cssi/SciSciGPT-SciSciNet huggingface dataset:
Regulation of cartilage collagenase by doxycycline.

OBJECTIVE: To investigate the ability of doxycycline to modulate collagenases, cytokines, and cytokine receptors in chondrocytes from osteoarthritic (OA) cartilage. METHODS: Chondrocytes were isolated from human OA cartilage and treated with doxycycline. Synthesis of collagenases, cytokines, and cytokine receptors was quantified by Northern and Western blot analysis and RNase protection assay. RESULTS: We observed significant inhibition of matrix metalloproteinases (MMP-1) and MMP-13 mRNA and protein production by chondrocytes, isolated from OA cartilage, after treatment with doxycycline. The decrease in collagenase protein level paralleled a decrease in mRNA for these enzymes, suggesting a transcriptional/posttranscriptional level of control. In addition, treatment with 10 microg/ml doxycycline resulted in 2.2-fold upregulation of transforming growth factor (TGF-beta3) and a significant decrease of interleukin 1alpha (IL-1alpha), IL-1beta, and IL-6 mRNA. Upregulation of TGF-beta RI and TGF-beta RII was also detected. These cytokines are known to affect collagenase expression and could contribute to inhibition of MMP-1 and MMP-13 production by OA chondrocytes. A decrease in IL-1alpha, IL-1beta, and IL-6 would reduce stimulation of MMP production, while an increase in TGF-83 would lead to downregulation of local proinflammatory cytokine production as well as of the collagenases themselves. CONCLUSION: Our findings show that a decrease in MMP-1 and MMP-13 collagenase production by articular chondrocytes in response to treatment with doxycycline can be explained by a regulatory effect of doxycycline on the production of cytokine and cytokine receptors.
Long-term consequences of electrical injury: neuropsychological predictors of adjustment.

AbstractObjective: Electrical injury (EI) produces an assortment of consequences for individuals. Survivors perform poorly on measures of attention and mental speed, memory, and emotional functioning. Moreover, sequelae are not always reported immediately following injury and often increase over the months following injury. It remains unclear whether the observed increase in neuropsychological and emotional symptoms over time is attributable to the delayed physical effects of EI or other factors that arise subsequent to injury, such as difficulty adjusting to post-injury limitations. Method: The current study utilized archival data to compare the neuropsychological and emotional complaints of EI survivors at two points during recovery, hypothesizing that Time 1 data would predict participants’ outcome at Time 2. Specifically, those with worse neuropsychological performance and greater depressive symptomatology at Time 1 would have worse long-term adjustment to injury and psychological symptomatology. Resu...
High-Resolution Neutron Capture and Total Cross Section Measurements for 192, 194, 195, 196Pt and the Astrophysical Rates for the 192, 194, 195, 196Pt(n, γ) Reactions

We have made the first experimental determinations of the astrophysical rates for the 192, 194, 195, 196Pt(n, γ) reactions across the range of temperatures needed for astrophysical models of the s process. Both neutron capture and total cross sections were measured for 192, 194, 195, 196Pt at the Oak Ridge Electron Linear Accelerator (ORELA) from 10 eV to 500 keV. The data were fitted using the R-matrix code SAMMY to obtain resonance parameters. These parameters as well as the measured cross sections in the unresolved region were used to obtain the astrophysical reaction rates for all these isotopes. We compare our results to previous data and theoretical reaction rates and discuss their astrophysical impact. For example, a classical analysis of the s-process branching at 192Ir using our new rates yields a much lower neutron density than previous analyses of other branchings, in agreement with the long-sought freeze-out effect predicted by dynamical (e.g. stellar) models.
Flow Behavior Characterization of a Polyacrylamide-Based Friction Reducer in Microchannels

Horizontal well and hydraulic fracturing have been proven to be effective technologies for increasing the recovery of shale gas reservoirs. During a fracturing treatment, a pair of main fractures i...
Clinical Experience in the Treatment of Distal Tibial Shaft Fractures

We treated 24 distal tibial shaft fractures in 19 men and 5 women with their average age being 41.8 years old and the average objective term being one year and two months, which included 15 open fractures, from Jan. '86 to Oct. '90.We treated the following cases as a primary treatment: 2 conservative cases, 4 cases used with external fixations, 6 with Ender nails, 3 with T plates, 5 with AO plates and 4 with May plates.Considering each case about the term of union, the degree of malunion and the operative result, we could get the following consequence. It took 12.0 weeks for the Ender nail group to union and 8.7 weeks for the plates group on an average. The valgus angulation developed more in the Ender nails group than the plates group. A better result could be found in the plates group, in which the treatment using May plate was extremely good.
International medical graduates as physician assistants.

UNLABELLED This study describes the MEDEX physician assistant (PA) program's experience with screening, educating, and graduating PA students who were international medical graduates (IMGs). METHODS The study reviewed IMG-PA demographics including country of origin; prior primary care practice; and current practice location, specialty, and medically underserved designation. Descriptive statistics and chi-square analysis or Fisher exact test summarize outcomes. RESULTS Thirty-nine IMG-PAs were graduated from 1991 through 2013. IMGs came from central and eastern Europe (48.7%), Asia (33.3%), and other regions. Most (69.2%) are women. Almost all (91.7%) practice in urban settings, 55.6% are in primary care, and 30.6% work in medically underserved areas. IMG-PAs in primary care were more likely to practice in underserved areas (P=0.009). CONCLUSION MEDEX has graduated IMG-PAs who possess appropriate clinical and professional PA skills.
Case 1: A 7-Year-Old with 1 Month of Ear Pain and 1 Day of Facial Weakness

1. Silvestre Duran, MD* 1. *Children’s Hospital of Michigan, Detroit, MI. A 7-year-old girl with no significant past medical history presents with right-sided ear pain and decreased hearing for 1 month and 1 day of decreased right-sided facial movement when smiling and talking. She was evaluated twice by her primary care physician and she has completed 2 courses of amoxicillin for otitis media. Yesterday she was evaluated at another institution for her facial weakness. While there, results of a complete blood cell count and basic metabolic panel were within normal limits, but head computed tomography (CT) scan results were concerning for a right-sided otomastoiditis. She was transferred today to our institution for further evaluation. Physical examination shows an alert and oriented patient in no distress. Weight and height are in the 50th and 75th percentiles respectively. She is afebrile, with a heart rate of 88 beats per minute, respiratory rate of 28 breaths per minute, and blood pressure of 108/58 mm Hg. Her right external auditory canal is occluded with dark, thick material and the right tympanic membrane is not visible. Her left ear examination yields unremarkable results. There is anterior cervical lymphadenopathy with no nodes greater than 1 cm in diameter. There is no mastoid tenderness or swelling. Neurologic examination shows right-sided weakness of the facial and forehead muscles. The rest of her physical examination findings are unremarkable. The pediatric radiologist interprets the noncontrast head CT scan results as complete opacification of the right mastoid air cells, including the petrous apex, and the right middle ear, which is concerning for a right otomastoiditis with erosive changes without definite intracranial …
Performance of a system to locate address blocks on mail pieces

The objective of an Address Block Location System (ABLS) is to determine the position and orientation of a destination address block in a mail piece image of either a letter, magazine, or parcel. The corresponding sub-image can then be presented to either a human or machine reader (OCR) to direct the mail piece to the appropriate sort category based on the ZIP code. ABLS is capable of dealing with a wide range of environments from those having a high degree of global spatial structure to those with no structure. The system consists of several specialized tools and a control structure so that the tools are opportunistically invoked and coordinated. Its performance on a training and testing image database of difficult cases is described.
Application of Ultrasonic Technique to Cure Characterization of Epoxies

During cure a polymer changes from viscous liquid to visco-elastic rubber, and finally, to a glassy state. On the microscopic level, polymer molecules grow into longer chains with branches and also crosslinking occurs [1,2].
Michigan Local Governments Increasingly Pursue Placemaking for Economic Development

This report presents Michigan local government leaders’ opinions regarding the community and economic development strategy known as placemaking, and its use by Michigan jurisdictions. By engaging in placemaking, policymakers attempt to capitalize on local assets in order to create appealing and unique places where people want to live, work, and play. When used for economic development, placemaking seeks to help a community attract and retain talented workers and the businesses that seek them. The findings in this report are based on statewide surveys of local government leaders in the Spring 2013 and Spring 2009 waves of the Michigan Public Policy Survey (MPPS).
Reactive transport of aqueous protons in porous media

Abstract The sorption of protons determines the surface charge of natural media and is therefore a first-order control on contaminant transport. Significant effort has been extended to develop chemical models that quantify the sorption of protons at the mineral surface. To compare these models’ effect on predicted proton transport, we present analytic solutions for column experiments through silica sand. Reaction front morphology is controlled by the functional relationship between the total sorbed and total aqueous proton concentrations. An inflection point in this function near neutral pH leads to a reversal in the classic front formation mechanism under basic conditions, such that proton desorption leads to a self-sharpening front, while adsorption leads to a spreading front. A composite reaction front comprising both a spreading and self-sharpening segment can occur when the injected and initial concentrations straddle the inflection point. This behavior is unique in single component reactive transport and arises due to the auto-ionization of water rather than electrostatic interactions at the mineral surface. We derive a regime diagram illustrating conditions under which different fronts occur, highlighting areas where model predictions diverge. Chemical models are then compared and validated against a systematic set of column experiments.
Improved Malware Classification Through Sensor Fusion Using Disjoint Union

In classifying malware, an open research question is how to combine similar extracted data from program analyzers in such a way that the advantages of the analyzers accrue and the errors are minimized. We propose an approach to fusing multiple program analysis outputs by abstracting the features to a common form and utilizing a disjoint union fusion function. The approach is evaluated in an experiment measuring classification accuracy on fused dynamic trace data on over 18,000 malware files. The results indicate that a naive fusion approach can yield improvements over non-fused results, but the disjoint union fusion function outperforms naive union by a statistically significant amount in three of four classification methods applied.
Loperamide-Induced Torsades de Pointes: A Case Series

Abstract Background Loperamide is an over-the-counter, inexpensive, antidiarrheal opioid that can produce life-threatening toxicity at high concentrations. Case Report 1 A 28-year-old man with a history of depression and substance abuse disorder (SUD) presented to the emergency department (ED) with shortness of breath and lightheadedness. He ingested large amounts of loperamide daily. The patient's initial electrocardiogram (ECG) demonstrated sinus rhythm, right axis deviation, undetectable PR interval, QRS 168 ms, and QTc 693 ms. He was administered intravenous sodium bicarbonate and magnesium sulfate and admitted to the intensive care unit, eventually developing Torsades de Pointes (TdP). He was given lidocaine and isoproterenol infusions, and an external pacemaker was placed. He was discharged in stable condition on hospital day (HD) 16. Case Report 2 A 39-year-old woman with a history of hepatitis C, depression, and SUD was transported to the ED after reported seizure-like activity. The patient experienced TdP in the ED and admitted to ingesting large amount of loperamide daily. An ECG demonstrated sinus rhythm, right axis deviation, PR interval 208 ms, QRS interval 142 ms, and QTc 687 ms. She was administered intravenous magnesium, sodium bicarbonate, and isoproterenol. After intensive care unit admission, the patient experienced no further TdP and was discharged on HD 6. Why Should an Emergency Physician Be Aware of This? Emergency physicians should proceed with caution when treating patients with loperamide toxicity. Even in asymptomatic patients and drug discontinuance, obtain consultation with a medical toxicologist, promptly treat ECG abnormalities aggressively, and admit all patients for further monitoring.
Inhibition of Proteolysis in Mozzarella Cheese Prepared from Homogenized Milk

Homogenization of milk was introduced almost 100 years ago to prevent the natural separation of milk phases, thus providing milk with more consumer appeal as a beverage and greater reliability and efficiency as a food ingredient (Trout, 1950). Many investigations of the physico-chemical changes that occur in milk during homogenization have been reviewed (Peters, 1964; Walstra, 1983), and there is now general agreement that the major effects are disruption of the fat globule membrane surrounding each droplet of milk fat (van Boekel and Walstra, 1989), an increase in the number of fat droplets and reduction in their size (Walstra, 1983), and formation of casein submicelles (Schmidt and Buchheim, 1970; Henstra and Schmidt, 1970). Each smaller fat droplet acquires a new “membrane” consisting of original fat globule membrane fragments complexed with casein submicelles (McPherson et al., 1984; Walstra and Oortwijn, 1982).
Hate Groups and Muslim Population Changes in the Fifty States: Does the Presence of Muslims Encourage Hate Group Formation?

The size of the Muslim population in the United States is growing, while the number of hate groups also continues to increase across the states. Based on the social dominance theory and group threat theory, there may be a link between these two dynamics as social dominators become concerned about their group status, i.e. white Christian males. This potential relationship is explored in this article. Although there were significant positive correlations between the number of hate groups and the size of the Muslim population, a panelled negative binomial regression with a number of relevant control variables found that there was not a significant relationship between these variables at the 0.05 probability level. The article further explores these findings and future research in this area.
RFLP band size standards: cell line K562 values from 1991 to 1997 proficiency studies.

Cell line K562 is the de facto forensic control material for forensic restriction fragment length polymorphism (RFLP) DNA profiling in the U.S. Fifty-one proficiency tests conducted from 1991 through 1997 enable a detailed description of RFLP measurement performance during this period. Sufficient data are available to define reference distributions for all commonly utilized and many less commonly reported genetic loci, for both HaeIII- and HinfI-based RFLP systems. The average measured size of HaeIII locus D1S7 and D5S110 bands has varied slightly over time; while relatively small, these temporal changes add to the overall interlaboratory measurement uncertainty. The characteristic standard deviation for HinfI RFLP system measurements has a nearly identical dependence on expected band size as does the standard deviation for HaeIII measurements. The ellipsoidal distance, K, is suggested for use as an RFLP data quality metric; the critical threshold value that on average excludes 1% of plausibly valid proficiency data for a given polymorphic locus is K1% = 14.2.
The end-points of the oxygen path: transport resistance in red cells and mitochondria.

The variation of oxygen pressure from red cell to mitochondrion is, for a given oxygen flux, determined by the distribution of transport resistance over the oxygen path. The total drop in oxygen pressure may be resolved into several component drops: (1) the red cell drop, from cell center to cell surface, (2) the transcapillary drop, from red cell surface to outer capillary wall, (3) the tissue drop, from the capillary wall to an interior point in the tissue, and (4) the mitochondrial drop, from tissue to mitchondrial interior. The frequently used Krogh model, as usually formulated, deals only with the tissue drop. The other components have received somewhat less attention in the literature. The transcapillary drop, which depends on hematocrit, blood flow rate, red cell geometry, capillary geometry, and other things, is by far the most complex. Some recent progress in the theory of this drop has been made — for example, the work of Federspiel and Sarelius (1984) on the effect of red cell spacing on oxygen delivery. Nevertheless, the transcapillary drop probably will be the last component to be understood quantitatively. The red cell drop and the mitochondrial drop, on the other hand, are readily amenable to analysis, and we summarize here our recent theoretical results on these parts of the oxygen path.
Individualized feedback and simulation-based practice in the Tactical Language Training System: An experimental evaluation

Students worked with versions of the Tactical Language Training System for Arabic that varied in the provision of individualized feedback, and access to a simulation environment for practicing foreign language skills. Post test results indicated that feedback led to stronger learning outcomes. Students who worked with the complete TLTS rated it as comparable to working one-on-one with a human instructor.
How Parent Perceptions Relate to Elementary Children’s Portable Technology Use by Gender and Grade Level

AbstractThis study examined how parents' reports of children’s technology use in the home varies by a child’s gender or grade level. Framed by technology adoption models, this mixed-method study gathered parent reports of their elementary child’s use of portable technology for entertainment and learning in the home, collected from 120 surveys and 13 individual interviews with survey respondents. Results across the four 2×2 ANOVAs yielded three significant main effects: gender and entertainment devices, gender and entertainment apps, grade-level and learning apps. No significant effects were found among any of the interaction variables or within the ANOVA summary for learning devices. Interview data revealed girls are interested in reading with Kindle, whereas parents are reluctant to provide boys with portable technology because of their preference to play games. Strategies are provided for teachers, support specialists, and parents to improve how children use technology. Implications for app developers a...
The Rotoscopic Uncanny: Aku no Hana and the Aesthetic of Japanese Postmodernity:

CGI has led to a theoretical revolution in media studies. What is cinema when reality can be created on a computer? What is animation when superflat 2D aesthetics are becoming haunted by 3D digital...
Reducing Implicit Bias: Association of Women Surgeons #HeForShe Task Force Best Practice Recommendations.

It is imperative to identify and act on potential barriers to the equitable treatment of women, and racial, ethnic, and sexual minorities within our professional surgical community. This includes the identification and counteraction of implicit biases, which are unconscious beliefs and attitudes that often drive our behaviors and decision-making, and eventually determine the climate of relative opportunity and challenge for those who are underrepresented within our field. Increasing diversity in universities, medical schools, residencies, and surgical departments will ultimately heighten the quality of our care, deepen our connection with patients, and further our achievements as surgeons and leaders in medicine and society. A tradition of excellence in surgery includes a rigorous pursuit of intellectual development and the questioning of implicit dogma, and for this reason we must actively work to eradicate unconscious biases that compromise the integrity of this pursuit. We recommend the following steps with an aim towards this goal: Commit to a Culture Shift Introduce Bias Literacy Provide Counter-Stereotypic Exposure Conduct an Introspective Departmental Assessment Implement Deliberative Processing Strategies for Hiring and Promotion Encourage Mentoring and Sponsorship Empower the individual
U.S. Supreme Court I.P. Cases, 1810-2019: Measuring & Mapping the Citation Networks

Intellectual property law in the United States, though shaped by key statutes, has long been a common-law field to a great degree. Many decades of decisional law flesh out the meaning of broad-textured, sparely worded statutes. Given the key roles of patent law and copyright law, both federal, the Supreme Court of the United States is i.p. law’s leading apex court. What are the major topical currents in the Supreme Court’s i.p. cases, both now and over the course of the Court’s work? This study uses network-analysis tools to measure and map the entirety of the Court’s i.p. jurisprudence. It goes deeper than existing studies of judicial citation networks by focusing on a topically defined subnetwork. It goes further than existing studies by analyzing, in addition to basic citation networks, a time series of co-citation networks — using techniques developed within bibliometrics, for mapping a scholarly field’s conceptual terrain, to track and describe doctrinal change. Emerging bottom up from the Court’s citations, the co-citation map charted here reveals, surprisingly, a core of antitrust and patent-misuse cases from the 1920s-1940s exerting significant influence on i.p. doctrine.
Coordination-induced O–H bond weakening in Sm(II)-water complexes

The combination of Sm(ii)-based reductants with water provides reagent systems that promote a range of reductions and bond-forming reactions that are endergonic based on known redox potentials. Despite the utility of these reagent systems, little work has been done to elucidate the basis for this unusual reactivity. Herein we present recent work designed to explore the underlying mechanistic basis for the unexpected reactivity of the Sm(ii)-water reducing system and demonstrate that O-H bond weakening induced by coordination of water to low valent samarium enables proton coupled electron transfer to substrates. We also demonstrate that coordination-induced bond weakening can be exploited and used to create extremely powerful reductants capable of reducing functional groups typically recalcitrant to reduction through single electron transfer alone.
Hydrogeological controls of arsenic and uranium dissolution into groundwater of the Pine Ridge Reservation, South Dakota

Abstract This study integrates geochemical modeling, spatial analysis and several statistical methods including principal component analysis, multivariate regression and cluster analysis to investigate hydrogeologic controls of arsenic and uranium contamination within groundwater of the Arikaree aquifer on the Pine Ridge Reservation (PRR). Located in southwestern South Dakota, the PRR is largely rural and many people rely on domestic supply wells completed in the Arikaree aquifer as their primary drinking water source. Locally, the White River Group, which unconformably underlies the Arikaree Group, is enriched in arsenic and uranium related to volcanic ash deposits and acts as a geogenic metal source. Geochemical data from over 250 groundwater samples were obtained through collaboration with the Oglala Sioux Tribe. Cluster spatial statistics analyses delineated four regions of statistically significant variations in groundwater chemistry that represent upgradient, intermediate, and downgradient portions of the Arikaree aquifer. Groundwater evolves as it flows through the Arikaree aquifer with increasing alkalinity, sodium, and pH along flow paths. These chemical changes are likely due to dissolution of carbonate minerals and volcanic ash. Thermodynamic calculations suggest increasing supersaturation of the groundwater with respect to calcite; thus, volcanic ash dissolution may be an important secondary source of alkalinity. Elevated alkalinity and pH levels were found to be the driving factors of arsenic and uranium mobility, and downgradient sections of the aquifer in the northern portions of the PRR are most likely to be impacted by metal(loid) contamination, with 73% of the wells in this grouping failing a USEPA maximum contaminant level for arsenic, uranium, and/or gross alpha.
Androgen deprivation therapy and statin therapy in prostate cancer patients.

205Background: Metastatic prostate cancer (mPC) is treated with androgen deprivation therapy( ADT). Duration of response to ADT predicts patient’s survival. It has been shown in observational studi...
Rural Job Loss to Offshoring and Automation

Labor market changes and resulting distributional effects in the United States have led to significant social, economic, and political turbulence over the past two decades. Wage and occupational polarization, static or declining wages, a 30% decline in manufacturing employment, and stark differences in regional outcomes provide the sense that some people and places are flourishing, but meanwhile others struggle. While trade, urbanization, and workplace automation undoubtedly yield many benefits, neither the benefits nor the potential costs are evenly distributed. In this study, we combine and extend several recent studies on offshorability risk and automation risk to examine the potential for job loss at the county level. Job loss risk is particularly high due to automation. Automation risk is geographically and socioeconomically concentrated, whereas risk due to offshoring is fairly evenly distributed. This uneven distribution of automation-related risk puts already vulnerable populations at greater risk, including those with lower levels of educational attainment and lower socioeconomic status. Additionally, the strong geographic correlation indicates that entire labor markets, particularly those in nonmetropolitan counties, are at risk for automation-related job losses in the future.
Continuous Glucose Monitoring Systems: Are They Useful for Evaluating Glycemic Control in Children with Hyperinsulinism?

Background: Effective treatment and close monitoring in children with congenital hyperinsulinism (HI) are important to prevent hypoglycemic-associated brain damage. The current monitoring approach involves measuring plasma glucose intermittently, but this does not provide a comprehensive assessment of glycemic control and may fail to detect episodes of hypoglycemia. Objective: To determine whether Dexcom G5®, a continuous glucose monitoring system (CGMS), is an accurate and effective method for monitoring glycemic control in children with HI. Methods: Cross-sectional, observational study in 15 children with HI. Participants wore a blinded Dexcom G5® device for 2 weeks. At the end of 2 weeks, data from the Dexcom G5® and home glucose meter were downloaded and analyzed. Results: Fourteen children (15–67 months) completed the study. Using Bland-Altman analysis, the mean (SD) difference between 1,155 paired CGM and glucose meter readings was –8.09 (53.76). The sensitivity and specificity of CGM to detect hypoglycemia (<70 mg/dL) were 86 and 81.4%, respectively. The positive predictive values for hypoglycemia and severe hypoglycemia (<54 mg/dL) detected by CGM were low (50.3 and 14.8%, respectively), while the negative predictive values were high (96.4% for glucose <70 mg/dL and 99.1% for glucose <54 mg/dL). Conclusion: Our study showed that CGM is not a reliable method to monitor for hypoglycemia, given the high number of false positive hypoglycemia readings. However, CGM can be useful in preventing unnecessary checks by glucose meter during times of normoglycemia. Therefore, the benefits of using CGM in patients with HI would be in guiding the need to check plasma glucose by glucose meter rather than point accuracy.
A Multiplexed HILIC-MS/HRMS Assay for the Assessment of Transporter Inhibition Biomarkers in Phase I Clinical Trials: Isobutyryl-Carnitine as an Organic Cation Transporter (OCT1) Biomarker

There is a growing interest in using endogenous compounds as drug transporter biomarkers to facilitate drug-drug interaction (DDI) risk assessment in early phase I clinical trials. Compared to other drug transporters, however, no valid biomarker for hepatic organic cation transporter (OCT) 1 has been described to date. The present work represents the first report of an endogenous compound, isobutyryl-l-carnitine (IBC), as a potential clinical OCT1 biomarker for DDI assessment. A hydrophilic interaction chromatography (HILIC)-mass spectrometry/high resolution mass spectrometry (MS/HRMS) assay with a simple sample preparation method was developed. The assay is capable of simultaneously quantifying multiple endogenous compounds, including IBC, thiamine, N1-methylnicotinamide (1-NMN), creatinine, carnitine, and metformin, which is a probe for OCT1 and OCT2 and MATE1 and MATE2K (multidrug and toxin extrusion proteins) in clinical studies. The HRMS assay was fit-for-purpose validated in human plasma and demonstrated good linearity, accuracy, and precision for all analytes. It was further applied to two phase I clinical trials to evaluate potential biomarkers for OCT1 and additional cation transporters (renal OCT2, MATE1, and MATE2K). The clinical data demonstrated that plasma IBC changes correlated well with in vitro data and supported its use as a liver OCT1 biomarker. The described HILIC-MS/HRMS assay can be used as a "biomarker cocktail" to simultaneously assess clinical DDI risk for the inhibition of OCT1/2 and MATEs in clinical studies with new drug candidates.
Suppression of Th2 cytokines as a potential mechanism for reduced antibody response following PFOA exposure in female B6C3F1 mice.

Abstract Perfluorooctanoic acid (PFOA), a member of the Per- and polyfluoroalkyl substances, is a highly persistent “forever” chemicals with increasing concern for its potential health effects. However, the mechanisms of PFOA immunotoxic effects are poorly understood. We assessed the antibody response to a physiological antigen stimulation and associated cytokine response upon PFOA exposure. The significant decrease in the IgM antibody response to the T cell dependent antigen keyhole limpet hemocyanin (KLH) at a dose lower than the previously documented LOAEL was accompanied by a significant reduction of the Th2 serum cytokines IL-5 and IL-13, a non-significant dose-response reduction of IL-4, a significant reduction of the Th1 cytokine IL-12, and a non-significant dose-response increase in IL-2 and IFNγ. PFOA significantly decreased the pro-inflammatory cytokines IL-17α and IL-1α, decreased (non-significantly but dose-response) IL-6, and a significantly increased TNFα. Overall, the modulation of serum Th1/Th2 cytokines could explain the reduction in antibody response, pointing to a potential role for T helper cells in the immunotoxicity of PFOA. Further, the higher than anticipated weight loss and increased liver weight, compared to previous studies using similar doses, highlight the potential importance of the route and duration of exposure, contributing to the total accumulated dose, in assessing the toxicity of PFOA.
The Combined Study of Serum Enzymes and Duodenal Contents in the Diagnosis of Pancreatic Disease

Summary 1.A combined study of the serum amylase and lipase activities and of volume, bicarbonate, and amylase activity of the duodenal contents after pancreozyminsecretin stimulation is described. Pancreozymin was given first, followed in 10 minutes by secretin, intravenously. 2.Pancreozymin-secretin test gave positive serum enzyme responses in 9 of 18 patients with chronic pancreatitis, in all of 3 cases of carcinoma of the ampulla of Vater, and in only one of 5 cases of carcinoma of the pancreas. A comparative study of pancreozymin and secretin and of secretin alone as the stimulant in some of these patients showed that the addition of pancreozymin increased the yield of positive serum enzyme responses. 3.Five of the 9 cases of chronic pancreatic disease with positive serum enzyme responses showed normal findings of the duodenal contents. On the other hand, the other 9 cases with normal serum enzyme response showed low values of the duodenal contents. 4.We recommend that in cases of suspected pancreatic disease, the provocative serum enzyme test with pancreozymin and secretin be done first; if negative, to be followed by a duodenal intubation study. The provocative serum enzyme test could be included as one of the tests in the routine investigation of chronic pancreatic disease.
A heuristic migration logic between firewalls in a federated cloud network

The hyper-connected cloud landscape is reliant on a composite security framework of hardware and cloud firewalls. Often, these security devices are managed by separate groups and operate as functional silos rather than integrated security mechanisms. As a result, cloud traffic is subjected to inefficient and redundant packet filtering. Hardware firewalls are optimized for greater throughput while virtualized firewalls can scale to match DoS attempts. To maximize the utility of each form factor, we developed an inline firewall architecture with a variable filtering point. The primary filtering point changes between hardware and cloud firewalls based on real-time conditions. The architecture incorporates heuristic-based migration logic. To define the heuristics, a performance evaluation was conducted following two test scenarios: spike tests and endurance test. Packet throughput was also assessed using JMeter. The results indicate that a threshold approach to filter-point migration maximizes network throughout while offering the insurance of on-demand scalability.
Resolution extension of counter-based DPWM using self-triggered method

The DPWM device is an important component in many industrial applications, such as motors, robots, DC/DC converters, and so on. However, the counter-based DPWM intends to extend its resolution, and thus the higher clock frequency is required. In this paper, by a cyclic self-trigger of monostable multivibrator, the proposed DPWM device can extend its resolution without increasing the reference clock frequency. Moreover, it also maintains as low hardware complexity as the conventional counter-based DPWM.
Numerical Modeling of Objects Near a Penetrable Interface

One of the classic problems of NDE, that of detecting flaws located near a planar interface, is also relevant to the operation of antennas close to, or penetrating, the earth’s surface. For these various cases, the total field (acoustic, electromagnetic or elastodynamic) can be expressed in terms of direct and interface reflected and transmitted components. In addition, a representation can be developed for the interface fields in terms of some suitable expansion (a continuous spectrum of cylindrical waves, for example). It is the latter feature of such problems that makes their numerical evaluation so challenging, and a self-consistent solution so expensive computationally.
A Person-Centered Examination of Adolescent Religiosity Using Latent Class Analysis

Empirical studies of religion’s role in society, especially those focused on individuals and analyzing survey data, conceptualize and measure religiosity on a single measure or a summary index of multiple measures. Other concepts, such as “lived religion,” “believing without belonging,” or “fuzzy fidelity,” emphasize what scholars have noted for decades: humans are rarely consistently low, medium, or high across dimensions of religiosity including institutional involvement, private practice, salience, or belief. A method with great promise for identifying population patterns in how individuals combine types and levels of belief, practice, and personal religious salience is latent class analysis. In this paper, we use data from the first wave of the National Study of Youth and Religion’s telephone survey to discuss how to select indicators of religiosity in an informed manner, as well as the implications of the number and types of indicators used for model fit. We identify five latent classes of religiosity among adolescents in the United States and their socio-demographic correlates. Our findings highlight the value of a person-centered approach to understanding how religion is lived by American adolescents.
Mechanisms of retroaxonal barrage firing in hippocampal interneurons

Key points • Persistent firing can be triggered in a population of inhibitory interneurons found in the hippocampus and neocortex. Repeated stimulation eventually triggers an autonomous barrage of spikes that is generated and maintained in the axon, followed by antidromic propagation to the soma. • This barrage of spikes is generated and maintained in the axon, followed by antidromic propagation to the soma. The mechanisms underlying this ‘retroaxonal barrage firing’ are unknown. • We find that retroaxonal barrage firing is Ca2+ dependent, is inhibited by the L-type Ca2+ channel blockers cadmium, nifedipine and verapamil, and does not require synaptic transmission. Loading the stimulated interneuron with BAPTA did not block barrage firing, suggesting that the required Ca2+ entry may occur in other cells. • Retroaxonal barrage firing was observed in mice lacking the Cx36 isoform (most common neuronal isoform), indicating that this particular isoform is not required. Abstract We recently described a new form of neural integration and firing in a subset of interneurons, in which evoking hundreds of action potentials over tens of seconds to minutes produces a sudden barrage of action potentials lasting about a minute beyond the inciting stimulation. During this persistent firing, action potentials are generated in the distal axon and propagate retrogradely to the soma. To distinguish this from other forms of persistent firing, we refer to it here as ‘retroaxonal barrage firing’, or ‘barrage firing’ for short. Its induction is blocked by chemical inhibitors of gap junctions and curiously, stimulation of one interneuron in some cases triggers barrage firing in a nearby, unstimulated interneuron. Beyond these clues, the mechanisms of barrage firing are unknown. Here we report new results related to these mechanisms. Induction of barrage firing was blocked by lowering extracellular calcium, as long as normal action potential threshold was maintained, and it was inhibited by blocking L-type voltage-gated calcium channels. Despite its calcium dependence, barrage firing was not prevented by inhibiting chemical synaptic transmission. Furthermore, loading the stimulated/recorded interneuron with BAPTA did not block barrage firing, suggesting that the required calcium entry occurs in other cells. Finally, barrage firing was normal in mice with deletion of the primary gene for neuronal gap junctions (connexin36), suggesting that non-neuronal gap junctions may be involved. Together, these findings suggest that barrage firing is probably triggered by a multicellular mechanism involving calcium signalling and gap junctions, but operating independently of chemical synaptic transmission.
Fine Structure of Haemophilus vaginalis

Haemophilus vaginalis 594 has a trilaminar cell wall, ribosomes, a fibrillar nucleoid, and both convoluted and simple mesosome-like bodies. Polar bulbous enlargements of the cell and multiple cross wall formations may explain its pleomorphism.
Molecular motors: Keeping the beat

Flagella and cilia can propel bacteria or cells through bends that travel from their base to their tip. In an attempt to find out what controls the timing of these waves, one group has studied sea-urchin flagella. They find that oscillatory movements can be generated by surprisingly simple substructures of each flagellum's core (or axoneme). Although the authors don't yet know what controls these oscillations, they discuss several possible explanations.
Enhanced Inhibition of Synaptic Transmission by Dopamine in the Nucleus Accumbens during Behavioral Sensitization to Cocaine

Neural adaptations in the nucleus accumbens (NAc), a key component of the mesolimbic dopamine (DA) system, are thought to mediate several of the long-term behavioral sequelas of chronic in vivo exposure to drugs of abuse. Here, we examine whether the modulation of excitatory synaptic transmission by DA in the NAc shell is modified after chronic cocaine exposure that induced behavioral sensitization. The DA-induced inhibition of AMPA receptor-mediated synaptic responses was enhanced in cocaine-treated mice, an effect that was caused by activation of D1-like receptors. DA did not enhance NMDA receptor-mediated synaptic responses in saline- and cocaine-treated mice or in the dorsal striatum of control mice. We hypothesize that the enhanced inhibitory effects of DA on synaptic transmission in the NAc are one of a number of adaptations that contribute to a decrease in excitatory drive to NAc after exposure to drugs of abuse.
Reduction of neurotransmitter receptor and G-protein expression in vivo and in vitro by antisense oligodeoxynucleotide treatment.

Publisher Summary The use of antisense oligodeoxynucleotides (ODNs) to reduce or eliminate the expression of specific proteins has become an increasingly important research tool. Although there is some disagreement about the precise mechanism of its action, the exquisite specificity of the ODN for its target is hardly disputed. The increased popularity and utilization of this approach have also spurred the establishment of many new businesses dedicated to the custom synthesis of antisense ODNs, in any number of shapes, forms, and styles, all at increasingly more affordable rates. This combination of specificity, availability, and affordability has allowed more and more investigators to utilize this molecular approach without the added expense of establishing a costly traditional molecular biology dimension within their laboratories. The use of ODNs has been especially fruitful when applied to neurotransmitter receptors and components of second-messenger systems and has allowed addressing questions about receptor/second-messenger interactions and second-messenger-mediated downstream events that have been difficult to answer. This chapter describes how antisense ODNs may be used in cultured cell lines and in intact animals to reduce the expression of neurotransmitter receptors and glyco (G) proteins.
Purification and Properties of Cytoplasmic and Mitochondrial Malate Dehydrogenases of Physarum polycephalum

Two isoenzymes of malate dehydrogenase (MDH) were demonstrated in plasmodia of Physarum polycephalum by polyacrylamide-gel electrophoresis. The more "cathodal" form was uniquely associated with mitochondria (M-MDH) and the other form was found in the soluble cytoplasm (S-MDH). The isoenzymes were separated by acetone fractionation of soluble plasmodial homogenates acidified to pH 5.0. The M-MDH was purified 201-fold by cetylpyridinium chloride treatment, fractionation with ammonium sulfate, gradient elution from sulfoethyl cellulose at pH 6.0, and Sephadex G-100 chromatography. The S-MDH was purified 155-fold by ammonium sulfate fractionation, diethylaminoethyl cellulose chromatography, gradient elution from sulfoethyl cellulose at pH 5.5, and Sephadex G-100 chromatography. The optimal cis-oxalacetate concentrations were 0.35 mM for M-MDH and 0.25 mM for S-MDH, and the optimal pH for both isoenzymes was 7.6 for oxalacetate reduction. The optimal l-malate concentrations were 5 mM for S-MDH and 6 mM for M-MDH, and both isoenzymes exhibited an optimal pH of 10.0 for L-malate oxidation. The Michaelis constants of S-MDH and M-MDH served to discriminate between the isoenzymes. The S-MDH was more heat-stable than the M-MDH. High concentrations of oxalacetate and malate inhibited S-MDH more than M-MDH. The isoenzymes were further distinguished by their utilization of analogues of nicotinamide adenine dinucleotide. Many properties of the Physarum isoenzymes were similar to those of more complex organisms, especially vertebrates.
Effect of Radiotherapy After Breast-Conserving Treatment in Women With Breast Cancer and Germline BRCA1/2 Mutations

PURPOSE: Recent laboratory data suggest a role for BRCA1/2 in the cellular response to DNA damage. There is a paucity of clinical data, however, examining the effect of radiotherapy (RT), which causes double-strand breaks, on breast tissue from BRCA1/2 mutation carriers. Thus the goals of this study were to compare rates of radiation-associated complications, in-breast tumor recurrence, and distant relapse in women with BRCA1/2 mutations treated with breast-conserving therapy (BCT) using RT with rates observed in sporadic disease. PATIENTS AND METHODS: Seventy-one women with a BRCA1/2 mutation and stage I or II breast cancer treated with BCT were matched 1:3 with 213 women with sporadic breast cancer. Conditional logistic regression models were used to compare matched cohorts for rates of complications and recurrence. RESULTS: Tumors from women in the genetic cohort were associated with high histologic (P = .0004) and nuclear (P = .009) grade and negative estrogen (P = .0001) and progesterone (P = .002) r...
Gastrointestinal morphology, tight junction gene expression, and microbiota of the Ossabaw obese pig model (816.1)

Obesity is characterized by chronic low-grade inflammation, with reduced gastrointestinal (GI) barrier function hypothesized to be a contributing factor. Animal models are invaluable for understand...
The contributions of numerosity and domain-general abilities to school readiness.

Contributions of domain-general and domain-specific numerical competencies were assessed on first graders’ number combination skill (NC) and word-problem skill (WP). Students (n = 205) between 5 and 7 years of age were assessed on 2 aspects of numerosity, 8 domain-general abilities, NC, and WP. Both aspects of numerosity predicted NC when controlling for domain-general abilities, but domain-general abilities did not account for significant additional variance. By contrast, when controlling for domain-general abilities in predicting WP, only precise representation of small quantities was uniquely predictive, and domain-general measures accounted for significant additional variance; central executive component of working memory and concept formation were uniquely predictive. Results suggest that development of NC and WP depends on different constellations of numerical versus more general cognitive abilities.
Suicide and suicide attempts in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD).

Background The current report describes individuals with bipolar disorder who attempted or completed suicide while participating in the Systematic Treatment Enhancement Program for Bipolar Disorder (STEP-BD) study.