cssi/SciSciGPT-SciSciNet huggingface dataset:
Colonizing other planets is a bad idea

Abstract Should humans seek to colonize outer space? I say no. I have worked in the space community for 35 years with a variety of programs and projects ranging from science to human space flight. My view as a social scientist is that humans are not sufficiently advanced, technologically and socially, to be establishing colonies on Mars, or any other place in space. Except for the threads of Russian cosmism, the ideology of space colonization and exploitation is largely Western, and Christian, as noted above. It appears to be some interpretation of Christian dominion, or dominionist, theology that drives colonization advocates to declare that humans are destined to fill the universe, that humans “must” colonize Mars, that outer space resources are there for the taking.The ideology of space exploration is in need of rejuvenation. The author advocates a visionof a human future in space in which humanity finds its way to a collective peaceful existence on Spaceship Earth, a way to work together to preserve life here and to look for life out there. Perhaps at some point in the distant future, humans might be ready –technologically and socially – to live together peacefully on other planets. But we are not there yet.
Quantified Uncertainty in Thermodynamic Modeling for Materials Design

Abstract Phase fractions, compositions and energies of the stable phases as a function of macroscopic composition, temperature, and pressure (X-T-P) are the principle correlations needed for the design of new materials and improvement of existing materials. They are the outcomes of thermodynamic modeling based on the CALculation of PHAse Diagrams (CALPHAD) approach. The accuracy of CALPHAD predictions vary widely in X-T-P space due to experimental error, model inadequacy and unequal data coverage. In response, researchers have developed frameworks to quantify the uncertainty of thermodynamic property model parameters and propagate it to phase diagram predictions. In most previous studies, uncertainty was represented as intervals on phase boundaries (with respect to composition or temperature) and was unable to represent the uncertainty in invariant reactions or in the stability of phase regions. In this work, we propose a suite of tools that leverages samples from the multivariate model parameter distribution to represent uncertainty in forms that surpass previous limitations and are well suited to materials design. These representations include the distribution of phase diagrams and their features, as well as the dependence of phase stability and the distributions of phase fraction, composition, activity and Gibbs energy on X-T-P location - irrespective of the total number of components. Most critically, the new methodology allows the material designer to interrogate a certain composition and temperature domain and get in return the probability of different phases to be stable, which can positively impact materials design.
Churchill and the Outbreak of the Second World War in Europe

Abstract Eighty years ago, World War II broke out in Europe. Remembering this anniversary provides an opportunity to reflect on what we might learn from studying the history of that hideous era. Of the many accounts on the war's origins, Winston Churchill offered one of the most insightful interpretations about how a return of great-power competition shattered Europe's peace. His condemnation of Great Britain's leaders for seeking to appease the Nazi dictator offers a sobering lesson in the failure of the world's democracies to arm themselves and band together to preserve the peace. Churchill lamented that democracy had been weighed in the balance and found wanting. His lamentation still serves as a warning against the folly of military weakness and foreign policy isolation.
Survival Advantage With Adjuvant Chemotherapy for Locoregionally Advanced Rectal Cancer: A Veterans Health Administration Analysis

BACKGROUND Adjuvant chemotherapy (AC) after chemoradiation (CRT) and surgery for locoregionally advanced rectal cancer (LARC) is a standard of care in the United States. This study examined the role, optimal regimen, and duration of AC using data from the largest integrated health system in the United States. PATIENTS AND METHODS Using the Veterans Affairs Central Cancer Registry, patients with stage II-III rectal cancer diagnosed in 2001 through 2011 who received neoadjuvant CRT and surgery with or without AC were identified. Kaplan-Meier analysis, log-rank tests, and propensity score (PS) adjustment analysis were used to assess survival. RESULTS A total of 866 patients were identified; 417 received AC and 449 did not (observation [OBS] group). Median follow-up was 109 months. Median disease-specific survival (DSS) was not reached. Six-year DSS was 73.7%; 79.5% for the AC group versus 68.0% for the OBS group. PS-matched analysis for DSS favored AC (P=.0002). Median overall survival (OS) was 90.8 months. Six-year OS was 56.7%; 64.3% for AC versus 49.6% for OBS. In PS-matched analysis, median OS was 117.4 months for AC and 74.3 months for OBS (P<.0001). A DSS advantage was seen when comparing ≥4 months with <4 months of AC (P=.023). No difference in DSS or OS was seen with single-agent versus multiagent AC. CONCLUSIONS In this population of patients with LARC treated with neoadjuvant CRT and surgery, OS and DSS were improved among those treated with AC versus OBS. DSS benefits were seen with ≥4 months of AC. No additional benefit was observed with multiagent therapy. In the absence of phase III data, these findings support the use of AC for LARC.
Crossing Domains for AU Coding: Perspectives, Approaches, and Measures

Facial action unit (AU) detectors have performed well when trained and tested within the same domain. How well do AU detectors transfer to domains in which they have not been trained? We review literature on cross-domain transfer and conduct experiments to address limitations of prior research. We evaluate generalizability in four publicly available databases. EB+ (an expanded version of BP4D+), Sayette GFT, DISFA and UNBC Shoulder Pain (SP). The databases differ in observational scenarios, context, participant diversity, range of head pose, video resolution, and AU base rates. In most cases performance decreased with change in domain, often to below the threshold needed for behavioral research. However, exceptions were noted. Deep and shallow approaches generally performed similarly and average results were slightly better for deep model compared to shallow one. Occlusion sensitivity maps revealed that local specificity was greater for AU detection within than cross domains. The findings suggest that more varied domains and deep learning approaches may be better suited for generalizability and suggest the need for more attention to characteristics that vary between domains. Until further improvement is realized, caution is warranted when applying AU classifiers from one domain to another.
Using smart phone technology can aid in better bowel preparation and improve healthcare delivery.

Commentary on: Guo B, Zuo X, Li Z, et al . Improving the quality of bowel preparation through an app for inpatients undergoing colonoscopy: a randomized controlled trial. J Adv Nurs 2019. doi: 10.1111/jan.14295 Colonoscopy is the standard method for screening, diagnostic evaluation and treatment of colorectal lesions.1 Quality of bowel preparation greatly impacts the success of colonoscopy in diagnostic yield, adenoma detection and patient safety.1 2 Multiple studies have shown that inpatients are more likely to have poor bowel preparation.2 Improving bowel preparation by combining conventional tools with newer technology can result in greater efficiency. …
A Bayesian Trust Inference Model for Human-Multi-Robot Teams

In this paper, we develop a Bayesian inference model for the degree of human trust in multiple mobile robots. A linear model for robot performance in navigation and perception is first devised. We then propose a computational trust model for the human multi-robot team based on a dynamic Bayesian network (DBN). In the trust DBN, the robot performance is the network input, the human trust feedback to each individual robot and the human intervention are the outputs (observations). The categorical Boltzmann machine is used to capture the multinomial distributions that model the conditional dependencies of the DBN. We introduce the expectation maximization (EM) algorithm for the model learning and personalization. A factorial form of the EM algorithm is adopted for the multi-robot system where each robot has its corresponding latent trust state in the human mind. Bayesian inference is conducted to find the trust states, i.e., the trust belief. Based on the inferred trust states, we further derive the formulation to predict human interventions for model validation. A simulated human-UAV collaborative search mission is conducted with humans-in-the-loop. The experiment results show the Bayesian trust inference model can infer the degrees of human trust in multiple mobile robots and also predict human interactions with relatively high accuracy (72.2 $$\%$$ ). These findings confirm the effectiveness of DBNs in modeling human trust towards multi-robot systems.
Origins of Elastic Properties in Ordered Block Copolymer/Nanoparticle Composites

We predict a diblock copolymer melt in the lamellar phase with added spherical nanoparticles that have an affinity for one block to have a lower tensile modulus than a pure diblock copolymer system. This weakening is due to the swelling of the lamellar domain by nanoparticles and the displacement of polymer by elastically inert fillers. Despite the overall decrease in the tensile modulus of a polydomain sample, the shear modulus for a single domain is unaffected by fillers.
TOWARD A THEORY OF SUPPLY CHAIN ENTREPRENEURIAL EMBEDDEDNESS IN DISRUPTED AND NORMAL STATES

The daunting effects of COVID-19 have motivated large firms to rethink supply chain designs and practices As a potential contribution to such change, we introduce the concept of supply chain entrepreneurial embeddedness (SCEE), which we define as the degree to which a large firm integrates small entrepreneurial business capabilities (e g , creativity, ingenuity, resourcefulness, rapid decision-making, and swift execution) within its supply chain We theorize that SCEE can be realized via at least three mechanisms—acquiring (i e , purchasing one or more small entrepreneurial firms), allying (i e , building cooperative alliances with such firms), and assimilating (i e , mimicking how such firms behave) We suggest that SCEE is valuable under normal conditions, but its value increases under duress Grounded in the concepts of structural inertia, requisite variety, mutualism, and real options, our core premise is that SCEE enables large firms to better navigate multiple and multidirectional concurrent changes in supply and demand, which in turn enhances firm performance We contextualize this core premise by theorizing that greater end-user proximity (wherein SCEE is located close to the final customer) and service centricity (wherein competition is primarily based on the service dimension of product–service bundles) enhance SCEE’s positive effects © 2020 Wiley Periodicals LLC
A Case of Diagnostic Difficulty: Transient Loss of Consciousness in Artery of Percheron Infarct.

The artery of Percheron (AOP) is a rare anatomical variant of the paramedian thalamic vessels in 7-10% of the general population. An AOP infarct can present with rare clinical manifestations like transient loss of consciousness (LOC) and lethargy, as was seen in the patient whose case is discussed in this report, due to the plethora of regulatory inputs and outputs by the thalamus, which cannot be compensated for because of the absence of anastomotic connections. The AOP supplies the reticular activating system (RAS), which regulates consciousness. Ischemia to this area from an AOP infarct can result in the transient LOC, which our patient experienced. The AOP is a small vessel that is often missed on a CT angiogram (CTA) alone due to low resolution. As a result, it is imperative that clinicians utilize MRI to diagnose AOP infarcts in patients who present with symptoms that raise concerns for decreased bilateral thalamic function and transient LOC.
Detecting of Pavement Marking Defects Using Faster R-CNN

AbstractPavement markings on roads and highways are used to guide the roadway users. They play an essential role in promoting efficient use of the roadway and drivers’ safety. Typically, pavement m...
Haplotype Allele Frequency (HAF) Score: Predicting Carriers of Ongoing Selective Sweeps Without Knowledge of the Adaptive Allele

Methods for detecting the genomic signatures of natural selection are heavily studied, and have been successful in identifying many selective sweeps. For the vast majority of these sweeps the adaptive allele remains unknown, making it difficult to distinguish carriers of the sweep from non-carriers. Because carriers of ongoing selective sweeps are likely to contain a future most recent common ancestor, identifying them may prove useful in predicting the evolutionary trajectory– for example, in contexts involving drug-resistant pathogen strains or cancer subclones. The main contribution of this paper is the development and analysis of a new statistic, the Haplotype Allele Frequency (HAF) score, assigned to individual haplotypes in a sample. The HAF score naturally captures many of the properties shared by haplotypes carrying an adaptive allele. We provide a theoretical model for the behavior of the HAF score under different evolutionary scenarios, and validate the interpretation of the statistic with simulated data. We develop an algorithm (\(\text {PreCIOSS}\): Predicting Carriers of Ongoing Selective Sweeps) to identify carriers of the adaptive allele in selective sweeps, and we demonstrate its power on simulations of both hard and soft selective sweeps, as well as on data from well-known sweeps in human populations.
The Mathematics of Discontinuity

Somehow it is appropriate if ironic that sharply divergent opinions exist in the mathematical House of Discontinuity with respect to the appropriate method for analyzing discontinuous phenomena. Different methods include catastrophe theory, chaos theory, fractal geometry, synergetics theory, self-organizing criticality, spin glass theory, and emergent complexity. All have been applied to economics in one way or another.
A new algorithm for computing projections on smooth convex sets

Summary form only given. An algorithm for computing the projection of a point onto a closed convex set is presented. It is assumed that the set is smooth. The procedure is a simple iterative scheme that generates a sequence of points starting from an initial guess of the solution. This sequence of points converges to the desired projection. The procedure also guarantees that at any point in the iteration, the generated approximate projection always lies on the boundary of the set. >
Biology, New Materialism, Ontology: Thinking About Biology as a Resource for Political Theory

In this paper, I want to explore the ways that political theorists might draw on contemporary biology as a resource for critical, creative, and imaginative thinking. Political theorists have been quite skilled in taking up systematic (and anti-systematic) theories of language, psyche, history, and cultural practice in order to challenge received understandings in political and scholarly life. However, unlike their historical forebears, they have not been as open to biology - this, presumably, because of the fear of eugenics and the abrogation of freedom that accompanies biological reductionism. It seems to me, however, that contemporary biology might readily serve a provocative and productive role in political theory. The idea here is not for theorists to become empirically correct in describing personhood or technically accurate in tracing the elements of action nor is it that they should see their intellectual task as merely the straightforward elaboration of the possible political implications of particular biological facts. Rather, the idea is to see biology as a resource for defamiliarizing our sense of the human - and of matter, space, time, and history, for example - and for questioning the presumptions about self-mastery, moral superiority, and political primacy that often accompany the assumption of human exceptionalism. This essay will likely acknowledge the importance of historically sensitive, discursive analyses of scientific knowledge but it will also suggest that contemporary biology might be conceived productively as a kind of new materialist ontology.
Anti-swing control of overhead crane based on double fuzzy controllers

Eliminating and controlling the swing of the crane are very important for increasing the work efficiency, decreasing hazard during loading and unloading operation. By the analysis of the simulation of the two-dimensional motion of overhead crane model, this paper obtained the basic domains of the displacement and tilt angle, applied the fuzzy control principle to ensure the structure of fuzzy control, design the membership functions of the input and output variables, and build the fuzzy controllers. The result of the simulation show that the design of the fuzzy controllers have a good performance which effectively inhibits the hoisting swing and make the car arrive at its destination accurately and it also has a strong anti-interference ability.
The participial oblique, a verb mood found only in Nunivak Central Alaskan Yup'ik and in Siberian Yupik

L’ile de Nunivak possede le plus divergent des dialectes de l’eskimo yup’ik central d’Alaska, langue parlee dans le sud-ouest de l’Alaska. Les divergences lexicales et phonologiques ont ete examinees precedemment ailleurs. Dans le present article, on discute de la forme et de la fonction du mode du verbe de type «oblique participial» que l’on trouve dans le yup’ik de Nunivak, mais dans aucun des autres dialectes du yup’ik central d’Alaska, et dans le yupik central siberien, langue parlee dans l’ile Saint-Laurent en Alaska et a la pointe de la Tchoukotka. On examine egalement les differences entre la forme tchoukotkane du mode et celle de l’ile Saint-Laurent, la presence du mode dans le yupik de Naukan et un eventuel «chainon manquant» dans la construction participiale des autres dialectes du yup’ik central d’Alaska.
Repairs to Damage Tolerant Aircraft

The results of displacement compatibility analysis, representing a variety of repair doubler and lap splice configurations, are presented with a view to illustrating how structural repairs can degrade the fatigue initiation life and damage tolerance capability of primary transport aircraft structure. Examples show that fatigue initiation life is directly related to the peak loads induced in the first fastener rows at the edges of repair doublers. Design of repairs to an equal or better static strength capability and the associated static strength analysis will not normally highlight these peak loads which can result in considerable degradation of structural fatigue life. Critical fastener loads, based on displacement compatibility analysis accounting for fastener flexibility, are parametrically presented for a variety of skin and doubler thicknesses. Suggestions are made on how repair designs can be modified to improve fatigue initiation life and subsequent fatigue crack detectability particularly in the event of multiple-site damage (MSD). The importance of riveting quality during repairs, often not up to initial manufacturing standards, is discussed with respect to fatigue initiation life. A simplified but conservative method to generate crack growth curves is discussed with a view to easing the analytical burden for the small modifiers. It is hoped that this information, together with conservative fatigue Sn data, will help the many small repair and modification stations gain an appreciation of the fatigue and damage tolerance quality of structural repairs. It is pointed out in the paper that the FAA regulations were amended in December, 1978 for new transport category aircraft and in May, 1981 for aging transport aircraft to include a damage tolerance philosophy. This means that any repair to a transport category airframe, which may effect threshold, frequency and type of inspection of principal structural elements, must be evaluated for it’s damage tolerance capability.
The self-avoiding walk in four dimensions

Recent progress on the self-avoiding walk on a four dimensional hypercubic lattice is presented. Methods for determining the long-time behavior of such walks by studying the Green's function are described.
Frequency Response of Pressure Sensor Configurations in Slip-Flow Conditions

A dynamic model is presented for pneumatic tubing and pressure sensor configurations in rarefied or slip-flow conditions. The model uses the linearized Navier-Stokes equations, with the boundary conditions extended to allow for rarefied conditions. At low pressure levels, the modified wall boundary condition allows fluid elements to slip when directly in contact with the tubing wall. This slippage effectively lowers fluid viscosity. Dynamic effects of the rarefied-flow extension are demonstrated by comparing rarefied-flow solutions to equivalent solutions generated using continuum-flow models. Lower viscosity resulting from rarefied flow causes the configuration response to be less damped than for similar conditions without molecular effects. Comparing steady-state response to data from a series of laboratory experiments validates the range of the rarefied-flow model. When pneumatic tubing is heated unevenly, rarefied flow forces the tube hot end to have higher pressure than the cold end, with no net flow along the tube. This pressure difference results in a dc offset in the measured pressure reading. Comparisons of the steady-state model to experimental data show that the slip-flow model is generally applicable for Knudsen numbers up to approximately 0.65. Beyond 0.7 Knudsen number, molecular effects dominate, and the model is no longer applicable to the problem physics.
Unraveling Cholesterol Catabolism in Mycobacterium tuberculosis: ChsE4-ChsE5 α2β2 Acyl-CoA Dehydrogenase Initiates β-Oxidation of 3-Oxo-cholest-4-en-26-oyl CoA.

The metabolism of host cholesterol by Mycobacterium tuberculosis (Mtb) is an important factor for both its virulence and pathogenesis, although how and why cholesterol metabolism is required is not fully understood. Mtb uses a unique set of catabolic enzymes that are homologous to those required for classical β-oxidation of fatty acids but are specific for steroid-derived substrates. Here, we identify and assign the substrate specificities of two of these enzymes, ChsE4-ChsE5 (Rv3504-Rv3505) and ChsE3 (Rv3573c), that carry out cholesterol side chain oxidation in Mtb. Steady-state assays demonstrate that ChsE4-ChsE5 preferentially catalyzes the oxidation of 3-oxo-cholest-4-en-26-oyl CoA in the first cycle of cholesterol side chain β-oxidation that ultimately yields propionyl-CoA, whereas ChsE3 specifically catalyzes the oxidation of 3-oxo-chol-4-en-24-oyl CoA in the second cycle of β-oxidation that generates acetyl-CoA. However, ChsE4-ChsE5 can catalyze the oxidation of 3-oxo-chol-4-en-24-oyl CoA as well a...
Regulation of Glycogen Synthase IDENTIFICATION OF RESIDUES INVOLVED IN REGULATION BY THE ALLOSTERIC LIGAND GLUCOSE-6-P AND BY PHOSPHORYLATION

The major yeast glycogen synthase, Gsy2p, is inactivated by phosphorylation and activated by the allosteric ligand glucose-6-P. From studies of recombinant proteins, the control can be accommodated by a three-state model, in which unphosphorylated enzyme has intermediate activity (state II). Glucose-6-P increasedV max/K m by about 2-fold (state III), whereas phosphorylation by the cyclin-dependent protein kinase Pcl10p/Pho85p decreasedV max/K m by ∼30-fold (state I). In the presence of glucose-6-P, state III is achieved regardless of phosphorylation state. The enzyme forms complexes in solution with the yeast glycogenin Glg2p, but this interaction appears not to affect control either by glucose-6-P binding or by phosphorylation. Scanning mutagenesis was applied to identify residues potentially involved in ligand binding. Of 22 mutant enzymes analyzed, seven were essentially inactive. Five mutant proteins were altered in their activation by glucose-6-P, and two were completely unaffected by the hexose phosphate. One of these, R586A/R588A/R591A (all three of the indicated Arg residues mutated to Ala), had wild-type activity and was normally inactivated by phosphorylation. A second mutant, R579A/R580A/R582A, had somewhat reduced V max, but its activity was not greatly reduced by phosphorylation. The Arg residues in these two mutants are restricted to a highly conserved, 13-residue segment of Gsy2p that we propose to be important for glucose-6-P binding and/or the ability of the enzyme to undergo transitions between activity states.
Variants located upstream of CHRNB4 on chromosome 15q25.1 are associated with age at onset of daily smoking and habitual smoking.

Several genome-wide association and candidate gene studies have linked chromosome 15q24–q25.1 (a region including the CHRNA5-CHRNA3-CHRNB4 gene cluster) with alcohol dependence, nicotine dependence and smoking-related illnesses such as lung cancer and chronic obstructive pulmonary disease. To further examine the impact of these genes on the development of substance use disorders, we tested whether variants within and flanking the CHRNA5-CHRNA3-CHRNB4 gene cluster affect the transition to daily smoking (individuals who smoked cigarettes 4 or more days per week) in a cross sectional sample of adolescents and young adults from the COGA (Collaborative Study of the Genetics of Alcoholism) families. Subjects were recruited from families affected with alcoholism (either as a first or second degree relative) and the comparison families. Participants completed the SSAGA interview, a comprehensive assessment of alcohol and other substance use and related behaviors. Using the Quantitative trait disequilibrium test (QTDT) significant association was detected between age at onset of daily smoking and variants located upstream of CHRNB4. Multivariate analysis using a Cox proportional hazards model further revealed that these variants significantly predict the age at onset of habitual smoking among daily smokers. These variants were not in high linkage disequilibrium (0.28<r2<0.56) with variants that have previously been reported to affect risk for nicotine dependence and smoking related diseases in adults. The data suggests that an age-associated relationship underlies the association of SNPs in CHRNB4 with onset of chronic smoking behaviors in adolescents and young adults and may improve genetic information that will lead to better prevention and intervention for substance use disorders among adolescents and young adults.
Oogenesis: Making the Mos of Meiosis

Meiosis is an ancient type of cell division whose advent allowed the evolution of sexual reproduction. The evolutionary history of the specialization that allowed gamete production to emerge from a simple reduction division has been unclear. New data now suggest that the molecular mechanisms involved in animal oocyte specialization may have origins that predate the emergence of bilaterian animals.
THE CORRECT SPECIFICATION OF OPPORTUNITY COST IN THE EVALUATION OF BOND ISSUE SIZE AND TIMING

ABSTRACT The question of when and in what quantity to obtain required bond financing takes on significance due to fixed flotation coats and the opportunity to invest excess long-term debt in marketable securities. In prior research, the optimal size and timing of bond issues is most often determined as the solution to a cost minimization problem. In this paper, we first demonstrate that previous studies have incorrectly identified the opportunity cost of excess debt. We then delineate the opportunity cost in a form consistent with modern capital structure theory. Our results indicate that a firm's capital structure and marginal tax rate are important determinants of the optimal size and timing of its bond issues.
Los Majos, el “españolísimo gremio” del teatro popular dieciochesco: sobre casticismo, inestabilidad y abyección

Los majos del teatro dieciochesco popular de Madrid se enorgullecian de su casticismo, o de su genuina “espanolidad” (en oposicion a “extranjeridad”). Sin embargo, desde el inicio de su formulacion literaria, los majos refieren al publico de teatro a las luchas subyacentes al cosmopolitismo urbano, tales como la inmigracion, la pobreza, el desplazamiento, y lo que Fumerton califica como unsettledness, una condicion de inestabilidad que caracterizaba la vida de un sinnumero de personas en el ambito urbano capitalino. Paradojicamente, dos caracteristicas esenciales de su “espanolidad” son la marginalizacion y la inestabilidad de los majos de Madrid. Los majos son a la vez familiares y extranjeros, centrales y perifericos; y a este respecto, hare valer la nocion de “lo abyecto” propuesta por Kristeva. Asi, los majos configuran una abyeccion inherente a la construccion cultural de la comunidad “castiza” madrilena en el pasado.
The development of prosthetic heart valves--lessons in form and function.

The 2007 Lasker Award for Clinical Medical Research was granted to Albert Starr and Alain Carpentier for their contributions to the development of the prosthetic heart valve. Dr. Elliot Chaikof discusses the evolution of heart-valve replacements. Albert Starr coinvented and implanted the first successful artificial heart valve in 1960. He is currently director of academic affairs and bioscience development at Providence Health System of Oregon.
Inhibition of proteasomal degradation of rpn4 impairs nonhomologous end-joining repair of DNA double-strand breaks.

Background The proteasome homeostasis in Saccharomyces cerevisiae is regulated by a negative feedback circuit in which the transcription factor Rpn4 induces the proteasome genes and is rapidly degraded by the assembled proteasome. The integrity of the Rpn4-proteasome feedback loop is critical for cell viability under stressed conditions. We have demonstrated that inhibition of Rpn4 degradation sensitizes cells to DNA damage, particularly in response to high doses of DNA damaging agents. The underlying mechanism, however, remains unclear. Methodology/Principal Findings Using yeast genetics and biochemical approach we show that inhibition of Rpn4 degradation displays a synthetic growth defect with deletion of the MEC1 checkpoint gene and sensitizes several checkpoint mutants to DNA damage. In addition, inhibition of Rpn4 degradation leads to a defect in repair of double-strand breaks (DSBs) by nonhomologous end-joining (NHEJ). The expression levels of several key NHEJ genes are downregulated and the recruitment of Yku70 to a DSB is reduced by inhibition of Rpn4 degradation. We find that Rpn4 and the proteasome are recruited to a DSB, suggesting their direct participation in NHEJ. Inhibition of Rpn4 degradation may result in a concomitant delay of release of Rpn4 and the proteasome from a DSB. Conclusion/Significance This study provides the first evidence for the role of proteasomal degradation of Rpn4 in NHEJ.
On cooperative instabilities of parallel vortex pairs

We present a combined analytical and numerical study of the instabilities of a pair of parallel unequal-strength vortices. We extend the analyses of a vortex in an external strain field (Crow, AIAA J. vol. 8, 1970, p. 2172; Widnall et al., J. Fluid Mech. vol. 66, 1974, p. 35) to include the orbital motion of the vortex pair. For counter-rotating pairs, the classic Crow-type periodic displacement perturbations are unstable for all vortex strength ratios, with fastest-growing wavelengths several times the vortex spacing. For co-rotating pairs, the orbital motion acts to suppress instability due to displacement perturbations. Instabilities in this case arise for elliptic perturbations at wavelengths that scale with the vortex core size. We also examine the influence of a second vortex pair by extending Crouch's (J. Fluid Mech. vol. 350, 1997, p. 311) analysis. Numerical results from a spectral initial-value code with subgrid-scale modelling agree with the growth rates from the theoretical models. Computations reveal the nonlinear evolution at late times, including wrapping and ring-rejection behaviour observed in experiments. A pair of co-rotating Gaussian vortices perturbed by noise develops elliptic instabilities, leading to the formation of vorticity bridges between the two vortices. The bridging is a prelude to vortex merger. Analytic, computational and experimental results agree well at circulation Reynolds numbers of order .
The urban environment and children's health: soils as an integrator of lead, zinc, and cadmium in New Orleans, louisiana, U.S.A.

Abstract Soils are evaluated as a diagnostic tool of environmental conditions that influence health. The samples for this study are urban topsoil (0–2.5 cm depth) samples ( n =4026) analyzed for Pb, Zn, and Cd by inductively coupled plasma-atomic emission spectrometry (ICP-AES). The parent materials for New Orleans soils are derived from the Mississippi River, and alluvium from the Bonnet Carre Spillway ( n =31) serve as control samples for this study. The urban samples were stratified by census tract ( n =286). Blood Pb (BL) levels of children ≤6 years were also stratified by census tract and paired with soil Pb (SL) ( n =175). A significant association ( P =1.2×10 −23 ) was found between median BL and median SL. The association was modeled by BL=3.06+0.33 (SL) 0.5 (correlation coefficient=0.69 between the modeled BL and the observed BL and P =3.5×10 −22 ). A median SL threshold (≥310 μg g −1 and −1 ) for higher metal census tracts (HMCTs) and lower metal census tracts (LMCTs), respectively, represents median BL exposures above and below 9 μg dL −1 . HMCTs and LMCTs were characterized by demographic and socioeconomic data. HMCTs are more likely ( P =4.5×10 −6 ) inhabited by Blacks than by Whites. Of 13,803 children ≤6 years in HMCTs, 75% are Black and 22% are White, with other making up the remaining 3%. In LMCTs, the Black to White children ratio is 50:50. In HMCTs, socioeconomic indicators for Blacks are depressed compared to Whites. Zn and Cd are potentially phytotoxic in HMCTs. Children exhibit a steep rise in BL at SL −1 , and empirically, a safe SL for most children is around 80 μg g −1 . SL is a useful diagnostic tool, and curtailing SL may complement primary Pb prevention for children.
Cyclopia (synophthalmia) in Smith-Lemli-Opitz syndrome: First reported case and consideration of mechanism.

Here we present a 24-week fetus with Smith–Lemli–Opitz syndrome (SLOS), alobar holoprosencephaly (HPE) and cyclopia (synophthalmia). Following birth, we suspected SLOS in this fetus due to the additional findings of ambiguous genitalia and bilateral 2–3 toe syndactyly. The diagnosis of SLOS was confirmed by finding an elevated amniotic fluid 7-dehydrocholesterol level (9,890 ng/ml; normal range = 3–9 ng/ml), and molecularly by detecting two different mutations in the DHCR7 gene, the gene causing SLOS. The first mutation was an IVS8-1G>T change and the second was a deletion of exons 3 and 4; this latter mutation has not been reported previously. The mother carries the deletion, while the father carries the splice-site mutation. Also of note, the father has an abnormally low total plasma cholesterol level (104–109 mg/dl). This is the most severe case of HPE described in any patient with SLOS. We postulate that the HPE in this case resulted from severe impairment of Sonic Hedgehog signaling secondary to abnormal cholesterol metabolism; however, the unique combination of mutations in the fetus functionally appears to be no different from other homozygous null mutations reported in DHCR7. Therefore, there must be other yet to be identified factors that contributed to the severity of HPE in SLOS. © 2010 Wiley-Liss, Inc.
Quality Insights: The DEJI Model for Quality Design, Evaluation, Justification, and Integration

Quality is at the intersection of efficiency, effectiveness, and productivity. Efficiency provides the framework for quality in terms of resources and inputs required to achieve the desired level of quality. Effectiveness comes into play with respect to the application of product quality to meet specific needs and requirements of an organisation. Productivity is an essential factor in the pursuit of quality as it relates to the throughput of a production system. To achieve the desired levels of quality, efficiency, effectiveness, and productivity, a new research framework must be adopted. In this column, we present a potential quality enhancement model for quality design, evaluation, justification, and integration (DEJI) based on the product development application presented by Badiru (2012). The model is relevant for research efforts in quality engineering and technology applications.
Filamentous fabrics in low-temperature mineral assemblages: are they fossil biomarkers? Implications for the search for a subsurface fossil record on the early Earth and Mars

Abstract The subsurface has been recognized as a possible habitat for microbial life on Mars. An analogous fossil record of subsurface life is nearly missing on Earth. Here we present evidence of the widespread occurrence of such a record: tubular filamentous structures with typical core diameters of 1– 2 μm were found as inclusions in minerals deposited from low-T ( 140 localities worldwide. Filaments are frequently organized in composite structures with architectures similar to microbial mats. Filaments thickly encrusted by minerals exhibit gravity-oriented structures of macroscopic dimensions that are similar to stalactites. Environments of formation are sites of low-T water circulation in macroporous rocks such as volcanics, oxidized ores, limestone solution cavities and cavernous macrofossils. The age of occurrence ranges from Precambrian to Subrecent. We interpret the filamentous structures as permineralized and encrusted microbial filaments based on the following arguments: tubular construction of filaments with constant core diameters typical of microbes ( 1.5±1.1 μm ), coalescence of filaments to form mat-like structures, gravity draping of micron-thin filaments indicating an originally flexible consistency, and restriction to low-T mineral assemblages. These filamentous structures formed in subsurface environments are similar in size, morphology and construction to fossilized microbes observed in modern terrestrial and marine thermal springs. This newly recognized fossil record of subterranean microbial life opens up new perspectives in the study of the paleobiology of the terrestrial subsurface and in the exploration for fossil life on Mars. Potential host rocks on Mars include major nonsedimentary units such as volcanics and impactites.
Severe Encephalomyelitis in an Immunocompetent Adult with Chromosomally Integrated Human Herpesvirus 6 and Clinical Response to Treatment with Foscarnet plus Ganciclovir

Human herpesvirus 6 has rarely been identified as a cause of encephalitis in immunocompetent adults. We describe a patient who had severe encephalomyelitis, hypoglycorrhachia, and human herpesvirus 6 identified in his cerebrospinal fluid and serum and who recovered after treatment with foscarnet and ganciclovir. Human herpesvirus 6 should be considered in immunocompetent patients with encephalitis.
Computing Sensitivity Analysis of Vehicle Dynamics Based on Multibody Models

Vehicle dynamics simulation based on multibody dynamics techniques has become a powerful tool for vehicle systems analysis and design. As this approach evolves, more and more details are required to increase the accuracy of the simulations, to improve their efficiency, or to provide more information that will allow various types of analyses. One very important direction is the optimization of multibody systems. Sensitivity analysis of the dynamics of multibody systems is essential for design optimization. Dynamic sensitivities, when needed, are often calculated by means of finite differences but, depending of the number of parameters involved, this procedure can be very demanding in terms of time and the accuracy obtained can be very poor in many cases if real perturbations are used. In this paper, several ways to perform the sensitivity analysis of multibody systems are explored including the direct sensitivity approaches and the adjoint sensitivity ones. Finally, the techniques proposed are applied to the dynamical optimization of a five bar mechanism and a vehicle suspension system.Copyright © 2013 by ASME
An implicit integration algorithm for the finite element implementation of a nonlinear anisotropic material model including hysteretic nonlinearity

Abstract Fully implicit integration schemes have been demonstrated to be very robust and efficient for nonlinear elastoplastic and elastic–viscoplastic models and enjoy widespread use in finite element formulations. The paper introduces a new form of fully implicit local and global algorithms for the integration of nonlinear elastoplastic constitutive laws including anisotropic plasticity and hysteretic small strain elastic nonlinearity. The local stress integration algorithm is based on a single step backward differentiation method with iterative solution for the predictor as well as the corrector steps. The global system of implicit nonlinear equations is solved with a quasi-Newton technique using a numerical tangent computed every load step by finite difference and optimized with iterative updating using the Broyden–Fletcher–Goldfarb–Shano (BFGS) procedure. The proposed numerical procedure is illustrated here through the implementation of a set of nonlinear constitutive equations describing the response of lightly overconsolidated cohesive materials. Numerical simulations of single element tests as well as a boundary value problem confirm the robustness, accuracy, and efficiency of the proposed algorithm at the local and global level.
Optimal design of prefilters for binary FSK discriminators

Prefilters are derived for delay-line discriminators for FSK systems which allow these simple demodulators to give optimum, or matched filter performance. Filters are presented which allow the demodulator to give optimum performance even when the tone spacing is a multiple of the minimum orthogonal spacing. Finally, an architecture is suggested that incorporates a tapped-delay-line to synthesise these prefilters.
Lazy cache invalidation for self-modifying codes

Just-in-time compilation with dynamic code optimization is often used to help improve the performance of applications that utilize high-level languages and virtual run-time environments, such as those found in smartphones. Just-in-time compilation introduces additional overhead into the instruction fetch stage of a processor that is particularly problematic for user applications-instruction cache invalidation due to the use of self-modifying code. This software-assisted cache coherence serializes cache line invalidations, or causes a costly invalidation of the entire instruction cache, and prevents useful instructions from being fetched for the period during which the stale instructions are being invalidated. This overhead is not acceptable for user applications, which are expected to respond quickly.In this work we introduce a new technique that can, using a single instruction, invalidate cache lines in page-sized chunks as opposed to invalidating only a single line at a time. Lazy cache invalidation reduces the amount of time spent stalling due to instruction cache invalidation by removing stale instructions on demand as they are accessed, as opposed to all at once. The key observation behind lazy cache invalidation is that stale instructions do not necessarily need to be removed from the instruction cache; as long as it is guaranteed that attempts to fetch stale instructions will not hit in the instruction cache, the program will behave as the developer had intended.
Authorship Is Continuous: Managing Code Plagiarism

Code plagiarism is an increasing problem in computer science courses. To deal with this problem, the Vipassana software tool gives instructors improved visibility into their students' programming process.
Reformulating Financial Problems and Interventions to Improve Psychosocial and Functional Outcomes in Cancer Patients and Their Families

Abstract Preventive, planned, and proactive interventions for cancer patients' and families' financial problems are more likely to be effective in the short run or over time to prevent or reduce negative psychosocial effects and compromised health or functional outcomes. Furthermore, financial problems that afflict one area may set off or aggravate negative outcomes in the other. These complicated and fractious biopsychosocial effects may fluctuate over time with changing financial stresses and strains and, in turn, lead to interventions that are delayed, crisis-driven, or focused excessively on relief of symptoms rather than on resolution of problems because inadequate health insurance and the need for financial interventions and referrals may not be apparent for a long time, if at all. Thus, targeted interventions and referrals may be crucial for the financial problems that undergird or worsen a host of changing biopsychosocial problems. The author concludes by recommending three financial interventions...
Nebivolol improves diastolic dysfunction and myocardial remodeling through reductions in oxidative stress in the transgenic (mRen2) rat

Angiotensin II contributes to myocardial tissue remodeling and interstitial fibrosis through NADPH oxidase-mediated generation of oxidative stress in the progression of heart failure. Recent data h...
Possessing Moral Concepts

Moral discourse allows for speakers to disagree in many ways: about right and wrong acts, about moral theory, about the rational and conative significance of moral failings. Yet speakers’ eccentricities do not prevent them from engaging in moral conversation or from having (genuine, not equivocal) moral disagreement. Thus differences between speakers are compatible with possession of moral concepts. This paper examines various kinds of moral disagreements and argues that they provide evidence against conceptual-role and informational atomist approaches to understanding our moral concepts. Conceptual role approaches fail because they cannot account for shared concepts among speakers with different commitments to the practical and conative ramifications of moral judgments. Informational atomist views fail because speakers need not be locked on to the same moral properties to share moral concepts.
The pricing of callable preferred stock

In this study, the authors use both the Black/Scholes European option model and the Barone-Adesi/Whaley American option model to estimate call option values implicit in seasoned callable preferred stock issues. Consistent with the finding that call features increase bond yields, a significant relationship is found between estimated option values and discounts of these securities’ market prices from their estimated income values. However, the size of the discount is only a fraction of what would be predicted by the American option model. Specifically, the market does not appear to take the “early exercise premium” into account. Furthermore, this discount seems to be isolated to in-the-money call features that have evolved to their final call price. Thus, incorporation of a call feature into a security’s indentures, with a deferment period and an initial premium call price, appears to represent a pure gain for the issuing corporation.