cssi/SciSciGPT-SciSciNet huggingface dataset:
Prevention of paclitaxel-induced neuropathy by formulation approach.

Abstract Chemotherapy-induced peripheral neuropathy (CIPN) is a major adverse effect of paclitaxel. Several liposome-based products have been approved and demonstrated superior efficacy and safety profiles for other drugs. The first objective of this work was to evaluate the effect of liposome formulation of paclitaxel (L-PTX) on neurotoxicity in-vitro and in-vivo in comparison to the standard Taxol® formulation. The second aim was to investigate the effect of formulation on paclitaxel biodistribution following intravenous administration in an animal model. Free paclitaxel was toxic to cell of neuronal origin (IC50 = 18.4 μg/mL) at a lower concentration than to lung cancer cells (IC50 = 59.1 μg/mL), and L-PTX demonstrated a comparable toxicity in both cell lines (IC50 = 31.8 and 33.7 μg/mL). Administration of L-PTX at 2 mg/kg per dose for a total of 4 doses on day 0, 2, 4, and 6 to rats did not result in increased sensitivity in response to mechanical or thermal stimulation of hind paws, in comparison to Taxol® administration at the same dose level that resulted in neuropathy. Paclitaxel biodisposition was evaluated for two formulations in plasma, liver, lung, brain, spinal cord, skin and muscle of rats after single intravenous dose at 6 mg/kg. The exposure to paclitaxel in brain, spinal cord, muscle, and skin was lower in the L-PTX group compared to Taxol® group. PEGylated liposomes containing paclitaxel were successfully developed and demonstrated reduced neurotoxicity in-vitro in neuronal cells and prevented development of peripheral neuropathy in-vivo. This proof of concept study showed that formulation in nanoparticles is a promising approach for reducing (or preventing) neurotoxicity caused by cancer drugs.
Global Cases in Best and Worst Practice in Crisis and Emergency Management

Ethical leadership; decision making; legitimacy; and public trust are underlying themes throughout most emergency and crisis management case studies. Disasters are complex and dynamic, and often te...
Mechanisms of Acquired Resistance to Targeted Therapy in NSCLC: Role of Repeat Biopsy and Nursing Considerations

Testing lung cancer tumors at the time of diagnosis for molecular driver mutations is widely accepted and recommended as best clinical practice, particularly for the subset of non-small cell lung cancers (NSCLC) with adenocarcinoma histology. Broad molecular profiling of tumors is part of the move towards personalized medicine, in which healthcare providers can use the unique genetic make-up of an individual’s tumor to identify treatment options that are specifically matched to that individual’s cancer. Identifying and harnessing the specific mutations in an individual’s tumor to guide treatment decisions leads to improved treatment response and better patient outcomes. Unfortunately, over time all tumors will develop escape mechanisms in the form of resistance or other mutations that allow them to overcome the efficacy of first-line anti-neoplastic therapies. Repeat biopsy (either through tissue or liquid biopsy) is an effective tool that healthcare providers can use to better understand the mechanisms of acquired resistance that have occurred in the tumor. The utility of repeat biopsy in EGFR and ALK mutant NSCLC patients is discussed, along with many of the known resistance mechanisms that may arise following targeted therapy for these mutations.
God hidden from God: on theodicy, dereliction, and human suffering

A number of theologians and philosophers have found theodical value in the theme of divine solidarity with human suffering. To further develop this theme, I examine what it would mean to assert that Christ on the cross participated in a representative sample of human suffering. Particular attention is paid to Christ’s cry of dereliction. I argue that if God through Christ identified with the very worst kinds of human suffering on the cross, then the cry of dereliction should be interpreted as indicating an epistemic break between God and Christ, and not merely an attentional disruption. According to this account, Christ’s death cry expressed his temporary inability to grasp the significance of his passion and death. In this way, Christ on the cross suffered the full effects of divine hiddenness, thus sharing with horror-sufferers the experience of meaning-negating suffering.
Doping on demand in 2D devices

High-resolution doping patterns can be reversibly written in van der Waals heterostructures using a combination of an electron beam and a back-gate voltage.
Effects of predation pressure and prey density on short-term indirect interactions between two prey species that share a common predator

1. Generalist predators are important contributors to reliable conservation biological control. Indirect interactions between prey species that share a common generalist predator can influence both community dynamics and the efficacy of biological control.2. Laboratory cage experiments investigated the impact of the combined consumptive and non-consumptive effects of predation by adult Hippodamia convergens as a shared predator on the population growth and relative abundance of Acyrthosiphon pisum and Aphis gossypii as prey species. Predation pressure and prey density were varied.3. At low predation pressure the indirect interaction between aphid species was asymmetrical with a proportionally greater negative impact of predation on A. gossypii than on A. pisum. At intermediate predation pressure, the indirect interaction became symmetrical. At high predation pressure and higher levels of prey density, it was asymmetrical with greater negative impact on A. pisum, often driven to local extinction while A. gossypii populations persisted.4. A linear mixed-effects model including early population growth of both aphid species and predation pressure explained 96% and 92% of the variation in the population growth of A. pisum and A. gossypii, respectively, over an 8-day period. The overall effect of shared predation on the indirect interaction between the two aphid species is best described as apparent commensalism, where A. pisum benefited from early population growth of A. gossypii, while A. gossypii was unaffected by early population growth of A. pisum. Considering these indirect interactions is important for conservation biological control efforts to be successful.
RANKLed by the Complexity of Signaling in Breast Cancer Metastasis to the Brain.

Abstract Background Receptor activator of nuclear factor κB (RANK) and its ligand, RANKL, are essential for mammary gland development and play a vital role in breast carcinogenesis. RANKL-RANK signaling also drives thermoregulation and modulates inflammatory activation in the brain. The expression of RANKL in primary breast cancer (BC) has been negatively associated with brain metastases, while significantly higher levels of RANK are seen in BC with brain metastases. We examined the expression of RANK and RANKL in BC metastasis to the brain. Patients and Methods We examined the expression of RANK and RANKL in 40 cases of BC metastasis to the brain. Results RANK was variably expressed in BC cells but minimally expressed in the adjacent brain parenchyma. In contrast, the expression of RANKL was minimal in metastatic BC but highly variable in tumoral stroma. RANKL expression in normal brain stroma obtained during autopsy was negligible. Histologic grade and BC subtypes were not significantly associated with RANK expression in metastatic BC. A significant negative correlation between RANK in metastatic BC and RANKL in tumoral stroma was identified (P Conclusion RANK expressed by primary BC and RANKL detected in the tumor microenvironment together participate in cancer development, while the same principle may operate at distant sites. Further investigation is necessary to provide additional insight into the role of the RANKL-RANK pathway in BC progression and to investigate the potential efficacy of therapeutic strategies targeting these molecules in BC metastasis to the brain.
Cartoon Network: A tool for open-ended exploration of neural circuits

Cartoon Network is an open-source simulator for neural circuits. It was designed to provide a microworld for the playful exploration of neural networks (similar to the niche Logo/Scratch fills for computer programming). The simulator makes it easy to construct and experiment with closed-loop circuits, enabling students to explore how small sets of neurons can generate complex patterns of activity (oscillations, reverberation). Cartoon Network can be connected to the Finch robot from BirdBrain Technologies, a cheap USB robotics platform. This enables students to design a nervous system for a Finch, creating sensory neurons which read Finch inputs (touch, light, and temperature), motor neurons which control Finch outputs (wheels, lights, and sound), and interneurons to produce intrinsic activity and/or link together inputs and outputs in ways that can produce complex and surprising behaviors. Students use Cartoon Network by taking on structured challenges (For example, can you make the Finch follow a light? Can it turn and run when it bumps a wall?) that require deep engagement with important principles of neural circuit operation (e.g., lateral inhibition, parallel processing, positive- and negative-feedback). On successfully completing a challenge, students can systematically explore the neural properties that help control the behavior, compare their work to other successful designs, and/or reflect on how the circuit they designed might be modified via evolution to produce different behaviors. Cartoon Network has proven an engaging and effective activity for undergraduates and is accessible for students as young as late elementary school. Download it for free at: https://github.com/rcalinjageman/cartoon_network.
Emergency Medicine Residency Curricular Innovations: Creating a Virtual Emergency Medicine Didactic Conference

Currently, there is a pandemic forcing social distancing and, consequently, traditional in-person education must shift to a virtual curriculum to protect all parties and continue professional development. Recognizing that not all emergency medicine (EM) content can be taught through a virtual platform, we propose a model for nearly all EM resident didactic conference adaptation to a virtual format to meet the needs of the adult learner while protecting all participants from the current coronavirus pandemic.
Environmental Socialization Incidents with Implications for the Expanded Role of Interpretive Naturalists in Providing Natural History Experiences

Natural history has all but disappeared from formal education in the United States. This places the responsibility of introducing people to natural history within nonformal educational settings, wi...
Transposable elements that cause dysgenesis also contribute to postzygotic isolation in the Drosophila virilis clade

Although hybrid incompatibilities are readily observed in interspecific crosses, the genetic basis of most incompatibilities is still unknown. One persistent hypothesis is that hybrid dysfunction is due to a mismatch between parental genomes in selfish elements and the genes that regulate the proliferation of these elements. In this study, we evaluated the potential role of transposable elements in hybrid incompatibilities by examining hybrids between Drosophila virilis, a species that is polymorphic for the transposable element Penelope, and a closely related species, Drosophila lummei, that lacks active Penelope elements. Given the established role of Penelope elements in hybrid dysgenesis among D. virilis strains, we predicted that interspecies crosses that involve D. virilis with Penelope elements will exhibit greater hybrid incompatibility than crosses involving D. virilis without Penelope. We observed both prezygotic and postzygotic isolation, the magnitude of which was dependent on the specific cross. Using F1 and backcross experiments to rule out alternative genetic incompatibilities, we demonstrated that amplified reproductive isolation in the interspecific cross involving Penelope-carrying D. virilis can be explained by the action of TEs that induce dysgenesis within D. virilis. These experiments demonstrate that TEs can contribute to the expression of hybrid incompatibilities via presence/absence polymorphisms. Further, our data indicate that the same TEs can cause distinct incompatible phenotypes in intraspecific crosses (male sterility) compared to interspecific hybrid crosses (inviability).
DISK EMISSION FROM MAGNETOHYDRODYNAMIC SIMULATIONS OF SPINNING BLACK HOLES

We present the results of a new series of global, three-dimensional, relativistic magnetohydrodynamic (MHD) simulations of thin accretion disks around spinning black holes. The disks have aspect ratios of H/R approx. 0.05 and spin parameters of a/M = 0, 0.5, 0.9, and 0.99. Using the ray-tracing code Pandurata, we generate broadband thermal spectra and polarization signatures from the MHD simulations. We find that the simulated spectra can be well fit with a simple, universal emissivity profile that better reproduces the behavior of the emission from the inner disk, compared to traditional analyses carried out using a Novikov-Thorne thin disk model. Finally, we show how spectropolarization observations can be used to convincingly break the spin-inclination degeneracy well known to the continuum-fitting method of measuring black hole spin.
NOx sequestration by calcium aluminate cementitious materials

Abstract This study quantifies NOx uptake efficiency and explores NOx binding mechanisms in calcium aluminate cementitious (CAC) materials. Comparison between unmodified and TiO2-modified CAC separates intrinsic NOx binding mechanisms from those related to photocatalysis. Attributed to surface-related heterogeneous reactions, the NOx binding occurs in unmodified CAC at nitrite-to-nitrate ratio of 1: 1.3 and can be increased with surface area. The photocatalytic reactions in TiO2-modified CAC increase NOx uptake, and ~50% of converted NOx resists releasing back into the environment via dissolution. Compared to previously studied ordinary portland cement (OPC) materials, CAC increases NOx uptake capacity and demonstrates a more permanent NOx binding, potentially mitigating concerns related to the release of previously bound N-species in OPC. Examination of the interaction between NOx and a synthetic pure aluminum-bearing phase shows that the permanent NOx uptake in CAC could be largely attributed to the chemical binding of converted NOx within aluminum-bearing phases.
Respiratory disease and respiratory physiology: Putting lung function into perspective: Paediatric asthma

Dealing with paediatric asthma in daily practice, we are mostly interested in the airway function: the hallmark of asthma is the variability of airway patency. Various pulmonary function tests (PFT) can be used to quantify airway caliber in asthmatic children. The choice of the test is based on the developmental age of the child, knowledge of the diagnosis/underlying pathophysiology, clinical questions and reasoning, and treatment. PFT is performed to monitor the severity of asthma and the response to therapy, but can also be used as a diagnostic tool, and to study growth and development of the lungs and airways. This review aims to provide clinicians an overview of the differences in assessing PFT in infants and preschool children compared with older cooperative children, which tests are feasible in infants and young children, the limitations of and usefulness of these tests, and of their interpretation in these age groups.
Technology Scaling Challenge and Future Prospects of DRAM and NAND Flash Memory

Memory manufactures are facing the challenges of technology scaling beyond 1xnm node DRAM and NAND flash memory. Even though we are managing to overcome patterning issue, we are still fighting against cost reduction and electrical limitation. In this paper, the scaling limitations and challenges of both DRAM and NAND are reviewed, and the future prospects with promising solutions are also addressed for high density DRAM and 3D NAND flash memory.
Adaptive Control of Nonlinear Systems: A Tutorial

We present a tutorial overview of recent Lyapunov-based results in adaptive control of nonlinear systems. Design tools like backstepping, overparametrization, and tuning functions are illustrated via simple examples. We also discuss the recently introduced “κ-terms”, which endow the resulting adaptive systems with new properties, such as boundedness without adaptation and systematic transient performance improvement through trajectory initialization.
A secure checkpointing protocol for survivable server design

Secure checkpointing appears to be a useful technique for designing survivable systems These are fault-tolerant systems that are robust against malicious security attacks Secure checkpointing, however, is not easily done Without adequate protection, the checkpointing process can be attacked and compromised The checkpointing data can be subjected to malicious attacks and be a source of security breach In this paper, we present a new secure checkpointing scheme that is robust against malicious attacks Our approach uses strong cryptographic techniques for data confidentiality and integrity, Byzantine agreement protocols for compromised peer detection and information dispersal techniques for reliability and availability.
Quantum generation of neural networks

This paper shows how the new field of quantum computing can be applied to the creation of neural network circuits. Quantum computing is capable of processing huge numbers of quantum states simultaneously, in parallel, ("quantum parallelism"). In theory, QC ought to be able to process all possible points in a 2/sup N/ search space (of N bit bit-strings). If N is large, 2/sup N/ is gigantic, making a systematic search with a classical computer impossible. This paper presents an extended example of a simple QC algorithm applied to the generation of neural network circuits.
Muddy Decisions: Gold in the Chocó, Colombia

Abstract As gold prices rose between 2002 and 2012, Afro-descendant gold miners confronted illegal outsider-owned gold mines on their land in Colombia’s northwest Choco department. This article examines why these Afro-descendant miners, who used hand tools and techniques, often invited the outsiders, who used heavy machinery and mercury, to work their mines. Their reasons included: familial pressure over land, profit sharing, high prices, access to gold, and dangerous working conditions. The decision to invite in the outsiders complicates the conventional narrative of a coercive relationship between outsiders and Afro-descendant communities, even as the relationship produced worse than expected outcomes for both sides.
Rules of Engagement in the Conflict Between Businesses and Consumers in Online Contracts

In its purest form, the law of contracts is premised on the ideal of a transaction between parties of equal bargaining strength, who enter a mutually binding and beneficial agreement through the give and take of an open and fair negotiation. But the realities of a modern market economy have required adjustments to that ideal. The law pertaining to adhesion contracts provides an apt example of one such adjustment. In those agreements, the negotiated contract gives way to the form contract in order to promote efficiencies of scale that will benefit both businesses and consumers (and the economy in general) by permitting the parties to forego the formalities of negotiation and mutual assent. This alteration to contract law was justified to allow businesses to reduce their transaction costs, which translates as a benefit to consumers in the form of lower prices for goods and services. Any such adjustment, however, should not undermine the basic idea of a mutually beneficial agreement between the parties.
Phenobarbital and related compounds as novel inhibitors of γ-glutamyltranspeptidase

Abstract The reaction of γ-glutamyltranspeptidase with phenobarbital or with thiobarbituric acid resulted in a irreversible loss of its enzymatic activity. The inactivation followed pseudo-first-order kinetics. Half-maximal velocity of inactivation (Ki) at 37°C in the presence of phenobarbital or thiobarbituric acid was calculated to be 43 mM and 20 mM, respectively. The inactivation of the enzyme activity by both these inhibitors was prevented by serine borate, a known competitive inhibitor, and by the substrate, reduced glutathione, suggesting an active-site-directed nature of these inhibitors. Maleate provided slight protection against inactivation by thiobarbituric acid. Complete inactivation of the enzyme with tritium-labeled phenobarbital resulted in a stoichiometric incorporation of radioactivity into the enzyme protein. Upon sodium dodecyl sulfate polyacrylamide gel electrophoresis of tritium-labeled phenobarbital-enzyme complex, nearly all the radioactivity was found to be associated with the small subunit (Mr = 22 000) of the enzyme, indicating that the catalytic component of the enzyme is on the small subunits.
Site-specific effects of gastrin-releasing peptide in the suprachiasmatic nucleus

The effects of gastrin-releasing peptide (GRP) on the circadian clock in the suprachiasmatic nucleus (SCN) are dependent on the activation of N-methyl-d-aspartate (NMDA) receptors in the SCN. In this study, the interaction between GRP, glutamate and serotonin in the regulation of circadian phase in Syrian hamsters was evaluated. Microinjection of GRP into the third ventricle induced c-fos and p-ERK expression throughout the SCN. Coadministration of an NMDA antagonist or 8-hydroxy-2-di-n-propylamino-tetralin [a serotonin (5-HT)1A,7 agonist, DPAT] with GRP limited c-fos expression in the SCN to a region dorsal to GRP cell bodies. Similar to the effects of NMDA antagonists, DPAT attenuated GRP-induced phase shifts in the early night, suggesting that the actions of serotonin on the photic phase shifting mechanism occur downstream from retinorecipient cells. c-fos and p-ERK immunoreactivity in the supraoptic (SON) and paraventricular hypothalamic nuclei also increased following ventricular microinjection of GRP. Because of this finding, a second set of experiments was designed to test a potential role for the SON in the regulation of clock function. Syrian hamsters were given microinjections of GRP into the peri-SON during the early night. GRP-induced c-fos activity in the SCN was similar to that following ventricular administration of GRP. GRP or bicuculline (a γ-aminobutyric acidA antagonist) administered near the SON during the early night elicited phase delays of circadian activity rhythms. These data suggest that GRP-induced phase-resetting is dependent on levels of glutamatergic and serotonergic neurotransmission in the SCN and implicate activity in the SON as a potential regulator of photic signaling in the SCN.
Perceived occurrence of the second of two closely spaced stimuli in a long movement.

A 75-deg. movement of the arm in the vertical plane was used to examine the conscious perception of the apparent time of occurrence of a reversal signal S2. A marked perceptual delay was found whether S2 occurred during or after the reaction time to the first stimulus. This finding was consistent with Henry’s memory drum theory of neuromotor response, as well as with the efference theory of conscious perception proposed by Festinger and associates.
Dissociation of the inotropic effect of digitalis from its effect on atrioventricular conduction.

Abstract The relation between sequential changes in left ventricular contractility and atrioventricular (A–V) nodal conduction and refractoriness was assessed in open chest dogs during intravenous administration of acetylstrophanthidin (5 μg/kg) at 5 minute intervals until toxic arrhythmias developed. At each time interval, high fidelity left ventricular pressure, its electronic derivative (dP/dt) and a His bundle electrogram were simultaneously recorded and the A–V nodal refractory period was measured by graded trains of stimuli. Animals were studied with an intact autonomic state (Group I), with pharmacologic blockade of both the beta adrenergic and parasympathetic system (Group II) and with parasympathetic blockade (Group III). Whereas contractility increased in response to small doses of digitalis, displaying a linear dose-response relation independent of autonomic tone, A–V nodal transmission indexes responded minimally to less than 50 percent of the toxic dose of digitalis, and the response was dependent upon autonomic tone. These results indicate a dissociation between the effects of digitalis on contractility and A–V transmission in that the major drug action on the ventricular contractile mechanism is a direct, linear one in contrast to the nonlinear response of A–V nodal transmission, which is predominantly mediated through the autonomic system. Clinically, these observations imply that the optimal dose and serum level of digitalis required to treat congestive heart failure may differ significantly from those required to treat supraventricular tachycardias, the therapeutic response of the latter being largely determined by the underlying autonomic tone.
DNA hybridization-induced reorientation of liquid crystal anchoring at the nematic liquid crystal/aqueous interface.

Interactions between DNA and an adsorbed cationic surfactant at the nematic liquid crystal (LC)/aqueous interface were investigated using polarized and fluorescence microscopy. The adsorption of octadecyltrimethylammonium bromide (OTAB) surfactant to the LC/aqueous interface resulted in homeotropic (untilted) LC alignment. Subsequent adsorption of single-stranded DNA (ssDNA) to the surfactant-laden interface modified the interfacial structure, resulting in a reorientation of the LC from homeotropic alignment to an intermediate tilt angle. Exposure of the ssDNA/OTAB interfacial complex to its ssDNA complement induced a second change in the interfacial structure characterized by the nucleation, growth, and coalescence of lateral regions that induced homeotropic LC alignment. Fluorescence microscopy showed explicitly that the complement was colocalized in the same regions as the homeotropic domains. Exposure to noncomplementary ssDNA caused no such response, suggesting that the homeotropic regions were due t...
High-Speed I/O Tests in High-Volume Manufacturing

As high speed IO buses increase in number on emerging devices, new test challenges will drive changes in tester configuration and performance. HVM Tester pin capabilities will shift away from pure digital test to include coverage for high speed functional, AC characterization, and performance based tests. Production test economics will challenge these solutions to be provided at low cost with test time efficiency for large pin count configurations.
How do 14-3-3 proteins work? – Gatekeeper phosphorylation and the molecular anvil hypothesis

14-3-3 proteins were the first signaling molecules to be identified as discrete phosphoserine/threonine binding modules. This family of proteins, which includes seven isotypes in human cells and up to 15 in plants, plays critical roles in cell signaling events that control progress through the cell cycle, transcriptional alterations in response to environmental cues, and programmed cell death. Despite over 30 years of research, distinct roles for most isotypes remain unknown. Though 14-3-3 proteins perform different functions for different ligands, general mechanisms of 14-3-3 action include changes in activity of bound ligands, altered association of bound ligands with other cellular components, and changes in intracellular localization of 14-3-3-bound cargo. We present a speculative model where binding of 14-3-3 to multiple sites on some ligands results in global ligand conformational changes that mediate their biological effects. For these multi-site ligands, one binding site is likely to function as a ‘gatekeeper’ whose phosphorylation is necessary for 14-3-3 binding but may not always be sufficient for full biological activity. If correct, then 14-3-3 may prove to be a bona fide phosphodependent signaling chaperone.
Expression of heritable biochemical markers from various pecan tissues

Isozyme expression of malate dehydrogenase (MDH), phosphoglucomutase (PGM), and phosphoglucose isomerase (PGI) were examined from 12 tissues of pecan by starch gel electrophoresis. Tissue type, stage of development, and extraction method had little effect on isozyme expression of MDH or PGM but did influence PGI expression. Additional PGI bands were observed from seed tissue and soaked pollen. A direct relationship was observed between PGI expression from seed tissue and eventual expression from the germinated seedling. Additional PGI bands from soaked pollen were thought to be produced from structural changes and not due to more efficient extraction. The genotype of immature pecan seeds could be determined for Mdh-1, Pgi-2, and Pgm-1 provided cellular endosperm had developed. Watery endosperm did not contain detectable levels of the study enzymes. The advantages of uniform isozyme expression among various tissues and ability to determine the genotype of immature pecan seed are discussed.
Intracellular conversion of the RNA of Sindbis virus to a double-stranded form

Abstract A simple procedure for the preparation of Sindbis virus labeled with uridine- 3 H was devised. The product was radiochemically pure by several criteria. During the first hour of infection some of the RNA of this labeled virus was found in a more slowly sedimenting form that was resistant to RNase and had other properties of double-stranded RNA. This conversion of parental viral RNA to a double-stranded form was not seen when protein synthesis was inhibited. A viral mutant with a temperature-sensitive block in viral RNA synthesis likewise showed no conversion of parental viral RNA to a double-stranded form at a nonpermissive temperature.
Interface enabled defects reduction in helium ion irradiated Cu/V nanolayers

Abstract Sputter-deposited Cu/V nanolayer films with individual layer thickness, h, varying from 1 to 200 nm were subjected to helium (He) ion irradiation at room temperature. At a peak dose level of 6 displacements per atom (dpa), the average helium bubble density and lattice expansion decrease significantly with decreasing h. The magnitude of radiation hardening decreases with decreasing individual layer thickness, and becomes negligible when h is 2.5 nm or less. This study indicates that nearly immiscible Cu/V interfaces spaced a few nm apart can effectively reduce the concentration of radiation induced point defects. Consequently, Cu/V nanolayers possess enhanced radiation tolerance, i.e., reduction of swelling and suppression of radiation hardening, compared to monolithic Cu or V.
An Analysis for the Composition and Film Thickness of Organic Layered Photoconductors. Part I: Complex Refractive Indices over the Infrared for Hydroxysquarilium and Chlorodiane Blue Charge Generation Dyes

The composition and film thickness of organic layered photoconductors containing the charge generation dyes hydroxysquarilium and chlorodiane blue are analyzed by specular reflectance infrared spectroscopy. The analysis involves recording the infrared spectrum of the photoconductor after the dye layer is coated onto an appropriate substrate. Since the IR spectra are recorded in a specular reflection mode, modeling is required in order to understand the relationship between reflectance and film thickness for the dye layers. Thus a dispersion analysis is used to determine the complex refractive indices over the infrared for the charge generation dyes hydroxysquarilium and chlorodiane blue.
Self-induced decoherence approach: Strong limitations on its validity in a simple spin bath model and on its general physical relevance

The ``self-induced decoherence'' (SID) approach suggests that (1) the expectation value of any observable becomes diagonal in the eigenstates of the total Hamiltonian for systems endowed with a continuous energy spectrum, and that (2) this process can be interpreted as decoherence. We evaluate the first claim in the context of a simple spin bath model. We find that even for large environments, corresponding to an approximately continuous energy spectrum, diagonalization of the expectation value of random observables does in general not occur. We explain this result and conjecture that SID is likely to fail also in other systems composed of discrete subsystems. Regarding the second claim, we emphasize that SID does not describe a physically meaningful decoherence process for individual measurements, but only involves destructive interference that occurs collectively within an ensemble of presupposed ``values'' of measurements. This leads us to question the relevance of SID for treating observed decoherence effects.
Heterotypic control of basement membrane dynamics during branching morphogenesis.

Many mammalian organs undergo branching morphogenesis to create highly arborized structures with maximized surface area for specialized organ function. Cooperative cell–cell and cell–matrix adhesions that sculpt the emerging tissue architecture are guided by dynamic basement membranes. Properties of the basement membrane are reciprocally controlled by the interacting epithelial and mesenchymal cell populations. Here we discuss how basement membrane remodeling is required for branching morphogenesis to regulate cell–matrix and cell–cell adhesions that are required for cell patterning during morphogenesis and how basement membrane impacts morphogenesis by stimulation of cell patterning, force generation, and mechanotransduction. We suggest that in addition to creating mature epithelial architecture, remodeling of the epithelial basement membrane during branching morphogenesis is also essential to promote maturation of the stromal mesenchyme to create mature organ structure. Recapitulation of developmental cell–matrix and cell–cell interactions are of critical importance in tissue engineering and regeneration strategies that seek to restore organ function.
Solution of a Two-Dimensional Inverse Radiation Problem Using Evolutionary Algorithms

While solving inverse problems stability of the solutions is an issue. Stability ensures that solutions obtained are physically possible and not just mathematically feasible. Techniques like Truncated Singular Value Decomposition (TSVD), Tikhonov’s regularization have been used to stabilize solutions. These are called regularization techniques, which involve selection of regularizing parameters. The choice of these regularizing parameters dictates the accuracy of solutions obtained. In this paper an Evolutionary Algorithm (EA) based optimization procedure is used to solve an inverse radiation problem in a rectangular enclosure. The fitness function and the mutation operator have been designed to eliminate the need for regularization. The evolutionary technique developed in this paper ensures a better search on the fitness landscape, without the additional effort of choosing regularization parameters.Copyright © 2004 by ASME
Crito 51A-C: to what does Socrates owe obedience?

Though many scholars have attempted to resolve the apparent inconsistency between Apology 29C-D and Crito 51A-C,I I do not think that any has done an adequate job. As ingenious as some of these attempts have been, they either leave crucial parts of the Socratic puzzle unsolved or they complicate the puzzle still further. The cause of this widespread failure, I shall argue, has been almost universal inattention to the full text of the Laws' speech in the Crito.2 My intent, however, is not so much to identify the shortcomings of my predecessors as to focus attention on that speech, for, when carefully read, it not only helps us solve the traditional dilemma, but also sheds needed light on Socrates' puzzling relationship with the Athenian polis. In other words, I shall employ the dilemma presented by the Apology and the Crito as a point of departure into an investigation of Socrates' understanding of the allegiance he owes to his polity.3
Capti-speak: a speech-enabled web screen reader

People with vision impairments interact with web pages via screen readers that provide keyboard shortcuts for navigating through the content. However, web browsing with screen readers can be a frustrating experience mainly due to time and effort spent on locating the desired content through the extensive use of keyboard shortcuts. This gets even worse if users have limited shortcut vocabulary or are not familiar with the structure of a particular webpage. Augmenting screen readers with a speech input interface has the potential to alleviate the above limitations. This paper describes the design, implementation, and evaluation of Capti-Speak, a speech-enabled screen reader for web browsing, capable of translating speech utterances into browsing actions, executing the actions, and providing audio feedback. The novelty of Capti-Speak is that it leverages a custom dialog model, designed exclusively for non-visual web access, for interpreting speech utterances. A user study with 20 blind subjects showed that Capti-Speak was significantly more usable and efficient compared to the regular screen reader, especially for ad-hoc browsing, searching, and navigating to the content of interest.
Excess ribonucleotide reductase R2 subunits coordinate the S phase checkpoint to facilitate DNA damage repair and recovery from replication stress

Ribonucleotide reductase (RNR), which consists of R1 and R2 subunits, catalyzes a key step of deoxyribonucleoside triphosphate (dNTP) synthesis for DNA replication and repair. The R2 subunit is controlled in a cell cycle-specific manner for timely DNA synthesis and is negatively regulated by p53 in response to DNA damage. Herein we demonstrate that the presence of excess R2 subunits in p53(-/-) HCT-116 human colon cancer cells protects against DNA damage and replication stress. siRNA-mediated stable knockdown (>80%) of excess R2 subunits has no effect on proliferative growth but results in enhanced accumulation of gamma-H2Ax and delayed recovery from DNA lesions inflicted by exposure to cisplatin and Triapine. This accentuated induction of gamma-H2Ax in R2-knockdown cells is attributed to reduced ability to repair damaged DNA and overcome replication blockage. The lack of excess R2 subunits consequently augments chk1 activation and cdc25A degradation, causing impeded cell progression through the S phase and enhanced apoptosis in response to DNA damage and replication stress. In contrast, the level of R1 subunits appears to be limiting, since depletion of the R1 subunit directly activates the S phase checkpoint due to replication stress associated with impaired RNR activity. These findings suggest that excess R2 subunits facilitate DNA damage repair and recovery from replication stress through coordination with the S phase checkpoint in the absence of functional p53. Thus, the level of the R2 subunit constitutes an important determinant of the chemosensitivity of cancer cells and serves as a potential target for enhancement of DNA-damage based therapy.
Genome-Wide Analysis of Menin Binding Provides Insights into MEN1 Tumorigenesis

Multiple endocrine neoplasia type I (MEN1) is a familial cancer syndrome characterized primarily by tumors of multiple endocrine glands. The gene for MEN1 encodes a ubiquitously expressed tumor suppressor protein called menin. Menin was recently shown to interact with several components of a trithorax family histone methyltransferase complex including ASH2, Rbbp5, WDR5, and the leukemia proto-oncoprotein MLL. To elucidate menin's role as a tumor suppressor and gain insights into the endocrine-specific tumor phenotype in MEN1, we mapped the genomic binding sites of menin, MLL1, and Rbbp5, to approximately 20,000 promoters in HeLa S3, HepG2, and pancreatic islet cells using the strategy of chromatin-immunoprecipitation coupled with microarray analysis. We found that menin, MLL1, and Rbbp5 localize to the promoters of thousands of human genes but do not always bind together. These data suggest that menin functions as a general regulator of transcription. We also found that factor occupancy generally correlates with high gene expression but that the loss of menin does not result in significant changes in most transcript levels. One exception is the developmentally programmed transcription factor, HLXB9, which is overexpressed in islets in the absence of menin. Our findings expand the realm of menin-targeted genes several hundred-fold beyond that previously described and provide potential insights to the endocrine tumor bias observed in MEN1 patients.
USING COMPUTERIZED STUDY GUIDES TO INCREASE PERFORMANCE ON GENERAL PSYCHOLOGY EXAMINATIONS: AN EXPERIMENTAL ANALYSIS

The effectiveness of using a commercially available computerized study guide to improve performance on examinations in two general psychology courses was investigated. The experimental design required 37 students to use a computerized study guide on two examinations and not on two others, counterbalanced across two classes. Analysis suggested that use of the study guides was associated with an increase in examination scores. These commercially available computerized study guides may be effective because they use many empirically established general principles of learning.
Map4k4 Negatively Regulates Peroxisome Proliferator-activated Receptor (PPAR) γ Protein Translation by Suppressing the Mammalian Target of Rapamycin (mTOR) Signaling Pathway in Cultured Adipocytes*

The receptor peroxisome proliferator-activated receptor γ (PPARγ) is considered a master regulator of adipocyte differentiation and promotes glucose and lipid metabolism in mature adipocytes. We recently identified the yeast Sterile 20 (Ste20) protein kinase ortholog, Map4k4, in an RNA interference-based screen as an inhibitor of PPARγ expression in cultured adipocytes. Here, we show that RNA interference-mediated silencing of Map4k4 elevates the levels of both PPARγ1 and PPARγ2 proteins in 3T3-L1 adipocytes without affecting PPARγ mRNA levels, suggesting that Map4k4 regulates PPARγ at a post-transcriptional step. PPARγ degradation rates are remarkably rapid as measured in the presence of cycloheximide (t½ = 2 h), but silencing Map4k4 had no effect on PPARγ degradation. However, depletion of Map4k4 significantly enhances [35S]methionine/cysteine incorporation into proteins, suggesting that Map4k4 signaling decreases protein translation. We show a function of Map4k4 is to inhibit rapamycin-sensitive mammalian target of rapamycin (mTOR) activity, decreasing 4E-BP1 phosphorylation. In addition, our results show mTOR and 4E-BP1 are required for the increased PPARγ protein expression upon Map4k4 knockdown. Consistent with this concept, adenovirus-mediated expression of Map4k4 decreased PPARγ protein levels and mTOR phosphorylation. These data show that Map4k4 negatively regulates PPARγ post-transcriptionally, by attenuating mTOR signaling and a 4E-BP1-dependent mechanism.
Response to Desmopressin as a Function of Urine Osmolality in the Treatment of Monosymptomatic Nocturnal Enuresis: A Double-Blind Prospective Study

AbstractTo determine if urine osmolality parameters can predict whether children with primary monosymptomatic nocturnal enuresis will respond to desmopressin, we conducted a prospective, double-blind, placebo-controlled study in 96 children 8 to 14 years old. Following a 2-week baseline screening interval patients with at least 6 of 14 wet nights were randomized to double-blind regimens of desmopressin or placebo. Urine specimens for osmolality were collected at 6 p.m. and 6 a.m. on 3 consecutive days during the baseline and the 2, 14-day treatment periods.A significantly greater proportion of desmopressin treated children had an excellent (2 or fewer wet nights in 14 days) or good (greater than 50 percent reduction in wet nights) response compared with placebo treated children (p = 0.004 and p = 0.002 for treatment periods 1 and 2, respectively). Children treated with desmopressin reported a significantly lower number of wet nights than placebo treated children during both treatment periods (p = 0.0258 a...
Is public sociology such a good idea

Michael Burawoy’s call for a public sociology disciplined by professional and policy sociology, on the one side, and driven by critical sociology, on the other, exposes the ideological biases of sociology to publics. In so doing, public sociology will thwart non-ideological efforts for sociology to exert influence on broader publics and on political decision-makers. In order for sociology to be able to influence public opinion and the decisions of key players in the political and economic arenas, it will need to earn respect through a long evolutionary process of careful research and explanation without ideological fervor. To expose the ideological biases of sociology will thwart this evolutionary process. In contrast, sociology would be much better to develop an engineering mentality in addressing issues, problems, and concerns of publics in present-day societies.
First-principles calculation of the electronic and optical properties of the organic superconductor κ-(BEDT-TTF) 2 Cu(NCS) 2

The electronic structure and the optical properties of the organic superconductor \ensuremath{\kappa}-(BEDT-TTF${)}_{2}$Cu(NCS${)}_{2}$ are fully elucidated by means of first-principles self-consistent local-density calculation. The band effective masses on the Fermi surfaces are found to be ${\mathit{m}}_{\mathrm{\ensuremath{\alpha}}}^{\mathit{b}\mathrm{*}}$=1.77 m and ${\mathit{m}}_{\mathrm{\ensuremath{\beta}}}^{\mathit{b}\mathrm{*}}$=3.50 m, and the density of state at the Fermi level is 12.8/eV cell. These results are quite different from the existing calculations based on semiempirical methods, and are in much better agreement with experiments. Remarkable similarities in the electronic structure between the organic superconductors and the alkali-doped fullerene superconductors are pointed out and the implications discussed.
A Novel Function for SNAP29 (Synaptosomal-Associated Protein of 29 kDa) in Mast Cell Phagocytosis

Mast cells play a critical role in the innate immune response to bacterial infection. They internalize and kill a variety of bacteria and process antigen for presentation to T cells via MHC molecules. Although mast cell phagocytosis appears to play a significant role during bacterial infection, little is known about the proteins involved in its regulation. In this study, we demonstrate that the SNARE protein SNAP29 is involved in mast cell phagocytosis. SNAP29 is localized in the endocytic pathway and is transiently recruited to Escherichia coli (E. coli)-containing phagosomes. Interestingly, overexpression of SNAP29 significantly increases the internalization and killing of E. coli, while it does not affect mast cell exocytosis of inflammatory mediators. To our knowledge, these data are the first to demonstrate a novel function of SNAP29 in mast cell phagocytosis and have implications in protection against bacterial infection.