cssi/SciSciGPT-SciSciNet huggingface dataset:
Failure mode transition speeds in an impact loaded prenotched plate with four thermoviscoplastic relations

Four different thermoviscoplastic relations, namely, the Litonski–Batra, Johnson–Cook, Bodner–Partom and the power law are used to model the thermoviscoplastic response of a material. Each one of these relations accounts for strain hardening, strain-rate hardening and thermal softening of the material. The material parameters in these relations are found by solving an initial-boundary-value problem corresponding to simple shearing deformations so that the computed effective stress vs. the effective plastic strain curves match closely with the experimental data of Marchand and Duffy who tested thin-walled HY-100 steel tubes in torsion. These four viscoplastic relations are used to analyze dynamic thermomechanical deformations of a prenotched plate impacted on the notched side by a cylindrical projectile made of the same material as the plate. The impact loading on the contact surface is simulated by prescribing the time history of the normal component of velocity and null tangential tractions. A plane strain state of deformation is assumed to prevail in the plate and its deformations are studied for different values of the impact speed. The in-house developed finite element code employs constant strain triangular elements, one point integration rule, and a lumped mass matrix. The Lagrangian description of motion is used to describe deformations of the plate. The coupled nonlinear partial differential equations are first reduced to coupled nonlinear ordinary differential equations (ODEs) by using the Galerkin approximation. The ODEs are integrated by using the stiff solver, LSODE, which adaptively adjusts the time step size and computes the solution within the prescribed accuracy. Results computed with the four constitutive relations are found to be qualitatively similar to each other and the general trends agree with the experimental observations in the sense that at low speed of impact, a brittle failure ensues at a point on the upper surface of the notch tip. However, at high impact speeds, a ductile failure in the form of a shear band initiates first from a point on the lower surface of the notch tip. The predicted speed at which the failure mode transitions from brittle to ductile is different for the four viscoplastic relations. The effects of the notch tip radius and the yield strength of the material in a quasistatic simple tension/compression test on the failure-mode transition speed have been ascertained.
Learning Disabled Children's Conversational Competence: An Attempt to Activate the Inactive Listener.

Learning disabled children have been found to be less likely than nondisabled children to request clarification of ambiguous messages provided by adults. This study tested a strategy deficit hypothesis as one source of this conversational deficit by assessing the effects of a brief intervention which highlighted the appropriate response strategy, i.e., question-asking. Learning disabled and non-disabled children in grades four, five, and six played the listener role in a referential communication task requiring them to select referents based on messages varying in informational adequacy. Although group and grade differences replicated previous findings, the intervention condition had no effect on the children's performance on a posttest. An analysis of referent selections indicated that the inactive listeners were overrelying on the Maxim of Quantity, the Gricean principle that cooperative speakers provide informative messages. These results suggest that conversational development depends on children's increasing ability to recognize contexts in which these conversational principles do not apply.
An Analytical Performance Model for Partitioning Off-Chip Memory Bandwidth

With the emergence of multi-programmed workloads for Chip Multiprocessors (CMP), Quality of Service (QoS) of each co-scheduled application on the CMP is increasingly gaining importance. As more and more applications are consolidated into a single chip to compete for the limited off-chip memory bandwidth, off-chip memory bandwidth partitioning makes an increasing impact on system performance. Although various existing heuristic-based memory scheduling schemes have achieved significant system performance improvement by better partitioning the bandwidth, it is still not clear what are the best ways to partition off-chip bandwidth for improving different system performance objectives. The goal of this paper is to understand how off-chip memory bandwidth partitioning affects various system performance objectives. To achieve this goal, we propose an analytical model that is simple yet powerful enough to reveal the relationship between various memory bandwidth partitioning schemes and different system performance objectives. From our model, optimal memory bandwidth partitioning schemes for different system-level objectives are derived. Experimental results from a cycle-accurate full-system simulator show that, for heterogeneous workloads, performance improvements over No_partitioning/Equal_partitioning in terms of harmonic weighted speedup, minimum fairness, weighted speedup and sum of IPCs are 20.3%/2.1%, 49.8%/38.7%, 32.8%/7.6% and 64.2%/24%, on average, with our corresponding optimal partitioning schemes (i.e., Square_root, Proportional, Priority_APC, Priority_API), respectively.
Application of Magnetic Amplitude Inversion In Exploration For Natural Gas In Volcanics

SUMMARY We present a case study on the use of magnetic amplitude inversion in imaging volcanics that are buried in sedimentary basins and have strong remanent magnetization. The application arises in exploration of natural gas hosted in volcanic units. We show that combined with reliable approaches for magnetic anomaly separation, amplitude inversion can overcome the lack of information on magnetization direction and effectively identify the volcanic units at large depths.
Lady Crabs, Ovalipes ocellatus , in the Gulf of Maine

The Lady Crab ( Ovalipes ocellatus ), mainly found south of Cape Cod and in the southern Gulf of St. Lawrence, is reported from an ocean beach on the north shore of Massachusetts Bay (42°28'60"N, 70°46'20"W) in the Gulf of Maine. All previously known Gulf of Maine populations north of Cape Cod Bay are estuarine and thought to be relicts of a continuous range during the Hypsithermal. The population reported here is likely a recent local habitat expansion.
Survival Efficacy of Adjuvant Cytosine-Analogue CS-682 in a Fluorescent Orthotopic Model of Human Pancreatic Cancer

Adjuvant treatment with the cytosine analogue 1-(2-C-cyano-2-deoxy-β-d- arabino -pentofuranosyl)- N 4-palmitoylcytosine (CS-682) results in a highly significant increase in survival in the aggressive orthotopic MIA-PaCa-2 human pancreatic cancer mouse model. Seven days after implantation, mice were randomized into eight groups, depending on whether they were to be treated by tumor resection, 5 weeks of CS-682 chemotherapy at 40–60 mg/kg once daily, or both. Throughout the course of treatment, noninvasive optical whole-body imaging based on brilliant red fluorescent protein expression of the tumor permitted visualization and quantification of primary, metastatic, and recurrent disease. Total tumor burden negatively correlated with survival. Untreated mice died of disseminated disease with a median survival of 26 days. Surgical resection alone conferred a small but significant survival advantage (median survival, 28 days, P = 0.03). Primary CS-682 treatment at all doses also significantly prolonged survival compared with untreated animals ( P < 0.05) and was more effective than surgery alone at doses of 50 and 60 mg/kg (median survival, 34 days, P = 0.045, and 38.5 days, P = 0.03, respectively). Maximal survival (median, 48 days, with 30% of animals surviving longer than 60 days) was achieved by adjuvant CS-682 (50 mg/kg), given after surgical resection of the primary pancreatic tumor ( P = 0.004 compared with surgery alone). The results demonstrate that adjuvant oral administration of CS-682 for pancreatic cancer is highly effective with acceptable toxicity, suggesting its potential for cure of this disease in appropriate combinations.
Six Challenges to Theoretical and Philosophical Psychology

Psychology is not a young science anymore: as the textbooks tell us, it won its independence, from philosophy, a century and a half ago, through the efforts of such luminaries as Gustav Fechner and William James. And yet, if an offhand remark by a long-dead philosopher on psychology’s conceptual confusion still touches a raw nerve in some of us psychologists, it is probably because psychology’s intellectual roots have been all along, and will likely remain, firmly planted in the philosophy of mind. Philosophy and psychology may be seen as rivals insofar as each counts the other as a proper part of its subject matter. This standoff can, however, be resolved in a peaceful and productive manner, if we only realize that psychological science and the philosophy of mind are also natural partners, because these disciplines have joint custody over some of the most daunting – and most exciting – questions that humanity ever dared to contemplate. This partnership is too precious to be treated casually: arguably, the most momentous theoretical advances in psychology are typically motivated by deeply philosophical considerations, and the best thinking in the philosophy of mind is inspired by, and reflects back upon, scientific findings and theories. An exemplary approach to the relationship between philosophy and psychology is the one advocated by Quine (1969, pp. 126–127): My position is a naturalistic one; I see philosophy not as a priori [...] groundwork for science, but as continuous with science. I see philosophy and science as in the same boat – a boat which, to revert to Neurath’s figure as I so often do, we can rebuild only at sea while staying afloat in it. There is no external vantage point, no first philosophy.
Design parameter variation and structural response

A general power series method is developed to aid in obtaining changes in the response variable due to changes in design parameters. The approach is considered for eigenvalue problems and systems of simultaneous equations which may represent static, dynamic and stability response problems. Particular emphasis is placed upon the eigenvalue problem and techniques for improving the calculations form the power series are suggested utilizing modified Rayleigh quotient expressions. Each of the methods proposed is treated computationally by the formulation of a finite element solution of column elastic stability. Investigations of solution accuracy versus percentage variation in element stiffness, whether the method underestimates or overestimates the changes, and the required number of eigenvalue solutions are presented.
Venous Irritation Related to Intravenous Administration of Phenytoin versus Fosphenytoin

Study Objective. To compare the frequency, severity, and time course of venous irritation after administration of a single intravenous dose of phenytoin with an equimolar dose of fosphenytoin, a water-soluble phenytoin prodrug. Design. Randomized, double-blind, two-period, crossover study. Setting. University hospital clinical research unit. Patients. Twelve healthy volunteers within 15% of ideal body weight and with no clinically significant abnormalities on physical examination, medical history, or laboratory assessment. Interventions. Volunteers randomly received a 30-minute infusion of phenytoin sodium 250 mg (250 mg/5 ml) or an equimolar dose of fosphenytoin 375 mg (375 mg/5 ml). Subjects returned for the crossover treatment 14–21 days later. Measurements and Main Results. Subjects assessed venous irritation (pain, burning, itching), and investigators evaluated phlebitis (erythema, swelling, tenderness), induration, exudation, and cording. Phenytoin was associated with a significantly higher degree of pain at the infusion site in all subjects and a significant degree of phlebitis in eight subjects (p<0.05); cording occurred in six subjects. The time course of phenytoin-induced phlebitis was bimodal. Erythema and tenderness were prominent at the end of the infusion and again at 24 hours. Cording was first noted between 24 hours and 1 week after infusion. In contrast, fosphenytoin was associated with mild pain in two subjects, one incident of phlebitis, and no erythema or cording. Conclusions. Fosphenytoin administration resulted in significantly less venous irritation and phlebitis compared with an equimolar dose of phenytoin. The clinical use of this water-soluble phenytoin prodrug should minimize the frequency and severity of infusion-site reactions and should allow convenient, rapid, intravenous administration of drug, undiluted or admixed with intravenous solutions.
EMG for assessing the recovery of voluntary movement after acute spinal cord injury in man

Objective: Multi-channel electromyogram (EMG) was used to examine the pattern and time-course of voluntary contraction recovery in subjects with acute traumatic spinal cord injury (SCI), concentrating on the latest time after injury at which a given muscle would begin to show voluntary recruitment. Methods: We conducted repeated measures of voluntary contractions of 12 lower limb muscles (for all subjects) and 12 upper-limb muscles (for subjects with cervical injury), beginning within days of the injury and extending for 1 or more years post-injury. The EMG interference pattern was scored in a blinded fashion from tape records. Results: We recruited 229 subjects, including 152 from whom repeated measures were made. Several different patterns of recovery were identified. For persons with motor-incomplete injury to the cervical or thoracic spine, EMG recruitment had not yet occurred by 5 weeks post-injury in roughly 1/2 of all lower limb muscles, and prolonged delays between injury and recruitment onset were sometimes seen. Injury to the thoracolumbar spine was frequently associated with very long delays (i.e. . 1 year) between injury and resumption of volitional contraction of distal lower limb muscles. Discussion: The incidence of neurologically incomplete SCI is rising. In such subjects, delays of 1 or more months between injury and the onset of voluntary contraction are common for muscles of the distal upper limbs (for cervical injury) and lower limbs. Given the abbreviated period of in-patient rehabilitation now routine in the United States, these subjects in particular will benefit from frequent follow-up evaluations to assess spontaneous recovery and design appropriate rehabilitation strategies to maximize functional independence. Moreover, the potential for delayed recovery must be considered when designing and implementing novel clinical interventions for treating SCI, to better differentiate between spontaneous and treatment-related improvements in neurologic function. q 2004 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.
Contributions of Behavioural Decision Theory to Research in Political Science

Cet article aborde la question de l'application de la Theorie de la Decision Comportementale (BDT) a deux domaines de la recherche en Sciences-Politiques, le comportement electoral et les relations internationales. On commence par un bref survol de la BDT, puis on passe a ce qui n'est maintenant que l'amorce de l'exploitation de la BDT dans les Sciences-Politiques. Dans le premier exemple, notre interet est focalise sur les decisions prises par le public et dans le second sur celles prises par les elites politiques, mais la distinction masse-elite peut se reveler secondaire par rapport aux situations dans lesquelles emergent les decisions electorales ou de politique etrangere. Dans la presentation de ces deux exemples, on tente de replacer l'investigation reposant sur les apercus de la BDT dans le contexte plus vaste de la recherche dans ce secteur. This paper discusses the application of behavioural decision theory (BDT) to two areas of political science research: voting behaviour and international relations. We begin with a brief overview of BDT, and then turn to what is now only the beginnings of the utilisation of BDT in political science. In the first instance we focus on decision making by the mass public, and in the second on decision making by political elites, but, as we shall see, the mass-elite distinction may not be as important as the different situations or contexts in which voting and foreign policy decisions are typically made. In both instances, we will try to put research relying on the insights of behavioural decision theory into a broader context of research in the field.
Health and Safety in Family Day Care Homes: Association Between Regulatory Non-compliance and Lower Median Income.

Objectives To determine frequency of non-compliance with child care regulations among family day care homes (FDCH) and identify the role of income in compliance. Methods We analyzed non-compliance in 746 routine, unannounced inspection and re-inspection reports of FDCH collected by the Connecticut Department of Public Health licensing specialists in 2007–2008 and linked results to median income of zip code data. We grouped the 83 state regulations into 12 regulation categories, analyzed 11 categories, and used latent class analysis to classify each FDCH as high or low compliance for each category. We used logistic regression analysis to estimate the odds ratios of low compliance. Results Among the 746 FDCH inspections (594 first inspections and 152 re-inspections), we found high rates of non-compliance in inspection regulations in immunizations (32.9 %), water temperature (35.6 %) and hazards (30.0 %). Among the 11 regulation categories, 4 categories (indoor safety, emergency preparedness, child/family/staff documentation, and qualifications of provider) had regulations with high non-compliance. Median household income of FDCH zip code was lower for re-inspection sites than for inspection sites ($34,715 vs. $57,118, p < 0.0001) and FDCH in the lowest quartile of income had greater odds of low compliance in indoor safety (OR 1.86, 95 % CI 1.04, 3.35, p < 0.05). Conclusions The majority of FDCH were in compliance with the majority of regulations, yet there are glaring non-compliance issues in inspections and re-inspections and there are income-based inequities that place children at higher risk who are already at high risk for suboptimal health outcomes.
The Council on Accreditation of Park, Recreation, Tourism, and Related Professions: 2013 Standards-- The Importance of Outcome-Based Assessment and the Connection to Student Learning.

The Council for Higher Education Accreditation (CHEA) adopted recognition standards in 2006 requiring regional and professional accreditors such as the Council on Accreditation of Park, Recreation,...
Mining incomplete data with many attribute-concept values and "do not care" conditions

In this paper we present novel experimental results comparing two interpretations of missing attribute values: attribute-concept values and "do not care" conditions. Experiments were conducted on 12 data sets with many missing attribute values using the MLEM2 rule induction system. In the experiments, three kinds of probabilistic approximations were used: singleton, subset and concept; with the error rate of the induced rules evaluated by ten-fold cross validation. The results of the experiments compared two interpretations of missing values, attribute-concept values and "do not care" conditions, finding the best result among the three probabilistic approximations. The outcomes show that for two cases the better performance was accomplished using attribute-concept values, for one case the better performance was accomplished using "do not care" conditions. For remaining three cases the difference in performance was not statistically significant (5% significance level).
A Review of “Promoting Positive Parenting: An Attachment-Based Intervention”

Promoting Positive Parenting: An Attachment-Based Intervention, written and edited by Femmie Juffer, Marian J. Bakermans-Kranenburg, and Marinus H. van IJzendoorn, is an excellent resource for rese...
The Social Aspect of Language

Which is conceptually primary, the idiolect or the language? If the former, the apparent absence of a social norm makes it hard to account for success in communication; if the latter, the danger is that the norm has no clear relation to practice. Michael Dummett thinks that by promoting the primacy of the idiolect I run afoul of Wittgenstein’s ban on private languages; in my view Dummett, by making language primary, has misplaced the essential social element in linguistic behavior. In this paper I want to try to sort out and clarify the issues involved.
Optical pharmacokinetics to assess the permeability of angiogenic neovasculature

The method of Optical Pharmacokinetics is used for noninvasive measurement of drug concentrations in tissue. A rapid sequence of such measurements, following administration of a short bolus of appropriate optical contrast agent, can be used to assess the permeability of neovasculature, hence angiogenesis.
Development of an Unnatural Amino Acid Incorporation System in the Actinobacterial Natural Product Producer Streptomyces venezuelae ATCC 15439

Many Actinobacteria, most notably Streptomyces, produce structurally diverse bioactive natural products, including ribosomally synthesized peptides, by multistep enzymatic pathways. The use of site-specific genetic incorporation of unnatural amino acids to investigate and manipulate the functions of natural product biosynthetic enzymes, enzyme complexes, and ribosomally derived peptides in these organisms would have important implications for drug discovery and development efforts. Here, we have designed, constructed, and optimized unnatural amino acid systems capable of incorporating p-iodo-l-phenylalanine and p-azido-l-phenylalanine site-specifically into proteins in the model natural product producer Streptomyces venezuelae ATCC 15439. We observed notable differences in the fidelity and efficiency of these systems between S. venezuelae and previously used hosts. Our findings serve as a foundation for using an expanded genetic code in Streptomyces to address questions related to natural product biosynthesis and mechanism of action that are relevant to drug discovery and development.
Intraplant and Interplant Movement of Bemisia argentifolii (Homoptera: Aleyrodidae) Crawlers

Whitefly crawlers are thought to move only a few millimeters after eclosing from the egg before settling to feed. In the field, however, we observed that crawlers of Bemisia argentifolii Bellows & Perring appeared to move from senescent leaves on which they hatched to new leaves higher up on the plant. Laboratory studies were conducted to determine if crawlers were capable of moving upward to leaves higher up on the plant (intraplant movement), or laterally between plants (interplant movement). B. argentifolii crawlers readily moved along the stem of 4 test plants and settled on leaves 2:50 mm from their initial point of origin on the stems. Crawlers traveled an average distance of 73.5 ± 2.0,69.9 ± 3.5,64.3 ± 2.2 and 55.0 ± 0.9 mm on broccoli, Brassica oleracea variety botrytis L.; annual sowthistle, Sonchus oleraceus L.; prickly lettuce, Lactuca serriola L.; and cheeseweed, Malva parvifolia L., respectively, to find a suitable leaf on which to settle. The maximum distance traveled by a single individual from the point of origin to settling on a leaf was 204 mm on annual sowthistle. Eighty to 100% of the crawlers successfully reaching a leaf settled on the abaxial surface; the remainder settled on the adaxial surface. Between 7 and 12% of the crawlers successfully moved between the test plants, migrating from a senescent leaf of 1 plant (source leaf) to a healthy leaf (destination leaf) of a 2nd plant. Crawler movement may be important in whitefly overwintering because emerging crawlers can move from senescent leaves, which would not support development to the adult stage, to healthy leaves on either the same or adjacent plants where they can complete their development.
Intermolecular Energy Transfer Dynamics at a Hot-Spot Interface in RDX Crystals.

The phonon mediated vibrational up-pumping mechanisms assume an intact lattice and climbing of a vibrational ladder using strongly correlated multiphonon dynamics under equilibrium or near-equilibrium conditions. Important dynamic processes far from-equilibrium in regions of large temperature gradient after the onset of decomposition reactions in energetic solids are relatively unknown. In this work, we present a classical molecular dynamics (MD) simulation-based study of such processes using a nonreactive and a reactive potential to study a fully reacted and unreacted zone in RDX (1,3,5-trinitro-1,3,5-triazocyclohexane) crystal under nonequilibrium conditions. The energy transfer rate is evaluated as a function of temperature difference between the reacted and unreacted regions, and for different widths and cross-sectional area of unreacted RDX layers. Vibrational up-pumping processes probed using velocity autocorrelation functions indicate that the mechanisms at high-temperature interfaces are quite dif...
An optimum selection strategy of reflective cracking mitigation methods for an asphalt concrete overlay over flexible pavements

AbstractReflective Cracking (RC) has been a daunting challenge in pavement maintenance and rehabilitation (M&R), yet, still, after several decades of research, no exclusive solution prevails. Moreover, RC mitigation methods have shown significant variation in in situ performance. Therefore, a technique tailored to select an effective RC mitigation method is essential for the success of pavement M&R. In this study, a life cycle cost (LCC) and multi-criteria decision-making (MCDM) analyses were conducted to evaluate the effectiveness of currently available RC mitigation methods and to select the optimal method for an asphalt concrete overlay above flexible pavements. The MCDM includes three components: LCC, performance, and materials (recyclability). These criteria determine the selection ranking of each RC mitigation method. In addition, the effects of the priority level including cost, performance, and recyclability on the final decision were evaluated by conducting a series of sensitivity analysis under ...
Adsorption of Rectorite to Basic Safranine in Water

Rectorite is used as adsorbent to dispose basic safranine in water in this paper.Effects of shaking time,pH value,rectorite dosage and initial concentration of basic safranine on the adsorption efficiencies are inspected.Adsorption isotherm is determined,and adsorption kinetics law is simulated by Bangham formula.The results show that shaking time,pH value,rectorite dosage and initial concentration of basic safranine are the main factors to affect adsorption efficiencies.To basic safranine solutions with initial concentration of 50 mg/L,the optimal conditions are as follows: shaking time is 30 minutes,rectorite dosage is 200mg/100mL,and pH is 6.The adsorption isotherm appears "S" shape which can be fitted by Freundlich model.The adsorption kinetics law conforms to Bangham model.
Diversity analysis of predominant intestinal microflora in children with Cow's milk protein allergy

Objective To investigate the diversity of predominant intestinal microflora in children with Cow's milk protein allergy. Methods Collecting the feces from 7initially diagnosed cases of children with Cow's milk protein allergy and 5healthy control participants.The universal primer of the bacterial 16SrDNA-V3region was used as primer and the total genomic bacterial DNA were used as a template.After PCR amplification,denaturing gradient gel electrophoresis(DGGE) analysis was performed.The results analysis was applied by Quantity One software. Results There was significant difference in the diversity of the predominant intestinal microflora in children with Cow's milk protein allergy and healthy control, and the intestinal microflora diversity of Cow's milk protein allergy was higher.The participants in allergy group and control group could be divided into different two clusters.The results indicated that the predominant intestinal microflora in the two groups were different.Similarity analysis showed that allergic group similarity was range from 27%~72%;the healthy control group similarity was range from 28%~64%. Conclusions The diversity of the predominant intestinal microflora in children with Cow's milk protein allergy changed significantly compared with healthy children.Intestinal microecological balance might be the underlying causes of cow's milk protein allergy.
Mechanisms for activation of proteolysis in uremia.

Both acute (ARF) and chronic (CRF) renal failure are commonly accompanied by evidence of abnormal protein metabolism, including negative nitrogen balance and anthropometric changes, consistent with loss of lean body mass. It would be advantageous to identify the causes and mechanisms underlying defects in protein metabolism which are associated with renal failure because defective protein conservation is one of the major factors causing morbidity in CRF and the high mortality rate in patients with ARF due to sepsis and/or trauma.1 Evidence that we and others have gathered indicates that stimulation of catabolic pathways by the metabolic abnormalities resulting from loss of renal function is likely to be the most important cause of abnormal protein turnover in uremic patients.
Stevens’s Late Lyrics: ‘His Actual Candle Blazed with Artifice’

May I begin my final chapter schematically, if not reductively? In the early poems of Harmonium Stevens is fascinated with surfaces – with sounds, smells, and oddities of linguistic combination for their own sake. In the middle poems he is preoccupied with using experience in the service of creating abstract truths about the nature of poetry and fiction and the imagination. Finally, in the late poems he creates a dialogue within the speaker’s consciousness between sensations and abstractions. In The Rock (1950), as we shall see, Stevens rejects self-immersion in the life of the poem as an end in itself, and in ‘Not Ideas About the Thing but the Thing Itself’ (1954) he insists that the abstractions must respond to – and be in epistemological service to – ideas. To dwell among surfaces is a kind of solipsism, if not cynicism. For the late Stevens, cynicism is the mortality of attitude and sarcasm the mortality of speech. Playfulness is at the service of a deep need for definition.
On the contribution of active galactic nuclei to the high-redshift metagalactic ionizing background

Motivated by the claimed detection of a large population of faint active galactic nuclei (AGN) at high redshift, recent studies have proposed models in which AGN contribute significantly to the z > 4 H I ionizing background. In some models, AGN are even the chief sources of reionization. If correct, these models would make necessary a complete revision to the standard view that galaxies dominated the high-redshift ionizing background. It has been suggested that AGN-dominated models can better account for two recent observations that appear to be in conflict with the standard view: (1) large opacity variations in the z ~ 5.5 H I Lyman-alpha forest, and (2) slow evolution in the mean opacity of the He II Lyman-alpha forest. Large spatial fluctuations in the ionizing background from the brightness and rarity of AGN may account for the former, while the earlier onset of He II reionization in these models may account for the latter. Here we show that models in which AGN emissions source >~ 50 % of the ionizing background generally provide a better fit to the observed H I Lyman-alpha forest opacity variations compared to standard galaxy-dominated models. However, we argue that these AGN-dominated models are in tension with constraints on the thermal history of the intergalactic medium (IGM). Under standard assumptions about the spectra of AGN, we show that the earlier onset of He II reionization heats up the IGM well above recent temperature measurements. We further argue that the slower evolution of the mean opacity of the He II Lyman-alpha forest relative to simulations may reflect deficiencies in current simulations rather than favor AGN-dominated models as has been suggested.
Abstract 832: Preventing the progression of estrogen receptor-negative/HER2-overexpressing early stage breast disease by lapatinib

Tamoxifen and aromatase inhibitors (AIs) have shown efficacy to prevent estrogen receptor positive (ER+) breast cancer; however, there is no effective prevention strategy for ER- breast cancer. HER2 overexpression (HER2+) can be detected in up to 40% of ER- breast cancers and it has been reported to promote the progression of early stage breast cancer. Here, we tested the feasibility of lapatinib to prevent ER-/HER2+ early stage breast disease. Our data showed that lapatinib reduced the proliferation and increased the apoptosis in an in vitro ER-/HER2+ early breast disease model. Furthermore, lapatinib treatment in the HER2-driven MMTV-neu mouse model from early stage of disease development (atypia, at 10 weeks of age) significantly delayed tumor initiation and progression as detected by mammary gland biopsy and fiber optic micro-endoscope (FOME) imaging. Mechanistically, we found that lapatinib inhibited GLUT4 upregulation and increased glucose up-taking in HER2-overexpressing cells. These results suggested that lapatinib is a promising agent for the prevention/intervention of ER- and HER2+ breast cancers. Our study brings better understanding of the mechanism underlying ER-/HER2+ early stage breast disease progression to cancer and our strategy of cancer prevention with low-dose kinase inhibitor could be rapidly translated into the clinic for other cancer types in the near future. Citation Format: Sunil Acharya, Jia Xu, Xiao Wang, Shalini Jain, Hai Wang, Qingling Zhang, Joseph Bower, Rebecca Richards-Kortum, Dihua Yu. Preventing the progression of estrogen receptor-negative/HER2-overexpressing early stage breast disease by lapatinib. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 832.
Psychometric Testing of the Self-Care of Coronary Heart Disease Inventory (SC-CHDI).

Although coronary heart disease (CHD) requires a significant amount of self-care, there are no instruments available to measure self-care in this population. The purpose of this study was to test the psychometric properties of the Self-Care of Coronary Heart Disease Inventory (SC-CHDI). Using the Self-Care of Chronic Illness theory, we developed a 22-item measure of maintenance, management, and confidence appropriate for persons with stable CHD and tested it in a convenience sample of 392 adults (62% male, mean age 61.4 ± 9.6 years). Factorial validity was tested with confirmatory factor analysis. Convergent validity was tested with the Medical Outcomes Study MOS-SAS Specific Adherence Scale and the Decision Making Competency Inventory (DMCI). Cronbach alpha and factor determinacy scores (FDS) were calculated to assess reliability. Two multidimensional self-care scales were confirmed: self-care maintenance included “consultative behaviors” (e.g., taking medicines as prescribed) and “autonomous behaviors” (e.g., exercising 30 minute/day; FDS = .87). The multidimensional self-care management scale included “early recognition and response” (e.g., recognizing symptoms) and “delayed response” (e.g., taking an aspirin; FDS = .76). A unidimensional confidence factor captured confidence in each self-care process (α = .84). All the self-care dimensions were associated with treatment adherence as measured by the MOS-SAS. Only self-care maintenance and confidence were associated with decision-making (DCMI). These findings support the conceptual basis of self-care in patients with CHD as a process of maintenance that includes both consultative and autonomous behaviors, and management with symptom awareness and response. The SC-CHDI confidence scale is promising as a measure of self-efficacy, an important factor influencing self-care. © 2016 Wiley Periodicals, Inc.
A new lease on half-life

Proteins are an important and growing class of therapeutics, but their clinical use is hampered by a “here today, gone today” problem—rapid clearance from the bloodstream. This short half-life often necessitates frequent injections that reduce patient compliance and increase costs. A common delivery strategy to overcome this issue is the conjugation of a shielding polymer such as polyethylene glycol (PEG) to the surface of the protein drug. Polymer conjugation elongates serum half-life, improves stability and solubility, and reduces the body’s immune response to the protein. However, the carrier also can spur an unwanted immune response. Now, Qi and colleagues describe a protein-polymer conjugation strategy that substantially increases protein serum half-life without promoting an antigenic response. In some patients, the production of anti-PEG antibodies to PEGylated drugs compromises continued treatment. Furthermore, some individuals never treated with PEGylated drugs harbor anti-PEG antibodies in their bloodstream, likely in response to the many PEG-containing consumer products used today. The authors developed their new protein-polymer conjugate by growing a single chain of a PEG-like brush polymer, called POEGMA, from the C terminus of the peptide exenatide—a 4.1-kDa drug that improves insulin production in type 2 diabetes patients and exhibits a half-life in mice of only about 2 hours. In contrast, the administration of a 55-kDa exenatide-POEGMA conjugate significantly improved the pharmacokinetic profile, facilitating a reduction in blood glucose levels for 120 hours in mice (compared with 6 hours for the unmodified exenatide). It was hypothesized that because the PEG side chains on the POEGMA were very short (≤ 9 units), they would not react with anti-PEG antibodies. Upon incubation with serum from patients with anti-PEG antibodies, exenatide-POEGMA conjugates with 9-unit PEG side chains exhibited reduced antibody binding compared with two positive controls, PEGylated drugs. Through the creation of alternative exenatide-POEGMA conjugates with much shorter (3-unit) PEG side chains, antigenicity was completely eliminated without compromising extended therapeutic effect in a fed mouse model. Prior to translation, future work is needed to assess immunogenicity—that is, the ability of conjugates to generate new antibody responses—in addition to antigenicity in a living system. Y. Qi et al. , A brush-polymer/exendin-4 conjugate reduces blood glucose levels for up to five days and eliminates poly(ethylene glycol) antigenicity. Nat. Biomed. Eng. 10.1038/s41551-016-0002 (2016). [[Abstract]][1] [1]: http://doi.org/10.1038/s41551-016-0002
Mixed Model Association with Family-Biased Case-Control Ascertainment

Mixed models have become the tool of choice for genetic association studies; however, standard mixed model methods may be poorly calibrated or underpowered under family sampling bias and/or case-control ascertainment. Previously, we introduced a liability threshold based mixed model association statistic (LTMLM) to address case-control ascertainment in unrelated samples. Here, we consider family-biased case-control ascertainment, where cases and controls are ascertained non-randomly with respect to family relatedness. Previous work has shown that this type of ascertainment can severely bias heritability estimates; we show here that it also impacts mixed model association statistics. We introduce a family-based association statistic (LT-Fam) that is robust to this problem. Similar to LTMLM, LT-Fam is computed from posterior mean liabilities (PML) under a liability threshold model; however, LT-Fam uses published narrow-sense heritability estimates to avoid the problem of biased heritability estimation, enabling correct calibration. In simulations with family-biased case-control ascertainment, LT-Fam was correctly calibrated (average χ2 = 1.00), whereas Armitage Trend Test (ATT) and standard mixed model association (MLM) were mis-calibrated (e.g. average χ2 = 0.50-0.67 for MLM). LT-Fam also attained higher power in these simulations, with increases of up to 8% vs. ATT and 3% vs. MLM after correcting for mis-calibration. In 1,269 type 2 diabetes cases and 5,819 controls from the CARe cohort, downsampled to induce family-biased ascertainment, LT-Fam was correctly calibrated whereas ATT and MLM were again mis-calibrated (e.g. average χ2 = 0.60-0.82 for MLM). Our results highlight the importance of modeling family sampling bias in case-control data sets with related samples.
Just say no to paxos overhead: replacing consensus with network ordering

Distributed applications use replication, implemented by protocols like Paxos, to ensure data availability and transparently mask server failures. This paper presents a new approach to achieving replication in the data center without the performance cost of traditional methods. Our work carefully divides replication responsibility between the network and protocol layers. The network orders requests but does not ensure reliable delivery - using a new primitive we call ordered unreliable multicast (OUM). Implementing this primitive can be achieved with near-zero-cost in the data center. Our new replication protocol, Network-Ordered Paxos (NOPaxos), exploits network ordering to provide strongly consistent replication without coordination. The resulting system not only outperforms both latency - and throughput-optimized protocols on their respective metrics, but also yields throughput within 2% and latency within 16 ms of an unreplicated system - providing replication without the performance cost.
Pediatric residents’ attitudes and practice patterns regarding transition to adult-oriented care

Background: Most youth with chronic illness will survive into adulthood. The complexity of the medical history and care in these patients necessitates a well-planned and coordinated transition over...
Fabry Disease: prevalence of affected males and heterozygotes with pathogenic GLA mutations identified by screening renal, cardiac and stroke clinics, 1995–2017

Background Fabry Disease (FD), an X linked lysosomal storage disease due to pathogenic α-galactosidase A ( GLA ) mutations, results in two major subtypes, the early-onset Type 1 ‘Classic’ and the Type 2 ‘Later-Onset’ phenotypes. To identify previously unrecognised patients, investigators screened cardiac, renal and stroke clinics by enzyme assays. However, some screening studies did not perform confirmatory GLA mutation analyses, and many included recently recognised ‘benign/likely-benign’ variants, thereby inflating prevalence estimates. Methods Online databases were searched for all FD screening studies in high-risk clinics (1995–2017). Studies reporting GLA mutations were re-analysed for pathogenic mutations, sex and phenotype. Phenotype-specific and sex-specific prevalence rates were determined. Results Of 67 studies, 63 that screened 51363patients (33943M and 17420F) and provided GLA mutations were reanalysed for disease-causing mutations. Of reported GLA mutations, benign variants occurred in 47.9% of males and 74.1% of females. The following were the revised prevalence estimates: among 36820 (23954M and 12866F) haemodialysis screenees, 0.21% males and 0.15% females; among 3074 (2031M and 1043F) renal transplant screenees, 0.25% males and no females; among 5491 (4054M and 1437F) cardiac screenees, 0.94% males and 0.90% females; and among 5978 (3904M and 2074F) stroke screenees, 0.13% males and 0.14% females. Among male and female screenees with pathogenic mutations, the type 1 Classic phenotype was predominant (~60%), except more male cardiac patients (75%) had type 2 Later-Onset phenotype. Conclusions Compared with previous findings, reanalysis of 63 studies increased the screenee numbers (~3.4-fold), eliminated 20 benign/likely benign variants, and provided more accurate sex-specific and phenotype-specific prevalence estimates, ranging from ~0.13% of stroke to ~0.9% of cardiac male or female screenees.
The anterior knee: normal variants, common pathologies, and diagnostic pitfalls on MRI

The anterior aspect of the knee is host to an array of normal variants and potential pathology. These normal anatomic variants are often encountered and may mimic pathologies, leading to unnecessary work-up and treatments. On the other hand, there are several subtle abnormalities that may be easily overlooked or mistaken for variants or other injuries or diseases. Recognition of these diagnostic challenges is essential for radiologists to make an accurate diagnosis. This article reviews normal anatomical variants of ligaments, tendons, bones, and other important structures of the anterior knee, focusing on magnetic resonance imaging features. Commonly encountered injuries and abnormalities of the anterior knee and their diagnostic pitfalls are also discussed, highlighting findings on magnetic resonance imaging.
The development of predatory aggression and defense in the domestic cat (Felis catus): II. Development of aggression and defense in the first 164 days of life

In this study we examined the development of the conflict between attack and defense in kittens from 14 to 164 days of age. Clear and separable stages of development approach, followed by withdrawal, followed by play with conspecifics, attack on prey, and conflict between attack and defense were evident in the first 52 days of life. Attack behaviors emerged out of the context of an earlier defensiveness and a transiently increasing playfulness. Primarily those behaviors related to effective adult predatory attack continued after play behaviors waned. Differences in development of attack of kittens which were later to become aggressive or nonaggressive as adults were primarily accounted for by differences in defensive responses toward prey early in life. These differences emerged within the first month of life and prior to any prey behaviors that normally elicit defense in the adult cat. These data suggest that an experientially resistant neural-developmental process of mechanisms controlling defense in the cat is a powerful factor in shaping the course of development of attack and defense. The authors gratefully acknowledge the technical assistance of Glenn Harrison, Alex Stiglick, and Balraj Riar in scoring the behavioral data. The contribution of Olga Stokan to the analysis of the data is also gratefully recognized. We also wish to thank Martin Graham for his aid in preparation of figures for the manuscript. The support and encouragement of Dr. John Fentress in the initial stages of this study cannot be adequately recognized. We wish to express our warmest thanks to Dr. Fentress, without whose help these studies would never have been completed.
The Inter- and Intra-Granular Resistivity of Beta-Alumina

The electrical properties of polycrystalline beta-alumina involve two features not encountered with single crystals—tortuosity and grain boundaries. The former, the elongation of the conduction path arising from the random orientation of the individual grains, will only be touched upon in this paper. Rather, the main concerns are with a model for separating measured impedances into intergranular (grain boundary) and intragranular (crystal) components, with practical methods for determining the parameters characterizing these components, and with variations in parameter values with composition.