cssi/SciSciGPT-SciSciNet huggingface dataset:
The role of intrinsic incentives and corporate culture in motivating innovation

Abstract This paper examines the optimal incentive scheme in motivating people to innovate under ambiguity. When an innovation’s prospects are ambiguous, the use of extrinsic, high-powered incentives can lead the agent’s beliefs about the project’s outcome to deviate from that of the principal’s, which consequently deters innovation. The deterrent effect, however, is alleviated for firms in which agents have strong intrinsic incentives to adhere to firms’ goals and missions. In equilibrium, extrinsic and intrinsic incentives are complementary, and firms that face greater uncertainty invest more in fostering intrinsic incentives. Hence, firms that pursue more exploratory and radical innovation invest more in creating corporate identity and culture.
Ransomware Detection Using Deep Learning in the SCADA System of Electric Vehicle Charging Station

The Supervisory control and data acquisition (SCADA) systems have been continuously leveraging the evolution of network architecture, communication protocols, next-generation communication techniques (5G, 6G, Wi-Fi 6), and the internet of things (IoT). However, SCADA system has become the most profitable and alluring target for ransomware attackers. This paper proposes the deep learning-based novel ransomware detection framework in the SCADA controlled electric vehicle charging station (EVCS) with the performance analysis of three deep learning algorithms, namely deep neural network (DNN), 1D convolution neural network (CNN), and long short-term memory (LSTM) recurrent neural network. All three-deep learning-based simulated frameworks achieve around 97% average accuracy (ACC), more than 98% of the average area under the curve (AUC) and an average F1-score under 10-fold stratified cross-validation with an average false alarm rate (FAR) less than 1.88%. Ransomware driven distributed denial of service (DDoS) attack tends to shift the state of charge (SOC) profile by exceeding the SOC control thresholds. Also, ransomware driven false data injection (FDI) attack has the potential to damage the entire BES or physical system by manipulating the SOC control thresholds. It's a design choice and optimization issue that a deep learning algorithm can deploy based on the tradeoffs between performance metrics.
Transitioning From Ideas to Action: Trends in the Enforcement of Soft Law for the Governance of Artificial Intelligence

As a governance tool, the advantages of soft law (e.g., lack of jurisdiction, minimal barriers of entry, and disposition for experimentation) make it a viable alternative to manage emerging technologies that are continuously evolving. A barrier to soft law’s utilization is its most cited weakness, a reliance on the alignment of incentives. Once an entity is convinced that the enforcement of soft law is in their interests, the next step is the creation of mechanisms to ensure that their ideas are transformed into action. This article explores trends in the use of mechanisms within soft law programs to govern methods and applications of artificial intelligence (AI). Using a database of over 600 AI soft law programs, this piece identifies the diverse array of options available to organizations in their efforts to implement and enforce their programs.
Evaluation of Complexity Measures for Deep Learning Generalization in Medical Image Analysis

The generalization error of deep learning models for medical image analysis often increases on images collected with different devices for data acquisition, device settings, or patient population. A better understanding of the generalization capacity on new images is crucial for clinicians' trustworthiness. Although significant efforts have been recently directed toward establishing generalization bounds and complexity measures, there is still a significant discrepancy between the predicted and actual generalization performance. As well, related large empirical studies have been primarily based on validation with general-purpose image datasets. This paper presents an empirical study that investigates the correlation between 25 complexity measures and the generalization abilities of deep learning classifiers for breast ultrasound images. The results indicate that PAC-Bayes flatness and path norm measures produce the most consistent explanation for the combination of models and data. We also report that multi-task classification and segmentation approach for breast images is conducive toward improved generalization.
Bayesian inverse uncertainty quantification of a MOOSE-based melt pool model for additive manufacturing using experimental data

Abstract Additive manufacturing (AM) technology is being increasingly adopted in a wide variety of application areas due to its ability to rapidly produce, prototype, and customize designs. AM techniques afford significant opportunities in regard to nuclear materials, including an accelerated fabrication process and reduced cost. High-fidelity modeling and simulation (M&S) of AM processes is being developed in Idaho National Laboratory (INL)’s Multiphysics Object-Oriented Simulation Environment (MOOSE) to support AM process optimization and provide a fundamental understanding of the various physical interactions involved. In this paper, we employ Bayesian inverse uncertainty quantification (UQ) to quantify the input uncertainties in a MOOSE-based melt pool model for AM. Inverse UQ is the process of inversely quantifying the input uncertainties while keeping model predictions consistent with the measurement data. The inverse UQ process takes into account uncertainties from the model, code, and data while simultaneously characterizing the uncertain distributions in the input parameters–rather than merely providing best-fit point estimates. We employ measurement data on melt pool geometry (lengths and depths) to quantify the uncertainties in several melt pool model parameters. Simulation results using the posterior uncertainties have shown improved agreement with experimental data, as compared to those using the prior nominal values. The resulting parameter uncertainties can be used to replace expert opinions in future uncertainty, sensitivity, and validation studies.
Multidisciplinary Design Optimization Approach to Integrated Space Mission Planning and Spacecraft Design

Space mission planning and spacecraft design are tightly coupled and need to be considered together for optimal performance; however, this integrated optimization problem results in a large-scale Mixed-Integer Nonlinear Programming (MINLP) problem, which is challenging to solve. In response to this challenge, this paper proposes a new solution approach to this MINLP problem by iterative solving a set of coupled subproblems via the augmented Lagrangian coordination approach following the philosophy of Multi-disciplinary Design Optimization (MDO). The proposed approach leverages the unique structure of the problem that enables its decomposition into a set of coupled subproblems of different types: a Mixed-Integer Quadratic Programming (MIQP) subproblem for mission planning and one or more Nonlinear Programming (NLP) subproblem(s) for spacecraft design. Since specialized MIQP or NLP solvers can be applied to each subproblem, the proposed approach can efficiently solve the otherwise intractable integrated MINLP problem. An automatic and effective method to find an initial solution for this iterative approach is also proposed so that the optimization can be performed without the need for a user-defined initial guess. In the demonstration case study, a human lunar exploration mission sequence is optimized with a subsystem-level parametric spacecraft design model. Compared to the state-of-the-art method, the proposed formulation can obtain a better solution with a shorter computational time even without parallelization. For larger problems, the proposed solution approach can also be easily parallelizable and thus is expected to be further advantageous and scalable.
Sampling on NISQ Devices: "Who’s the Fairest One of All?"

Modern NISQ devices are subject to a variety of biases and sources of noise that degrade the solution quality of computations carried out on these devices. A natural question that arises in the NISQ era, is how fairly do these devices sample ground state solutions. To this end, we run five fair sampling problems (each with at least three ground state solutions) that are based both on quantum annealing and on the Grover Mixer-QAOA algorithm for gate-based NISQ hardware. In particular, we use seven IBM Q devices, the Aspen-9 Rigetti device, the IonQ device, and three D-Wave quantum annealers.For each of the fair sampling problems, we measure the ground state probability, the relative fairness of the frequency of each ground state solution with respect to the other ground state solutions, and the aggregate error as given by each hardware provider. Overall, our results show that NISQ devices do not achieve fair sampling yet. We also observe differences in the software stack with a particular focus on compilation techniques that illustrate what work will still need to be done to achieve a seamless integration of frontend (i.e. quantum circuit description) and backend compilation.
Hormonal Regulation of Organic and Phosphoric Acid Release by Barley Aleurone Layers and Scutella.

The release of acid from the aleurone layer and scutellum of barley (Hordeum vulgare L. cv Himalaya) was investigated. Aleurone layers isolated from mature barley grains acidify the external medium by releasing organic and phosphoric acids. Gibberellic acid and abscisic acid stimulate acid release 2-fold over control tissue incubated in 10 mM CACl2. Gibberellic acid causes medium acidification by stimulating the release of phosphoric and citric acids, whereas abscisic acid stimulates the release of malic acid. The accumulation of these acids in the incubation medium buffers the medium against changes in pH, particularly between pH 4 and 5. The amounts of amino acids that accumulate in the medium are low (2–12 nmol/layer) compared to other organic and phosphoric acids (100–500 nmol/layer). The scutellum does not play a major role in medium acidification but participates in the uptake of organic acids. The organic acid composition of the starchy endosperm changes after 3 d of imbibition; malic, succinic, and lactic acids decrease, whereas citric and phosphoric acids remain unchanged or increase. These results indicate that during postgerminative growth, the acidity of the starchy endosperm is maintained by acid production by the aleurone layer.
Shrink-Wraps: Who Should Bear the Cost of Communicating Mass-Market Contract Terms?

The paper examines the equilibrium quality of mass market contract terms, such as those in end user license agreements, when consumers can read and search for a better set of terms. Firms compete over price and quality of the terms. They can also choose to disclose (speak) the terms to consumers at cost. While all consumers must incur positive search (reading) cost to understand the terms, not everyone cares about the terms equally and they can also buy without reading. The paper examines two legal regimes: one that imposes a duty to read on the consumers and the other that imposes a duty to speak (disclose) on the firms. While neither regime strictly dominates the other in terms of social welfare, the paper shows that (1) as the reading or speaking cost converges to zero, the social welfare continuously converges to the first best; (2) consumers will have different preferences over duty-to-speak and duty-to-read regimes; and (3) the quality of the terms of non-disclosing firms may be higher. The results are consistent with the current chasm among scholars and courts over mandatory disclosure policy and also with the recent empirical findings.
Rough Sets and Neural Networks Application to Handwritten Character Recognition by Complex Zernike Moments

The paper presents a hand-written character recognition by the data mining and knowledge discovery software system RoughNeuralLab. In recognition experiments the Zernike moments were applied as the extracted features of character images. For further feature reduction the rough set theory method was applied as a front end of neural network. Eventually the error backpropagation neural network classifiers were designed for the reduced feature subsets.
WTO’s Identity Crisis (reviewing Joost Pauwelyn, Conflict of Norms in Public International Law: How WTO Law Relates to Other Rules of International Law (2003))

Joost Pauwelyn has written an extensive and thought-provoking treatise on the interaction of norms in public international law (PIL), in particular between norms of World Trade Organization (WTO) and non-WTO norms, through a conceptual lens of "conflict." His main argument is non-WTO norms should be able to "trump" WTO norms under certain circumstances. After framing the concept of norm conflict in PIL (Chapter 1), and defining the nature of WTO law ("reciprocal" obligations) vis-a-vis that of other branches of PIL such as human rights and international environmental law ("integral" obligations) (Chapter 2), the book unfolds its conflict thesis, including hierarchy of sources (Chapter 3), two mutually exclusive modes of norm interaction, which are accumulation and conflict (Chapter 4), conflict avoidance (Chapter 5), and conflict resolution (Chapters 6 and 7). The final Chapter attempt to apply the conflict thesis developed in previous Chapters to the specific situation of WTO dispute settlement. This review will chiefly focus on the nature, or identity, of the WTO as it is described and defined by Pauwelyn when he addresses the norm conflict between WTO rules and non-WTO rules. The review concludes that Pauwelyn's thesis of conflict resolution risks weakening the WTO system through encroaching upon the WTO's identity.
Inviscid Model of Two-Dimensional Vortex Shedding by a Circular Cylinder

A discrete vortex model based on potential flow and boundary-layer interaction, rediscretization of shear layers, and circulation dissipation is developed to determine the characteristics of an impulsively started flow about a circular cylinder. The evolution of the flow from the start to very large times, lift and drag forces, Strouhal number, oscillations of the separation and stagnation points, and the vortex-street characteristics are calculated and compared with experiments. b CD CL Cpb c D fv h / j m N n q Re St s ds t At U u v w z F 7 6 X v p Nomenclature = longitudinal spacing of vortices = drag coefficient = lift coefficient = base pressure coefficient = radius of the cylinder - diameter of the cylinder ,D = 2c = vortex shedding frequency = transverse spacing of vortices = an index = distance to nascent vortex from cylinder = number of vortices on a sheet = an index = total velocity at a point = Reynolds number, UD/v = Strouhal number, fvD/ U = distance along a sheet = point vortex spacing = time or Ut/c for U= 1 and c = 1 - numerical step size = velocity of the ambient flow = x component of velocity -y component of velocity = complex velocity potential = complex variable = circulation = circulation per unit length = angle measured from ( - c,0) = dissipation parameter = kinematic viscosity of fluid = density of fluid = vorticity
Bidirectional Estimators for Light Transport

Most of the research on the global illumination problem in computer graphics has been concentrated on finite-element (radiosity) techniques. Monte Carlo methods are an intriguing alternative which are attractive for their ability to handle very general scene descriptions without the need for meshing. In this paper we study techniques for reducing the sampling noise inherent in pure Monte Carlo approaches to global illumination. Every light energy transport path from a light source to the eye can be generated in a number of different ways, according to how we partition the path into an initial portion traced from a light source, and a final portion traced from the eye. Each partitioning gives us a different unbiased estimator, but some partitionings give estimators with much lower variance than others. We give examples of this phenomenon and describe its significance. We also present work in progress on the problem of combining these multiple estimators to achieve near-optimal variance, with the goal of producing images with less noise for a given number of samples.
The Continuing Incidence of Natural Decrease in American Counties

In 2002, more American counties (985) experienced natural decrease than at any time in the nation's history. The incidence of natural decrease has diminished since then, but remains near record levels. It is most common in rural areas remote from metropolitan centers. Spatial concentrations exist in the Great Plains, Corn Belt, and East Texas, with scattered pockets in the Ozark-Ouachita Uplands, Upper Great Lakes, and Florida. A multivariate spatial-error regression model demonstrates that natural decrease is a consequence of the complex interaction between fertility, mortality, and migration over a protracted period and is symptomatic of fundamental changes in the demographic structure of an area. Age-structure changes resulting from protracted, age-specific migration are a primary cause of natural decrease. Temporal variations in fertility also have a significant impact, but counties experiencing natural decrease do not have fertility levels below the national average. Language: en
Transesophageal echocardiography using cypress-miniaturized echocardiogram unit: initial clinical experience.

Transesophageal echocardiography (TEE) was introduced clinically in the United States in 1987. Recent technologic advances have resulted in the creation of a small portable hand-carried ultrasound (HCU) device that can be easily carried throughout the hospital with greater flexibility for cardiac imaging. These HCU devices have harmonic, color, and spectral Doppler (continuous/pulsed wave). Siemens Medical Solutions USA, Inc. has incorporated a TEE connector, which connects to its Cypress (highly miniaturized echocardiogram unit) and allows the performance of a TEE with this unit, which is mildly heavier than a typical HCU. We describe our initial clinical experience with this unit. The image quality is comparable to routine TEEs, with the advantages of shorter duration, portability, affordable cost, avoiding the use of high-end machine from the echo lab, availability of non-HCU units for other studies, and preventing the need for an echo technician to be involved in the procedure. (ECHOCARDIOGRAPHY, Volume 22, November 2005)
SPARC participates in the branching morphogenesis of developing fetal rat lung.

Adhesion of cells to components of the extracellular matrix has been shown to be critical in normal lung development, particularly during the pseudoglandular stage, when conducting airways are forming through a process of branching morphogenesis. Expression of factors that inhibit cellular adhesion might also modulate branching morphogenesis. SPARC is a secreted glycoprotein that exhibits antiadhesive effects on cultured cells and is widely expressed in embryonic tissues. In this report, we examine the distribution of SPARC in fetal rat lung during development and its effect on the process of branching morphogenesis. Immunohistochemistry and in situ hybridization studies revealed that SPARC was present in the airway epithelial cells during the pseudoglandular stage of lung development, and in blood vessels and smooth muscle cells associated with airways during the canalicular and saccular stages of development. We used an in vitro model of rat lung branching morphogenesis to examine airway branching in th...
Highly Fluorinated Poly(arylene ether ketone) Prepared by a CaH2-Mediated Polycondensation Reaction

A new reaction procedure has been developed for the polycondensation of hexafluorobisphenol A (6F-BPA) with bis(pentafluorophenyl) ketone (BPK) in dimethylacetamide (DMAc). In this reaction, CaH 2 has been used as a base to facilitate the formation of the phenolate; an alkali metal fluoride was used as a catalyst. Unlike the conventional poly-condensation reactions, this procedure avoided producing water during the reaction, and hence, azeotropic distillation with the assistant of a low-polar co-solvent is not required. This improvement maintains the high polarity of the reaction medium; consequently, the selectivity of the reaction at the para-position of BPK is significantly enhanced and polymers with high molecular weights (M n ca. 30 000 Da) can be obtained with very low branching contents (less than 3 mol-%) and free of any cross-linked gel particles. In addition to avoiding the formation of water in the reaction, the use of CaH 2 also reduced the concentration of the fluoride ion in the solution. These effects minimize chain degradation reactions such as hydrolysis. The use of CaO instead of CaH 2 for this reactionproduces similar effects. In the case of CaO, traces of water can be introduced into the reaction. The presence of trace amounts of water increases the polycondensation rate, probably due to the enhanced ionization of the phenolate. However, it also causes a hydrolysis of polymer chains, resulting in the elimination of the ketone group in the polymer backbone. Fortunately, this side reaction is highly water and temperature dependent, and can be efficiently prevented by using CaH 2 or conducting the reaction at a lower temperature (<65°C).
Modified troponin I as a candidate marker for chronic heart failure: a top-down perspective.

1. Zhang J, Guy MJ, Norman HS, Chen YC, Xu Q, Dong X, Guner H, Wang S, Kohmoto T, Young KH, Moss RL, Ge Y. Top-down quantitative proteomics identified phosphorylation of cardiac troponin I as a candidate biomarker for chronic heart failure. J Proteome Res. 2011;10:4043–4065. ### Study Hypothesis Despite the high incidence and mortality associated with chronic heart failure (CHF), few biomarkers for its diagnosis are approved for clinical practice. Therefore, new markers and diagnostic options are the object of intense research. In this study, Zhang et al address this need by testing their hypothesis that the levels of modified cardiac troponin I (cTnI) correlate with the development of HF. Intriguingly, quantification of cTnI is well established in clinical practice for the assessment and diagnosis of myocardial infarction. Consequently, the team precisely quantified 2 well-established posttranslational modifications (PTMs) of cTnI (ie, phosphorylation and truncation) in tissue specimens from healthy and gradations of diseased hearts. The study eloquently demonstrated a correlation between the levels of phosphorylated cTnI and the degree of deterioration in cardiac function. ### How Was the Hypothesis Tested? Modified forms of cTnI were assessed in the study. Notably, PTMs are emerging as new determinants of phenotypic complexity, potentially making them more descriptive of a specific biological condition, including disease, than aggregate protein levels. In fact, the fast-paced development of technological platforms that separate, measure, and characterize several thousands of proteins …
Experimental characterization of straight spectrometer slits

Abstract A technique for calibrating slit width for straight spectrometer slits based on the diffraction of laser radiation is described. Related slit properties and calibration apparatus are discussed.
A Note on the Equivalence of Two Methods of Fitting a Straight Line through Cumulative Data

Abstract When measurements are made on the same experimental item at successive stages of an experiment, the experimental errors include components which are cumulative in nature, and are hence not independent. This dependence may be removed by using incremental changes in the experimental item as the yield variable, and then using a weighted least squares approach to estimate the parameters of the model, assumed to be linear. Alternately, the original cumulative data may be used directly, and Aitken's method of weighted least squares applied to obtain the parameter estimates. These estimates are shown to be identical.
History and Development of the NRCS Lag Time Equation

Many of the hydrologic methods that are used in engineering practice today resulted from the Spring Flood of 1936, which blanketed the Northeastern portion of the United States. Because of the flood damage that was caused by this rainfall-snowmelt event, many federal agencies including the U.S. Army Corp of Engineers and the Soil Conservation Service (SCS) implemented the hydrologic theories that were available in the literature at this time and developed hydrologic procedures for design flow estimation. Sherman had recently published his unit hydrograph theory in 1932, and later in 1938 Snyder, who had been charged by the Water Resource Council to develop a synthetic unit hydrograph, published his famous paper. The SCS unit hydrograph theory was developed by Victor Mockus in the late 1950s. Most if not all of the theories at that time reported the rainfall-runoff process for floods as a surface phenomenon, and as such those theories all required some type of a timing parameter to estimate watershed response time. This article documents the development of the SCS lag equation.
Leukotriene B4 metabolism by hepatic cytochrome P-450.

Abstract Leukotriene B4 (LTB) was found to be metabolized by suspensions of rat liver microsomes in the presence of NADPH and oxygen. The rate of LTB metabolism was also measured in reconstituted systems of both micelles and phospholipid vesicles containing cytochrome P-450-LM2, NADPH cytochrome P-450 reductase, and cytochrome b5. A 1 uM concentration of LTB was metabolized by rat hepatic microsomes at a rate of 4 pmol LTB/min/nmole P-450, and by vesicle and micelle reconstituted systems at 3 pmole/min/nmole P-450-LM2. At this rate a 10 g rat liver exposed to 1 uM LTB can metabolize 30 ug per hour. In that the leukotrienes are pharmacologically active at nanomolar concentrations, hepatic metabolism may be an important pathway of leukotriene inactivation.
The effect of intestinal fat on histamine-stimulated gastric secretion

Abstract The effect of intraduodenal fat infusion on histamine-stimulated gastric acid secretion was studied in dogs with Heidenhain pouches; there was a significant inhibition of acid output but there was no significant change in acid concentration. This suggests that intraduodenal fat infusion inhibits gastric water secretion to the same extent as it inhibits gastric acid secretion. Histamine caused a marked initial increase in pepsin output (“washout” effect), followed by a secondary sustained increase. The intraduodenal administration of fat abolished the secondary increase in pepsin secretion. The depressant effect of intraduodenal fat on gastric acid and pepsin secretion may play a significant role in the prevention of peptic ulceration.
Uric acid in the malpighian tubules of some blattellid cockroaches

Abstract 1. 1. Uric acid has been positively identified in the Malpighian tubules of three urate-voiding cockroach species—Parcoblatta fulvescens (S. and Z.), Shawella couloniana (S.) and Simploce hospes (P.). 2. 2. In secreting tubules, uric acid occurs in the lumen of the middle and proximal regions and occasionally in the distal tips. 3. 3. Urates are present in the tubule lumen as small spherules which form an opaque white slurry. 4. 4. Urates are discharged into the hindgut in sufficient quantities to obscure the presence of food residues in urate-containing fecal pellets. 5. 5. Birefringent materials occur in vacuoles within the tubule cells, which may indicate vesicular transport of urate.
SiP testing strategy for automobile LSI

Recently LSI for automobile is requested SiP or bare chip assembly. It is necessary for it to reduce the substrate size and to increase electrical performance. But current technology is satisfied with their request technically, but it is not reasonable in production cost. So I mention about Wafer level burn-in and Wafer level AC testing, which is necessary proceeding in the near future.
Climatic, Tectonic, and Biotic Evolution in Continental Cores: Colorado Plateau Coring Project Workshop; St. George, Utah, 13–16 November 2007

A workshop was convened in St. George, Utah, to advance planning for the Colorado Plateau Coring Project (CPCP). The vast continental basins of the southwestern United States, particularly well exposed on the Colorado Plateau and its environs, contain one of the richest stratigraphic records of early Mesozoic age (between roughly 145 and 250 million years ago). This time period was punctuated by two of the major mass extinctions in the past 550 million years and witnessed the evolutionary appearance of the modern biota and dramatic climate changes on the continents. Since the mid-nineteenth century, classic studies of these basins, their strata, and their fossils have made this sequence instrumental in framing our context for the early Mesozoic world. Nonetheless, striking ambiguities in temporal resolution, uncertainties in global correlations with other early Mesozoic strata, and major doubts about latitudinal position still hamper testing of the major competing climatic, biotic, and tectonic hypotheses.
A new method for the determination of direct insolation

Abstract A method of determining direct normal insolation by using two fixed pyranometers was developed and tested. Experimental data for two different configurations are presented. The results are such that the method presented could reasonably be substituted for the standard tracking pyrheliometer in situations in which the use of such a pyrheliometer is not practicable.
Cellulase production by Trichoderma reesei when cultured on xylose‐based media supplemented with sorbose

The ability of L-sorbose to stimulate cellulase production In shake flask culture of Trichoderma reesei was examined in mineral salts media (initial pH 5.0) containing either 1.0% D-xylose, 1.0% cellulose, and/or 0.1, 0.3, or 0.5% L-sorbose. When sorbose was the only carbon source, growth was limited, little substrate was utilized, pH increased, and cellulase activity was not apparent. The other carbon sources promoted good growth, pH dropped sharply to 2.5–3.0, substrate was utilized rapidly, and cellulase activity was detected. After three weeks of fermentation, twice as much cellulase activity was detected in the medium containing only cellulose as the carbon source, as compared to xylose as the carbon source. Cellulase activity was higher when media contained xylose supplemented with sorbose compared to xylose as the only carbon source. At 0.3 and 0.5% levels of sorbose supplementation of xylose-based media, cellulase activity was similar to that in cellulose-based media.
Interview: Predictive markers in colorectal cancer: where are we now?

Heinz-Josef Lenz speaks to Ruth Williamson, Commissioning Editor: Heinz-Josef Lenz is Professor of Medicine and Professor of Preventive Medicine, and holds the Kathryn Balakrishnan Chair for Cancer Research. He is associate director of clinical research and co-chair of the Gastrointestinal Oncology Program at the University of Southern California (USC) Center for Molecular Pathways and Drug Discovery at the University of Southern California Keck School of Medicine and USC/Norris Comprehensive Cancer Center in Los Angeles (CA, USA). Dr Lenz received his medical degree from Johannes-Gutenberg Universitat in Mainz, Germany, and went on to complete a residency in hematology and oncology at the Eberhard-Karls Universitat Tubingen, Germany, before completing clerkships in oncology and hematology at George Washington University (WA, USA) and the Beth Israel Hospital of Harvard Medical School (MA, USA), respectively. He completed a postdoctoral fellowship in the Department of Biochemistry and Molecular Biology at...
Improved bioavailability to the brain of glycosylated Met-enkephalin analogs

Abstract The blood–brain barrier prevents the entry of many potentially therapeutic peptide drugs to the brain. Glycosylation has shown potential as a methodology for improving delivery to the CNS. Previous studies have shown improved bioavailability and improved centrally mediated analgesia of glycosylated opioids. In this study we investigate the effect of glycosylation on the cyclic opioid peptide [ d -Cys2,5,Ser6,Gly7] enkephalin. The peptide was glycosylated on the Ser6 via an O-linkage with various sugar moieties and alignments. The peptides were then investigated for receptor binding, physiochemical attributes, in situ brain uptake in female Sprague–Dawley rats and antinociception in male ICR mice. Glycosylation resulted in a slight decrease in affinity to the δ-opioid receptor, and mixed effect on binding to the μ-opioid receptor. There was a significant decrease in lipophilicity resulting from glycosylation and a slight reduction in binding to bovine serum albumin. In situ perfusion showed that brain uptake was improved by up to 98% for several of the glycosylated peptides, and the nociceptive profiles of the peptides, in general, followed the rank order of peptide entry to the brain with up to a 39-fold increase in A.U.C.
Influence of roughness distributions and correlations on x-ray diffraction from superlattices.

Interfacial roughness in superlattices is currently a topic of significant interest as a result of its impact on device applications and its influence on thin-film phenomena. In this work we examine the effects of interfacial roughness on x-ray diffraction from superlattices. By means of a Taylor expansion of the amplitude reflection coefficient of the multilayer, we present general expressions for the specular, diffuse, and total diffracted intensity from a rough multilayer and examine how these quantities are influenced by roughness distributions and correlations among the interfaces
The debate on DDT

The paper reviews the early toxicologic and pharmacologic studies carried out by the author and his associates from 1943 to 1947, which were largely responsible for launching DDT as an agent for the control of typhus, malaria, yellow fever, and related vector-borne diseases. After reviewing recent studies conducted at the University of Miami, which dealt with organochlorine pesticides in human tissues, the tumorigenicity of aldrin, dieldrin and endrin (rat), six-generation mouse and three-generation dog reproduction studies, synergism of DDT and aldrin (dog), and the fate of DDT and aldrin during a period of severe starvation (rat), it is pointed out that it is primarily the overuse and misuse of DDT in pest control that have caused the pollution in our ecology. It is emphasized that the requirements for pest control differ the world over and that it must therefore be left to the national regulatory agencies to legislate the safe use of DDT and related pesticides. It is recommended that future human and animal studies with DDT and its derivatives give consideration to: (a) the balance and metabolism of the various hormones, (b) reproduction (estrus, libido, mammary development, milk production, (c) hepatic microsomal enzyme activities, (d) cancer prevention and cancer production, (e) excessive body weight changes induced by disease, unbalanced diet or starvation, and (f) the effects of DDT and its derivatives when absorbed in combination with other related and even unrelated compounds.
Topic manipulation and conversational participation as a function of familiarity in school-age language-impaired and normal language peers.

Abstract This study investigated the topic manipulation skills and conversational participation of school-age language-impaired children (LI) in interactions with normal language peers. The subjects consisted of eight dyads of a normal language child and a language-impaired child balanced for approximate age and sex. They ranged in age from 5.11 to 7.11 years of age. The subjects participated in two conversations in order to explore the effects of familiarity on conversational participation. The subjects were unfamiliar with each other before the study began. Fifteen to twenty minutes of discourse were taped, transcribed, and analyzed for the number and proportion of topics maintained, topics introduced, topics reintroduced, topics shaded, and the number and proportion of back channel responses produced in Session 1 and Session 2. A behavioral measure was included to clarify whether conversational non- assertiveness was related to a behavioral style of interaction. No significant differences were found between the LI children and the normal children for the number and proportion of topics maintained, topics introduced, or topics shaded. However, the LI subjects did produce significantly more topic reintroductions than the normal subjects. The number and proportion of back channel responses was not found to differ significantly between the two groups. A familiarity effect was demonstrated by a reduction in the number of utterances produced. in Session 2 as compared to Session 1 as the children interacted less in the second conversation. Several interpretations of the results are discussed.
Cone input to bipolar cells in the turtle retina.

Abstract Action spectra were obtained by intracellular recordings from bipolar cells of the retina of turtle Pseudemys scripta. All bipolar cells responded independently to spots and annuli. Bipolar cells could be broken down into two main categories which differed in the dependence of centersurround interactions on changes in wavelength. In the first category, center-surround antagonism occurred regardless of the wavelengths used. Spectral analysis of these cells showed that both the center and surround received their major input from red cones. With chromatic adaptation, green cone input was detected in the center response of some cells. In the second category, activation of the surround was antagonistic to the center for some wavelengths and synergistic for others. These cells had a color-opponent center of the R/G type imbedded in a non-opponent surround. The surround spectral sensitivity curve could be matched by a simple linear sum of the spectral sensitivities of red-cone-dominated L1 horizontal cells and C-R/GB horizontal cells. Theories concerning the formation of bipolar cell receptive fields are discussed. It is concluded that simple feedback from red cones to green cones via L1 horizontal cells cannot fully account for the chromatic properties of the bipolar cells reported in this study.
EFFECTS OF FLUCTUATING AND CONSTANT TEMPERATURES AND CHEMICALS IN THERMAL EFFLUENT ON GROWTH AND SURVIVAL OF THE AMERICAN LOBSTER (Homarus americanus)1

The effects of long-term exposure to a fluctuating temperature regime typical of that produced by coastal electric generating stations were investigated for juvenile Homarus americanus held in individual rearing containers. Juveniles reared in a 15–22°C daily temperature fluctuation for 126 days had significantly slower growth than those reared at a constant 22°C. They also had significantly higher mortality and less resistance to a high stress temperature (31°C) than those reared at the constant temperature. Exposure to fluctuating temperatures for 1–2 weeks had no evident effect on growth and survival, suggesting that such short-term exposures would not be harmful in commercial culture. Related experiments were conducted to assess effects of thermal effluent water chemistry and 4 constant temperatures on growth and survival of larvae and juveniles (Stages I-XI). There were no significant differences in growth and survival among lobsters held in either thermal effluent or intake water at a given temperature (16, 20, 24, or 26°C), indicating that effluent water chemistry had no apparent effects. There were significant differences in growth of both larvae and juveniles held at the 4 constant temperatures. Survival of juvenile lobsters was not affected significantly by temperature, while that of larvae was. Juvenile lobsters molted more frequently at successively higher temperatures. However, these individuals were not larger than those produced by slower molting at 20°C. This was attributed to absence of a corresponding increase in feeding rate and the relatively high oxygen consumption rates observed at 24 and 26°C.
Southeast Asian Culture, Human Development, and Business Competitiveness

Competition and entrepreneurship are driving forces in the development of economic systems. They create jobs, new opportunities to generate value, and lead to the fulfillment of personal career and life goals. As such, it is important to understand the basic economic and cultural factors that influence these activities in developing economies. We undertook a series of analyses in an examination of a heterogeneous sample of economic zones in Southeast Asia. Results illustrate relations between national culture, human development, and business and growth competitiveness. Implications hold that human development and power distance are enablers of entrepreneurial activities in these cultural and national settings. Our contribution is instrumental to development of public policy and regulatory guidelines for facilitating entrepreneurial activity in the developing economies of Southeast Asia.
Treatment of atrioventricular node reentrant tachycardia with encainide: reversal of drug effect with isoproterenol.

Abstract To determine the efficacy of encainide in the treatment of atrioventricular (AV) node reentrant tachycardia, Holter electrocardiographic (ECG) monitoring, exercise treadmill testing and programmed electrical stimulation were performed in 16 patients while they were taking no medication and after steady state levels were reached during treatment with encaini+de (75 to 200 mg/day; mean 117 ± 47). In addition, to study the possible reversal of drug effects by sympathetic stimulation, AV node conduction and tachycardia induction were reassessed during isoproterenol infusion (1 to 3 μg/min), a dose calculated to increase the rest heart rate by 25 ± 10%. Sustained AV node reentrant tachycardia could be initiated in all 16 patients in the control state, in 2 patients after encainide and in 10 patients during isoproterenol infusion. The shortest mean atrial paced cycle length sustaining 1:1 AV conduction was 358 ± 57 ms during the control study, which increased to 409 ± 59 ms with encainide (p During a mean follow-up period of 19 ± 10 months, significant clinical recurrences occurred in 4 of the 10 patients in whom tachycardia could still be initiated with encainide (with or without isoproterenol). In contrast, no significant episodes occurred in the six patients in whom tachycardia could not be induced with encainide despite isoproterenol infusion. Suppression of atrial or ventricular ectopic activity with encainide during Holter ECG monitoring did not appear to correlate with clinical recurrence. It is concluded that: 1) encainide is an effective agent for control of AV node reentrant tachycardia, primarily by virtue of its depressant effect on retrograde pathways; and 2) failure to induce tachycardia in the medicated state despite isoproterenol infusion predicts freedom from tachycardia recurrence.
Educational Research in Latin America

The present paper consists of four primary sections. First, we describe the historical context of educational research in Latin America. In the second section, we focus on various theoretical frameworks that are applied to educational research in the region. We identify the main institutions involved in this research in the third section. Finally, in conclusion we offer suggestions that we consider to be of greatest priority for the future of educational research in Latin America.
Almost complete intersections

Abstract We establish the structures of some almost complete intersections from the structure theorem of codimension three Gorenstein ideal of Buchsbaum and Eisenbud and investigate the bound for the multiplicity conjectured by Herzog and Srinivasan for almost complete intersections. We also give some partial results in the case when I is the almost complete intersection ideal linked to a complete intersection in one step.
Human Proteinase-3 Expression Is Regulated by PU.1 in Conjunction with a Cytidine-rich Element

Abstract Human proteinase-3 is one of three serine proteinases present in the azurophil granules of polymorphonuclear leukocytes along with elastase and cathepsin G. Proteinase-3 gene expression is confined to the promyelocytic stage of polymorphonuclear leukocyte maturation. The present investigation identifies elements responsible for this highly controlled tissue- and developmental-specific expression of proteinase-3. Within the first 200 base pairs of the proteinase-3 promoter, two elements were identified as important for expression, these elements at −101 and −190 confer the majority of the activity. The element at −101 has a PU.1 consensus. It binds a myeloid nuclear protein of approximately 45 kDa that “supershifts” with PU.1 antibody and is competed by the CD11b PU.1 element. The element at −190 has a core sequence of CCCCGCCC (CG element). The cytidines but not the guanidine are essential for promoter activity. The CG element binds a second nuclear protein with a molecular mass of approximately 40 kDa that is found in cells of myeloid lineage as well as non-myeloid HeLa cells. However, the proteinase-3 promoter is not active in HeLa cells which suggests that the CG element alone is not sufficient for proteinase-3 gene expression. Maturation of promyelocytic cells results in an inhibition of proteinase-3 gene expression and a reduction in nuclear protein binding to the PU.1 and CG elements. Similar elements occur in the elastase and cathepsin G promoters. Using the elastase and cathepsin G PU.1 and CG-like elements as probes results in identical band-shift patterns to that obtained with proteinase-3 PU.1 and CG elements. These data suggest that there is cooperative interaction between a PU.1 and a CG element with a consensus of CCCCXCCC and that they are important control elements for tissue- and developmental-specific expression of azurophil serine proteinases of polymorphonuclear leukocytes.
Rapid and robust detection methods for poison and microbial contamination.

Real-time on-site monitoring of analytes is currently in high demand for food contamination, water, medicines, and ingestible household products that were never tested appropriately. Here we introduce chemical methods for the rapid quantification of a wide range of chemical and microbial contaminations using a simple instrument. Within the testing procedure, we used a multichannel, multisample, UV–vis spectrophotometer/fluorometer that employs two frequencies of light simultaneously to interrogate the sample. We present new enzyme- and dye-based methods to detect (di)ethylene glycol in consumables above 0.1 wt % without interference and alcohols above 1 ppb. Using DNA intercalating dyes, we can detect a range of pathogens (E. coli, Salmonella, V. Cholera, and a model for Malaria) in water, foods, and blood without background signal. We achieved universal scaling independent of pathogen size above 104 CFU/mL by taking advantage of the simultaneous measurement at multiple wavelengths. We can detect contamin...