cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract B23: DNA damage response in responder lymphocytes reduces vaccine efficacy following alkylating chemotherapy.

The effect of alkylating chemotherapy on cancer vaccines is controversial, with numerous reports of immune stimulation via Treg depletion following cyclophosphamide and temozolomide treatment. Using a pre-clinical model of a cancer vaccine in both naive and tumor bearing animals, we observed that the direct anti-proliferative effect of drugs such as temozolomide or cyclophosphamide reduced the quantity of vaccine induced immune responses in a dose dependent manner. Amounts of temozolomide exposure in mice that duplicated human pharmacokinetic exposure and lymphopenia led to lower numbers of CD8 T cells elicited by vaccination with the model antigen ovalbumin. In vitro experiments with purified OT-I CD8 T cells implicated activation of DNA damage responses within strongly proliferating cells as the cause of this diminished immunity. ATM phosphorylation was greater in temozolomide or cyclophosphamide exposed OT-I cells stimulated with the canonical SIINFEKL peptide relative to variant peptides that trigger weaker TCR signaling. In vaccinated mice, this activation of DNA damage response in lymphocytes receiving the highest intensity TCR signals lead to lower avidity of responder cells for cognate antigen and lower effector function. These quantitative and qualitative defects of vaccine driven responses lead to inferior efficacy and loss of survival benefit in murine models. Mice bearing ovalbumin peptide expressing glioma had faster tumor growth and shorter survival following temozolomide and vaccine relative to vaccine only treated mice. Similar defects of vaccine generated responses and a loss of survival benefit relative to controls were observed in response to a neo-antigen vaccine following cyclophosphamide pre-treatment in melanoma bearing mice. The clinical relevance of this finding is demonstrated by a phase II cancer vaccine trial in metastatic melanoma patients where vaccine only patients survived a median of 4.2 years versus less than 8 months in patients treated with low dose cyclophosphamide before vaccine. Citation Format: Adam J. Litterman, David M. Zellmer, Karen L. Grinnen, Arkadiusz Z. Dudek, David A. Largaespada, John R. Ohlfest. DNA damage response in responder lymphocytes reduces vaccine efficacy following alkylating chemotherapy. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology: Multidisciplinary Science Driving Basic and Clinical Advances; Dec 2-5, 2012; Miami, FL. Philadelphia (PA): AACR; Cancer Res 2013;73(1 Suppl):Abstract nr B23.
Development and Application of a Flexibility-Based Method for Multi-Scale Design

A flexibility-based approach is presented for the solution of multiscale engineering design problems. The methodology is aimed at enhancing distribution of design activities and reducing the number of costly iterations between multiple engineering teams operating on different scales. This goal is achieved by exchanging flexible families of solutions rather than single point solutions, thereby reducing the need for iteration between scales. The effectiveness of the approach is illustrated by a two-level problem involving the system-level design of a gas turbine engine and the mesoscale design of cellular material for the combustor liner. A multi-objective design problem formulation is used to obtain families of prismatic cellular materials that embody a range of tradeoffs between conflicting thermal and structural performance objectives. The results are communicated to the system level and a solution is chosen to meet system-level goals as closely as possible. The effectiveness of the method is evaluated by comparison with a benchmark integrated design method. The approach facilitates identification of satisfactory or nearly optimal solutions quickly and with minimal iterations between scales.
The relation of geology to dry-weather stream flow in Ohio

The regime of dry-weather flow of several streams in Ohio is presented by flow-duration curves. For comparison, the index of ground-water flow for each basin is the discharge in cubic feet per second per square mile which is exceeded 90 per cent of the time. These indices are shown on a map of Ohio, and are discussed with respect to known geological conditions. It is concluded that stream-flow records provide useful inferences to ground-water geology, but the converse is not true.
Volatilization of Chlorinated Hydrocarbons from Water

Coefficients for the volatilization from water of 1,1,1-trichloroethane and 1,2-dichloroethane were measured in a stirred tank. Experiments at constant mixing conditions over a wide range of concentrations showed that the volatilization coefficient was independent of concentration, confirming the assumption that volatilization is a first order process. Simultaneous measurements of the volatilization coefficient and the oxygen absorption coefficient over a wide range of mixing conditions showed that the chlorinated hydrocarbon/oxygen coefficient ratios for both compounds were independent of mixing conditions. Ratios of 0.596 and 0.621 were obtained for 1,1,1-trichloroethane and 1,2-dichloroethane, respectively.
HLA-DM and HLA-DO: bi-directional regulation of function, tuned by pH (APP3P.103)

Peptide processing and loading onto MHC-II in endosomes occurs across a wide pH range. We studied pH effects on DM/DO regulation of peptide loading in vitro, using soluble, recombinant molecules, including a stabilized mutant DO dimer (sDOAP11A) that inhibits DM normally. We tested different DO:DM ratios at pH 4.6-7.2 during loading of 4 HLA alleles. DO alone had no effect. DM inhibition was diminished at lower DO:DM ratios, implying stable DM association is required for DO effect. Inhibition occurred across the pH range, but was reduced at pH 4.6. Using a narrower pH gradient (4.56-5.30), across which DM function is equivalent, we identified DO as the primary target of pH effects. DO activity was reduced after pre-incubation at pH 5.4, and longer exposure, lower pH and higher temperature enhanced this effect. FRET analysis of DM/DO at low pH was consistent with DO release rather than conformational change of intact complexes. SPR, bio-layer inferometry and ELISA assays showed reduced DM/DO association at pH≤4.85, suggesting released DO binds back inefficiently. With pre-incubation at pH 4.6 or 5.4, DM-DOwt complexes acquired DM-like activity; analysis of active SEC fractions indicated presence of free DM. Pre-incubation of sDM alone at these pHs caused aggregation. Complexes of full-length DM and DOwt showed similar behavior to soluble molecules. We conclude that low pH generates free DM by releasing DO, which both inhibits and chaperones DM.
Flexible artificially-networked structure for ambient/high pressure solar steam generation

The heat localization approach has promised a new route to solar steam generation with a higher efficiency than that of the current bulk heating approaches. In this approach, the material structure localizes the absorbed solar energy, forms a hot spot, and wicks the fluid to the hot spot for steam generation. The non-equilibrium nature of this approach minimizes energy losses leading to its superior performance compared to equilibrium approaches. However, to date, the generated steam is only at ambient pressure and not suitable for high pressure applications. Herein, we report development of a flexible artificially-networked material structure that is highly efficient for ambient and high pressure steam generation with integrity for large-scale and varied geometrical implementations. This flexible material is composed of a porous polymer skeleton coated with exfoliated graphite and artificially-networked 3D veins. The porous skeleton and the interconnected veins are developed in two distinct fabrication steps. The structure generates steam in the temperature range of 100–156 °C and at the pressure range of 100–525 kPa under solar irradiation. This material structure promises a robust and highly efficient approach for solar steam generation for both ambient pressure applications (e.g. solar ponds and desalination) and high pressure applications (e.g. power generation, solar cooling technologies, and hygiene systems).
GENDER DIFFERENCES IN LANGUAGE PRODUCTION

Summary.-For 40 right-handed adults there were only five of 74 linguistic variables associated with gender dtfferences in language production. Four were related to the linguistic parameter of syntax and one to semantics. No diFferences were noted for the linguistic parameters of phonology and pragmatics. Limited data are available on gender dfierercnces in language production with regard to the four linguistic parameters of semantics, pr.ig~natics, syntax, and phonology. We assessed such daerences for men and women throueh ebc~rdr~ons of connected sveech (1). . . Participants were 40 right-handed Caucasian adults who passed a screening test for hearing and had between 9 and 12 years of formal education. There were 20 younger subjects (10 men and 10 women) between 20 and 29 years and 20 older subjects (10 men and 10 women) between 70 and 79 vears. Subiects were given three discourse tasks in a random order to elicit conversational speech. The narrative task required describing a personal memorable experience; the procedural task required describing a procedure composed of sequential steps, e.g., "Tell me in as much detail as possible how you would wash a car"; the pictogram task involved describing seven frames of a "Tank McNamara" comic strip. Each subject was tested individually, and all verbal responses were audiotaped for subsequent analysis. Experimental procedures were completed in a single session of 45 minutes or less. Of the 74 linguistically related variables analyzed ~tatistically,~ only five were significantfour related to syntax and one to semantics. For syntax, men produced more complex utterances but made more incomplete utterances within the procedural task. Women produced more sentences at the two simolest sentence levels. On the semantic Darameter. women vroduced significantly more revisions than men. Analysis suggested that the language production capabilities of men and women are similar in most respects. One-way analyses of variance showed over-all significant differences in verbal output under the three stimulus conditions for both total words (F2,3,= 15.6, p< .01) and utterances (F2 15.7, p< .01). For both, the narrative context [M of 622.4 (f 655.9) total words and 59.9 (f 60.0) total utterances] produced more responses than did the procedural context [M of 266.3 (? 189.5) total words and 25.6 (f 17.7) total utterances] or the pictogram [M of 197.6 (+ 119.8) total words and 21.1 (f 11.5) total utterances]. Although the familiar narrative context ~roduced the greatest number of responses, the unfamiliar pictogram context produced the greatest number of linguistic errors and may be the most sensitive of the three contexts to language-produccion dzferences.
Combating curse of dimensionality in resilient monitoring systems: Condition for lossless decentralized inferences

Resilient monitoring systems (RMS) are sensor networks that degrade gracefully under cyber-attacks on their sensors. The recently developed RMS, while being effective in the attacked sensors identification and isolation, exhibited a drawback in their operation - an exponentially increasing assessment time as a function of the number of sensors in the network. To combat this curse of dimensionality, a decomposition approach has been proposed, which led to a dramatic reduction of the assessment time, irrespective of the sensor network dimensionality. However, the information losses due to this approach, which involves decentralized inference calculations, have not been investigated. The current paper is intended to carry out such an investigation, and, specifically, derive a condition under which the inference calculations lead to no loss of information. The development is based on matrices, which characterize the coupling of process variables being monitored, and on the Renyi-2 entropy.
Music and the Crisis of the Modern Subject by Michael L. Klein: (2015). Bloomington, IN: Indiana University Press. 191 pp., $40.00. 978-0-253-01722-2 (Cloth)

In Music and the Crisis of the Modern Subject, Michael Klein takes on the somewhat difficult task of injecting French-style continental theory into the heavily Germanic field of musicology. Althoug...
Obesity's effect on asthma extends to diagnostic criteria.

Background The use of inflammatory biomarkers to delineate the type of lung inflammation present in asthmatic subjects is increasingly common. However, the effect of obesity on these markers is unknown. Objectives We aimed to determine the effect of obesity on conventional markers of inflammation in asthmatic subjects. Methods We performed secondary analysis of data from 652 subjects previously enrolled in 2 Asthma Clinical Research Network trials. We performed linear correlations between biomarkers and logistic regression analysis to determine the predictive value of IgE levels, blood eosinophil counts, and fraction of exhaled nitric oxide values in relationship to sputum eosinophil counts (>2%), as well as to determine whether cut points existed that would maximize the sensitivity and specificity for predicting sputum eosinophilia in the 3 weight groups. Results Overall, statistically significant but relatively weak correlations were observed among all 4 markers of inflammation. Within obese subjects, the only significant correlation found was between IgE levels and blood eosinophil counts ( r = 0.33, P Conclusions In obese asthmatic subjects conventional biomarkers of inflammation are poorly predictive of eosinophilic airway inflammation. As such, biomarkers currently used to delineate eosinophilic inflammation in asthmatic subjects should be approached with caution in these subjects.
DC-bus voltage regulation for DC distribution system with controllable DC load

This paper shows a dc-bus voltage regulation for a dc distribution system integrated with a single-phase bidirectional inverter through using a control method to operate with no grid information, and without contributing the solar DC-DC converter. This system can intelligently and efficiently operate in islanding mode when load shedding is employed to regulate the DC bus voltage with providing the demand response requirements. Also, this enables controllable loads to ride-through grid outages, and it can be used as a retrofit solution for existing topologies applicable to any type of controllable DC loads with increasing the efficiency and improving the reliability. The primary simulation results are presented for a system in both grid tied and islanded mode indicates that the proposed system can satisfactorily regulate the common bus voltage, and ride through the blackout.
Laser-Induced Breakdown Spectroscopy for Qualitative Analysis of Metals in Simulated Martian Soils

This laboratory introduces students to laser-induced breakdown spectroscopy (LIBS) for the analysis of metals in soil and rock samples. LIBS employs a laser-initiated spark to induce electronic excitation of metal atoms. Ensuing atomic emission allows for qualitative and semiquantitative analysis. The students use LIBS to analyze a series of standard samples that contain various elements and construct a table of emission line wavelengths for each element analyzed. Students then identify metals in various soil and rock samples. Students gain valuable experience in qualitative analysis using an important spectroscopic tool, while gaining hands-on experience with a spectrometer employing a high energy laser pulse as an excitation source. The LIBS spectrometer is applicable to upper and lower division chemistry courses and can be used as an effective demonstration tool for students in 5th to 12th grade.
Provisional Patent Application as a Real Option in the Patent-Secrecy Tradeoff

Little empirical research has explored how the real options lens can inform the way firms make decisions about IP strategy. This paper examines when firms obtain secrecy options in patenting. I pro...
Target Acquisition: Performance Measures, Process Models, and Design Implications

Two types of movement tasks that have been studied from an engineering psychology perspective are continuous tracking and target acquisition. These two types of tasks can be distinguished by their goals. The goal of a continuous tracking task is typically to minimize the time-averaged discrepancy between a target and the output of some dynamic system. Keeping an aircraft on a predetermined flight path or regulating the headway between one’s own automobile and another vehicle are examples of continuous tracking tasks. In contrast, the goal of a target acquisition task is to bring the output of a dynamic system to some desired terminal state. Moving one’s finger to a numerical entry key on a calculator or positioning one’s automobile in a parking space are examples of target acquisition tasks. Often continuous tracking is preceded by target acquisition in order to bring the target within close range of the tracking system. This chapter will discuss target acquisition tasks. A discussion of continuous tracking tasks can be found in the chapters by Stassen and by Allen, McRuer, and Thompson.
Connecting with global consumers through corporate social responsibility initiatives: A cross-cultural investigation of congruence effects of attribution and communication styles

Abstract This study proposes that consumers' attribution styles influence how they respond to corporate social responsibility (CSR) messages. The current study employs a cross-cultural experiment to examine the interplay of consumer attribution styles and message types on the outcome of CSR communication, and reveals a significant interaction between attribution style and CSR message. Individuals with a dispositional attribution style responded more favorably to evidence-based CSR messages than to belief-based messages, while those with a situational attribution style responded more favorably to belief-based messages than to evidence-based messages. This study extends cross-cultural research into the area of CSR communication and offers practical guidelines for international marketers and corporations on how to communicate their CSR involvement to global consumers.
An Approach to Toxicant Isolation from a Produced Water Source in the Santa Barbara Channel

Produced water (PW) composition can be highly variable among formations, but in all cases appears to be very complex, consisting of non-polar and polar organic compounds, as well as inorganic cations and anions, and combinations of these diverse chemical catagories (National Research Council, 1985; Boesch and Rabalais, 1987). Little is known about the composition of even major chemical catagories of PW such as polar organic compounds and inorganic anions, and only the transition and B-type (Stumm and Morgan, 1981) metals and hydrocarbons have received attention with respect to effects, fate and transport (Boesch and Rabalais, 1987). The complexity of PW and lack of information on major chemical catagories directly leads to formidable obstacles to understanding of the distribution and effects of PW as: (a) it is logistically not feasible to analyze for even a small portion of the known constituents present, not to say of the unknown constituents; (b) just the known constituents represent vastly different physical and chemical properties, and therefore can have different transport characteristics; (c) the known constituents range from very stable to those that are readily transformed, and therefore can have different fates; and, (d) because of all the above, if unknown constituents are playing a major role in environmental effects of PW, their presence may continue to go chemically undetected, and therefore may wreak havoc with interpretation and relevance of future modeling studies.
Understanding protein motions by computational modeling and statistical approaches

Because of its appealing simplicity, the elastic network model (ENM) has been widely accepted and applied to study many molecular motion problems, such as the molecular mechanisms of chaperonin GroEL-GroES function, allosteric changes in hemoglobin, ribosome motions, motor-protein motions, and conformational changes in general. In this dissertation, the ENM is employed to study various protein dynamics problems, and its validity is also examined by comparing with experimental data. First, we apply principal component analysis (PCA) to identify the essential protein motions from multiple structures (X-ray, NMR and MD) of the HIV-1 protease. We find significant similarities between the first few of these key motions and the first few low-frequency normal modes from the ENM, suggesting that the ENM provides a coarse-grained and structurally-based explanation for the experimentally observed conformational changes. Second, we extend these approaches from a single protein (HIV-1 protease) to thousands of proteins whose multiple NMR structures are available. We also find close correspondence between the experimentally observed dynamics and the ENM predicted ones, indicating the validity of using the ENM to computationally predict protein dynamics. Third, we develop a regression model for the isotropic B-factor predictions by combining the protein rigid body motions with the ENM. The new model shows significant improvements in B-factor predictions. Fourth, we further examine the validity of using the ENM to study protein motions. We use the anisotropic form of ENM to predict the anisotropic temperature factors of proteins. It presents a timely and important evaluation of the model, shows the extent of its accuracy in reproducing experimental anisotropic temperature factors, and suggests ways to improve the model. Finally, we apply the ENM to study a dataset of 170 protein pairs having “open” and “closed” structures, and try to address how well a conformational change can be predicted by the ENM and how to improve the model. The results indicate that the applicability of ENM for explaining conformational changes is not limited by either the size of the studied protein
The Potential Impact of Scribes on Medical School Applicants and Medical Students with the New Clinical Documentation Guidelines

The presence of scribes in various specialties, including internal medicine, is being heralded as a way to decrease clinician documentation time and burnout. Many medical school applicants become scribes to understand life as a doctor and gain clinical experience. Scribing is already perceived by some as a new key to successfully gaining entrance to medical school. One season of our admissions data showed that scribes were more likely to be admitted (OR = 1.61). Scribes may also inadvertently make it harder for medical schools to secure clinical placements for medical students. While trained scribes are highly valued by providers struggling to deal with increasing documentation burdens, supervising or training scribes also requires time that cannot be devoted to teaching. Medical documentation duties could provide valuable learning experiences for medical students. The recent ruling allowing medical students to contribute directly to clinical documentation without requiring redocumentation by supervisors gives medical schools and clinician-educators an opportunity to consider the unintended consequences of the scribe movement for medical education. Educators should consider when and how students can maximize the educational benefits of participating in patient documentation despite the templated methods commonly used in electronic health record (EHR) systems.
Identification of alcohol-binding site(s) in proteins using diazirine-based photoaffinity labeling and mass spectrometry

Defining molecular targets of alcohol and understanding the molecular mechanism of alcohol actions are necessary to develop effective therapeutics for alcohol use disorder (AUD). Here, we describe a detailed protocol for identifying alcohol-binding site(s) in proteins using diazirine-based azialcohol as photoaffinity labeling agents. Upon photoirradiation, azialcohol photoincorporates into alcohol-binding proteins. The stoichiometry and site of azialcohol photoincorporation can be determined using high-resolution mass spectrometry. Identification of the alcohol-binding residues in protein followed by measuring the biological significance of these residues in regulating alcohol action are important steps in characterizing the molecular targets of alcohol.
Species of the Maera-clade collected from Japan. Part 2: genera Austromaera Lowry Springthorpe, 2005 and Quadrimaera Krapp-Schickel Ruffo, 2000 (Crustacea: Amphipoda: Maeridae).

One species of Austromaera Lowry & Springthorpe, 2005 and four species of Quadrimaera Krapp-Schickel & Ruffo, 2000 included in the Maera clade, are described from Japan. Austromaera ariakensis sp. nov. is described, based on collections from Ariake Sea and can be distinguished from its congeners by the acutely produced coxa 1 and the merus of gnathopod 2 with a small posterodistal spine. Quadrimaera gotoensis sp. nov. from Goto Islands in Nagasaki Prefecture has a small quadrate excavation on the middle palmar margin of the male gnathopod 2. This new species is different from Q. mirandella Appadoo, Myers & Fagoonee, 2002 having such an excavation, in the larger posterodistal tooth of the male gnathopod 2 propodus and the wider bases of the pereopods 5–7. Quadrimaera pacifica (Schellenberg, 1938) was collected from many localities from Iwate Prefecture to Ariake Sea. This species is characterized by the transverse palm of the male gnathopod 2 with the large posterodistal tooth, the small rounded excavation in the middle and the anterior lobe narrower and produced more distally than the posterior lobe. Morphology of Q. pacifica is variable in the posterior excavation of the male gnathopod 2 palm, the uropod 3 rami and the distal end of the telson. Quadrimaera quadrimana (Dana, 1853) from the south of Yakushima Island in Kagoshima Prefecture has a distinct palm of the male gnathopod 2 with three excavations. Quadrimaera setibasis sp. nov. collected from the intertidal zone in Osaka Prefecture has a setose basis of the pereopod 6 like Q. schellenbergi (Ruffo 1938), but the bases of the pereopods 5 and 7 are not setose. A key to species of Austromaera in the world is provided.
Herbal Medicines as Adjuncts to Cancer Chemotherapy—Part 2: Non-Immune Support

Abstract Part 1 of this article focused on immunomodulating herbal adjuncts to chemotherapy treatment. Part 2 highlights herbal therapies for specific adverse side effects, including nausea, vomiti...
Museums engaging diverse Millennials in community dialogue

In 2016, Levine Museum of the New South (LMNS) developed an innovative Sustained Dialogue program aimed at engaging and training a diverse group of Millennials in dialogue. University researchers p...
Embodied and Non-bodied Selves

This chapter engages the work of Descartes and how ideas of mind/body dualism have been presented in science fiction. I discuss critiques of the Cartesian model, particularly in regard to consciousness. Is the mind/consciousness/soul separate from the body? If so, can the body exist without the soul—for example, a clone (The Island, House of Scorpion)? Conversely, can there be a thing such as pure consciousness (Westworld, Her, Star Trek) that exists either as an avatar or as a computer program? Both of these conversations bring ideas of personhood into question, and the question of soul-having—specifically, is it inherent in a person?
Confirmation of success rate of landmark-based caudal blockade in children using ultrasound: A prospective analysis.

Background Caudal epidural anesthesia is a frequently performed regional anesthesia block in infants and young children. Traditional landmark-based blind needle insertion remains the norm with no immediate, objective method to determine the presence of local anesthetic in the epidural space. Increasingly, ultrasound-imaging is used in pediatric regional anesthesia with demonstrated improvements in block efficacy and efficiency. The value of ultrasound-imaging in confirming success rate of traditional caudal placement is not well defined. Aim To assess the success rate of conventional landmark-based caudal technique using ultrasound-imaging. Methods Prospective observational study of 30 children ages 1 month to 7 years undergoing surgical procedures with consent for caudal blockade. Provider success rate of caudal blockade placed by landmark technique was measured using ultrasound-imaging of needle tip and local anesthetic flow in the epidural space. Results Ultrasound-imaging demonstrated 80% success to correct positioning of the needle tip and local anesthetic in the epidural space. Failure was associated with decreasing experience and presence of anatomic variances. All improperly positioned needles were subsequently successfully positioned using real-time ultrasound-imaging. Mean time for confirmatory ultrasound-imaging (SD; range) was 1 minute (0.3; 1-3). Conclusion The use of ultrasound-imaging can be used to identify proper needle placement in the sacral epidural canal and facilitate subsequent corrected placement.
Pre-conception exposure to THC fails to impact nicotine reward in adult offspring.

Abstract Exposure to environmental stimuli in one generation can produce altered behavioral and neurobiological phenotypes in descendants. Recent work has shown that parental exposure to cannabinoids alters the rewarding properties of other abused drugs in the subsequent generation. However, whether preconception Δ9-tetrahydrocannabinol (THC) administration modifies the affective properties of nicotine in offspring is unknown. To address this question, male and female rats (F0) received THC (0 or 1.5 mg/kg) throughout the adolescent window and were bred on PND 65. In Experiment 1, adult F1-THC and F1-Veh progeny (males and females) underwent nicotine locomotor sensitization procedures during which nicotine (0 or 0.4 mg/kg) was administered every other day for five exposures, and locomotor activity was recorded on each exposure followed by a final nicotine challenge. There was no cross-generational effect of THC on nicotine locomotor sensitization, although acute exposure to nicotine produced greater activity in females relative to males independent of THC history. In Experiment 2, adult F1-THC and F1-Veh progeny (males and females) were implanted with jugular catheters and trained to self-administer nicotine (0.03 mg/kg/infusion). Following acquisition, all subjects were allowed to self-administer nicotine on a number of reinforcement schedules, e.g., FR2, FR5 and PR, followed by dose response and extinction procedures. Across all indices, F1-THC and F1-Veh subjects displayed similar IVSA of nicotine with no sex differences. The fact that there was no evidence of cross-generational effects of THC on nicotine suggests that such effects are drug-specific.
Phase I Study of Cabozantinib and Nivolumab Alone or With Ipilimumab for Advanced or Metastatic Urothelial Carcinoma and Other Genitourinary Tumors.

PURPOSE We assessed the safety and efficacy of cabozantinib and nivolumab (CaboNivo) and CaboNivo plus ipilimumab (CaboNivoIpi) in patients with metastatic urothelial carcinoma (mUC) and other genitourinary (GU) malignances. PATIENTS AND METHODS Patients received escalating doses of CaboNivo or CaboNivoIpi. The primary objective was to establish a recommended phase II dose (RP2D). Secondary objectives included objective response rate (ORR), progression-free survival (PFS), duration of response (DoR), and overall survival (OS). RESULTS Fifty-four patients were enrolled at eight dose levels with a median follow-up time of 44.6 months; data cutoff was January 20, 2020. Grade 3 or 4 treatment-related adverse events (AEs) occurred in 75% and 87% of patients treated with CaboNivo and CaboNivoIpi, respectively, and included fatigue (17% and 10%, respectively), diarrhea (4% and 7%, respectively), and hypertension (21% and 10%, respectively); grade 3 or 4 immune-related AEs included hepatitis (0% and 13%, respectively) and colitis (0% and 7%, respectively). The RP2D was cabozantinib 40 mg/d plus nivolumab 3 mg/kg for CaboNivo and cabozantinib 40 mg/d, nivolumab 3 mg/kg, and ipilimumab 1 mg/kg for CaboNivoIpi. ORR was 30.6% (95% CI, 20.0% to 47.5%) for all patients and 38.5% (95% CI, 13.9% to 68.4%) for patients with mUC. Median DoR was 21.0 months (95% CI, 5.4 to 24.1 months) for all patients and not reached for patients with mUC. Median PFS was 5.1 months (95% CI, 3.5 to 6.9 months) for all patients and 12.8 months (95% CI, 1.8 to 24.1 months) for patients with mUC. Median OS was 12.6 months (95% CI, 6.9 to 18.8 months) for all patients and 25.4 months (95% CI, 5.7 to 41.6 months) for patients with mUC. CONCLUSION CaboNivo and CaboNivoIpi demonstrated manageable toxicities with durable responses and encouraging survival in patients with mUC and other GU tumors. Multiple phase II and III trials are ongoing for these combinations.
Screening for Adverse Childhood Experiences in a Pediatric Emergency Department

Background: Adverse Childhood Experiences (ACEs), classically defined as abuse, violence exposure, and family dysfunction, have been shown to cause long-term negative health effects. Data from the 2011-12 National Survey of Children’s Health (NSCH) revealed that 31.3% of children 0-17 years old in the United States have been exposed to ACEs. This study aimed to define the prevalence of ACEs in a pediatric ED. Methods: This was a prospective, observational …
UTILIZAÇÃO DO VIDEOJOGO A SLOWER SPEED OF LIGHT PARA O ENSINO DA TEORIA DA RELATIVIDADE ESPECIAL

Neste trabalho buscou-se facilitar a assimilacao dos conteudos pelos alunosutilizando-se de metodologias atrativas como jogos didaticos atraves do uso detecnologias da informatica para o estudo da Teoria da Relatividade Especial deAlbert Einstein. A ferramenta utilizada na segunda etapa da RP foi um videojogodesenvolvido pelo MIT intitulado A Slower Speed a Light juntamente comquestionarios de multipla escolha para verificacao da aprendizagem dos estudantes.
Multicomponent, multiphase interactions in fuel-cell inks

Abstract Fuel cell catalyst layers (CLs) are porous electrodes that are fabricated from CL inks: colloidal dispersions of catalyst particles and ion-conducting polymer (ionomer), dispersed in solvent(s). The complex interactions between the ink components ultimately dictate CL microstructure and electrochemical performance. To control the CL formation process and optimize fuel cell performance, knowledge of these ink interactions is vital. In this review, we analyzed data from ink-focused papers to elucidate how ink parameters (solvent type, ionomer-to-carbon ratio, etc.) impact ink interactions and CL performance. We then discuss these results in the context of the current understanding of two critical ink interactions: ionomer/solvent and ionomer/catalyst particle interactions.
De los trasplantes legales a las traducciones legales: la globalización del plea bargaining y la tesis de la “americanización” en el proceso penal

The paper analyses the alleged influence of the American legal system in foreign jurisdictions. The main argument focuses on the plea bar- gaining in Criminal Law Procedures and the so called “legal transplants”. According to the article, the idea of “translation” fits better with the real phenomenon of legal ideas and institutions travelling abroad. Against the thesis of the americanization of other legal systems, the article analyses the development of the plea bargaining in four different jurisdictions
α-Keto acid dehydrogenase complexes

Abstract The mammalian pyruvate dehydrogenase complex contains a core, consisting of dihydrolipoyl transacetylase, to which pyruvate dehydrogenase and dihydrolipoyl dehydrogenase (a flavoprotein) are joined. Electron microscopic studies indicated that the design of the transacetylase is based on icosahedral (532) symmetry and, therefore, it would be expected to contain 60 very similar, if not identical, polypeptide chains. Evidence is presented that the bovine kidney and heart dihydrolipoyl transacetylases are very similar and that each enzyme does indeed consist of 60 apparently identical polypeptide chains. Each chain apparently contains 1 molecule of covalently bound lipoic acid. The molecular weight of the transacetylase is about 3.12 ± 0.20 million. The pyruvate dehydrogenase components of the bovine kidney and heart pyruvate dehydrogenase complexes are also very similar. The uncomplexed enzymes have a molecular weight of about 154,000 and possess the subunit structure α2β2. The molecular weights of two subunits are about 41,000 and 36,000, respectively. Only the α-subunit undergoes phosphorylation in the presence of pyruvate dehydrogenase kinase and ATP. Possible functions of the two subunits are discussed. It appears that the bovine kidney and heart pyruvate dehydrogenase complexes contain about 60 pyruvate dehydrogenase units (αβ) but only 10–12 flavoprotein chains.
Fish Oil and Cell Proliferation Kinetics in a Mammary Carcinoma Tumor Model

In vivo bromodeoxyuridine (BrdUrd) labelling and bivariate BrdUrd/DNA analysis was used to evaluate cell cycle kinetics in a rat tumor model known to be sensitive to dietary fatty acid manipulation. Fish oil supplementation significantly reduced the rate of BrdUrd movement relative to DNA content, indicating prolongation of the DNA replication time. This finding, which accounted for most of the decrease in tumor growth rate in the fish oil-fed group, represents the first description of an alteration in S phase duration by an extrinsic factor. The significance of this finding is discussed in relation to current understanding of cell cycle regulation.
Does Microfinance Help the Ultrapoor Cope with Seasonal Shocks? Evidence from Seasonal Famine (Monga) in Bangladesh

This paper uses a unique data set on 150,000 ultrapoor households in Bangladesh to analyze whether microfinance helps cope with aggregate shocks such as seasonal famine. To address selection on unobservables, we use two alternative approaches: an instrumental variables strategy that exploits a natural nonlinearity arising from the interaction of self-selection by households with the MFI screening, and the `Minimum-Bias Bias-Corrected' estimator due to Millimet and Tchernis (2010) that corrects for endogeneity bias without exclusion restrictions. The empirical results suggest that microfinance improves food security of a relatively better-off household, but may not have any robust effect on the food security of the poorest of the poor. Evidence is strong that microfinance helps households to avoid distress sale of labor, and reduces the probability of short term migration in search of work during Monga.
Nudging Mechanisms for Technology Adoption

We study the adoption dynamics of two competing technologies and the efficacy of viral pricing strategies for driving adoption. Our model considers two incompatible technologies of differing quality and a market in which user valuations are heterogeneous and subject to network effects. We provide partial characterization results about the structure and robustness of equilibria and give conditions under which the higher quality technology purveyor can make significant inroads into the competitor's market share. We then show that myopic best-response dynamics in our setting are monotonic and convergent, and propose two pricing mechanisms that use this insight to help the entrant technology seller tip the market in its favor. Comparable implementations of both mechanisms reveals that the non-discriminatory strategy, based on a calculated public price subsidy, is less costly and just as effective as a discriminatory policy.
Potassium permanganate elicits a shift of the external fish microbiome and increases host susceptibility to columnaris disease

The external microbiome of fish is thought to benefit the host by hindering the invasion of opportunistic pathogens and/or stimulating the immune system. Disruption of those microbial communities could increase susceptibility to diseases. Traditional aquaculture practices include the use of potent surface-acting disinfectants such as potassium permanganate (PP, KMnO4) to treat external infections. This study evaluated the effect of PP on the external microbiome of channel catfish and investigated if dysbiosis leads to an increase in disease susceptibility. Columnaris disease, caused by Flavobacterium columnare, was used as disease model. Four treatments were compared in the study: (I) negative control (not treated with PP nor challenged with F. columnare), (II) treated but not challenged, (III) not treated but challenged, and (IV) treated and challenged. Ribosomal intergenic spacer analysis (RISA) and pyrosequencing were used to analyze changes in the external microbiome during the experiment. Exposure to PP significantly disturbed the external microbiomes and increased catfish mortality following the experimental challenge. Analysis of similarities of RISA profiles showed statistically significant changes in the skin and gill microbiomes based on treatment and sampling time. Characterization of the microbiomes using 16S rRNA gene pyrosequencing confirmed the disruption of the skin microbiome by PP at different phylogenetic levels. Loss of diversity occurred during the study, even in the control group, but was more noticeable in fish subjected to PP than in those challenged with F. columnare. Fish treated with PP and challenged with the pathogen exhibited the least diverse microbiome at the end of the study.
Use of continuous positive airway pressure after rhinoplasty, septoplasty, and sinus surgery: A survey of current practice patterns

Objective To explore current practice patterns in the use of continuous positive airway pressure (CPAP) following nasal or sinus surgery. Study Design Cross-sectional survey. Methods An electronic 24-question survey was created to evaluate surgeon practice patterns for restarting CPAP after nasal surgery. We also explored factors contributing to their decisions (1–5 Likert scale) and complications believed to be directly related to restarting CPAP. Factors with a median rating score greater than 3 out of 5 were deemed “important.” Subgroup analyses were performed to assess the impact of practice setting and clinical experience. Results A total of 407 physicians completed the survey (27.4% response rate for those that opened the e-mail). The majority of surgeons temporarily stop CPAP after nasal surgery, generally for 1 to 2 weeks, although the range of time is wide. There are also many surgeons who do not stop CPAP after any of these procedures and who reported that complications were fairly minimal. Severity of obstructive sleep apnea (OSA) was deemed important for all procedures. There were additional patient and surgery-specific factors considered important for each individual surgery. Subgroup analysis revealed significant differences in physician practice setting and clinical experience. Conclusion Regarding the use of CPAP after nasal surgery, considerable variation existed in the practice patterns of physicians. Severity of OSA was universally considered important, but the remaining factors were less consistent. A comparative study investigating the outcomes of various protocols is necessary. Level of Evidence N/A. Laryngoscope, 125:2612–2616, 2015
Incorporation of In Vitro Synthesized Reovirus Double-Stranded Ribonucleic Acid into Virus Corelike Particles

Abstract When reovirus double-stranded ribonucleic acid (dsRNA) was synthesized in vitro by using a large-particulate fraction (LP-fraction) from reovirus-infected L cells, a significant amount of the 3H-labeled dsRNA product was incorporated into reovirus corelike particles bound to the LP fraction. These corelike particles were found to be indistinguishable from virus core derived by chymotryptic digestion of virions when compared on the basis of their (i) resistance to chymotryptic digestion, (ii) buoyant density in CsCl, (iii) particle size as determined by agarose chromatography, (iv) elution characteristics from diethylaminoethyl-Sephadex, and (v) resistance of the incorporated 3H-dsRNA to ribonuclease digestion in 0.01 m NaCl. When the replicase reaction was partially inhibited by NaCl, there was an accumulation of particles that were less dense than the virus core. All of the results indicate that some virus core assembly takes place during the in vitro replicase reaction.
Observations of Marketing on Food Packaging Targeted to Youth in Retail Food Stores

There is growing evidence that exposure to food marketing influences dietary preferences among youth. Few studies exploring this association, however, have focused on the retail food store environment where families negotiate the influence of food and beverage marketing on purchasing practices. Consequently, we sought to examine: (i) the extent to which foods marketed on the internet and television to youth are also available and marketed in retail food stores, and (ii) whether differences exist in the marketing practices across store types and by neighborhood racial composition. In 2008, a cross-sectional survey of 118 food stores was conducted in four Midwestern cities in the United States. Results showed that 82% of stores assessed carried items commonly marketed to youth via television or the internet. The items most likely to have some type of marketing technique were noncarbonated drinks (97.7%), fruit and cereal bars (76.9%), and soda (62.2%). Grocery stores were significantly more likely than convenience stores to have marketing for breads and pastries (34.6% vs. 17.9%), breakfast cereals (52.0% vs. 22.9%), cookies and crackers (54.2% vs. 25.3%), dairy (70.8% vs. 42.7%), and ice cream (23.8% vs. 9.8%). Stores located in black neighborhoods were significantly more likely to have marketing, in comparison to white neighborhoods, for breads and pastries (35.7% vs. 17.1%), breakfast cereals (44.4% vs. 25.0%), and cookies and crackers (48.1% vs. 26.3%). Our results highlight the importance of examining food marketing techniques in the retail food store environment, where visual cues from television and the internet may be reinforced.
Progressive changes in the morphology of fluvial terraces and scarps along the Rappahannock River, Virginia.

Progressive geomorphic changes in the flight of fluvial terraces along the Rappahannock River, Virginia, provide a framework for analysing the effect of time on landforms. The oldest terrace is probably no younger than early Quaternary, and the youngest major fill terrace probably correlates with the high sea level of the last major interglacial. A uranium-series date of 187,000 yr has been obtained on coral from marine sediments related to this terrace. Indices of terrace preservation, especially drainage densities and area to perimeter ratios, show systematic changes with terrace age. Hence, these variables appear to satisfactorily indicate relative age, and could perhaps be used to estimate actual ages if suitably calibrated. The morphology of scarps formed by entrenchment of the fluvial terraces is more variable than analogous morphology of fault scarps and wave-cut bluffs. However, measurements of the fluvial scarps clearly indicate that for a given terrace age, higher scarps tend to have steeper slopes, and that for a given scarp height, older scarps tend to have gentler slopes. The terrace forms themselves are preserved for at least several million years. Depositional features such as bars and channels with l–3m of relief are preserved on terraces on the order of 105 yr old. Scarps related to the formation of terraces of this age are well preserved and have slopes of about 6–8 degrees where the scarp height is about 5 m. The preservation of fluvial landforms and scarps suggests that, if fault scarps comparable to these features were commonly formed by earthquakes in low relief areas of the eastern United States, many should be recognizable.