academic writing from the web using BootCaT. The procedure uses terms distinctive of different registers and disciplines in COCA to locate and gather web pages containing them.
Second-Order Proof Rules

Proof rules in law dictate when facts have been proven. They do so by specifying a level of proof such as by a preponderance of the evidence, by clear and convincing evidence, or beyond a reasonable doubt. The rules function to serve two goals: accuracy (minimizing errors) and fairly allocating the risk of error. I argue that these rules fail to serve their goals, and I propose and argue for second-order proof rules that will better align decision-making with these goals. The second-order rules have the potential to improve not only factual decision-making at trial but also decisions implementing procedural rules that depend on judgments about the sufficiency of the evidence. These include summary judgment and judgment as a matter of law in civil cases and sufficiency challenges by criminal defendants.
Editorial Commentary: Improving Prescribers to Advance Antimicrobial Stewardship

In an era of ever-increasing antibiotic resistance, antimicrobial stewardship plays avital role in improving patient outcomes and ensuring the appropriate use of these agents. In this issue of Clinical Infectious Diseases, Hamilton et al acknowledge that most formalized antimicrobial stewardship programs (ASPs) do not currently employ a routine intervention with the antibiotic prescriber at the point of prescription [1]. These authors suggest that point-of-prescription interventions with frontline healthcare providers have the potential to expand existing ASPs and provide alternative approaches to performing stewardship at institutions without ASPs. While it is true that a multidisciplinary team often assumes the responsibility for direct patient care in the inpatient setting, the overwhelming majority of prescriptions, including those for antibiotics, are written by physicians. Thus, if we are to place the responsibility of appropriate antimicrobial use on physicians at the point of prescribing, it is pertinent to examine the perceptions and knowledge of these prescribers toward stewardship and appropriate antimicrobial use. In 2013, Abbo et al conducted a multicenter electronic survey evaluating the perceptions and knowledge of antimicrobial education and prescribing of fourthyear medical students from 3 medical schools intheUnitedStates[2].Only 40% of the respondents were even familiar with the term “antimicrobial stewardship,” and 90% reported that they would like more education on the appropriate use of antimicrobials. Just 15% had completed a clinical infectious diseases rotation while in medical school, and <33% understood the correct spectrum of antimicrobials and felt well prepared to streamline and de-escalate antimicrobial therapy. The students’ mean correct knowledge score on an assessment using 11 clinical vignettes was 51%. Although this survey evaluated medical students with limited clinical experience, similar results have been demonstrated in surveys of inpatient internal medicine physicians [3]. In one survey, 97% of physicians believed that widespread and inappropriate use of antibiotics was an important cause of resistance, and only 66% believed that a reduction in antimicrobial use was an effective remedy, compared with the 95% of infectious diseases physicians who believed this was an effective approach [3]. In a similar survey, 94.8% of clinicians
Duration of periods of euthymia in patients with dysthymic disorder.

OBJECTIVE: The purpose of this study was to assess the duration of periods of euthymia in patients with dysthymia. METHOD: All patients with dysthymia who came to the Center for Anxiety and Depression over a 10-month period (N=22) were interviewed by the author regarding the duration of their euthymic episodes. RESULTS: The 22 patients with dysthymia reported euthymic periods from 2 to 30 days (mean=8.0 days, SD=6.6). CONCLUSIONS: The euthymic period of up to 2 months that is specified in DSM-IV for dysthymic disorder might confound the results of clinical trials. Data from additional groups of dysthymic patients would be useful when considering this issue for DSM-V.
Teaching high school students to use heuristics while reading historical texts.

The purpose of this study was to test the effectiveness of different types of instruction and texts on high schools students' learning of (a) history content and (b) a set of heuristics that historians use to think critically about texts. Participants for the study were 128 male and 118 female students, ages 16 and 17 years, from 2 high schools in the western United States. Eight history classrooms were randomly assigned to 1 of 4 interventions: (a) traditional textbooks and content instruction, (b) traditional textbooks and heuristic instruction, (c) multiple texts and content instruction, or (d) multiple texts and heuristic instruction. The heuristic instruction explicitly taught sourcing, corroboration, and contextualization. Students were administered pretests on their content knowledge and their use of heuristics. After an intervention of 3 weeks, students were readministered the content knowledge and heuristics posttests. A mixed-model analysis of covariance indicated that across all conditions, students who read multiple texts scored higher on history content and used sourcing and corroboration more often than students who read traditional textbook material. Findings highlight the importance of reading multiple texts to deepen content knowledge and facilitate the use of heuristics that historians typically use.
Personality traits and leptin.

Leptin is an adipose-derived hormone that plays a significant role in food intake and energy storage by relaying information between peripheral tissue and the central nervous system. When functioning normally, leptin acts as a signal to the brain to stop eating. Higher levels of leptin typically reduce appetite, but the elevated level found in obese individuals is thought to be due to reduced sensitivity to leptin signaling (i.e., leptin resistance). In addition to its association with physiological factors such as obesity and inflammation (1), leptin has been implicated in a number of cognitive and psychological processes. Although leptin may have neuroprotective effects (2), elevated levels have been associated with poor psychological outcomes, including subjective stress (3) and post-traumatic stress disorder (4), although the findings are mixed on the association between leptin and depression (5, 6). There is reason to suspect that other psychological factors, specifically personality traits, may be related to circulating levels of leptin. Individuals high in Neuroticism and low in Conscientiousness are more prone to being overweight or obese (7-10), are more likely to experience weight fluctuations (10), have higher levels of inflammation (11, 12), and are more vulnerable to depression (13). The present study examines the association between personality and leptin in a large sample of community-dwelling adults. Given their association with obesity, inflammation, and psychological distress, we hypothesized that high Neuroticism and low Conscientiousness would be associated with higher levels of leptin. In addition to the five broad domains, we examine the association with more specific aspects, or facets of personality. We hypothesize that facets that have previously been linked to obesity (higher impulsiveness, higher assertiveness, lower activity, lower order, lower self-discipline, and lower deliberation) will be associated with higher leptin; we present the results for the remaining facets as exploratory analyses. We also examine whether the associations between personality and leptin are independent of body mass index (BMI), waist circumference, and inflammatory markers associated with both leptin and personality (interleukin-6 [IL-6], c-reactive protein [CRP], white blood cells [WBC]). Because the association between personality and leptin may depend on age and it may differ between the sexes, we examine whether these associations vary by age and sex. Finally, we hypothesize that the association between personality traits and adiposity will be partially mediated by higher levels of leptin.
Unification of problem solving environment implementation layers with XML-based specifications

This paper describes how a design approach based on specifications via XML is used to unify the implementation layers of a problem solving environment WBCSim. WBCSim is a Web based simulation system designed to increase the productivity of wood scientists conducting research on wood-based composites manufacturing processes. WBCSim serves as a prototypical example for the design, construction, and evaluation of small-scale problem solving environments. WBCSim supports five process models. An XML datasheet is tailored for each model. The WBCSim interface layer, server scripts, and database management system all use this XML datasheet to improve the usability and maintainability of the three layers - client, server, developer - comprising the WBCSim system. A detailed description of the WBCSim system architecture is presented, along with a typical scenario of usage.