cssi/SciSciGPT-SciSciNet huggingface dataset:
Novel siRNA formulation to effectively knockdown mutant p53 in osteosarcoma

Objectives The tumor suppressor p53 plays a crucial role in the development of osteosarcoma. The primary objective of this study is to develop and optimize lipid based nanoparticle formulations that can carry siRNA and effectively silence mutant p53 in 318–1, a murine osteosarcoma cell line. Methods The nanoparticles were composed of a mixture of two lipids (cholesterol and DOTAP) and either PLGA or PLGA-PEG and prepared by using an EmulsiFlex-B3 high pressure homogenizer. A series of studies that include using different nanoparticles, different amount of siRNAs, cell numbers, incubation time, transfection media volume, and storage temperature was performed to optimize the gene silencing efficiency. Key findings Replacement of lipids by PLGA or PLGA-PEG decreased the particle size and overall cytotoxicity. Among all lipid-polymer nanoformulations, nanoparticles with 10% PLGA showed highest mutant p53 knockdown efficiency while maintaining higher cell viability when a nanoparticle to siRNA ratio equal to 6.8:0.66 and 75 nM siRNA was used. With long term storage the mutant p53 knockdown efficiency decreased to a greater extent. Conclusions This study warrants a future evaluation of this formulation for gene silencing efficiency of mutant p53 in tissue culture and animal models for the treatment of osteosarcoma.
Servant Leadership and Gender

Some scholars claim servant leadership is a gender-neutral leadership style that may enhance perceptions of women leaders by de-emphasizing the masculine traits typically expected of leaders. However, others argue servant and leader are gender-laden terms, creating a superior-subordinate paradox that mirrors the female-leader paradox. Despite debate over whether servant leadership minimizes gender biases based in leader stereotypes, multiple case studies illustrate the way some women self-identify as servant leaders, attaining leadership roles through service. Servant leadership may allow women leaders to enact the social roles of gender and leader in authentic ways, leading to enhanced follower perceptions and ethical decision making consistent with a feminine ethic of care. Taken together, these possibilities make the intersections between servant leadership and gender worthy of continued exploration.
Performance enhancement of a computational persistent homology package

In recent years, persistent homology has become an attractive method for data analysis. It captures topological features, such as connected components, holes, voids, etc., from a point cloud by finding out when these features appear and disappear in the filtration sequence. In this project, we focus on improving the performance of Eirene, a fancy computational persistent homology package. Eirene is a 5000-line open-source software implemented by using the dynamic programming language Julia. We use the Julia profiling tools to identify the performance bottlenecks and develop different methods to manage the bottlenecks, including the parallelization of some time-consuming functions on the multicore/manycore hardware. The empirical results show that the performance can be greatly improved.
A fulminant hepatic failure model in the rat : Involvement of interleukin-1β and tumor necrosis factor-α

The development of a fulminant hepatic failure (FHF) model is necessary for evaluating the efficacy of extracorporeal liver support systems. Recognizing the multifaceted functions of the liver, including synthesis and degradation, we investigated blood chemistry, histological findings, and survival rate in d-galactosamine (GalN)-intoxicated rats. The pathophysiologic response of inflammatory cytokines, interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), was also measured. Sprague-Dawley rats (200–300 g) were divided into two groups: GalN and saline injection. Rats were killed at 1, 3, 6, 12, 24, 36, 48, 72, and 168 hr after intraperitoneal injection of GalN (1.4 g/kg) or saline. In both groups, liver-specific markers, liver histology, and IL-1β and TNF-α levels in blood and liver tissue were analyzed. In a second series of experiments, the survival rates were examined after two administrations of GalN at 1.0, 1.4 or 2.0 g/kg, at a 12-hr interval. In the GalN injection group, the liver-specific markers reached peak levels between 36 and 48 hr after injection. Histologically, hepatocellular necrosis was seen at 6–48 hr, followed by a regenerative phase occurring between 72 and 168 hr. IL-1β and TNF-α levels in liver tissue peaked at 12 hr and 1 hr, respectively. The levels of these cytokines in blood, however, did not change significantly. The survival rates at day 7 for 1.0, 1.4 or 2.0 g/kg GalN injected twice were 77.8%, 16.7%, and 0%, respectively. These results suggest that single and double injection of GalN enable the development of reversible and irreversible FHF models. The results also indicate that IL-1β and TNF-α are useful markers of liver injury.
The Role of Thought Experiments in Science and Science Learning

In this chapter, we review selected studies of thought experiments used by both experts and students and attempt to develop some useful definitions and conceptual distinctions. We then apply these in an analysis of a classroom episode as an example of the roles thought experiments can play in productive whole class discussions. We are interested in this area because thought experiments are one example of the kinds of creative reasoning of which experts and students appear to be capable under the right conditions.
Managing difficult behaviors in patients with dementia.

There are nonpharmacological approaches to managing behavioral and psychological symptoms of dementia and the difficulties associated with evaluating and implementing these approaches. Virtual Mentor is a monthly bioethics journal published by the American Medical Association.
Identification of governing physical processes of irregular combustion through machine learning

This study is concerned with the data-driven analysis of predictive parameters associated with regime transition for ignition and detonation. To this end, we introduce machine learning as a technique to analyze the predictive capability of these parameters. Machine learning enables the critical evaluation of combustion regimes from disparate sources and allows for a generalized comparison of the parameters. The parameter set is composed of features that have been found to be effective in classifying ignition regimes and are supposed to have a universality in predicting the regularity of the ignition process. Three different configurations are examined: weak ignition shock tubes, mild ignition in rapid compression machines, and the regularity of cellular detonations. All configurations are demonstrated to show a strong sensitivity to the heat deposition time of the chemical reaction. Additionally, detonations are found to be primarily sensitive to the heat release and show that an increased chemical sensitivity has a regularizing effect when plotted against the heat release rate. The data are found to be well classified with only one or two parameters, indicating that a universal, governing parameter is plausible.
Broadening Participation in Undergraduate Research Experiences (UREs): The Expanding Role of the Community College.

Through the efforts of the National Science Foundation–funded Community College Undergraduate Research Initiative, community colleges have taken an active role in broadening participation in underg...
The effect of intrathyroidal versus intraperitoneal bevacizumab on thyroid volume and vasculature flow in a rat model

Background: Several clinical conditions increase thyroid gland vascularity, impacting surgical blood loss. Bevacizumab has been observed to reduce thyroid function, possibly through its effect on gland angiogenesis. This study aimed to determine if bevacizumab has any effect on thyroid vascularity as measured by gland volume and superior thyroid artery (STA) flow velocity in the normal rat thyroid. Methods: Sixteen adult female Sprague-Dawley rats were placed under general anesthesia to measure baseline thyroid gland characteristics. A Vevo 2100 high-frequency ultrasound with 40 mHz transducer was used to obtain STA flow measurements and thyroid gland dimensions. Four rats served as controls. Six rats received intrathyroidal (IT) injections and 6 received intraperitoneal (IP) injections of bevacizumab (4–5 mg/kg). After two weeks ultrasound measurements were repeated. Results: Pretreatment animals displayed similar thyroid volume and vascularity. Thyroid volume decreased (62.583 vs . 42.161, P=0.004) after IP administration of bevacizumab, and blood flow measurements did not change [peak velocity 75.896 vs . 76.7, P=0.96, average velocity 45.748 vs . 43.867, P=0.88, or resistivity index (RI) 30.345 vs . 25.32, P=0.60]. IT bevacizumab did not change thyroid volume (55.229 vs . 58.16, P=0.64). The average peak (73.191 vs . 100.589 cm/s, P=0.03) and mean (45.047 vs . 62.843 m/s, P=0.03) velocities were increased, but did not differ in the RI (0.619 vs . 0.632, P=0.82). No differences were noted on VEGF or CD 31 immunohistochemical analysis. Conclusions: Single systemic administration of bevacizumab appears to decrease thyroid volume without an effect on STA flow, VEGF or CD31 staining. These preliminary findings support further study of pharmacologic intervention in thyroid conditions characterized by increased angiogenesis and vascularity, such as iodine deficiency, Graves disease, and hypothyroidism.
"If horns you love, if horns you crave...": A Closer Look at Early American Powderhorns

Observing the frontiersmen he encountered in the Carolinas on the eve of the American Revolution, English traveler J.F.D. Smythe paid particular attention to their attire. Along with their fringed linen hunting shirts—a garment known mostly in Pennsylvania and points south prior to the war—he noted that their powder horns, carved with a “variety of whimsical figures,” were a key element of the backwoodsmen’s style. By the 1770s, they had also become important recordkeeping tools on which soldiers, settlers, and American Indians etched their names, war records, and other significant information.
Military-related risk factors in female veterans and risk of dementia

Objective To determine whether diagnoses of traumatic brain injury (TBI), posttraumatic stress disorder (PTSD), and depression, alone or in combination, increase dementia risk among older female veterans. Methods This cohort study included data from 109,140 female veterans ≥55 years of age receiving care from Veterans Health Administration medical centers in the United States between October 2004 and September 2015 with at least 1 follow-up visit. TBI, PTSD, depression, and medical conditions at study baseline and incident dementia were determined according to ICD-9-CM codes. Fine-Gray proportional hazards models were used to determine the association between military-related risk factors and dementia diagnosis, accounting for the competing risk of death. Results During follow-up (mean 4.0 years, SD 2.3), 4% of female veterans (n = 4,125) developed dementia. After adjustment for demographics and medical conditions, women with TBI, PTSD, and depression had a significant increase in risk of developing dementia compared to women without these diagnoses (TBI-adjusted subdistribution hazard ratio [adjusted sHR] 1.49, 95% confidence interval [CI] 1.01–2.20; PTSD adjusted sHR 1.78, 95% CI 1.34–2.36; and depression-adjusted sHR 1.67, 95% CI 1.55–1.80), while women with >1 diagnosis had the highest risk for dementia (adjusted sHR 2.15, 95% CI 1.84–2.51). Conclusions We found that women with military-related risk factors had an ≈50% to 80% increase in developing dementia relative to women without these diagnoses, while female veterans with multiple risk factors had a >2-fold risk of developing dementia. These findings highlight the need for increased screening of TBI, PTSD, and depression in older women, especially female veterans.
Management of Peripheral Venoarterial Extracorporeal Membrane Oxygenation in Cardiogenic Shock.

Objectives:Cardiogenic shock is a highly morbid condition in which inadequate end-organ perfusion leads to death if untreated. Peripheral venoarterial extracorporeal membrane oxygenation is increasingly used to restore systemic perfusion despite limited understanding of how to optimally titrate supp
THE EFFECTS OF THE INCENTIVE SYSTEMS AND ORGANIZATIONAL CULTURE ON STRATEGY SURROGATION

The purpose of this study was to investigate the impact of an important aspect of an organizational context, specifically organizational culture, and different types of compensation schemes on strategy surrogation. Strategy surrogation occurs when managers focus on the measures in the strategic performance measurement systems (SPMS) on which they are compensated and completely or partially lose focus on the overall strategic objectives of the organization. This study utilized a 2x2 between-participants experimental design that manipulates organizational culture (control-dominant vs. flexibility-dominant) and the type of compensation scheme (fixed pay vs. pay-for-performance). The study was conducted online with 80 participants from the Amazon Mechanical Turk (MTurk) as proxies for managers. The results show that employees operating under a control-dominant culture do not surrogate more than employees operating under a flexibility-dominant culture. Additionally, the type of organizational culture does not moderate the relationship between incentive systems and strategy surrogation. However, employees operating under a pay-for-performance compensation scheme significantly surrogate more than employees operating under a fixed pay compensation scheme. The study contributes to the incentives and organizational culture literature as well as strategy surrogation research by examining institutional factors that may inhibit or exacerbate surrogation. Additionally, the study contributes to the judgment and decision-making literature by highlighting employees’ decision-making outcomes under different compensation schemes.
Urban Grassland Management Implications for Soil C and N Dynamics: A Microbial Perspective

Urban grasslands are turfgrass dominated landscapes of varying functions and uses that are ubiquitous in areas associated with human population growth and urbanization. While these landscapes are perceived to serve a primarily aesthetic function, they provide a multitude of beneficial ecosystem functions that impervious surfaces do not provide. Urban grassland soils have been shown to accumulate carbon (C) and nitrogen (N) for decades, matching native grasslands and eastern hardwood forest soils in terms of C and N densities. The establishment and maintenance of urban grasslands alters many microbially-mediated biogeochemical processes in soils, including soil organic matter (SOM) dynamics. Despite strong evidence of alterations to soil C and N cycling, the impacts of maintaining urban grasslands on soil microbiomes and their functions remain understudied compared to other ecosystems. Typical management practices can directly and indirectly affect edaphic factors in urban grasslands, which in turn, could impact soil processes mediated by microorganisms. We reviewed the existing literature on urban grassland management, focusing on how mowing, fertilization, irrigation, grass species composition, and soil cultivation could impact the composition and function of soil microorganisms. Although sparse, the literature indicates that the techniques used to maintain urban grassland habitats broadly select for copiotrophic microorganisms adapted to higher resource availability. Additionally, the studies indicate that greater soil fertility and plant productivity found in urban grasslands facilitate the accumulation of soil C and N, as well as SOM as compared to other land-use types. However, effects on soil biology and biogeochemistry depend on specific management practices, which are quite variable. Future research on soil C and N dynamics in urban grasslands should focus on the dominant component of this ecosystem—residential lawns—however, much of the existing scientific literature featuring turfgrass systems focus heavily on golf courses, athletic fields, and major tourist parks.
The tip of the VgrG spike is essential to functional type VI secretion assembly in Acinetobacter baumannii

Abstract The type VI secretion system (T6SS) is a critical weapon in bacterial warfare between Gram-negative bacteria. Although invaluable for niche establishment, this machine represents an energetic burden to its host bacterium. Acinetobacter baumannii is an opportunistic pathogen that poses a serious threat to public health due to its high rates of multidrug resistance. In some A. baumannii strains, the T6SS is transcriptionally downregulated by large multidrug-resistance plasmids. Other strains, such as the clinical isolate AbCAN2, express T6SS-related genes but lack T6SS activity under laboratory conditions, despite not harboring these plasmids. This suggests that alternative mechanisms exist to repress the T6SS. Here, we employed a transposon mutagenesis approach in AbCAN2 to identify novel T6SS repressors. Our screen revealed that the T6SS of this strain is inhibited by a homolog of VgrG, an essential structural component of all T6SSs reported to date. We named this protein inhibitory VgrG (VgrGi). Biochemical and in silico analyses demonstrated that the unprecedented inhibitory capability of VgrGi is due to a single amino acid mutation in the widely conserved C-terminal domain of unknown function DUF2345. We also show that unlike in other bacteria, the C-terminus of VgrG is essential for functional T6SS assembly in A. baumannii. Our study provides insight into the architectural requirements underlying functional assembly of the T6SS of A. baumannii. We propose that T6SS-inactivating point mutations are beneficial to the host bacterium, as they eliminate the energy cost associated with maintaining a functional T6SS, which appears to be unnecessary for A. baumannii virulence. Importance Despite the clinical relevance of A. baumannii, little is known about its fundamental biology. Here, we show that a single amino acid mutation in VgrG, a critical T6SS structural protein, abrogates T6SS function. Given that this mutation was found in a clinical isolate, we propose that the T6SS of A. baumannii is likely not involved in virulence, an idea supported by multiple genomic analyses showing that the majority of clinical A. baumannii strains lack proteins essential to the T6SS. We also show that, unlike in other species, the C-terminus of VgrG is a unique architectural requirement for functional T6SS assembly in A. baumannii, suggesting that over evolutionary time, bacteria have developed changes to their T6SS architecture, leading to specialized systems.
Advances in Testing for Dysphagia

Dysphagia refers to the subjective sensation of difficulty swallowing. Normal swallowing relies on a complex series of voluntary and involuntary neuromuscular events, propelling food along the oropharyngeal cavity through the esophageal lumen and into the stomach. When these functions are impaired, dysphagia related to oropharyngeal or esophageal dysfunction can occur. Dysphagia itself encompasses a broad differential diagnosis, including more benign etiologies such as esophageal strictures and hiatal hernias to more alarming processes such as achalasia or malignancy. Establishing the etiology of dysphagia requires a comprehensive understanding of the various radiologic, endoscopic, and manometric tools clinically available. These diagnostic techniques range from various fluoroscopic protocols, fiberoptic endoscopic evaluation of swallowing (FEES), and esophagogastroduodenoscopy (EGD) to high-resolution esophageal manometry (HRM) and functional lumen imaging probe (FLIP), each complementary with specific strengths and limitations. This chapter aims to provide a comprehensive review of diagnostic tools commonly utilized in dysphagia, with discussion focusing on mechanisms of action, protocol, and diagnostic yield.
Unusually High Prevalence of Silent Stroke and Cerebral Vasculopathy in Hemoglobin SC Disease

Introduction Children and adults with sickle cell disease (SCD) suffer from overt stroke, the prevalence of which has been reported to be 11% Methods We retrospectively analyzed charts of 131 children and adults with (SCD) who sought care at the University of Missouri between 2000 and 2018, between the ages of 1- 65 years. Clinical, laboratory, Transcranial Doppler (TCD) ultrasound, and Magnetic Resonance Imaging/Angiography (MRI/MRA) data for clinically documented overt stroke, SCI and vasculopathy were analyzed. An expert neuroradiologist analyzed all the MRI/MRAs in a blinded manner. Fisher's exact tests for categorical data and two-sided t-tests for continuous data analysis were used. P value Results Of the 131 individuals analyzed, 9 were excluded from the study due to incomplete clinical information. The genotype consisted of HbSS 72 (59.0%), HbSC 39 (32.0%), and HbS/β Thal 11(9.0%) (Table 1). The overall prevalence of cerebrovascular complications were 30%, 17.7% and 22.2% in the HbSS, HbSC and HbS/β Thal (p-0.47), respectively (Table 2). Among HbSC individuals, those with stroke and cerebral vasculopathy had a marginally higher serum creatinine compared to those without complications (p-0.08) (Table 3). Prevalence of proteinuria was higher in individuals with cerebrovascular lesions (p-0.015). Of the SCD related complications, acute chest syndrome (57.7% versus 33.8%; p-0.038), gall bladder stones with cholecystectomy (53% versus 23%; p-0.006) and pulmonary hypertension (46.2% versus 7.8%, p- Conclusion We noted a higher prevalence of neurovascular complications in individuals with HbSC than previously reported by the Cooperative Study of Sickle Cell disease. The prevalence of cerebrovascular complications in comparison group of HbSS was similar to that reported previously in CSSD cohort. This study indicates that both silent stroke and vasculopathy occur in HbSC and appeared to be more prevalent than overt stroke. As TCD screenings are not routinely used in individuals with HbSC, MRI may be warranted to detect SCI and cerebral vasculopathy. Larger prospective studies are required to understand genetic and non-genetic risk factors associated with stroke in children and adults with HbSC for establishment of prevention, early detection, and treatment modalities. References 1. Blood 2011 Jan 27;117(4):1130-40 2. Blood 2002 Apr 15;99(8):3014-8 3. Blood 2015 125:416-417; Download : Download high-res image (1MB) Download : Download full-size image Disclosures Balasa: Novartis: Honoraria, Other: Medical Advisory Board; Genetech: Honoraria, Other: Medical Advisory Board; Sanofi-Genzyme: Honoraria, Other: Medical Advisory Board; Takeda: Honoraria, Other: Medical Advisory Board; Octapharma: Honoraria, Other: Medical Advisory Board; Bayer: Honoraria, Other: Medical Advisory Board.
Exome-wide age-of-onset analysis reveals exonic variants in ERN1, TACR3 and SPPL2C associated with Alzheimer’s disease

Despite recent discovery in GWAS of genomic variants associated with Alzheimer9s disease (AD), its underlying biological mechanisms are still elusive. Discovery of novel AD-associated genetic variants, particularly in coding regions and from APOE e4 non-carriers, may provide more insights into the understanding of the pathology of AD. In this study, we carried out exome-wide association analysis of age-of-onset of AD with ~20,000 subjects, and placed more emphasis on APOE e4 non-carriers. Using Cox mixed-effects models, we find that age-of-onset shows a stronger genetic signal than AD case-control status, capturing many known variants with stronger significance, and also revealing three new variants. We identified two novel rare variants, rs56201815, a synonymous variant in ERN1, from the analysis of APOE e4 non-carriers, and a missense variant rs144292455 in TACR3. In addition, we detected rs12373123, a common missense variant in SPPL2C in the MAPT region, associated with age-of-onset of AD in APOE e4 non-carriers. In an attempt to unravel their regulatory and biological functions, we found that the minor allele of rs56201815 was associated with lower average FDG uptake across five brain regions in ADNI. Our eQTL analyses based on 6198 gene expression samples from ROSMAP and GTEx revealed that the minor allele of rs56201815 was associated with elevated expression of ERN1, a key gene triggering unfolded protein response (UPR), in multiple brain regions, including posterior cingulate cortex and nucleus accumbens. Our cell type-specific eQTL analysis of based on ~80,000 single nuclei in prefrontal cortex revealed that the protective minor allele of rs12373123 significantly increased expression of GRN in microglia, and was associated with MAPT expression in astrocytes. These findings provide novel evidence supporting the hypothesis of the potential involvement of the UPR to ER stress in the pathological pathway of AD, and also provide more insights into underlying regulatory mechanisms behind the pleiotropic effects of rs12373123 in multiple degenerative diseases including AD and Parkinson9s disease.
Fully automatic quantification of individual ganglion cells from AO-OCT volumes via weakly supervised learning

Quantitative features of individual ganglion cells (GCs) are potential paradigm changing biomarkers for improved diagnosis and treatment monitoring of GC loss in neurodegenerative diseases like glaucoma and Alzheimer’s disease. The recent incorporation of adaptive optics (AO) with extremely fast and high-resolution optical coherence tomography (OCT) allows visualization of GC layer (GCL) somas in volumetric scans of the living human eye. The current standard approach for quantification – manual marking of AO-OCT volumes – is subjective, time consuming, and not practical for large scale studies. Thus, there is a need to develop an automatic technique for rapid, high throughput, and objective quantification of GC morphological properties. In this work, we present the first fully automatic method for counting and measuring GCL soma diameter in AO-OCT volumes. Aside from novelty in application, our proposed deep learningbased algorithm is novel with respect to network architecture. Also, previous deep learning OCT segmentation algorithms used pixel-level annotation masks for supervised learning. Instead in this work, we use weakly supervised training, which requires significantly less human input in curating the training set for the deep learning algorithm, as our training data is only associated with coarse-grained labels. Our automatic method achieved a high level of accuracy in counting GCL somas, which was on par with human performance yet orders of magnitude faster. Moreover, our automatic method’s measure of soma diameters was in line with previous histological and in vivo semi-automatic measurement studies. These results suggest that our algorithm may eventually replace the costly and time-consuming manual marking process in future studies.
Amplifier Input Matching for NF-Gain-Linearity Compromise

In this paper we investigate the effect of amplifier input matching on the noise figure, gain, and linearity design tradeoff, with the goal of developing a single-amplifier solution able to operate as either a PA or LNA. We evaluate the large-signal linearity performance of an amplifier with a noise-matched input compared to an identical amplifier with gain-matched input, and the effects on efficiency and noise figure. The prototype amplifier is designed at 3 GHz and realizes 42.86 dBm CW output power and 67% PAE at 3 dB gain compression. With a noise-matched input the amplifier realizes a 2 dB reduction in gain and 7.7 percentage point reduction in PAE compared to the gain-matched amplifier, but a 3 dB improvement in IMD3 at 33.5 dBm output power under a 1-MHz spaced two-tone signal excitation.
Public Health Competencies for Chiropractic Programs

The public health contribution of various health care professions is shaped by their education and areas of expertise. Growing recognition of musculoskeletal pain as a top driver of health care exp...
angiomotin regulates budding and spread of ebola virus

The Ebola virus (EBOV) VP40 matrix protein (eVP40) orchestrates assembly and budding of virions in part by hijacking select WW-domain-bearing host proteins via its PPxY late (L)-domain motif. Angiomotin (Amot) is a multifunctional PPxY-containing adaptor protein that regulates angiogenesis, actin dynamics, and cell migration/motility. Amot also regulates the Hippo signaling pathway via interactions with the WW-domain-containing Hippo effector protein Yes-associated protein (YAP). In this report, we demonstrate that endogenous Amot is crucial for positively regulating egress of eVP40 virus-like particles (VLPs) and for egress and spread of authentic EBOV. Mechanistically, we show that ectopic YAP expression inhibits eVP40 VLP egress and that Amot co-expression rescues budding of eVP40 VLPs in a dose-dependent and PPxY-dependent manner. Moreover, results obtained with confocal and total internal reflection fluorescence microscopy suggested that Amot's role in actin organization and dynamics also contributes to promoting eVP40-mediated egress. In summary, these findings reveal a functional and competitive interplay between virus and host proteins involving the multifunctional PPxY-containing adaptor Amot, which regulates both the Hippo pathway and actin dynamics. We propose that our results have wide-ranging implications for understanding the biology and pathology of EBOV infections.
Postpyloric feeding tube placement at the bedside: Complication rate and impact on length of stay

BACKGROUND Postpyloric feeding tube (PPFT) placement is essential for the ongoing nutrition care of critically ill children requiring noninvasive and invasive ventilation. PPFTs are placed by a variety of providers, including advanced practice nurses (APNs), surgeons, gastroenterologists, and radiologists. Complication rates, time to enteral nutrition (EN) following placement, and association with length of stay (LOS) have not been well documented. METHODS A query of the electronic medical record identified patients in the pediatric intensive care unit (PICU) in whom PPFTs were placed. A retrospective chart review was performed to identify patient demographics; PPFT placement provider, indication, and duration; PICU LOS; hospital LOS; and patient pediatric risk of mortality (PRISM) scores. RESULTS A total of 452 PPFTs were placed in 346 patients , with 318 placed by APNs. There was only one complication in 452 placed PPFTs. PRISM scores between patient groups for APN-placed PPFTs and non-APN-placed PPFTs were not significantly different. Mean time from hospital admission to PPFT placement was 1.5 days (APN) to 2.0 days (non-APN) (P < .02). Spearman correlation coefficients demonstrated shorter hospital and PICU LOS were associated with shorter duration to insertion. CONCLUSION Overall complication rates of PPFT insertion is very low and do not significantly differ between provider type , even in patients with higher PRISM scores. Additionally, early time to insertion of PPFT is associated with decreased hospital and PICU LOS. Further research is needed to determine if the earlier time to insertion of PPFTs is associated with the achievement of goal feeds.
Functional expression of aryl hydrocarbon receptor as a potential novel therapeutic target in human multiple myeloma

The etiology of multiple myeloma (MM) remains incompletely understood; however, epidemiologic studies have suggested a possible link between exposure to environmental aromatic hydrocarbons-which serve as exogenous ligands for the aryl hydrocarbon receptor (AHR), which has been implicated in cancer biology-and development of monoclonal gammopathy of undetermined significance (MGUS) and MM. Herein, we demonstrate the functional expression of AHR in MM cell lines and primary human MM samples. AHR is expressed in putative MM 'stem cells' and advanced clinical stages of MM, and functionally contributes to MM tumor cell phenotype and proliferation. Antagonism of AHR directly impairs MM cell viability and increases MM cell susceptibility to immune-mediated clearance. Furthermore, our findings indicate that AHR antagonism may represent an effective means to enhance the function of other drugs, such as anti-CD38 antibodies, in future clinical studies. Taken together, these data identify AHR as a novel target for MM therapy.
The Credibility of Management Earnings Forecasts for Firms that Meet or Beat Analysts’ Forecast Benchmarks

Based on Graham et al.’s (2005) survey, CFOs believe financial performance impacts the credibility of their forecasts. We examine this link by testing whether management earnings forecasts (MEFs) of firms meeting/beating analysts’ forecast benchmarks exhibit greater credibility than MEFs of firms missing these benchmarks, based on the informativeness of forecast news. We find for meet/beat firms, the association of forecast news with cumulative abnormal returns is stronger than for miss firms, thus providing evidence of the credibility meeting/beating forecasts provides, but the difference diminishes when firms narrowly beat their benchmarks. Finally, we test whether meet/beat firms use the increased credibility to provide credible guidance about future performance, finding that the association of forecast news with forecast errors is smaller for meet/beat firms than for miss firms, which supports the beliefs of the CFOs surveyed in Graham et al. (2005) that meeting/beating AF benchmarks increases the credibility of their forecasts.
Extending the bidding format to promote demand response

We propose an extended bidding structure to allow more realistic demand characteristics and behaviors to be expressed via flexible bids. In today's ISO-run energy markets, demand bid formats are all separable over time. However, a significant and growing segment of demand can be shifted across time and therefore has no way to bid its true valuation of consumption. We propose additional bid types that allow deferrable, adjustable and storage-type loads to better express their value, and thus elicit demand response in the most natural way – via direct participation in the market. We show that the additional bid types are easily incorporated into the existing market with no technological barrier and that they preserve the market's efficiency and incentive-compatibility properties. Using real market data, we give a numerical demonstration that the extended bid format could substantially increase social welfare, and also present additional insight on storage expansion scenarios.
SPINOZA AND PROCESS ONTOLOGY

In this paper, I put forward some remarks supporting a reading of Spinoza's metaphysics in terms of process ontology, that is, the notion that processes or activities, rather than things, are the most basic entities. I suggest that this reading, while not the only possible one, offers advantages over the traditional substance-properties interpretation. While this claim may sound implausible vis-a-vis Spinoza's language of ‘substance’ and ‘attributes’, I show that process ontology illuminates important features of Spinoza's thought and can facilitate solutions to some interpretive problems.
A taxonomy of theorem-proving strategies

This article presents a taxonomy of strategies for fully-automated general-purpose first-order theorem proving. It covers forward-reasoning ordering-based strategies and backward-reasoning subgoal-reduction strategies, which do not appear together often. Unlike traditional presentations that emphasize logical inferences, this classification strives to give equal weight to the inference and search components of theorem proving, which are equally important in practice. For this purpose, a formal notion of search plan is given and shown to apply to all classes of strategies. For each class, the form of derivation is specified, and it is shown how inference system and search plan cooperate to generate it.
Penetrating keratoplasty after radial keratotomy. A report of six patients.

Background: For more than 15 years, radial keratotomy has increased in popularity as an option for treating myopia in the United States. During this period of time, the procedure has been modified to improve results and decrease complications. Despite these changes, complications from radial keratotomy continue to occur. The authors report six cases of penetrating keratoplasty performed to correct significant loss of vision resulting from complications of radial keratotomy. Methods: The surgical records of one author (WR) were reviewed retrospectively for penetrating keratoplasties performed for complications of radial keratotomy. Results: Six cases of penetrating keratoplasty performed for complications of radial keratotomy were found. Severe loss of vision was the indication for surgery in each case, and was associated with aggressive and repeated incisional refractive attempts to correct astigmatism, hyperopic overcorrection, residual myopia, or refractive errors associated with keratoconus. Glare associated with subepithelial scarring and irregular astigmatism were the primary findings associated with loss of vision. Conclusions: Despite advances in technique and instrumentation, radial keratotomy is limited in the amount of myopia it can correct. The risk for loss of vision increases with increasing number of incisions, intersecting incisions, very small optical zones, and keratoconus.
3D Synthetic Environment Representation Using the Non-Manifold 3D Winged-Edge Data Structure

A Non-Manifold data structure for the modeling of 3D synthetic environments is proposed. The data structure uses a boundary representation (B-rep) method. B-rep models 3D objects by describing them in terms of their bounding entities and by topologically orienting them in a manner that enables the distinction between the object’s interior and exterior. Consistent with B-rep, the representational scheme of the proposed data structure includes both topologic and geometric information. The topologic information encompasses the adjacencies involved in 3D manifold and non-manifold objects, and is described using a new, extended Winged-Edge data structure. This data structure is referred to as “Non-Manifold 3D Winged-Edge Topology”. The time complexity of the newly introduced data structure is investigated. Additionally, the Non-Manifold 3D Winged-Edge Topology is being prototyped in a Web-Based virtual reality application. The prototype data consists of Military Operation in Urban Terrain (MOUT) data for Camp LeJeune, North Carolina. The application is expected to be ideal for training and simulation exercises as well as actual field operations requiring on-site assistance in urban areas.
Nocturnal Hypertension and Attenuated Nocturnal Blood Pressure Dipping is Common in Pediatric Lupus

Hypertension is an important manifestation of systemic lupus erythematosus (SLE) but reports of prevalence vary between 20-70% in published reports of adult and pediatric patients. For both children and adults with SLE, the clinical diagnosis and management of hypertension has traditionally been based on guidelines developed for the general population. In clinical trials, the criteria used for defining participants with hypertension are mostly undefined. As a first step towards formally assessing the blood pressure (BP) patterns of children diagnosed with SLE, 24-hr ambulatory BP monitoring data was analyzed on clinic patients who presented with prehypertension or stage I hypertension. In this pediatric SLE cohort (n=10), 20% met daytime criteria for a diagnosis of hypertension. Patterns of BP elevation varied widely with white coat, masked, isolated systolic, and diastolic nocturnal hypertension all identified. Nocturnal hypertension was detected in 60% and attenuated nocturnal BP dipping in 90% of both hypertensive and normotensive SLE patients. In SLE patients, the median nighttime systolic and diastolic loads were 25% and 15.5% compared with median daily loads of 12.5% and 11.5%. Daytime and nighttime systolic and diastolic BP load and nocturnal dipping was compared to a control population consisting of 85 non-SLE patients under 21 years old with prehypertension or stage 1 hypertension presenting to hypertension clinic. Median systolic BP dipped 5.3 mmHg in SLE patients compared to 11.9 mmHg in non-lupus ( p-value = 0.001). Median diastolic BP dipped 12.9 mmHg versus 18.5 mmHg in non-lupus ( p-value = 0.003). Patterns of BP dysregulation in pediatric SLE merit further exploration. Children with or without SLE displaying prehypertensive or stage 1 casual BP measurements had similar rates of hypertension by ambulatory BP monitoring. However, regardless of BP diagnosis, and independent of kidney involvement, there was an increased proportion with attenuated nocturnal dipping and nocturnal hypertension in SLE patients.
Do Governments Hide Resources from Unions? The Influence of Public Sector Unions on Financial Reporting Choices

This study explores whether unionized municipalities use aspects of governmental (or “fund”) accounting to obscure the amount of resources available through the use of fund balance accounts. I first investigate whether governments with unions report more resources outside of the general fund, a primary measure of operating performance, and instead within less visible funds where financial statement users are less likely to focus. Second, I explore whether unionized governments hold resources within less transparent general fund balance account categories – that is, have higher ratios of reserved or designated fund balance. Primary findings are consistent with both hypotheses. Corroborating analysis reveals that effects are magnified when unions have the ability to strike or are located in states without right-to-work laws. Overall, the evidence suggests that unionized governments shelter resources within less visible accounts and funds to avoid reporting large discretionary resources.
Antibody-nanotube microelectronic device to detect live breast cancer cells in blood

A3 Circulating tumor cells imply advanced diseases. Current methods for detecting circulating tumor cells require multiple technically demanding steps carried out by highly trained personnel. We hypothesized that single wall carbon nanotube (SWCNT) devices might provide an accurate, sensitive, simple and swift alternative to detect human breast cancer cells in single drops of blood. SWCNT transistors fabricated by employing airbrushing, surface functionalization were optimized by dual ultrasonication and polymer coating to maximize their performance. Specific and non-specific antibodies were attached to the exterior surfaces of the SWCNTs to render them specific for target biomolecules. Devices were challenged with several cancerous/non-cancerous human cell lines. Individual specific cancer cells could be detected by monitoring the 60% reduction of the device conductance upon specific cell binding. Non-specific cancer cells exhibited less than 5% conductance drop. Specific pairs of cancer cells with their cognate antibodies showed more than 10 times change of conductance over non-specific pairs, illustrating the sensitivity and selectivity of the SWCNT-antibody device. We postulate that the free energy change due to multiple simultaneous cell-antibody binding events exerted stress along the nanotube surface, decreasing its electrical conductivity due to an increase in band gap. Because the free energy change upon cell-antibody binding, the stress exerted on the nanotube, and the change in conductivity are specific to a specific antigen-antibody interaction, these properties might be used as a fingerprint for molecular sensing of circulating cancer cells. From optical microscopy observations during sensing, it appears that the binding of a single cell to a single nanotube field effect transistor produced the change in electrical conductivity. Thus we report a nanoscale oncometer with single cell sensitivity that functions in a drop of fresh blood.This work was supported by DAMD W81XWH-06-1-0668, NSF CAREER award ECS 0546328, and NIH INBRE grant RR016472-06.
CCR2+ monocytes contribute to hematoma clearance and long-term functional recovery after experimental intracerebral hemorrhage (HUM1P.324)

CCR2 + inflammatory monocytes worsen early neurological injury in mouse models of intracerebral hemorrhage (ICH), but their potential roles during recovery are unclear. The purpose of this work was to determine how CCR2 + monocytes influence repair and recovery after ICH. All mice in this study were subjected to the blood injection ICH model, whereby 25 μl of blood were injected into the striatum, a brain region involved in motor coordination. To first determine if monocytes have the capacity to phagocytose debris in the brain, we added 1-μm carboxylate beads to the injected blood. Using an ImageStreamX MarkII imaging flow cytometer, we found that CCR2 + monocytes engulf more beads than resident microglia at day 1 (4.35 ± 2.23 vs. 0.23 ± 0.45 beads, p -/- bone marrow was transplanted into CD45.1 hosts to create chimeras with normal microglia, but few circulating monocytes. Controls received C57BL6 marrow. Ccr2 -/- chimeric brains contained significantly more residual hemoglobin 7 days after ICH than controls (8.92 ± 1.03 vs. 3.96 ± 2.80 μl, p + monocytes in ICH clearance. Importantly, Ccr2 -/- bone marrow chimeras exhibit severe motor deficits following an LPS challenge 14 days after ICH, whereas controls exhibit minimal deficits. Together, these data suggest CCR2 + monocytes are important regulators of hematoma clearance and are necessary for functional recovery.
Prosecutorial Indiscretion: Encouraging the Department of Justice to Rein in Out of Control Qui Tam Litigation Under the Civil False Claims Act

This Article explores how the incentives created by the civil False Claims Act (FCA), a qui tam statute that is the government’s primary litigation tool for combating fraud, influence the Department of Justice’s (DOJ) prosecution of fraud actions. Over the past twenty years, the government and relators have recovered more than $18 billion in FCA actions, of which more than $11 billion was recovered in qui tam actions filed by private persons. Though other commentators have explored the policies underlying the FCA and even the FCA’s incentives to “blow the whistle” and file a qui tam action, no one has closely analyzed the incentives that impact the government’s subsequent decision whether to take over, dismiss, or allow the relator to proceed with a qui tam action. This Article’s examination of these incentives reveals that the FCA improperly discourages the DOJ from wresting control of errant qui tam actions from relators.As a result, over the last twenty years, 94% of qui tam FCA suits that the DOJ has allowed to proceed (totaling more than 3,000 actions) have been dismissed without recovering any funds. These non-meritorious suits have exacted a heavy toll on defendants, the judicial system, and the public as a whole. Meanwhile, the non-intervened qui tam actions that have succeeded in recovering funds present a different problem: FCA liability has expanded haphazardly without any guarantee that the new theories of liability will work to the public’s benefit. These problems have combined to alienate regulated industries, threaten public confidence in the legitimacy of the government’s fight against fraud, and endanger future industry cooperation in government enforcement initiatives. Where other commentators have urged drastic changes to the FCA to try to resolve these issues, this Article concludes that the problems can be largely ameliorated by two relatively minor amendments that would encourage the DOJ to exercise its intervention and dismissal powers more aggressively, without losing the current benefits of FCA litigation.