cssi/SciSciGPT-SciSciNet huggingface dataset:
Nanoparticles for plant disease management

Abstract Engineered nanoparticles (NPs) (1–100 nm) that have demonstrated activity in suppressing plant diseases are metalloids, metallic oxides, nonmetals, and carbon nanomaterials. NPs have been integrated into disease management strategies as bactericides/fungicides and as nanofertilizers to enhance plant health. Although there are reports of over 18 different NPs of single element and carbon nanomaterials affecting disease and/or plant pathogens, only Ag, Cu, and Zn have received much attention thus far. Some NPs act directly as antimicrobial agents while others function more in altering the nutritional status of the host and thus activate defense mechanisms. For example, NPs of Ag and Cu can be directly toxic to microorganisms. Other NPs of B, Cu, Mn, Si, and Zn appear to function in host defense as fertilizers. As demand for food production increases against a warming climate, nanoparticles will play a role in mitigating the new challenges in disease management resulting in a reduction in active metals and other chemical inputs.
Contact Zones and Their New Monstrosities

In this concluding chapter, the author revisits the idea of reclaimed monstrosity, connecting it with the image of the migrant as a monster (as invader) and with the viewing of different products of migration as dangerous. Eljaiek-Rodriguez highlights this discussion as crucial to understanding contemporary political landscapes where the fear of foreigners has a prominent place. The author discusses ways in which the highly localized can, in contrast, ultimately cease to produce fear in those outside the local cultures who cannot surmount the seeming “foreignness” of the horror.
Structure-Activity Relationships of Central Nervous System Penetration by Fatty Acid Amide Hydrolase (FAAH)-Targeted Thyromimetic Prodrugs

Thyroid hormone (TH) action is of clinical interest in treating demyelinating diseases of the central nervous system (CNS). Two amide prodrugs of sobetirome, a potent thyroid hormone agonist, were previously shown to significantly improve CNS selective distribution of the parent drug through hydrolysis in the CNS by fatty acid amide hydrolase (FAAH). This concept is elaborated upon here with a series of 29 amide prodrugs targeting FAAH. We identify that conservative aliphatic modifications such as the N-methyl (4), N-ethyl (5), N-fluoroethyl (15), and N-cyclopropyl (18) substantially favor selective CNS distribution of the parent drug in mice. Additionally, lead compounds exhibit moderate to good rates of hydrolysis at FAAH in vitro suggesting both enzymatic and physicochemical properties are important parameters for optimization. Both 4 and 15 were orally bioavailable while retaining appreciable CNS parent drug delivery following an oral dose. The pharmacokinetic parameters of 4 over 24 h postdose (i.v. and p.o.) were determined.
Beyond Econometrics: A Roadmap Towards Financial Machine Learning

One of the most exciting recent developments in financial research is the availability of new administrative, private sector and micro-level datasets that did not exist a few years ago. The unstructured nature of many of these observations, along with the complexity of the phenomena they measure, means that many of these datasets are beyond the grasp of econometric analysis. Machine learning (ML) techniques offer the numerical power and functional flexibility needed to identify complex patterns in a high-dimensional space. However, ML is often perceived as a black box, in contrast with the transparency of econometric approaches. This article demonstrates that each analytical step of the econometric process has a homologous step in ML analyses. By clearly stating this correspondence, our goal is to facilitate and reconcile the adoption of ML techniques among econometricians.
Exploring the influence of neighborhood walkability on the frequency of use of greenspace

Abstract The use of greenspace has been linked to multiple wellbeing benefits, however there are many factors that influence whether or not residents visit greenspace. In this study, we explore the factors that influence the frequency of greenspace visitation, with a focus on perceptions of walkability, travel mode, and proximity to greenspace. We use a questionnaire to capture perceptions and behaviors of residents (N = 309) and greenspace users (N = 103) in Tucson, Arizona. We estimated binary logistic regression models to identify predictors of daily, weekly, monthly, and yearly visits to greenspace. Results suggest that perceptions of walkability, along with mode of travel, and proximity to greenspace are associated with the frequency of use of greenspace. Walkability elements that were found to influence the probability of greenspace visitation include perceptions of traffic safety (pedestrian and biking infrastructure), surveillance (the extent to which people inside buildings can see pedestrians on the street), and community (spaces that allow social interaction). This study provides empirical evidence to support policies that will improve walkability in neighborhoods so that public health goals of increasing physical activity and wellbeing are achieved.
Scaling laws for the propulsive performance of three-dimensional pitching propulsors - ADDENDUM

Scaling laws for the thrust production and energetics of self-propelled or fixed-velocity three-dimensional rigid propulsors undergoing pitching motions are presented. The scaling relations extend the two-dimensional scaling laws presented in Moored & Quinn (AIAA J., 2018, pp. 1–15) by accounting for the added mass of a finite-span propulsor, the downwash/upwash effects from the trailing vortex system of a propulsor and the elliptical topology of shedding trailing-edge vortices. The novel three-dimensional scaling laws are validated with self-propelled inviscid simulations and fixed-velocity experiments over a range of reduced frequencies, Strouhal numbers and aspect ratios relevant to bio-inspired propulsion. The scaling laws elucidate the dominant flow physics behind the thrust production and energetics of pitching bio-propulsors, and they provide guidance for the design of bio-inspired propulsive systems.
The use of high-dose cervical spinal cord stimulation in the treatment of chronic upper extremity and neck pain

Background Dorsal column spinal cord stimulation is used for the treatment of chronic neuropathic pain of the axial spine and extremities. Recently, high-dose (HD) thoracic dorsal column stimulation for paresthesias has been successful. This study evaluates the utility of HD stimulation in the cervical spine for managing upper neck and upper extremity pain and paresthesias. Methods Three patients suffering from cervical and upper extremity chronic pain were assessed. Each underwent a two-stage process that included a trial period, followed by permanent stimulator implantation. Therapy included the latest HD stimulation settings including a pulse width of 90 μs, a frequency setting of 1000 Hz, and an amplitude range of 1.5 amps-2.0 amps. Pain relief was measured utilizing relative percent pain improvement as self-reported by each patient before and after surgery. Results After permanent implantation, (range 15-21 months), all three patients continued to experience persistent pain and paresthesia relief (70%-90%). Conclusions In three patients, HD cervical spinal cord stimulation successfully controlled upper extremity chronic pain/paresthesias.
Gendered Embodiment of the Ethnographer during Fieldwork in a Conflict Region of India

Militarization and various forms of state repression are continuous factors shaping daily life and practices in Manipur. Within this context my paper grapples with the impossibility of preparing fo...
Major Components of Preimplantation Genetic Testing

Preimplantation genetic testing (PGT) is now an established clinical option in reproductive medicine. One of the main components of PGT is obtaining biopsy material from oocytes and embryos, which may be obtained from three major sources: (1) matured oocytes from which the first and second polar body (PB1 and PB2) are removed; (2) eight-cell cleavage-stage embryo, from which a single blastomere is removed; and (3) blastocyst-stage embryo, from which 5–10 cells are removed. The main emphasis in this section is on the blastocyst biopsy procedure, which is presently a standard, with a few original developments in the methods described in detail.
Abstract LB-399: Late interferon-gamma blockade improves antitumor efficacy of anti-CTLA-4 and anti-PD-1 combination treatment

The FDA has approved the use of immune checkpoint blockade antibodies targeting cytotoxic T-lymphocyte antigen-4 (CTLA-4) and programmed cell death-1 (PD-1) for cancer. Patients with metastatic melanoma that receive anti-CTLA-4 have a 22% 10-year overall survival rate, while those treated with anti-PD-1 have a 34% 5-year overall survival rate. The combination treatment of both mediates a 64% overall survival rate. Current literature suggests interferon signaling mediates the expression of inhibitory receptors such as programmed death-ligand 1 (PD-L1) in tumor microenvironment that may affect the responseivness to immunotherapy. However, the role of interferon signaling network throughout the timecourse of treatment remains unclear. In the B16F10 melanoma model, we first show that activated T-cells in combination treated mice produce more interferon-gamma (IFN-gamma) than naive controls. Then, we have injected mice with anti-IFN-gamma antibody when 1) mice are first treated with combination CTLA-4/PD-1 blockade (early time point) and 2) the combination treatment is finished (late time point). We demonstrated that blocking IFN-gamma at the early time point compromises the antitumor efficacy of the combination treatment. In contrast, the antitumor efficacy of the combination treatment is improved and the expression of inducible co-stimulator (ICOS) on CD8 T-cells is increased if IFN-gamma is blocked at the late time point. Additionally, we found that the expression of PD-L1 in the tumor microenvironment is significantly reduced by IFN-gamma blockade at the late time point. Thus, we treated mice with anti-PD-L1 blocking antibody at the late time point and its antitumor tumor efficacy is similar to the mice treated with anti-IFN-gamma. It suggests that the improved antitumor efficacy of IFN-gamma blockade at the late time point in combination-treated mice is PD-L1 dependent. Collectively, we show that IFN-gamma has a complex and differential role throughout the time course of immunotherapy treatments, and this work suggests a potential combination treatment strategy with checkpoint blockade and late IFN-gamma blockade. Citation Format: Stephen Mok, Renee Chin, James P. Allison. Late interferon-gamma blockade improves antitumor efficacy of anti-CTLA-4 and anti-PD-1 combination treatment [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-399.
Prevalence of and Risk Factors for Emergency Department Visits Following Outpatient Gynecologic Surgery

Study Objective We aimed to identify the prevalence of emergency department (ED) visits following outpatient gynecologic surgery. Additionally, we aimed to identify patients at highest risk for ED visits. Design Retrospective cohort study. Setting Academic medical center. Patients or Participants Women (n=2,373) age 18 and older who underwent scheduled outpatient gynecologic surgery for a benign indication between November 2017 and September 2019. Interventions Any gynecologic surgery performed for benign indications. Measurements and Main Results We extracted demographic, clinical, and perioperative characteristics from the medical record. The primary outcome was evaluation at our institution's ED within 30 days of surgery. Patients who visited the ED, as compared to those who did not, were younger (median age 37 vs. 42, p=.02) and were more likely to have a history of abdominal surgery (67% vs. 56%, p=.02) or cardiopulmonary comorbidity (53% vs. 40%, p=.007). Additionally, patients who underwent intra-abdominal as opposed to vulvovaginal surgery (50% vs. 44%, p=.04) or who experienced a postoperative complication (9% vs 4%, p=.005) were more likely to visit the ED. A total of 109 (5%) patients visited our institution's emergency room 125 times within thirty days of surgery. Forty-five (36%) ED visits resulted in admission. When adjusted for ASA class, chronic pain comorbidities, procedure performed, operative time, blood loss, and attendance at a postoperative clinic visit, the following factors were associated with significantly increased or decreased odds of visiting the emergency room in multivariate analysis: increasing age (aOR 0.5; 95% CI 0.3-0.7), cardiopulmonary comorbidities (aOR 1.9; 95% CI 1.2-3.0), and undergoing prolapse surgery as opposed to other non-hysterectomy vulvovaginal procedures (aOR 0.2; 95% CI 0.1-0.6). Conclusion Emergency department visits were uncommon after outpatient gynecologic surgery but approximately one third resulted in admission. Increased counseling of younger patients and optimization of cardiopulmonary comorbidities may help reduce this burden.
Physically active learning in preschoolers: Improved self-regulation, comparable quantity estimation.

Abstract Background Providing physical activity during the school day may mitigate increasingly sedentary lifestyles among children. Young children may be susceptible to interference during learning and consolidation when performing physical activity concurrently with academic instruction. Methods Preschoolers (N = 72, mean age 5.1 ± 0.8 years, 50% female) completed a quantity estimation task before, following, and one week after engaging in either a 20-min physically active or sedentary lesson. Physical activity intensity and volume were measured using heart rate and pedometer step counts, respectively. Off-task behavior was recorded prior to and following the lesson. Results Children exhibited similar learning and retention, but an added benefit of physically active lessons was a 1900% step increase and a 58% reduction in off-task behavior. Conclusion Providing physically active lessons instead of sitting for extended periods of time in early childhood classrooms reduces sedentary behavior and improves self-regulation while not interfering with educational outcomes.
Nobody Wants to Be Narcan'd: A Pilot Qualitative Analysis of Drug Users' Perspectives on Naloxone.

Introduction Bystander naloxone distribution is an important component of public health initiatives to decrease opioid-related deaths. While there is evidence supporting naloxone distribution programs, the effects of increasing naloxone availability on the behavior of people who use drugs have not been adequately delineated. In this study we sought to 1) evaluate whether individuals' drug use patterns have changed due to naloxone availability; and 2) explore individuals' knowledge of, access to, experiences with, and perceptions of naloxone. Methods We conducted a pilot study of adults presenting to the emergency department whose medical history included non-medical opioid use. Semi-structured interviews were conducted with participants and thematic analysis was used to code and analyze interview transcripts. Results Ten participants completed the study. All were aware of naloxone by brand name (Narcan) and had been trained in its use, and all but one had either currently or previously possessed a kit. Barriers to naloxone administration included fear of legal repercussions, not having it available, and a desire to avoid interrupting another user's "high." Of the eight participants who reported being revived with naloxone at least once during their lifetime, all described experiencing a noxious physical response and expressed a desire to avoid receiving it again. Furthermore, participants did not report increasing their use of opioids when naloxone was available. Conclusions Participants were accepting of and knowledgeable about naloxone, and were willing to administer naloxone to save a life. Participants tended to use opioids more cautiously when naloxone was present due to fears of experiencing precipitated withdrawal. This study provides preliminary evidence countering the unsubstantiated narrative that increased naloxone availability begets more high-risk opioid use and further supports increasing naloxone access.
The Relationship Between First-Year Learning Communities and Academic Performance in Introductory Psychology and Sociology:

Objective:How do learning communities influence academic performance in Introductory Psychology?Method:The present research examines the relationship between participation in first-year students le...
PhaseCamouflage: Leveraging Adiabatic Operation to Thwart Reverse Engineering

This article focuses on thwarting reverse-engineering attacks and intellectual property (IP) theft by leveraging charge-recycling adiabatic circuits. The adiabatic circuit operation has recently received attention for the Internet-of-Things (IoT) applications due to high energy efficiency and enhanced security characteristics. Such applications typically consist of resource-constrained designs and are often deployed in the field, making them particularly vulnerable to malicious attacks. PhaseCamouflage is a circuit obfuscation technique that leverages the inherent phase differences (PDs) in power supply voltage of adiabatic logic gates and exhibits strong resistance against structural/removal attacks. The proposed method relies on inserting camouflaged PDs in the power supply voltage of subsequent logic gates while still producing a functional netlist. PhaseCamouflage is a unique logic obfuscation technique with low overhead, particularly applicable to pervasive computing applications where both efficiency and security are of primary concern.
Predictors of the Pressor Response to the Norepinephrine Transporter Inhibitor, Atomoxetine, in Neurogenic Orthostatic Hypotension

We previously reported that the norepinephrine transporter inhibitor, atomoxetine, improved standing blood pressure and lightheadedness in patients with neurogenic orthostatic hypotension (nOH). The purpose of the present study was to determine the predictors of the pressor response to atomoxetine. Patients with nOH who participated in the clinical trials (https://www.clinicaltrials.gov; Unique identifiers: NCT00223691 and NCT01316666) were included in this retrospective analysis. All subjects underwent autonomic function testing, plasma norepinephrine, systolic, diastolic blood pressure, and symptoms assessments, whereas seated and standing, before, and 60 minutes after a single dose of atomoxetine 18 mg. A subset of 25 patients underwent iodine-123-labeled metaiodobenzylguanidine scanning to estimate the degree of cardiac sympathetic denervation. A total of 99 subjects with nOH (67±9 years old, 40 women) participated in the study, 35 with multiple system atrophy, 52 with pure autonomic failure, and 12 with Parkinson disease. The average orthostatic decrease in their systolic blood pressure/diastolic blood pressure was -52±26/-22±15 mm Hg. Supine plasma norepinephrine levels predicted the standing systolic blood pressure (adjusted R2 was 0.12, F [3,80]=4.66, P=0.007) and diastolic blood pressure (adjusted R2 was 0.18, F [3, 80]=7.04, P=0.001) in response to atomoxetine. The increase in systolic blood pressure after atomoxetine was associated with the decrease in nOH-related symptoms (R2=0.14, F [1,44]=8.16 P=0.007). In conclusion, plasma norepinephrine was modestly associated with the pressor response to atomoxetine in patients with nOH. Additionally, the improvement in nOH-related symptoms was associated with the increase in the pressor response to atomoxetine.
Double trouble? Associations of parental substance use and eating behaviors with pediatric disordered eating

Abstract Objective Comorbidity between substance use disorders and eating disorders is common and related to severity of psychopathology. Parents’ eating disorder or substance use disorder have been examined independently and appear to be related to psychopathology in their children. However, no prior work has examined whether co-occurring substance use and eating disorder behaviors in parents relate to eating-disorder psychopathology and weight in their children. Method Participants (N = 435) were parents who completed an online cross-sectional survey. Parents reported their personal substance use and eating-disorder behaviors. Relationships between parental substance use (SUD), parental binge eating (ED), and co-occurring parental substance use and binge eating (SUDxED) with child eating-disorder psychopathology and weight were examined using linear regression. Parent age and sex, child age and sex, parent impulsivity and parent depression scores were included as covariates in analyses. Results Greater severity of co-occurring parental SUDxED behavior was associated with greater child eating-related psychopathology, including child binge eating and child purging. Additionally, greater parental binge eating (ED) alone was associated with greater child binge eating and overeating. Parental SUD and/or ED behavior were not related to child weight. Child age did not moderate relationships between parent SUDxED behaviors and child binge eating or overeating. Discussion Overall, parents with greater co-occurring substance use and eating disorder behaviors had children with more severe eating-disorder psychopathology. Clinicians working with families, and those seeking to prevent pediatric eating-related problems, should consider assessing and addressing parents’ psychopathology to improve prevention and treatment efforts.
Analysis of Single Surface Multipactor Discharge in the Frequency Domain

This work presents the frequency domain analysis of multipactor discharge on a dielectric surface with rf electric fields of single or two carrier frequencies, by using a one-dimensional multiparticle Monte Carlo (MC) simulator with adaptive time steps. The study shows that the single tone rf operation produces a normal electric field to the dielectric surface consisting of pronounced even harmonics of the driving rf frequency. The strength of a harmonic component is a function of the incident rf amplitude. For dual tone operation, the amplitude spectrum of the normal electric field reveals spectral peaks at various frequencies of intermodulation products of the rf carrier frequencies. Empirical equations are proposed to approximate the temporal profiles of the normal electric field in terms of its frequency components, for rf operation with either single or two carrier frequencies.
Minimizing Costs—Negative Dynamic Programming

This chapter focuses on the negative dynamic programming. The theoretical result for negative dynamic programs is that the policy determined by the optimality equation is optimal. A countable state space and a finite action space were assumed in the chapter. The chapter discusses optimal stopping problems. When in state i , the decision maker can either elect to stop, in which case he receives R( i ) and the problem terminates or to pay C( i ) and continue. If the decision is made to continue, the next state will be j with probability P ij . It is supposed that both the continuation costs C( i ) and the termination rewards R( i ) are nonnegative. If the process goes to state when the stopping action is chosen, then this is a two-action decision process. This decision process does not fit the framework of negative dynamic programming because it is not true that all costs are nonnegative. The chapter explains certain conditions to transform the process into one that does fit the necessary characteristics of negative dynamic programming.
Textured image segmentation: returning multiple solutions

Abstract Traditionally, the goal of image segmentation has been to produce a single partition of an image. This partition is compared to some `ground truth', or human approved partition, to evaluate the performance of the algorithm. This paper utilizes a framework for considering a range of possible partitions of the image to compute a probability distribution on the space of possible partitions of the image. This is an important distinction from the traditional model of segmentation, and has many implications in the integration of segmentation and recognition research. The probabilistic framework that enables us to return a confidence measure on each result also allows us to discard from consideration entire classes of results due to their low cumulative probability. The distributions thus returned may be passed to higher-level algorithms to better enable them to interpret the segmentation results. Several experimental results are presented using Markov random fields as texture models to generate distributions of segments and segmentations on textured images. Both simple homogeneous images and natural scenes are presented.
Adenylate cyclase system of human skeletal muscle

Abstract Human skeletal muscle plasmalemmal adenylate cyclase activation by catecholamines and guanyl nucleotides was investigated. The enzyme was selectively stimulated by different β-adrenergic catecholamines. Their order of potency was isoproterenol > epinephrine > norepinephrine. Phenylephrine, an α-adrenergic agonist, showed no effect. Stimulation of enzyme by β-agonists was stereospecific as (−)-isomers of isoproterenol and epinephrine were at least two orders of magnitude more potent than their corresponding (+)-isomers. The β-adrenergic blocking agents, propranolol and alprenolol, completely abolished the stimulation of adenylate cyclase by (−)-isoproterenol. Inhibition by β-blockers was also stereospecific, (−)-isomers being more effective inhibitors than their corresponding (+)-isomers. This selectivity and stereospecificity suggests that the human plasmalemmal adenylate cyclase is closely associated with the β-adrenergic receptors. Purine nucleotides, particularly GTP and to a lesser extent ITP, further enhanced the catecholamine-sensitive, but not the basal, adenylate cyclase. Pyrimidine nucleotides, UTP and CTP, were without any effect on the enzyme activity. Of the guanosine compounds tested only GTP, and to a lesser extent GDP, enhanced the enzyme activity in the presence of (−)-isoproterenol, while guanosine, GMP and cyclic GMP were ineffective. 5′-Guanylyl imidodiphosphate (GMP-PNP), a non-phosphorylating analog of GTP, was a more profound activator of catecholamine-sensitive adenylate cyclase than GTP. In contrast to GTP, GMP-PNP stimulated the basal enzyme activity. The plasmalemmal adenylate cyclase showed greater affinity towards GTP ( K m 3·10 −7 M) than towards GMP-PNP ( K m 2·10 −6 M). Profound augmentation by GTP and GMP-PNP of plasmalemmal adenylate cyclase in the presence of (−)-isoproterenol appeared to be a function of the β-adrenergic receptor because propranolol completely abolished their effects; GTP competitively inhibited that marked augmentation caused by GMP-PNP, suggesting that both nucleotides interact at similar sites on the enzyme system. Kinetic studies revealed that the predominant effect of guanyl nucleotides was to enhance the catalytic activity of the enzyme without altering its affinity for ATP, (−)-isoproterenol or Mg 2+ . It is concluded that the human plasmalemmal adenylate cyclase is closely associated with the β-adrenergic receptor and that the guanyl nucleotides are potent regulators of the plasmalemmal enzyme.
“Micro” versus “small” family businesses: a multinational analysis

Purpose – The purpose of this paper is to compare “micro” enterprise (0-9 employees) to “small” enterprise (10-49 employees) family businesses with regard to 12 important managerial characteristics in eight countries: Argentina, Croatia, Egypt, France, Kosovo, Kuwait, Serbia, and the USA (n=601). Design/methodology/approach – The research methodology was survey research. To statistical test 12 hypotheses, MANCOVA was run to compare differences between micro and small family business, while controlling for years in business. Findings – Six significant differences were: “small” firms are more likely to employ non-family member managers, are more likely to engage in the formulation of succession plans, are more likely to utilize outside advisory services, make greater use of sophisticated financial management methods, and have a more formal management style than “micro” firms; but the influence of the founder is greater in “micro” firms. Practical implications – For practitioners and consultants the findings...
Large Occlusion Stereo

A method for solving the stereo matching problem in the presence of large occlusion is presented. A data structure—the disparity space image—is defined to facilitate the description of the effects of occlusion on the stereo matching process and in particular on dynamic programming (DP) solutions that find matches and occlusions simultaneously. We significantly improve upon existing DP stereo matching methods by showing that while some cost must be assigned to unmatched pixels, sensitivity to occlusion-cost and algorithmic complexity can be significantly reduced when highly-reliable matches, or ground control points, are incorporated into the matching process. The use of ground control points eliminates both the need for biasing the process towards a smooth solution and the task of selecting critical prior probabilities describing image formation. Finally, we describe how the detection of intensity edges can be used to bias the recovered solution such that occlusion boundaries will tend to be proposed along such edges, reflecting the observation that occlusion boundaries usually cause intensity discontinuities.
Preliminary mass-balanced 3-D reconstructions of the Alps and surrounding areas during the miocene

The masses of sediment in the Molasse Basins of Switzerland, Germany and Austria total 0.299×1021 g. In the Neogene, other sediment shed north of the Alps went to the Rhine Graben (0.03×1021 g), and on to the northern European plains and North Sea (0.81×1021 g). During the Quaternary, the drainage systems were drastically reorganized, with the Danube capturing streams that drain the German and Austrian Alps, and delivering the sediment to the Pannonian Basin (0.15×1021 g) and on to the Black Sea (0.31×1021 g). Sediment shed to the west has entered the Bresse and Rhone Grabens (0.05×1021 g) and been deposited in the Rhone Delta (0.19×1021 g) and on the floor of the Gulf of Lions (0.24×1021 g). Sediment shed from the south side of the Alps resides in the Po Basin and Adriatic Sea that have total sediment masses of 0.38×1021 g and 0.36×1021 g respectively. Mass balanced reconstructions suggest that during the Chattian and Aquitanian (Late Oligocene-Early Miocene) thrusting in Switzerland, southern Germany and western Austria (Vorarlberg-Tyrol) resulted in mountains of Himalayan height, with elevations up to 7 km. Erosion attacked these mountains, existing sediments in the Molasse basins alone are equivalent to a layer 0.5 km thick, but represent only a fraction of the material originally deposited in them. Sediments equivalent to another 1.7 km thickness occur in the more peripheral basins. Sediment supply was greatly reduced in the middle Early Miocene (Burdigalian) indicating that the elevation of the mountains had decreased more rapidly than can be explained by erosion alone, which, after isostatic adjustment would have reduced the elevations only to about 5 km. The loss of elevation might have been due to a slow (ca. 1 my) flexural response to the narrow load on the southern edge of the European continental block, or to physical collapse of the mountains.
Spatial Receptive Fields of Primary Auditory Cortical Neurons in Quiet and in the Presence of Continuous Background Noise

Spatial receptive fields of primary auditory (AI) neurons were studied by delivering, binaurally, synthesized virtual-space signals via earphones to cats under barbiturate anesthesia. Signals were broadband or narrowband transients presented in quiet anechoic space or in acoustic space filled with uncorrelated continuous broadband noise. In the absence of background noise, AI virtual space receptive fields (VSRFs) are typically large, representing a quadrant or more of acoustic space. Within the receptive field, onset latency and firing strength form functional gradients. We hypothesized earlier that functional gradients in the receptive field provide information about sound-source direction. Previous studies indicated that spatial gradients could remain relatively constant across changes in signal intensity. In the current experiments we tested the hypothesis that directional sensitivity to a transient signal, as reflected in the gradient structure of VSRFs of AI neurons, is also retained in the presence of a continuous background noise. When background noise was introduced three major affects on VSRFs were observed. 1) The size of the VSRF was reduced, accompanied by a reduction of firing strength and lengthening of response latency for signals at an acoustic axis and on-lines of constant azimuth and elevation passing through the acoustic axis. These effects were monotonically related to the intensity of the background noise over a noise intensity range of approximately 30 dB. 2) The noise intensity-dependent changes in VSRFs were mirrored by the changes that occurred when the signal intensity was changed in signal-alone conditions. Thus adding background noise was equivalent to a shift in the threshold of a directional signal, and this shift was seen across the spatial receptive field. 3) The spatial gradients of response strength and latency remained evident over the range of background noise intensity that reduced spike count and lengthened onset latency. Those gradients along the azimuth that spanned the frontal midline tended to remain constant in slope and position in the face of increasing intensity of background noise. These findings are consistent with our hypothesis that, under background noise conditions, information that underlies directional acuity and accuracy is retained within the spatial receptive fields of an ensemble of AI neurons.
Vertebrate Agmatinases: What Role Do They Play in Agmatine Catabolism?

Whereas agmatine in vertebrates may be derived from multiple sources such as the diet, endogenous synthesis via arginine decarboxylase, and possibly also from enteric bacteria, agmatinase is the only enzyme specific for agmatine catabolism. As it hydrolyzes a guanidino group within agmatine and also contains signature amino acid residues that act as ligand binding sites for the Mn(++) cofactor, agmatinase is classified as a member of the arginase superfamily. Very little information is available regarding how much agmatine in vertebrate species is catabolized by agmatinase versus other enzymes such as diamine and amine oxidases. Moreover, comparisons of primary sequences of several vertebrate agmatinases demonstrate that several residues essential for catalytic activity are not conserved in the mouse. This leads to the prediction that the agmatinase protein in mouse has little or no catalytic activity, not only raising questions about the physiologic routes of agmatine disposal in this organism, but also suggesting the existence of species-specific differences in mechanisms for regulating agmatine levels.
Imaging three-dimensional rotational diffusion of plasmon resonant gold nanorods using polarization-sensitive optical coherence tomography

We demonstrate depth-resolved viscosity measurements within a single object using polarized optical scattering from ensembles of freely tumbling plasmon resonant gold nanorods (GNRs) monitored with polarization-sensitive optical coherence tomography. The rotational diffusion coefficient of the GNRs is shown to correlate with viscosity in molecular fluids according to the Stokes-Einstein relation. The plasmon resonant and highly anisotropic properties of GNRs are favorable for microrheological studies of nanoscale properties.
Age differences in reading time allocation for propositionally dense sentences.

Abstract Younger and older adults read and immediately recalled a set of sentences which varied in propositional density. Reading was self-paced and sentence reading time was measured. Older adults spent differentially more time reading the propositionally dense sentences, and although the overall recall performance of older adults was slightly poorer than that of younger adults, age differences were constant across propositional density. Consistent with the Slowing Hypothesis, an analysis of effective reading time (time spent per proposition recalled) demonstrated that older adults were spending proportionately more time to effectively encode the sentences. In addition, a relative memorability analysis (Stine & Wingfield, 1988, 1990a) suggested that the increase in propositional density did not particularly disrupt the organization of the text representation for older adults in this self-paced reading situation. This contrasts with earlier findings in a listening situation. These data provide support for...
General anesthesia research: aroused from a deep sleep?

A region of the hypothalamus that is critical in controlling sleep/wake states is now shown to mediate the sedative effects of anesthetics that act at the GABAA receptor.
Abstract 4843: Neutrophil elastase enhances adaptive immunity via increase of peptide presentation and downregulation of T cell inhibitory molecules

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Introduction: Neutrophil elastase (NE) is an inflammatory mediator that is taken up by breast cancer cells. We have previously shown that NE uptake increases susceptibility to lysis by cytotoxic T lymphocytes (CTL) targeting the tumor antigens PR1 and cyclin E. We investigated whether NE uptake alters adaptive immunity by affecting MHC class I antigen presentation and T cell inhibitory molecules. Methods: MDA-MB-231 breast cancer cells were maintained in standard media ± NE. Healthy donor HLA-A2+ peripheral blood mononuclear cells were used to generate antigen specific CTL by pulsing dendritic cells with E75, a HER2-derived epitope we are currently investigating as a vaccine in clinical trials. Calcein-AM cytotoxicity assays evaluated E75-specific lysis. Flow cytometry was used to show NE uptake, HLA-A2, pan-HLA class I (HLA-ABC) and PD-L1 surface expression. Western blot analysis was used to show total MHC class I heavy chain, B2M, LMP2, TAP1, calnexin and tapasin expression. Relative PD-L1 mRNA levels were determined using qPCR. Results: NE uptake enhanced tumor cell lysis by E75-specific CTL at all effector to target (E:T) ratios (lysis for 20 to 1 E:T ratio was 50% ± 7 for NE treated vs 28% ± 7 for untreated, p < 0.05), and led to an increase in HLA-A2 and HLA-ABC surface expression (p < 0.05; Table). However, NE uptake did not change total expression of MHC class I or components of the MHC class I pathway. Additionally, NE uptake led to a decrease in PD-L1 surface expression and transcript levels (p < 0.05; Table). Conclusion: NE increases tumor antigen presentation as well as MHC class I on the cell surface. However, NE uptake does not change total MHC class I expression or expression of MHC class I antigen processing components, suggesting that NE increases peptide availability as a mechanism of increased MHC class I antigen presentation. NE also leads to the downregulation of PD-L1. Together, our data indicate that NE uptake enhances adaptive immune responses. View this table: Citation Format: Akhil Chawla, Anne V. Philips, Na Qiao, Pariya Sukhumalchandra, Celine Kerros, Gheath Alatrash, Jeffrey J. Molldrem, Elizabeth A. Mittendorf. Neutrophil elastase enhances adaptive immunity via increase of peptide presentation and downregulation of T cell inhibitory molecules. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4843. doi:10.1158/1538-7445.AM2014-4843
Human low density lipoprotein receptor fragment. Successful refolding of a functionally active ligand-binding domain produced in Escherichia coli

The low density lipoprotein (LDL) receptor plays a key role in cholesterol homeostasis, mediating cellular uptake of lipoprotein particles by high affinity binding to its ligands, apolipoprotein (apo) B-100 and apoE. The ligand-binding domain of the LDL receptor contains 7 cysteine-rich repeats of approximately 40 amino acids; each repeat contains 6 cysteines, which form 3 intra-repeat disulfide bonds. As a first step toward determining the structure of the LDL receptor, both free and bound to its ligands, we produced in Escherichia coli a soluble fragment containing the ligand-binding domain (residues 1–292) as a thrombin-cleavable, heat-stable thioredoxin fusion. Modest amounts (5 mg/liter) of partially purified but inactive fragment were obtained after cell lysis, heat treatment, thrombin cleavage, and gel filtration under denaturing conditions. We were able to refold the receptor fragment to an active conformation with approximately 10% efficiency. The active fragment was isolated and purified with an LDL affinity column. The refolded receptor fragment was homogeneous, as determined by sodium dodecyl sulfate or non-denaturing polyacrylamide gel electrophoresis and isoelectric focusing. The purified fragment did not react with fluorescein-5-maleimide, indicating that all 42 cysteines were disulfide linked. In addition, the refolded fragment exhibited properties identical to those of the intact native receptor: Ca2+-dependent binding and isoform-dependent apoE binding (apoE2 binding
E-cadherin tethered to micropatterned supported lipid bilayers as a model for cell adhesion.

Cell−cell adhesion is a dynamic process requiring recruitment, binding, and reorganization of signaling proteins in the plane of the plasma membrane. Here, we describe a new system for investigating how this lateral mobility influences cadherin-based cell signaling. This model is based on tethering of a GPI-modified E-cadherin protein (hEFG) to a supported lipid bilayer. In this report, membrane microfluidics and micropatterning techniques are used to adopt this tethered protein system for studies with the anchorage-dependent cells. As directly formed from proteoliposomes, hEFG exhibits a diffusion coefficient of 0.6 ± 0.3 μm2/s and mobile fraction of 30−60%. Lateral structuring of the supported lipid bilayer is used to isolate mobile proteins from this mixed mobile/immobile population, and should be widely applicable to other proteins. MCF-7 cells seeded onto hEFG-containing bilayers recognize and cluster this protein, but do not exhibit cell spreading required for survival. By micropatterning small anch...
Fast watershed aided by target detection

The Watershed algorithm has been studied extensively, and has been applied to image segmentation due to its accuracy and robustness. However, the watershed requires a large amount of memory, and is computationally intractable for segmenting large images. In this paper, we introduce a novel hierarchical region-of-interest (ROI) detection scheme, which is used as a prelude to segmentation. With the help of the detection algorithm, watershed segmentation can be applied to the small detected regions, rather than to the entire image. Therefore, it can process large images by selectively segmenting ROIs. We focus on our new ROI detection algorithm, and how it is integrated into a system for large-image segmentation. We demonstrate the efficiency of the proposed scheme by processing a variety of images.
Analysis of deformation-induced surface morphologies in steel sheet

The surfaces of strained mild steel sheet specimens were examined with scanning laser confocal microscopy. Rigorous assessments were employed to establish the form of the roughness data. The small deviations from the ideal conditions observed in these assessments indicated that the stochastic process responsible for surface roughening does not conform to stationary, Gaussian, Markov statistics. As physical considerations make violations of the stationary and Markov properties unlikely, it was concluded that even small discrepancies in the Gaussian fit have substantial influences on the quality of roughening behavior characterizations. This also confirms that deformation-induced surface roughness occurs by a small number of statistically dominant mechanisms. Analyses of the mean amplitude (Rq) and spatial distributions both exhibited sharp changes in behavior at approximately 4% strain. Since the physical meanings of the two analyses are independent, it was concluded that this common behavior correlated with a change in dominant roughening mechanism.
Mixed-mode-I/II fracture of polytetrafluoroethylene

The current work deals with mixed-mode-I/II fracture in polytetrafluoroethylene (PTFE). Mode-I fracture in PTFE 7C has previously been shown to exhibit strong phase dependence with a brittle-to-ductile transition associated with the room temperature phase transitions. Increases in fracture toughness around room temperature and above result from the onset of stable fibril formation bridging the crack plane and increased plastic energy dissipation. Mixed-mode-I/II loading conditions are achieved using a modified compact tension specimen with Arcan type fixtures. The fracture toughness δVC of PTFE 7C exhibits a 42% decrease from pure mode-I to near mode-II loading due to a marked decrease in fibril formation.
Is it really a mismatch negativity? An assessment of methods for determining response validity in individual subjects

Abstract Mismatch negativity (MMN) responses were collected from 86 normal school-age children in response to synthesized speech syllables, /wa/ and two variants of /ba/. Waveform characteristics and statistical properties of the responses were analyzed across stimulus conditions in order to assess methods for determining response validity in individuals. Methods were compared using signal detection theory techniques. Criteria based on measurements of response area, onset latency, and duration were the best indicators of response validity. Also a promising indicator of validity was the interval of significance based on Z transformations determined by considering the variance of the underlying noise distribution. Correlations of individual responses with the grand average and integral calculations of the response negativity showed somewhat lower d′ values. Statistical methods which utilized response subaverages were the poorest indicators of response validity. Likely the methods are limited primarily by the signal to noise ratio of the MMN compared to the underlying physiologic noise. Improvement of the signal to noise ratio remains a significant factor in the interpretation of MMN for individual subjects.
Gender differences in regional brain response to visceral pressure in IBS patients.

In two experiments including a total of 30 irritable bowel syndrome patients, symptom-mimicking rectal pressure stimuli elicited changes in regional neural activation as measured by positron electron tomography (PET) cerebral blood flow images. Although most stimuli were not rated as painful, rectal pressure increased regional cerebral blood flow (rCBF) in areas commonly associated with somatic pain, including the anterior cingulate, insula, prefrontal cortex, thalamus, and cerebellum. Despite similar stimulus ratings in male and female patients, regional activations were much stronger for males. In both experiments, rectal pressure activated the insula bilaterally in males but not in females. Insula activation was associated most strongly with objective visceral pressure, whereas anterior cingulate activation was associated more with correlated ratings of subjective discomfort. The insula is discussed as a visceral sensory cortex. Several possible reasons for the insula gender effect are proposed.