cssi/SciSciGPT-SciSciNet huggingface dataset:
Glutamate transporter currents in Bergmann glial cells follow the time course of extrasynaptic glutamate

Glutamate transporters in the central nervous system are expressed in both neurons and glia, they mediate high affinity, electrogenic uptake of glutamate, and they are associated with an anion conductance that is stoichiometrically uncoupled from glutamate flux. Although a complete cycle of transport may require 50-100 ms, previous studies suggest that transporters can alter synaptic currents on a much faster time scale. We find that application of L-glutamate to outside-out patches from cerebellar Bergmann glia activates anion-potentiated glutamate transporter currents that activate in <1 ms, suggesting an efficient mechanism for the capture of extrasynaptic glutamate. Stimulation in the granule cell layer in cerebellar slices elicits all or none alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor and glutamate transporter currents in Bergmann glia that have a rapid onset, suggesting that glutamate released from climbing fiber terminals escapes synaptic clefts and reaches glial membranes shortly after release. Comparison of the concentration dependence of both alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptor and glutamate transporter kinetics in patches with the time course of climbing fiber-evoked responses indicates that the glutamate transient at Bergmann glial membranes reaches a lower concentration than attained in the synaptic cleft and remains elevated in the extrasynaptic space for many milliseconds.
Reevaluating the Impact of Video Games

The evolution of the video game phenomenon is reviewed and contemporary data are presented. A survey assessing frequency and location of play and game preference was completed by 357 seventh- and eighth-grade students. In this middle-class sample, about two thirds of girls played video games at least one to two hours per week at home, but only 20% played in arcades. About 90% of boys played in the home and about 50% in arcades. Approximately half of preferred games were from one of two categories of violent games, while 2% of preferred games were educational. Parent education about the influence of the media should include recommendations to monitor game playing and influence game selection.
Electronically non-adiabatic interactions of molecules at metal surfaces: Can we trust the Born–Oppenheimer approximation for surface chemistry?

When neutral molecules with low levels of vibrational excitation collide at metal surfaces, vibrational coupling to electron-hole pairs (EHPs) is not thought to be strong unless incidence energies are high. However, there is accumulating evidence that coupling of large-amplitude molecular vibration to metallic electron degrees of freedom can be much stronger even at the lowest accessible incidence energies. As reaching a chemical transition-state also involves large-amplitude vibrational motion, we pose the basic question: are electronically non-adiabatic couplings important at transition states of reactions at metal surfaces? We have indirect evidence in at least one example that the dynamics and rates of chemical reactions at metal surfaces may be strongly influenced by electronically non-adiabatic coupling. This implies that theoretical approaches relying on the Born–Oppenheimer approximation (BOA) may not accurately reflect the nature of transition-state traversal in reactions of catalytic importance....
Scattered data interpolation tools in a microcomputer visualization environment

A package that can bridge the connection between scattered data sets and the highly structured sets required by graphics algorithms is described. Although export of evaluation data is a necessary capability, it is very important that this package has a fully featured three-dimensional graphics subsystem to interactively guide the researcher toward the final visualization results. At that point the option exists of using more sophisticated and more powerful graphics tools to achieve the desired presentation. The application presented has been designed to effectively meet these needs and to promote the awareness of the value of interpolation tools in visualization. Full details of this design are presented. >
Transcriptional Profiling of Cross Pathway Control in Neurospora crassa and Comparative Analysis of the Gcn4 and CPC1 Regulons

Identifying and characterizing transcriptional regulatory networks is important for guiding experimental tests on gene function. The characterization of regulatory networks allows comparisons among both closely and distantly related species, providing insight into network evolution, which is predicted to correlate with the adaptation of different species to particular environmental niches. One of the most intensely studied regulatory factors in the yeast Saccharomyces cerevisiae is the bZIP transcription factor Gcn4p. Gcn4p is essential for a global transcriptional response when S. cerevisiae experiences amino acid starvation. In the filamentous ascomycete Neurospora crassa, the ortholog of GCN4 is called the cross pathway control-1 (cpc-1) gene; it is required for the ability of N. crassa to induce a number of amino acid biosynthetic genes in response to amino acid starvation. Here, we deciphered the CPC1 regulon by profiling transcription in wild-type and cpc-1 mutant strains with full-genome N. crassa 70-mer oligonucleotide microarrays. We observed that at least 443 genes were direct or indirect CPC1 targets; these included 67 amino acid biosynthetic genes, 16 tRNA synthetase genes, and 13 vitamin-related genes. Comparison among the N. crassa CPC1 transcriptional profiling data set and the Gcn4/CaGcn4 data sets from S. cerevisiae and Candida albicans revealed a conserved regulon of 32 genes, 10 of which are predicted to be directly regulated by Gcn4p/CPC1. The 32-gene conserved regulon comprises mostly amino acid biosynthetic genes. The comparison of regulatory networks in species with clear orthology among genes sheds light on how gene interaction networks evolve.
Knowledge-Based Deformable Surface Model with Application to Segmentation of Brain Structures in MRI

We have developed a knowledge-based deformable surface for segmentation of medical images. This work has been done in the context of segmentation of hippocampus from brain MRI, due to its challenge and clinical importance. The model has a polyhedral discrete structure and is initialized automatically by analyzing brain MRI sliced by slice, and finding few landmark features at each slice using an expert system. The expert system decides on the presence of the hippocampus and its general location in each slice. The landmarks found are connected together by a triangulation method, to generate a closed initial surf ace. The surface deforms under defined internal and external force terms thereafter, to generate an accurate and reproducible bounda ry for the hippocampus. The anterior and posterior (AP) limits of the hippocampus is estimated by automatic analysis of the locati on of brain stem, and some of the features extracted in the initialization process. These data are combined together with a priori knowledge using Bayes method to estimate a probability density function (pdf) for the length of the structure in sagittal direc tion. The hippocampus AP limits are found by optimizing this pdf. The model is tested on real clinical data and the results show very good model performance 1 .
How Much Progress this Time

I must confess that although I was well aware that I was responsible for a technical presentation at this meeting, it had somehow escaped my attention until a few days ago that I was also scheduled for 45 minutes of introductory remarks as well. One felicitous result of this will be that the coffee break will come earlier than scheduled. For one panicky moment I thought of extracting from the sermon barrel some one of the several similar “Introductions” for which I have been responsible in recent years, hoping that with the information overload from which we all suffer no one would notice this was a replay. However, looking at the roster of distinguished and knowledgeable participants, it was clear I couldn’t get away with that, even with a bit of judicious hybridization of previous manuscripts. Besides, for the hybridization I couldn’t decide whether to use alternate lines or alternate paragraphs.
Detection of Listeria in crawfish processing plants and in raw, whole crawfish and processed crawfish (Procambarus spp.).

The foodborne pathogen Listeria monocytogenes represents a major concern to the food industry and particularly to producers of ready-to-eat (RTE) foods because of the severity of human listeriosis infections and because of the ubiquitous nature of this organism. Although several studies on the prevalence and sources of L. monocytogenes in various RTE seafoods have been conducted, limited information is available on the presence and potential sources of this organism in RTE crawfish products. We thus monitored the presence of L. monocytogenes and other Listeria spp. in the processing environment, in raw, whole crawfish, and in cooked crawfish meat from two processing plants. Samples were collected from the two plants throughout one crawfish season (April to June 2001) at 5 and 8 separate visits, respectively. At each visit, 6 raw, whole crawfish, 6 finished product samples (crawfish meat), and 14 mid- or end-of-processing environmental sponge samples were collected and tested for L. monocytogenes and Listeria spp. Of the 337 samples tested, 31 contained Listeria spp. Although Listeria innocua was the predominant Listeria spp. found (20 samples), four samples were positive for L. monocytogenes. L. monocytogenes was detected in three raw material samples and in one environmental sample. Listeria spp. were found in 29.5% of raw, whole crawfish (n = 78) and in 4.4%. of environmental samples (n = 181) but in none of the finished product samples. Among the environmental samples, Listeria spp. were found in 15.4% of the drains (n = 39) and in 5.1% of the employee contact surfaces (gloves and aprons) (n = 39) but in none of the samples from food contact surfaces. Even though a high prevalence of Listeria spp. was detected on raw materials, it appears that the heat treatment during the processing of crawfish and the practices preventing postprocessing recontamination can significantly reduce Listeria contamination of RTE crawfish meat.
The Larvae of the Sub-Family Orphilinae and Their Bearing on the Systematic Status of the Family Dermestidae (Col.)

In a recent paper I have discussed at some length the larval systematics of the sub-families of the Dermestidae . At the time I had not seen larvae of Orphilinae , nor had these been previously described, so I did not mention them.
Influence of Strontium Concentration on the Microstructure and Electrical Properties of Sol-Gel Derived Barium Strontium Titanate Thin Films

BaxSrl−xTiO3 thin films with varying Sr concentration were prepared on Pt coated Si substrates using methoxypropoxide based alkoxide precursors. Films were crystallized by heat treating at 700°C for 30 minutes in an oxygen atmosphere after deposition of each layer. Film thickness ranged from 230 to 260 nm. No evidence of tetragonality was observed in any of the compositions. Films with higher Sr concentrations had a larger average grain size, larger grain size distribution, and increased (111) orientation on (111) oriented Pt. The highest dielectric constant of -400 was found for Ba 0.5Sr0.5TiO3, although no direct correlation could be made between the composition and dielectric properties.
Urinary excretion of certain amino acids during ACTH and cortisone treatment of rheumatoid arthritis.

Summary and conclusionsRheumatoid arthritis patients treated with ACTH showed a highly significant increase in urinary free threonine, lysine, and tyrosine as determined as the average and maximum 24-hour excretion. Cortisone-treated patients excreted a highly significant amount of threonine and tyrosine at the maximum, but lysine was not increased significantly. Arginine excretion was not significantly affected by either ACTH or Cortisone. Supplementary medication did not affect significantly the responses of the patients to ACTH or Cortisone, chemically or clinically. Clinical improvement in all patients was both subjective and objective. The cause of the increase in urinary excretion of the amino acids herein reported is not known and may or may not be associated directly with the metabolic changes brought about by the remission of rheumatoid arthritis.
The impact of partial volume effect correction on the diagnostic performance of quantitative FDG-PET/CT parameters: A lesion based analysis of suspected lung malignancy.

1387 Objectives The role of partial volume effect correction (PVC)in the accurate quantitation of PET/CT parameters has been emphasized in phantom studies, However, limited number of clinical studies have investigated PVC. The purpose of this prospective study was to evaluate the potential of PVC on quantitative FDG­-PET/CT parameters in benign malignant differentiation of lesions in patients with suspected lung cancer. Methods One hundred suspected lung cancer lesions (60benign;40 malignant)with histopathological diagnosis were included in this study. All patients underwent FDG-­PET/CT imaging before surgery.Quantitative PET parameters such as SUVmax,SUVmean,pvcSUVmean,metabolic tumor volume(MTV),total lesion glycolysis(TLG=SUVmean*MTV) pvcTLG (pvcSUVmean*MTV)and SUVpeak were measured by using an adaptive contrast­ oriented thresholding segmentation & PVC algorithm. The diagnostic performance of parameters was compared by pairwise comparison of receiver operating characteristic (ROC) curves. We also performed a subgroup analysis for lesions with metabolic volume less than the median(MTV=6.6). Results FDG-PET/CT parameters showed superior diagnostic performance over volumetric parameters while the area under curve(AUC)were 0.90, 0.87, 0.86, 0.84, 0.82, 0.75, 0.55, for pvcSUVmean, SUVmax,SUVmean, SUVpeak, pvcTLG, TLG and MTV, respectively. In pairwise comparison of ROC curves, pvcSUVmean showed superior performance over SUVmean(p=0.04),SUVpeak (p=0.02)but not over SUVmax(p=0.16).Similarly,PVC enhanced the diagnostic performance of TLG. In subgroup analysis of small lesions pvcSUVmean had the highest performance compared to all other parameters with statistical significance. Conclusions In this study PVC improves the diagnostic performance of PET/CT in differentiating suspected lung lesions, particularly for small lesions and it could be considered as a potential source of quantification/diagnostic inaccuracy in future clinical studies.
Unmet Clinical Needs of Antithrombotic Treatment in BCR/ABL-Negative Myeloproliferative Neoplasms

A 25-year-old woman presents to your clinic with an established diagnosis of essential thrombocytosis. She has a platelet count <1000 × 109/L, reports no bleeding or history of venous thrombosis, is not taking contraceptives and has no additional risk factors for thrombosis.
Abstract 5183: Efficacy study of APX3330, a Ref-1 redox inhibitor, and Gemcitabine in a mouse pancreatic ductal adenocarcinoma model

High levels of apurinic/apyrimidinic endonuclease/redox factor 1 (APE1/Ref-1 or Ref-1) expression have been reported in numerous cancers such that Ref-1 is an emerging target in a variety of cancer types. Ref-1 is a dual function protein with both DNA repair activity as well as redox activity. Ref-1 is responsible for the repair of baseless sites in DNA caused by alkylation and oxidative DNA damage as well as regulating several transcription factors including HIF-1a, NFkB, AP-1, and STAT3. Using siRNA to knockdown Ref-1 in pancreatic ductal adenocarcinoma (PDAC) cells (MIA-PaCa-2), we quantitated Ref-1 expression following transfection with scrambled control and Ref-1 siRNA using Indica Lab9s HALO CytoNuclear software. Knockdown of greater than 85% greatly decreases the proliferation of PDAC cells, and supports Ref-1 as a target in pancreatic cancer. To assess the efficacy of targeting Ref-1 in vivo, a small molecule Ref-1 redox inhibitor, APX3330, was used in combination therapy with a PDAC standard of care agent, Gemcitabine, in a PDAC xenograft mouse model. In this study, NSG mice were treated with: Gemcitabine (35mg/kg), APX3330 (12.5, 25, and 50mg/kg), and combinations of APX3330 and Gemcitabine (12.5, 25, and 50mg/kg), as well as a vehicle control group. At termination of the study, tumors were harvested, tissue sections prepared, stained for HE 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5183.
Vesicovaginal fistulas in the developed world: An analysis of disease characteristics, treatments, and complications of surgical repair using the ACS-NSQIP database.

AIMS To analyze patient characteristics, complications, and surgical trends in vesicovaginal fistulas (VVF) from a national database. METHODS Current Procedural Terminology was used to identify patients undergoing VVF repair from the American College of Surgeons National Surgical Quality Improvement Project (NSQIP) database. Characteristics and treatments were identified. Logistic regression was used to identify characteristics associated with complications. RESULTS From 2006 to 2013, 200 patients underwent VVF repair. Mean age was 50.3 ± 12.3 years. A large proportion of patients were overweight (72%) and recent smokers (30%). Predominant comorbidities were heart disease (29%) and type 2 diabetes (9.5%). Of all VVF repairs, 65% were repaired vaginally. Concomitant procedures included hysterectomy (n = 6), reconstructive flaps (n = 13), and slings (n = 2). Post-operative complications occurred in 15% of patients. The most common complication was urinary tract infection (8%) followed by blood transfusion (3%). Compared to the vaginal approach, abdominal VVF repairs had higher overall morbidity (22% vs 7% P = 0.003), longer length of stay (3.5 ± 2.3 vs 1.6 ± 2 days P = 0.00) and were more likely to be associated with sepsis (4.3% vs 0% P = 0.02), blood transfusion (7.1% vs 0.8% P = 0.017), and readmission (10.1% vs 0.8% P = 0.003). In multivariate analysis, abdominal approach was a significant predictor of complications within 30 days (P = 0.03, P = 0.02). CONCLUSIONS In the US VVF remains a rare entity. Over half of VVFs were repaired vaginally. The occurrence of serious complications is low. A vaginal approach appears to be associated with fewer complications.
Cultural Barriers to Effective Enforcement of the Foreign Corrupt Practices in China

Many multinational companies (MNCs) doing business in China find that issues of corruption in business are common and dangerous problems. Such problems can expose MNCs to liability under the U.S. Foreign Corrupt Practices Act (FCPA) with all of its attendant serious consequences. MNCs need to realize that certain cultural elements -- respect for authority and a gift giving tradition -- create special pressures on their local employees to submit to requests for cash and non-cash benefits from government officials. It is not enough for MNCs to acknowledge that there may be cultural issues, but it is necessary for MNCs to understand, in detail, the common scenarios in which these cultural elements create social pressures on their employees to comply with requests from Chinese officials for payments. Only by understanding these common scenarios and implementing guidelines on how to respond in these specific situations, can the MNC implement an FCPA compliance program designed to effectively address these problems.
Changes in Hospital Inpatient Utilization Following Health Care Reform

Objective To estimate the effects of 2014 Medicaid expansions on inpatient outcomes. Data Sources Health Care Cost and Utilization Project State Inpatient Databases, 2011–2014; population and unemployment estimates. Study Design Retrospective study estimating effects of Medicaid expansions using difference-in-differences regression. Outcomes included total admissions, referral-sensitive surgical and preventable admissions, length of stay, cost, and patient illness severity. Findings In 2014 quarter four, compared with nonexpansion states, Medicaid admissions increased (28.5 percent, p = .006), and uninsured and private admissions decreased (–55.1 percent, p = .001, and –6.6 percent, p = .052), whereas all-payer admissions showed little change. Uninsured expansion effects were negative for preventable admissions (−24.4 percent, p = .068), length of stay (–9.3 percent, p = .039), total cost (−9.2 percent, p = .128), and illness severity (−4.5 percent, p = .397). Significant positive expansion effects were found for Medicaid referral-sensitive surgeries (11.8 percent, p = .021) and patient illness severity (2.3 percent, p = .015). Private and all-payer expansion effects for outcomes other than admission volume were small and mainly nonsignificant (p > .05). Conclusion Medicaid expansions did not change all-payer admission volumes, but they were associated with increased Medicaid and decreased uninsured volumes. Results suggest those previously uninsured with greater needs for inpatient services were most likely to gain coverage. Compositional changes in uninsured and Medicaid admissions may be due to selection.
Types of coproduction and differential effects on organizational performance: Evidence from the New York City school system

A growing body of literature explores the process of coproduction by citizens and government employees in providing goods and services, yet research that attempts to link coproduction to organizational performance offers contradictory findings. It is possible that these conflicting results are a consequence of trying to compare distinct categories of coproduction. This study identifies types of coproduction, classified by which organizational tasks citizens can influence during stages of policy design and implementation, and tests whether these types have different effects on student proficiency in Mathematics and English Language Arts using data from New York City schools between 2007 and 2009. This study then tests the degree to which different types of coproduction moderate the negative effect of environmental turbulence on performance. Results confirm that types of coproduction have varying effects on organizational performance and can reduce, and even eliminate, the negative effect of a turbulent environment on student outcomes.
Intelligent Broadcast For Large-Scale Sensor Networks

With advances in miniaturization, wireless communication, and the theory of self-organizing systems, it has become possible to consider scenarios where a very large number of networkable sensors are deployed randomly over an extended environment and organize themselves into a network. Such networks — which we term large-scale sensor networks (LSSN’s) — can be useful in many situations, including military surveillance, environmental monitoring, disaster relief, etc. The idea is that, by deploying an LSSN, an extended environment can be rendered observable for an external user (e.g., a monitoring station) or for users within the system (e.g., persons walking around with palm-sized devices). Unlike custom-designed networks, these randomly deployed networks need no pre-design and configure themselves through a process of self-organization. The sensor nodes themselves are typically anonymous, and information is addressed by location or attribute rather than by node ID. This approach provides several advantages, including: 1) Scalability; 2) Robustness; 3) Flexibility; 4) Expandability; and 5) Versatility. Indeed, this abstraction is implicit in such ideas as smart paint, smart dust, and smart matter.
Uniform and Efficient Exploration of State Space Using Kinodynamic Sampling-Based Planners

Sampling based algorithms such as RRTs have laid down the foundation for solving motion planning queries for systems with high number of degrees of freedom and complex constraints. However, lack of balanced state-space exploration of RRTs calls for further improvement of these algorithms. Factors such as drift, underactuation, system dynamics and constraints, and the lack of an energy/time based distance metric in state space can cause RRT propagation to be uneven. This paper focuses on improving the coverage of the RRT algorithm for physical systems that demonstrate a tendency to restrict the growth of RRT to certain regions of the state space. A localized principal component analysis based approach is proposed to learn the propagation bias of state-space points sampled on a grid during an offline learning phase. To compensate for this bias, expansion of the RRT in real-time is steered in the direction of the least principal component of the propagation of the state-space sample selected for expansion. The algorithm is tested on various systems with high degres of freedom and experimental results indicate improved and uniform state-space coverage.
Do accountable care organizations affect race mediated differences in cancer screening

131Background: Accountable care organizations (ACO) reflect a payment innovation aimed to orient incentives to improve quality and reduce waste. The objective of this study was to determine whether...
Degradation and metabolite formation of 17ß-estradiol-3-glucuronide and 17ß-estradiol-3-sulphate in river water and sediment.

Abstract Laboratory degradation tests with two model estrogen conjugates, 17s-estradiol-3-glucuronide (E2-3G) and 17s-estradiol-3-sulphate (E2-3S), using river water and sediment as inoculum under aerobic conditions were investigated. Throughout the 14-day incubation, degradation of E2-3G in river water, at environmentally-relevant level (25 ng/L), obeyed first-order kinetics with the formation of 17-s estradiol and estrone; in contrast, E2-3S was slowly converted to estrone-3-sulphate stoichiometrically. Degradation of the two conjugates across the spiking concentrations (0.01–1 μg/g) was much faster in sediment than in river water where 25 ng/L of conjugate standards were spiked, possibly due to relatively high population densities of microorganisms in sediment. De-conjugation of the thio-ester bond at C-3 position and oxidation at C-17 position were the predominant degradation mechanisms for E2-3G and E2-3S, respectively, with negligible presence of metabolites estrone-3-glucuronide for E2-3G and 17s-estradiol for E2-3S. In addition, delta-9(11)-dehydroestrone and 6-ketoestrone were determined as new metabolites of the two conjugates. Also, a lactone compound, hydroxylated estrone and a few sulfate conjugates were tentatively identified. With the observation of new metabolites, biodegradation pathways of E2-3G and E2-3S were proposed. The formation of new metabolites may pose unknown risks to aquatic biota.
Co-emission and welfare effects of electricity policy and market changes: Results from the EMF 32 model intercomparison project

Abstract From the simulation results of the Energy Modeling Forum's recently completed project on US greenhouse gas emission mitigation policies, this paper estimates and examines welfare effects of carbon dioxide (CO 2 ) pricing policies, fuel and technology cost changes, higher electricity demand growth, and limited nuclear generator lifetimes. Eight of the models in the study reported outputs sufficient to estimate damage from CO 2 , sulfur dioxide (SO 2 ), nitrogen oxides (NO X ), and methane, and three of those eight reported outputs sufficient to calculate consumer surplus, supplier profit, government revenue, and therefore total social surplus. Over approximately thirty years, the four CO 2 tax policies reduce emissions enough to reduce estimated CO 2 damage by $1 to $1.5 trillion, SO 2 damage by $1 to $1.3 trillion, and NO X and methane damage by smaller amounts, based on averaging the results from the relevant models. The estimated non-environmental social surplus cost of each of these policies is between 23% and 29% of its environmental benefit. The CO 2 cap-and-trade scenario, modeled after the Clean Power Plan, reduces estimated CO 2 damage and other emission damage each by $0.4 trillion, at a non-environmental social surplus cost estimated to be 17% of the environmental benefit. Changing the natural gas price changes SO 2 damage more than twice as much as it changes CO 2 damage. Estimated methane emissions move in the same direction as CO 2 emissions in every scenario other than the low natural gas price scenario, in which the methane increase counteracts an estimated 27% of the benefit from the CO 2 reduction but only 5% of the total net benefit. In addition, the paper explains the set of assumptions and methods used to estimate environmental damage, and briefly explains how the non-environmental parts of total social surplus can sometimes be computed from more common results if necessary.
Functional deregulation of KIT: link to mast cell proliferative diseases and other neoplasms

In this review, the authors discuss common gain-of-function mutations in the stem cell factor receptor KIT found in mast cell proliferation disorders and summarize the current understanding of the molecular mechanisms by which these transforming mutations may affect KIT structure and function leading to altered downstream signaling and cellular transformation. Drugs targeting KIT have shown mixed success in the treatment of mastocytosis and other hyperproliferative diseases. A brief overview of the most common KIT inhibitors currently used, the reasons for the varied clinical results of such inhibitors and a discussion of potential new strategies are provided.
On the Search for Reliable Human Aging Models: Understanding Aging by Nuclear Reprogramming

Reprogramming technologies, and particularly the generation of induced pluripotent stem cells (iPSCs), have demonstrated the possibility of personalized disease modeling in a dish. Importantly, the fact that pluripotent stem cells can give rise to all cell types of an organism, along with the technical progress allowing for their isolation, brings to mind fantasies like the fountain of youth and eternal regeneration and represents one of the most promising scientific fields with clinical implications. Furthermore, increasing evidence indicates that aging “defects” observed in patient somatic cells could be erased or alleviated by direct reprogramming towards pluripotency and rapidly recapitulated upon directed differentiation to specific cell lineages (Liu et al., Nature 472:221–225, 2011a). Thus, iPSC models of aging facilitate human aging studies by shortening the time required for physiological manifestation of aging-related defects from years, in the case of a human being, to days when stem cell models are applied. Moreover, the combination of gene-editing and iPSC models of aging will also allow for the generation of precisely targeted reporter cell lines of high value for studying normal differentiation processes and high throughput screens. However, a major concern regarding the use of iPSCs for disease modeling has to be taken into account prior to their broad application in drug discovery studies, which is that the use of patient-derived iPSCs bears another important experimental limitation, the lack of appropriate genetically matched control lines (Soldner et al., Cell 146:318–331, 2011; Liu et al., Cell Stem Cell 8:688–694, 2011b).
The effects of a recreational bike path on housing values in Muskego, Wisconsin.

In 2000, the city of Muskego, Wisconsin, cleaned an abandoned railroad corridor and opened a recreational bike path in its place. This study examines the impact of this trail and other amenities on local home values for an exurban community. Most prior studies estimating the value of bike paths use hedonic analysis on the local housing market, which controls for the varying characteristics of houses (e.g., square feet of floor space, number of bedrooms) without directly measuring the impact of amenities on the value of a particular house. This study employs hedonic analysis on nearly 7,000 home sales occurring between 1993 and 2016 in Muskego, Wisconsin. The results provide an estimate of the premium created by adding the recreational bike path amenity to the community by applying geospatial analysis to generate a continuous measure of the distance from each house in the area to the bike path. The analysis indicates the bike path had a statistically significant and positive impact, increasing values by 8.6% for homes located directly adjacent to the path. Prior to bike path installation, home values increased the farther away from the rail corridor they were located, averaging $0.75 per foot away from the path. After installation, distance from the bike path no longer influenced home values (other than those adjacent), as the former rail corridor was no longer a disamenity. The findings suggest that this bike path had strong positive effects over a relatively large geographic area, with homes in the entire city benefiting. Additional amenities assessed, such as lake, golf course, park, and school proximity, also added positively to home value. Subscribe to JPRA
Pharmaco-resistant Neonatal Seizures: Critical Mechanistic Insights from a Chemoconvulsant Model

Neonatal seizures are harmful to the developing brain and are associated with mortality and long-term neurological comorbidities. Hypoxic-ischemic encephalopathy (HIE) seizures represent a significant proportion of such seizures. Phenobarbital (PB) remains the first line anti-seizure drug (ASD) treatment but fails ~50% of the time. Translational models of neonatal seizures are crucial to investigating mechanisms underlying PB-resistance. A model of PB-resistant ischemic seizures in post-natal day 7 (P7) CD-1 mice reported K-Cl cotransporter 2 (KCC2) degradation that has been shown to be due to activation of the TrkB pathway. We investigated PB-efficacy in a pentyleneltetrazole (PTZ) model of neonatal seizures in the same strain and age using identical treatment protocols to gain insights into mechanisms underlying PB-resistance. A single dose of PTZ (80 mg/kg; IP) consistently induced repetitive seizures that did not progress to status epilepticus (SE). PB (25 mg/kg; IP, single dose) significantly suppressed the PTZ-induced seizures. This was associated with significant KCC2 upregulation and stable Na-K-Cl cotransporter 1 (NKCC1) expression at 24h. The TrkB pathway was not activated. PTZ seizure burdens were significantly higher than those reported for ischemic seizures, indicating seizure severity did not dictate the differences in PB-efficacy. Bumetanide (BTN) (0.1–0.2 mg/kg; IP) did not work as an anti-seizure agent, similar to the ischemic model. When investigating mechanisms underlying the emergence of PB-resistance in translational models, the method by which seizures are induced may dictate mechanisms underlying emergence of PB-resistance.
One-Class Support Vector Machines for Structural Health Monitoring on Wave Energy Converters

A wave energy converter (WEC) is a device that generates electricity from the kinetic energy of waves and the Department of Energy estimates that these devices could contribute significantly to energy production. However, WECs are not currently economically feasible due to high costs of repair and maintenance. Structural health monitoring (SHM) could be used to reduce these costs and make WECs efficient and deployable in large scale. This study investigates SHM techniques for the fiber reinforced plastics (FRPs) used to construct WECs. Data is collected using piezoelectric transducers on sample FRP plates. One of the primary hurdles with this problem is that the underlying structure of the FRPs is different for each plate, which results in significant variability in the collected data between plates. To overcome this issue, we propose using one-class support vector machines (OCSVMs) that can be trained solely on baseline examples from each plate. The OCSVM then detects anomalies and classifies them as damage. The numerical experiments demonstrate that the OCSVM can outperform traditional support vector machines (SVMs). Further, the OCSVM is only trained on baseline data from the plate being monitored while the tradition SVM requires data from the plate being monitored and the auxiliary data, both baseline and damage conditions, from other plates.
Anatomic Features of the Tibial Plateau Predict Outcomes of ACL Reconstruction Within 7 Years After Surgery.

Background:Multiple anatomic features of the femoral condyles and tibial plateau have been shown to influence knee biomechanics and risk of anterior cruciate ligament (ACL) injury. However, it rema...
Abstract WP153: Prenatal Alcohol Exposure Induces Glucose Intolerance and Exacerbates Stroke Severity in Middle-Aged Rats

Background and Purpose: Metabolic disorders and cardiovascular diseases in post-natal life have been linked to adverse prenatal environment. There is very little information on the developmental or...
A 51-Year-Old Man With Unresolved Pulmonary Infiltrates Following Streptococcus pneumoniae Pneumonia

Case Presentation A 51-year-old man presented to the clinic 8 weeks after a 6-day hospital admission for severe multilobar pneumonia caused by Streptococcus pneumoniae. His productive cough resolved after antibiotics, but he reported persistent dyspnea. He recounted a lifelong history of recurrent sinusitis but no previous episodes of pneumonia. The patient denied fever, weight loss, or tobacco, alcohol, or drug use. He worked as an upholstery craftsman with no work-related exposures. He had no bird or exotic animal exposures, and no history of travel outside Sacramento, California, where he lived. Aside from the recently completed 2-week course of levofloxacin, he was not taking any medications.
Adaptive Clinical Trial Designs with Surrogates: When Should We Bother?

The success of a new drug is assessed within a clinical trial using a primary endpoint, which is typically the true outcome of interest, e.g., overall survival. However, regulators sometimes approve drugs using a surrogate outcome --- an intermediate indicator that is faster or easier to measure than the true outcome of interest, e.g., progression-free survival --- as the primary endpoint when there is demonstrable medical need. While using a surrogate outcome (instead of the true outcome) as the primary endpoint can substantially speed up clinical trials and lower costs, it can also result in poor drug approval decisions since the surrogate is not a perfect predictor of the true outcome. In this paper, we propose combining data from both surrogate and true outcomes to improve decision-making within a late-phase clinical trial. In contrast to broadly used clinical trial designs that rely on a single primary endpoint, we propose a Bayesian adaptive clinical trial design that simultaneously leverages both observed outcomes to inform trial decisions. We perform comparative statics on the relative benefit of our approach, illustrating the types of diseases and surrogates for which our proposed design is particularly advantageous. Finally, we illustrate our proposed design on metastatic breast cancer. We use a large-scale clinical trial database to construct a Bayesian prior, and simulate our design on a subset of clinical trials. We estimate that our design would yield a 16% decrease in trial costs relative to existing clinical trial designs, while maintaining the same Type I/II error rates.
Design and repeatability analysis of desktop tool for rapid pre-cracking of notched ductile plastic fracture specimens

Abstract Fracture testing is a useful mechanical testing process to explore the properties and behavior of materials, one that has seen much development and refinement in recent decades. One of the most important steps in preparing samples for testing is the production of a sharp pre-crack to initiate crack propagation in a predictable way. While several methods have been developed for doing this, particularly for metals and brittle plastic materials, a quick and reliable method for more ductile materials is lacking. This paper describes the design and verification of a simple desktop-sized pre-cracking device which safely uses a razor blade and hammer to quickly produce straight and sharp pre-cracks of consistent depth in ductile polymeric material samples. To verify its capability and consistency, a series of tests was performed using both molded and 3-D printed acrylonitrile butadiene styrene (ABS). First, a series of 40 notched 25 mm × 9.5 mm ABS bars was pre-cracked, and the distance under the crack measured on both sides of the bar. Several bars were then broken along the cracks to examine the quality of the pre-crack front. These tests were then repeated 20 times each for two print orientations of fused deposition modeling (FDM) ABS printed at 100% density. All 80 pre-cracks were found to be straight, sharp, and within 1% of the nominal distance under the crack for all samples. The consistency of the pre-cracks throughout the sample cross-section was also observed to be excellent, with all 80 tests showing less than 0.25 mm of deviation, even on the highly-anisotropic FDM samples.
Raising binaries to LLVM IR with MCTOLL (WIP paper)

The need to analyze and execute binaries from legacy ISAs on new or different ISAs has been addressed in a variety of ways over the past few decades. Solutions using complementary static and dynamic binary translation techniques have been deployed in most real-world situations. As new ISAs are designed and legacy ISAs re-examined, the need for binary translation infrastructure re-emerges, and needs to be re- engineered all over again. Work is in progress with a goal to make such re-engineering efforts easier by using some of the software tools that would irrespectively be developed or available for a new or existing ISA. To that end, this paper presents a static binary raiser that translates binaries to LLVM IR. Native binaries for a new ISA are generated from the raised LLVM IR using the LLVM compiler backend. This technique enables development of a single raiser per legacy ISA, irrespective of the new target ISA. The result of such a raiser can then leverage compiler back-ends of new ISAs, thus simplifying the development of binary translator for the new ISA . This work leverages the existing LLVM infrastructure to implement a static raiser that currently supports raising x64 and Arm32 binaries to LLVM IR. The raiser is built as an LLVM tool – similar to llvm-objdump or clang and does not have any dependencies outside of those needed to build LLVM. This paper describes the phases of the raiser and gives the current status and limitations.
Feasibility of selection for high weed suppressive ability in soybean: Absence of tradeoffs between rapid initial growth and sustained later growth

In ecology, tradeoff theory has been used to understand differences among plant species in their competitive abilities. In efforts to develop weed-suppressive soybean, we found evidence of a tradeoff between the ability for rapid initial growth and the ability for sustained growth later in the season: early maturing lines displayed more rapid initial growth but ceased growth sooner. Such a tradeoff would increase the difficulty of obtaining a full-season weed-suppressive variety. To determine this tradeoff's existence and severity we examined two possible mechanisms that could lead to it. We tested whether early maturing soybean lines attain higher early relative growth rate than late-maturing soybean lines and whether early maturing soybean lines produce larger seeds by an environmentally-dependent or -independent mechanism. Early maturing lines had higher relative stem elongation rates than late lines but not higher relative dry weight or leaf area increase rates. In more northern locations and in years with shorter growing seasons, early maturity lines produced larger seeds than late maturing lines, implicating an environmentally-dependent rather than -independent mechanism causing seed size differences. Relative to early lines, when late lines mature, temperature and photoperiod are in greater decline, leading to a risk of incomplete seed fill. Resulting seed size decreases could lead to lower initial growth in late maturity lines and thus to an environmental rather than genetic or physiological cause of tradeoff between initial growth and sustained growth later in the season.
Identifying prognostic markers in autism spectrum disorder using eye tracking

While many children with autism spectrum disorder are now detected at young ages given the rise in screening and general awareness, little is known regarding the prognosis of early detected childre...
An ortholog of the Vasa intronic gene is required for small RNA-mediated translation repression in Chlamydomonas reinhardtii

Small RNAs (sRNAs) associate with Argonaute (AGO) proteins in effector complexes, termed RNA-induced silencing complexes (RISCs), which regulate complementary transcripts by translation inhibition and/or RNA degradation. In the unicellular alga Chlamydomonas, several metazoans, and land plants, emerging evidence indicates that polyribosome-associated transcripts can be translationally repressed by RISCs without substantial messenger RNA (mRNA) destabilization. However, the mechanism of translation inhibition in a polyribosomal context is not understood. Here we show that Chlamydomonas VIG1, an ortholog of the Drosophila melanogaster Vasa intronic gene (VIG), is required for this process. VIG1 localizes predominantly in the cytosol and comigrates with monoribosomes and polyribosomes by sucrose density gradient sedimentation. A VIG1-deleted mutant shows hypersensitivity to the translation elongation inhibitor cycloheximide, suggesting that VIG1 may have a nonessential role in ribosome function/structure. Additionally, FLAG-tagged VIG1 copurifies with AGO3 and Dicer-like 3 (DCL3), consistent with it also being a component of the RISC. Indeed, VIG1 is necessary for the repression of sRNA-targeted transcripts at the translational level but is dispensable for cleavage-mediated RNA interference and for the association of the AGO3 effector with polyribosomes or target transcripts. Our results suggest that VIG1 is an ancillary ribosomal component and plays a role in sRNA-mediated translation repression of polyribosomal transcripts.
Structure and Function of the Cytochrome P450 Monooxygenase Cinnamate 4-hydroxylase from Sorghum bicolor.

Cinnamate 4-hydroxylase (C4H; CYP73A) is a cytochrome P450 monooxygenase associated externally with the endoplasmic reticulum of plant cells. The enzyme uses NADPH-cytochrome P450 reductase as a donor of electrons and hydroxylates cinnamic acid to form 4-coumaric acid in phenylpropanoid metabolism. In order to better understand the structure and function of this unique class of plant P450 enzymes, we have characterized the enzyme C4H1 from lignifying tissues of sorghum (Sorghum bicolor), encoded by Sobic.002G126600 Here we report the 1.7 A resolution crystal structure of CYP73A33. The obtained structural information, along with the results of the steady-state kinetic analysis and the absorption spectroscopy titration, displays a high degree of similarity of the structural and functional features of C4H to those of other P450 proteins. Our data also suggest the presence of a putative allosteric substrate-binding site in a hydrophobic pocket on the enzyme surface. In addition, comparing the newly resolved structure with those of well-investigated cytochromes P450 from mammals and bacteria enabled us to identify those residues of critical functional importance and revealed a unique sequence signature that is potentially responsible for substrate specificity and catalytic selectivity of C4H.