cssi/SciSciGPT-SciSciNet huggingface dataset:
Abstract 4632: Decitabine for neuroblastoma cure: Target therapy induced ongoing acquisition of RD3 loss and reverts tumor evolution

Recently, we defined the novel tumor evolution stabilization role of Retinal degeneration protein 3 (RD3), regulating the metastatic state of neuroblastoma (NB) cells in vitro and their metastatic potential in vivo. Our earlier studies in various tumor models recognized the role of therapy resistant residual cells in tumor recurrence and relapse. Herein, we investigated the ongoing acquisition of RD3 transcriptional regulation in radiotherapy surviving NB cells and further identified the potential drug candidates that can reprogram and reinstate RD3 transcription in these cells. Human NB (SH-SY5Y, SK-N-AS) cells exposed to single dose (10, 20, 50cGY, 1, 2, 4Gy) or fractionated (FIR, 2Gy/Day for 5 days) irradiation resulted in significant transcriptional repression of RD3. Drug screening with a panel of drugs that are in current clinical use, those in pipelines or in developmental stages by exposing radioresistant cells identified many potential drug candidates that could effectively restore RD3 transcription in this setting. Evidently, we found RD3 promoter region hypermethylation drives its transcriptional regulation in therapy resistant cells. To that note, FDA approved hypomethylating agent decitabine significantly reinforced RD3 transcription in this setting and further promoted cellular differentiation and completely inhibited the formation of organized tumorosphere under stem-cell culture conditions. Together, these results demonstrate the ongoing acquisition of RD3 loss in therapy resistant cells and further recognized the mechanism of how RD3 is regulated in this setting. More importantly, this results of this study identified a drug candidate, that has been already in clinical use, that could be beneficial in mitigating therapy resistance and better clinical outcomes for the patients presented with high-risk advanced disease. Funding: NIH-COBRE-IP20GM103639-01, OUHSC-COM-Radiation Oncology Research Development Funds Citation Format: Aravindan Natarajan, Dinesh Babu Somasundaram, Sheeja Aravindan, Mohan Natarajan, Terence Herman. Decitabine for neuroblastoma cure: Target therapy induced ongoing acquisition of RD3 loss and reverts tumor evolution [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 4632.
Practical considerations on performing and analyzing CLIP-seq experiments to identify transcriptomic-wide RNA-protein interactions

RNA-binding proteins are important players in post-transcriptional regulation, such as modulating mRNA splicing, translation, and degradation under diverse biological settings. Identifying and characterizing the RNA substrates is a critical step in deciphering the function and molecular mechanisms of the target RNA-binding proteins. High-throughput sequencing of the RNA fragments isolated by crosslinking immunoprecipitation (CLIP-seq) is one of the standard techniques to identify the in vivo transcriptome-wide binding sites of the target RNA-binding protein. This method is widely used in functional and mechanistic characterizations of RNA-binding proteins. In this review, we provide several practical considerations on performing and analyzing CLIP-seq experiments. Particularly, we focus on how to perform CLIP-seq experiments on endogenous RNA-binding proteins. In addition, we provide a practical summary on how to choose and use computational pipelines from an increasing number of computational methods and packages that are available for analyzing the sequencing datasets from the CLIP-seq experiments. We hope these practical considerations will facilitate experimental biologists in performing and analyzing CLIP-seq experiment to obtain biologically relevant mechanistic insights.
Neurotoxicity of General Anesthetics

Several putative mechanisms have been demonstrated in various vitro and in in vivo experimental models which associate anesthetic exposure with neural cell injury and death in the developing brain. Furthermore, when young animals were followed long-term, the neonatal anesthesia exposure was associated with persistent behavioral and cognitive impairments. Several retrospective human studies of neurocognitive and behavioral disorders following childhood exposure to anesthesia are mixed in that some suggest similar associations while others do not. The two only prospective or bidirectional clinical studies so far published observed that otherwise healthy children who underwent short general anesthetics in conjunction with limited surgery (herniotomy) at very young age had no cognitive impairments later in life. No clinical studies so far have addressed the effects of longer exposures or were focused on specific patient populations potentially at risk for such outcomes. The implication of this information on anesthetic practice in pediatric patients remains to be seen.
Update in Cardiology: Evidence Published in 2016.

This update in cardiology covers important articles published in 2016 that addressed treatment of coronary artery disease and heart failure, primary prevention of cardiovascular disease, the histor...
Thioredoxin Reductase and Its Role as a New Drug Target

Amebiasis causes approximately 70,000 deaths annually and is the fourth cause of death from protozoan parasites in the world. It is treated primarily with metronidazole, which has adverse side effects and is mutagenic and carcinogenic. Also, emergence of metronidazole resistance is an increasing concern. Unfortunately, better therapeutic alternatives are lacking. Drug discovery efforts have led to reprofiling of older FDA-approved drugs. This approach is advantageous because safety and pharmacokinetic effects in humans have already been confirmed clinically and approved for use.
Disease-Modifying Agents

Disease-modifying treatment of multiple sclerosis (MS) has been rapidly evolving over the last two decades with a shift toward a more targeted and aggressive intervention early in the disease course. Long-term remission from disease activity can now be achieved using several different therapeutic options. Unfortunately, the risk of serious adverse events such as progressive multifocal leukoencephalopathy (PML) has also increased, and careful monitoring of treated patients is essential. Treatment options for progressive forms of MS are very limited.
Temporal Variability of Polycyclic Aromatic Hydrocarbons in Deep-Sea Cephalopods of the Northern Gulf of Mexico

As part of the effort to understand the effects of the Deepwater Horizon Oil Spill (DWHOS), we analyzed tissue from five species of midwater oceanic cephalopods in the northern Gulf of Mexico (GoM) during three time periods, including one period sampled fortuitously just before the spill (2010), and two periods sampled after the spill (2011 and 2015-2016). The species, Japetella diaphana, Abralia redfieldi, Histioteuthis corona, Leachia atlantica, and Onychoteuthis banksii were collected in three geographic areas in the GoM (east, south and southeast of the Macondo wellhead). Results indicate a shift in the composition of polycyclic aromatic hydrocarbons (PAHs) in the tissue of all cephalopods after 2010, with a more petrogenic source in 2011 that weathered and mixed with other sources in 2015-2016. Overall, PAH concentrations, as well as lipid content, were lower in 2011 relative to 2010 and 2015-2016, suggesting secondary effects to oil-residues exposure from the DWHOS. Collectively, PAHs in the tissues of deep-sea cephalopods indicate an episodic exposure to petrogenic PAHs that occurred between 2010 (pre-spill) and 2011, and continued through 2015-2016.
Race, class, and the retreat from debate

In “Setting the Record Straight”, Rashawn Ray (2020) points out that Black Lives Matter (BLM) helped to stimulate federal oversight of St. Louis and other cities (1396). It helped to make body came...
Verification of an improved equation-free projective integration method for neoclassical plasma-profile evolution in tokamak geometry

A brute-force, long-time gyrokinetic simulation of plasma profile evolution in magnetic fusion devices is not desirable due to large computational resource requirements and a possible accumulation of numerical error. The equation-free projective integration method of Keverekidis et al. [Commun. Math. Sci. 1(4), 715–762 (2003)] is one of the outstanding candidates in projecting micro-scale simulations to a longer timescale. However, its application to tokamak plasma has not been fruitful due to the appearance of spurious transient oscillations in the lifting process, which are present when the kinetic simulations are initialized with a simplified model distribution function and which make the kinetic simulations to deviate from the desired paths. In this work, a kinetically informed lifting algorithm is added to the equation-free projective integration method, which is then verified in the electrostatic gyrokinetic particle-in-cell code XGCa [R. Hager and C. S. Chang, Phys. Plasmas 23, 042503 (2016)] for a neoclassical ion heat transport problem with adiabatic electrons. This new lifting operator is demonstrated to control spurious transients, enabling an over four-times reduction in the overall computing time in the time-evolution of the ion temperature profile in an axisymmetric toroidal plasma. Further reduction in the computing time is found to be limited due to the stability properties of the linear least squares projective integrator.
Chapter 2 – The Schrödinger Wave Equation

The wave function ψ(x) and the energy E of the stationary states of a particle may be obtained by solving the Schrodinger time-independent equation −ℏ22md2ψdx2+V(x)ψ=Eψ. The Schrodinger time-independent equation is used in this chapter to find the wave function and the energy of a particle moving in an infinite and a finite potential well and to study the states of the simple harmonic oscillator. In each case, the possible energies of the particle correspond to those values of E for which there is a solution of the Schrodinger time-independent equation that satisfies the boundary conditions. The wave function, which is related to the probability of finding the particle in a particular region in space, may be used to calculate the average value of a function f(x) using the formula 〈f(x)〉=∫abf(x)|ψ(x)|2dx. The time evolution of the wave function is described by the Schrodinger time-dependent equation iℏ∂ψ(x,t)∂t=−ℏ22m∂2∂x2+V(x,t)ψ(x,t). For a particle moving in a constant potential, the solutions of the Schrodinger time-dependent equation are of the form ψ(x,t)=uE(x)e−iωt,ψ(x,t)=uE(x)e−iωt, where uE(x ) is a solution of the Schrodinger time-independent equation and ω=E/ℏω=E/ℏ.
Signal Transduction Mechanisms on Striatal Dopaminergic Neurons: Importance in Neurotrophism and Neuropathology

Publisher Summary This chapter describes signal transduction mechanisms on striatal dopaminergic neurons. Though there is a general agreement that the synaptic activation of dopamine (DA) containing neurons of substantia nigra (SN) can play an important role in affective behavior, motor coordination, and cognitive function, the molecular mechanisms operating the signal transduction at these synaptic inputs are not well characterized. Intracellular recordings from slice preparations indicate that SN neurons characteristically exhibit a prominent after-polarization followed by a very slow depolarization that triggers the generation of slow rate spontaneous action potentials. Such pacemaker-like activity of DA neurons of SN appears to be controlled by at least five differently regulated K+ and two Ca2+ conductances. Several lines of in vitro and in vivo investigations show that DA-aminobutyric acid (GABA) and the high concentrations of glycine and baclofen inhibit the spontaneous activity of DA neurons. On the other hand, DA neurons are excited in vivo by glutamate applied iontophoretically. This finding may suggest a function for corticofugal glutamatergic innervations impinging upon SN neurons. The chapter also discusses some aspects of signal transduction of glutamatergic and GABA receptors as they relate to the neurotrophic action and antagonism to glutamate excitotoxicity antagonism operated by GM1.
Individual Differences in Need for Cognition and Decision-Making Competence Among Leaders

When making decisions, people sometimes deviate from normative standards. While such deviations may appear to be alarmingly common, examining individual differences may reveal a more nuanced picture. Specifically, the personality factor of need for cognition (i.e., the extent to which people engage in and enjoy effortful cognitive activities; Cacioppo & Petty, 1982) may moderate decision makers’ susceptibility to bias, as could personality factors associated with being a leader. As part of a large-scale assessment of high-level leaders, participants completed a battery of decision-making competence and personality scales. Leaders who scored higher on need for cognition performed better on two of four components of a decision-making competence measure: framing and honoring sunk costs. In addition, the leader sample performed better than published controls. Thus, both individual differences in need for cognition and leadership experience moderate susceptibility to decision biases. Implications for broader theories of individual differences and bias are discussed.
Leveraging Human Resource Development Practice to Enhance Organizational Creativity: A Multilevel Conceptual Model:

Developing creativity is a critical challenge for the survival and success of businesses. Using Amabile’s dynamic componential theory of creativity as a framework, we examined the underexplored pot...
Social music festival brandscapes: A lexical analysis of music festival social conversations

Abstract Social media usage relative to music festivals has given rise to the Social Music Festival Brandscape (SMFB)—an ecosystem of festival experiences and social conversations where music festival brand value is co-created through discussions of festival experiences and attendances, artist performance celebrations, and evaluation of festival purchase exchanges. The present study applied machine learning-based lexical analysis to the ten largest U.S.-based music festivals and their communities across Instagram and Twitter and revealed post theme types of Time, Artists, Media, Location, Purchase Exchanges, Gratitude, Priming, Social Media Inducements, and Genre References to round out value co-creation activity within the Dialogue Zone of the SMFB model. Of particular note is that while these content themes emerged holistically in the SMFB dialogue, content theme misalignment occurred between festivals and communities where Media, Gratitude, and Priming content theme posts lacked the same frequency across community posts. Understanding the content of these dialogues within SMFBs is important for music festivals moving forward as they seek to build, re-establish, or re-trench music communities in the festival experience, and to determine if post theme misalignment is necessary for longer term, successful SMFB dialogue.
On malicious implants in PCBs throughout the supply chain

Abstract The PCB supply chain has become globally distributed such that PCBs are vulnerable to hardware Trojan attacks. Moreover, attacks on PCBs are possible even after a system is deployed. Various countermeasures have been proposed and efforts to develop board-level Trojan benchmarks are underway, but IC Trojan taxonomies do not capture important characteristics of PCB implants. This work surveys existing PCB countermeasures and examples of board-level Trojans to inform a new taxonomy suited for PCB Trojans. Our taxonomy reflects practically significant characteristics of board-level Trojans to guide development of board-level countermeasures and fair, comprehensive benchmark suites.
Association of epigenetic age acceleration with risk factors, survival, and quality of life in patients with head and neck cancer

Purpose Epigenetic age acceleration (EAA) is robustly linked with mortality and morbidity. This study examined risk factors of EAA and its association with overall survival (OS), progression-free survival (PFS), and quality of life (QOL) in patients with head and neck cancer (HNC) receiving radiation therapy. Methods and Materials Patients without distant metastasis were enrolled and followed before and at the end of radiation therapy and at 6 and 12 months after radiation therapy. EAA was calculated with DNAmPhenoAge at all 4 time points. Risk factors included demographic characteristics, lifestyle, clinical characteristics, treatment-related symptoms, and blood biomarkers. Survival data were collected until August 2020, and QOL was measured using Functional Assessment of Cancer Therapy–HNC. Results Increased comorbidity, symptoms unrelated to human papilloma virus, and more severe treatment-related symptoms were associated with higher EAA (P = .03 to P Conclusions Compared with demographic and lifestyle factors, clinical characteristics were more likely to contribute to faster biological aging in patients with HNC. Acceleration in epigenetic age resulted in more aggressive adverse events, including OS and PFS. EAA could be considered as a marker for cancer outcomes, and decelerating aging could improve survival and QOL.
Controlling Magnetism with an Electric Field in Multiferroic Complex Oxide Heterostructures: La0.7Sr0.3MnO3/BiFeO3

This is a copy of the slides presented at the meeting but not formally written up for the volume. Interactions at magnetic interfaces are central to the operation of virtually all magnetic heterostructures. When the interface is between two magnetic materials, the exchange interaction between spins at the interface is often a dominant force, and can dramatically change the magnetic response of the overall heterostructure. In ferromagnet (FM)/antiferromagnet (AFM) heterostructures, this interaction is often referred to as exchange anisotropy or bias and it has been widely used over the past decade in a wide array of applications such as magnetic recording heads, MRAMs, etc. The powerful implications of interactions between an AFM and a FM have been realized in a wide range of thin film heterostructure with both metallic and oxide constituents. There is, however, much less work on oxide-oxide FM/AFM systems. On the other hand, the development and understanding of functional oxide materials, especially multifunctional materials like BiFeO3 (BFO), have piqued the interest of researchers worldwide with the promise of coupling between order parameters such as ferroelectricity and antiferromagnetism. Recent research suggests that there is exchange coupling and anisotropy between the metallic ferromagnet Co0.9Fe0.1 (CoFe) and the multiferroic, antiferromagnet BFO, showing the possibility to create highly desirable multifunctional systems with new possibilities for device design. Such a result provides the driving force to create multifunctional oxide-oxide systems where exchange interactions could be much stronger then in metal/oxide structures due the added epitaxial nature of the interface. In this study, we use La0.7Sr0.3MnO3(LSMO)/BFO thin film heterostructures as a model system to explore the exchange interaction at an oxide interface. The heterostructures are grown on various vicinal cuts of SrTiO3 single crystal substrates using laser MBE. Structural analysis using x-ray diffraction, transmission electron microscopy and Rutherford backscattering spectrometry reveals high quality films with the pristine interfaces required for exchange coupling. First results from photoemission electron microscope (PEEM) studies reveal that the magnetic LSMO domain structure mimics underneath ferroelectric BFO domain structure, i..e, it is strongly pinned by the underlying AFM structure. The coupling behavior is being characterized by magnetic measurements (SQUID, VSM), which shows a strong enhancement in the coercivity of the LSMO layer, suggesting the existence of exchange bias coupling. We are probing the strength of this coupling using a combination of careful laser MBE growth experiments and physical property measurements. In this paper, we will report results of experiments in which the LSMO layer has been grown by laser MBE in the thickness range of 2-50nm on a [001] BFO layer.
Information and explanation: an inconsistent triad and solution

An important strand in philosophy of science takes scientific explanation to consist in the conveyance of some kind of information (e.g., Lewis, 1986; Railton, Synthese, 48, 233–56, 1981). Here I argue that this idea is also implicit in some core arguments of mechanists, some of whom (e.g., Craver, 2014) are proponents of an ontic conception of explanation that might be thought inconsistent with it (Piccinini & Craver, Synthese, 183, 283–311, 2011; Zednik, 2015). However, informational accounts seem to conflict with some lay and scientific commonsense judgments and a central goal of the theory of explanation, because information is relative to the background knowledge of agents (Dretske, 1981). Sometimes we make lay judgments about whether a model is an explanation simpliciter, not just an explanation relative to some particular agent. And as philosophers of explanation, we would like a philosophical account to tell us when a model is an explanation simpliciter, not just when a model is an explanation relative to some particular agent. Thus, even if one’s account of explanation is not concerned with explanation qua communicative or speech act, the account’s reliance on the concept of information generates a prima facie conflict between the claims that 1) explanation is the conveyance of information, 2) information is relative to the background knowledge of an agent, and 3) some models are explanations not relative to the background knowledge of any particular agent. I sketch a solution to this puzzle by distinguishing informationally what I call “explanation simpliciter” from what I call “explanation-to,” relativizing the latter to an individual’s background knowledge and the former to what I call “total scientific background knowledge”.
Dietary Calcium and Magnesium Are Associated With Lower Odds of Osteoporosis Among Puerto Rican Older Adults When Dietary Calcium to Magnesium Ratio Is Considered

Objectives Dietary calcium and magnesium have been shown to be beneficial for bone health primarily in non-Hispanic white populations. There are no studies of calcium and magnesium intake among Hispanics of Caribbean origin. A calcium to magnesium ratio (Ca: Mg) may be important due to their competitive nature during absorption. This study examined associations between dietary calcium and magnesium and osteoporosis, accounting for calcium to magnesium ratio among Puerto Rican adults
Impact of Performance Status on Response and Survival Among Patients Receiving Checkpoint Inhibitors for Advanced Solid Tumors.

PURPOSEClinical trials, which led to the approval of immune checkpoint inhibitors (ICI), have been almost exclusively performed in patients with good Eastern Cooperative Oncology Group performance ...
The Influence of Reproductive History on Post-Reproductive Mortality: A Case Study of Amish Women

The reproductive choices women make affect their health outcomes; however, the relevance of reproductive history on post-reproductive mortality varies according to the population under study. We examine whether the number of children a woman gives birth to, short birth intervals, late childbearing, having twins, and having children who die young have an influence on maternal mortality among the Amish. We use information from Amish directories to examine reproductive patterns of 228 women in this high fertility group. Our results indicate the patterns typically found for maternal mortality in the general population do not hold in our sample of Amish women. We suggest the mediating role of family and community is integral to understanding the maternal health patterns within the Amish community.
Laparotomie, Zugangswege, Exploration, Laparotomieverschluß

Viele operationsbedingte Komplikationen beruhen darauf, das die Freilegung des Operationsgebiets inadaquat — aufgrund einer nicht gut uberlegten und nicht ausreichend langen Inzision — erfolgte.
Bystander Interventions Can Improve Outcomes From Out-of-Hospital Cardiac Arrest.

North Carolina participates. The analysis was restricted to 11 counties that included 30% of the total population. During the study period, survival with favorable neurologic outcome increased from 7.1% (82/1149; 95% CI, 5.8%8.8%) in 2010 to 9.7% (129/1334; 95% CI, 8.2%-11.4%) in 2013
Secure acknowledgment of multicast messages in open peer-to-peer networks

We propose a new cryptographic technique, Acknowledgment Compression, permitting senders of multicast data to verify that all interested parties have either received the data or lost network connectivity. Joining the system and acknowledging messages both require bandwidth and computation logarithmic in the size of a multicast group. Thus, the technique is well-suited to large-scale, peer-to-peer multicast groups in which neither the source nor any single peer wishes to download a complete list of participants. In the event that sufficiently many nodes are malicious, a message may fail to verify. However, in such cases the source learns the real network address of a number of malicious nodes.
The 11th European Workshop on White Dwarfs

The 11th European Workshop on White Dwarfs was held in Tromso, Norway, on 1998 June 29–July 3. The meeting was part of a continuing biannual series that began in Kiel, Germany, in 1974. At the present meeting, there were 85 participants from 17 countries. The program consisted of 30 minute review talks given primarily by astronomers in the early years of their careers, 15 minute contributed talks, and 5 minute oral presentations by authors of poster papers. The meeting venue, amid the surroundings of mountainous Arctic landscapes and fjords, provided a stimulating environment (and 24 hours of daylight) for discussing the latest research on degenerate stars. Compared with the previous workshop, held 2 years ago in Blanes, Spain, the Tromso meeting contained (1) more results from the Whole Earth Telescope (WET), (2) several important new strides in understanding the overall chemical evolution and formation channels of white dwarfs, (3) more new developments in white dwarf magnetism, and (4) a greater emphasis on white dwarfs in binary systems, including white dwarfs in accreting binaries and the continuing search for double degenerates as Type Ia supernova progenitors. The highlights that follow are my personal view of the most significant papers. H. Shipman and J. Provencal reported unprecedented precision in the determination of white dwarf masses and radii from Hipparcos parallaxes. To cite just one example, 40 Eri B has and and thus lies preR 0.0136 R M 0.458 M , , cisely on the zero-temperature mass-radius relation for a carbon core. Surprisingly, however, three other well-known degenerates lie below the mass-radius relations for C, O, and even Mg! Indeed, Procyon B, with a mass of 0.59 M,, lies on the mass-radius relation for an Fe core. The possibility that some white dwarfs of such low masses may have Fe-rich cores sparked considerable discussion. Already, one theorist present (J. Isern) suggested an explanation for how a white dwarf could form with an iron core. It is remarkable that, for selected degenerates, a level of precision in the measurements of mass and radius has been attained that
La construcción de la imagen heroica a través del discurso periodístico: El caso de la activista peruana María Elena Moyano

This work tries to demonstrate that the social construction of the national hero/heroine as a symbol of courage and resistance generally arises within a period of social, political, and economic crisis. The national hero is a construction that is created in a moment characterized by the loss of public trust and the failure of government leaders to act. The creation of the heroic image functions as a socio-political tool. The article suggests that there is a close relationship between the history and the construction of heroic figures. Using the death of Peruvian activist Maria Elena Moyano as a concrete example, it demonstrates that journalistic discourse has the ability to create an heroic image around a person who has been given the traditional role that the hero has played in society since Antiquity.
Involvement of Cytokines in Lipopolysaccharide-Induced Facilitation of CGRP Release from Capsaicin-Sensitive Nerves in the Trachea: Studies with Interleukin-1β and Tumor Necrosis Factor-α

Lipopolysaccharide (LPS), an endotoxin, produces pain behavior, inflammation, and changes in immune function. Many of these effects are secondary to the production of cytokines. In the present study, we investigated the effect of LPS on the releasing function of afferent terminals as measured by calcitonin gene-related peptide (CGRP) release in ex vivo perfused rat trachea, and examined the possible role of the cytokines interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) as intermediaries in this effect. Systemic injection of LPS (0.75 mg/kg, i.p.) in adult rats induced an increase in body temperature followed by hypothermia, indicating ongoing infection. We observed that capsaicin-induced (0.1 microM) tracheal CGRP release was significantly enhanced in the LPS-treated animals after 5 hr. This enhancement of the peptide release by LPS was blocked by IL-1beta tripeptide antagonist Lys-D-Pro-Thr (10 microM) and mimicked by IL-1beta and TNF-alpha (10-100 pg/ml), suggesting that the potentiating effect of LPS on CGRP release is mediated by generation of IL-1beta and TNF-alpha. IL-1beta-induced augmentation of CGRP release was blocked by Lys-D-Pro-Thr. Additionally, the cyclooxygenase inhibitor ketorolac (10 microM) significantly attenuated the facilitatory effects of LPS and IL-1b, indicating involvement of prostanoids. These findings suggest that endotoxin treatment generated cytokines such as IL-1b and TNF-alpha that regulated the peripheral releasing function of primary sensory afferents by sensitizing the terminals and facilitating peptide release. This effect is prostanoid dependent.
A Foundational Architecture for Artificial General Intelligence

Implementing and fleshing out a number of psychological and neuroscience theories of cognition, the LIDA conceptual model aims at being a cognitive “theory of everything.” With modules or processes for perception, working memory, episodic memories, “consciousness,” procedural memory, action selection, perceptual learning, episodic learning, deliberation, volition, and non-routine problem solving, the LIDA model is ideally suited to provide a working ontology that would allow for the discussion, design, and comparison of AGI systems. The LIDA architecture is based on the LIDA cognitive cycle, a sort of “cognitive atom.” The more elementary cognitive modules and processes play a role in each cognitive cycle. Higher-level processes are performed over multiple cycles. In addition to giving a quick overview of the LIDA conceptual model, and its underlying computational technology, we argue for the LIDA architecture's role as a foundational architecture for an AGI. Finally, lessons For AGI researchers drawn from the model and its architecture are discussed.
Brief report: ultraviolet radiation exposure is associated with clinical and autoantibody phenotypes in juvenile myositis.

The idiopathic inflammatory myopathies (IIM) are a heterogeneous group of systemic autoimmune diseases with the common feature of chronic muscle inflammation of unknown etiology. In children, dermatomyositis (DM), characterized by skin rashes and photosensitivity, is the most common of the IIM, and polymyositis (PM), which lacks characteristic skin rashes, constitutes about 10% of childhood-onset patients. As in adult myositis, juvenile myositis is comprised of myositis-autoantibody subgroups which define phenotypes that are each associated with different demographic, clinical and laboratory features and outcomes (1). Some of these autoantibodies are associated with DM, such as anti-Mi-2 and anti-p155/140 (TIF1γ), and others are associated with PM, such as anti-signal recognition particle (1). Development of IIM is thought to be affected by genetic and environmental risk factors. Although HLA, cytokine polymorphisms and other immunogenetic loci have been identified as genetic risk factors for these diseases (1), little is known about their environmental risk factors. Seasonality in birth dates in subgroups of patients suggests a role for perinatal or neonatal environmental factors, including ultraviolet radiation (UVR), in the later development of these diseases (2). In registry studies, temporal associations with upper respiratory and gastrointestinal infections have been observed. Other exposures have also been observed, including development of symptoms after unusual sun exposure or sunburns (3). In adult IIM, studies in the United States and worldwide found a direct relationship between global surface UVR exposure and the proportion of patients with DM versus PM (4, 5). Seasonal differences in onset of PM/DM have been reported and are consistent with the role of UVR exposure (6). This relationship has not been examined in juvenile IIM (JIIM); therefore, we examined whether the prevalence of juvenile DM (JDM) compared with juvenile PM (JPM), as well as DM-specific autoantibodies, is associated with UVR exposure.
Urate in Parkinson's disease: more than a biomarker?

Parkinson’s disease (PD) is a progressive neurodegenerative disease with characteristic motor manifestations. Although appreciation of PD as a multisystem disorder has grown, loss of dopaminergic neurons in the substantia nigra remains a pathological and neurochemical hallmark, accounting for the substantial symptomatic benefits of dopamine replacement therapies. However, currently no treatment has been shown to prevent or forestall the progression of the disease in spite of tremendous efforts. Among multiple environmental and genetic factors that have been implicated in the pathogenesis of PD, oxidative stress is proposed to play a critical role. A recent confluence of clinical, epidemiological, and laboratory evidence identified urate, an antioxidant and end product of purine metabolism, as not only a molecular predictor for both reduced risk and favorable progression of PD but also a potential neuroprotectant for the treatment of PD. This review summarizes recent findings on urate in PD and their clinical implications.
Unraveling the chemical history of the Solar System as recorded in extraterrestrial organic matter

We have initiated an extensive program of molecular analysis of extraterrestrial or- ganic matter isolated from a broad range of meteorites (spanning multiple classes, groups, and petrologic types), including recent molecular spectroscopic analyses of the organic matter in the Comet 81P/Wild 2 samples. The results of these analyses clearly reveal the signature of multi- ple reaction pathways that transformed extraterrestrial organic matter away from its primitive roots. The most significant molecular transformation occurred in the post-accretionary phase of the parent body. However, each of the various chemical transformation trajectories point unam- biguously back to a common primitive origin. Applying a wide range of spectroscopic techniques we find that the primitive organic precursor is striking in its chemical complexity exhibiting a broad array of oxygen- and nitrogen-bearing functional groups. The π-bonded carbon exists as predominately highly substituted single ring aromatics, there exists no evidence for abun- dant, large, polycyclic aromatic hydrocarbons (PAHs). We find that the molecular structure of primitive extraterrestrial organics is consistent with synthesis from small reactive molecules, e. g. formaldehyde, whose random condensation and subsequent rearrangement chemistry at low temperatures leads to a highly cross-linked macromolecule.
Effect of Alumina on the Structure and Mechanical Properties of Spark Plasma Sintered Boron Carbide

Uniform densification of relatively thick (~7 mm) consolidated boron carbide plates at relatively low temperatures (e.g. 1800°C) and low facture toughness are two of the primary challenges for further development of boron carbide applications. This work reports that these two challenges can be overcome simultaneously by adding 5 wt% alumina as a sintering aid. Nearly fully dense (97%), fine grained boron carbide (B4C) samples were produced using spark plasma sintering at 1700°C and above in the B4C-5 wt% Al2O3 system. The alumina and boron carbide matrix reacted to form an Al5O6BO3 (a mullite-like phase) during sintering. The Al5O6BO3 phase facilitated uniform densification via liquid phase sintering. This secondary phase is dispersed throughout the intergranular pores, providing obstacles for crack propagation and resulting in tougher boron carbide ceramics.
Calibration of palletized workpiece systems for microfactories

Kinematic couplings have been used to create palletized system for part transfer in a microfactory. While kinematic couplings provide high repeatability, calibration is needed to achieve high interchangeability accuracy. In this paper, a generalized artifact-based methodology for pallet calibration and workpiece registration is developed. This calibration method uses the microfactory machines to both machine and measure artifacts to estimate the interchangeability errors. The error sources affecting the accuracy of calibration are analyzed and techniques are suggested to reduce these errors. Finally, the methodology is applied and validated for a specific microfactory application.
Causal factors in spinal cord injury: Patients' evolving perceptions and association with depression

Abstract Do spinal cord injured patients who accept responsibility for their injury cope better than those who blame others? Previous investigations have yielded conflicting answers to this question. On the assumption that some portion of the disparity in earlier findings derives from the failure of early investigators to conceptualize "blame" as a dynamic phenomenon, the present study approached the question via a longitudinal study. Specifically, we examined: (1) the evolution of patients' perceptions of responsibility for spinal cord injury, and (2) the changing association of this factor with depression over a 2-year period, beginning with inpatient rehabilitation. Eighteen men with traumatic spinal cord injury were evaluated during acute rehabilitation and again at 18 to 24 months following discharge. Patients assigned proportions of blame for their injury to four possible causal factors (self, environment, chance, others). Three indices of depression were derived from the Beck Depression Inventory (BDI). Eighty-nine percent of the subjects displayed shifts in pattern of blame assignment between initial and follow-up evaluations. Individuals whose self-blame score increased over time exhibited increased depression, as did those who came to attribute to "chance" lesser blame for their injury. During inpatient rehabilitation, no aspect of blame correlated significantly with any of the three BDI indices, although "other blame" and the cognitive/affective BDI index just failed to reach conventional levels (r = .43, p = .07). By contrast, at follow-up evaluation, "self blame" was positively correlated with both the cognitive/affective (r = .51, p = .03) and Total (r = .46, p = .05) BDI scores. All other correlations were not statistically meaningful. Though "true" responsibility for injury is difficult to ascertain, questions about causality and blame constitute aspects of patients' psychological reality, and as such, should be addressed by the treatment team. These findings underscore the importance of assisting patients in the process of resolving the issue of perceived responsibility for injury and focusing on responsibility for rehabilitation.
Interspeaker variation in the extent and perception of long-distance vowel-to-vowel coarticulation

Abstract The phenomenon of coarticulation is relevant for issues as varied as lexical processing and language change, but research to date has not determined with certainty how far such effects can extend. This study investigated the production and perception of anticipatory vowel-to-vowel (VV) coarticulation. First, 20 native speakers of English were recorded saying sentences containing multiple consecutive schwas followed by [i] or [а]. The resulting acoustic data showed significant VV coarticulatory influence up to three vowels before the context vowel, a greater distance than has been seen in previous studies. However, there was substantial variability among speakers in this regard. The perceptibility of these effects was then tested using behavioral methodology; even long-distance effects were perceptible to some listeners. Subjects’ coarticulatory production strength and perceptual sensitivity were positively, but only weakly, correlated. Although the very slowest speakers tended to coarticulate less than the rest, speech rate and coarticulatory strength were not significantly correlated for the group as a whole.
Pavlov as a psychophysiological scientist

It is suggested that Pavlov was not only a famous physiologist, but due to his work on the conditional reflex, he could be considered a behavioral scientist. In addition his work on experimental neurosis gives him the distinction of being a pioneer investigator in the area of psychological stress. Pavlov's research is viewed against a background of primitive research tools and unproductive subjective theories. Nineteenth century scientists who influenced Pavlov included Darwin, Botkin, Heidenhain, Gaskell and Bernard. Pavlov's research on the digestive system emphasized the role of the nervous system, launched the field of gastroenterology, and emphasized the concept of the conditional reflex. Pavlov's conditional reflex formulations were based on the theoretical formulations of Sechenov, and possibly the work of David Hartley. The discovery of secretin, by Bayliss and Starling, and its influence on the stomach led Pavlov to diminish his work on the digestive system and to focus his research on the conditional reflex phenomenon. Arguments which suggest that Pavlov worked as a behavioral scientist include his conceptual formulations, his research on traditional psychological topics and his investigation of psychiatric disorders. His conditioning research emphasized the individual differences of his animal subjects which led to his research on typology and experimental neurosis which formed the basis for his work on environmental stressors and psychopathology.
Developmental and nutritional regulation of the prepubertal heifer mammary gland: I. Parenchyma and fat pad mass and composition

Prior to puberty, elevated nutrient intake has been shown to negatively affect prepubertal mammary development in the heifer. The objective of this study was to evaluate the effects of increased nutrient intake on mammary development in Holstein heifers at multiple body weights from birth through puberty. Specifically, this study evaluated the effects of nutrient intake and body weight at harvest on 1) total weight and DNA content of the parenchyma (PAR) and mammary fat pad (MFP) and 2) PAR and MFP composition. Starting at 45 kg of body weight, heifers (n = 78) were assigned to either a restricted (R) or elevated (E) level of nutrient intake supporting 650 (R) or 950 (E) g/d of body weight gain. Heifers were harvested at 50-kg increments from 100 to 350 kg of body weight. Mammary fat pad weight and DNA content were greater in E- than in R-heifers. Additionally, E-heifers had a greater fraction of lipids and a smaller fraction of protein in their MFP than did R-heifers. Parenchyma weight and DNA were lower in E- than in R-heifers; however, when analyzed with age as a covariate term, treatment was no longer a significant term in the model. Level of nutrient intake had no effect on the lipid, protein, or hydroxyproline composition of the PAR. Collectively, these data demonstrate that PAR is refractory to the level of nutrient intake whereas MFP is not. Furthermore, the covariate analysis demonstrated that age at harvest, not the level of nutrient intake, was the single greatest determinant of total PAR DNA content.
An examination of coherent structures in a lobed mixer using multifractal measures in conjunction with the proper orthogonal decomposition

A 'lobed mixer' device that enhances mixing through secondary flows and streamwise vorticity is presently studied within the framework of multifractal-measures theory, in order to deepen understanding of velocity time trace data gathered on its operation. Proper orthogonal decomposition-based knowledge of coherent structures has been applied to obtain the generalized fractal dimensions and multifractal spectrum of several proper eigenmodes for data samples of the velocity time traces; this constitutes a marked departure from previous multifractal theory applications to self-similar cascades. In certain cases, a single dimension may suffice to capture the entire spectrum of scaling exponents for the velocity time trace.
Schottky-barrier-type Graphene Nano-Ribbon Field-Effect Transistors: A study on compact modeling, process variation, and circuit performance

Graphene Nano-Ribbon Field-Effect Transistors (GNR-FETs) have emerged as promising next-generation devices. In particular, Schottky-barrier-type GNRFETs (SB-GNRFETs) have piqued interest due to their ambipolar I-V characteristics. Despite manufacturing successes, the lack of a SPICE-compatible compact model of SB-GNRFETs has hindered studies on evaluating the performance of this emerging technology on the circuit level. In this paper, we present the first SPICE-compatible model of SB-GNRFETs that takes various design parameters into account, which not only enables circuit-level simulations, but also provides a means to evaluate process variation, including effects of channel length, transistor width, oxide thickness, and graphene-specific edge roughness. With this model, we are able to explore the design space of SB-GNRFETs, evaluate delay and power performance of SB-GNRFET circuits, and compare them with conventional Si-CMOS and Metal-Oxide-Semiconductor-(MOS-)GNRFETs. Our study shows that SB-GNRFETs have higher speed and higher power dissipation, and have lower energy delay product than both Si-CMOS and MOS-GNRFETs, while MOS-GNRFETs are potentially good for low-power applications despite the presence of graphene-metal contact resistance that are not present in SB-GNRFET circuits. Two practical factors severely degrade the performance and even affect the functionality of SB-GNRFET circuits: 1) edge roughness and 2) limitation on operating point shifting.
Interstellar diamonds in meteorites

Primitive meteorites contain up to 400 ppm of a very fine-grained type of carbon tentatively called C-delta. Evidence is presented here that part of all of the C-delta is primary, not shock-produced, diamond formed by stellar condensation as a metastable phase. It appears that interstellar dust contains diamond.
Your scorecard for financial liquidity

Today's leading edge companies are using treasury management as a strategic weapon—to create value and attract investors. How well is your company doing this? © 2000 John Wiley & Sons, Inc.