cssi/SciSciGPT-SciSciNet huggingface dataset:
FDA Approval Summary: Dabrafenib and Trametinib for the Treatment of Metastatic Non‐Small Cell Lung Cancers Harboring BRAF V600E Mutations

On June 22, 2017, the Food and Drug Administration expanded indications for dabrafenib and trametinib to include treatment of patients with metastatic non-small cell lung cancer (NSCLC) harboring BRAF V600E mutations. Approval was based on results from an international, multicenter, multicohort, noncomparative, open-label trial, study BRF113928, which sequentially enrolled 93 patients who had received previous systemic treatment for advanced NSCLC (Cohort B, n = 57) or were treatment-naive (Cohort C, n = 36). All patients received dabrafenib 150 mg orally twice daily and trametinib 2 mg orally once daily. In Cohort B, overall response rate (ORR) was 63% (95% confidence interval [CI] 49%-76%) with response durations ≥6 months in 64% of responders. In Cohort C, ORR was 61% (95% CI 44%-77%) with response durations ≥6 months in 59% of responders. Results were evaluated in the context of the Intergroupe Francophone de Cancerologie Thoracique registry and a chart review of U.S. electronic health records at two academic sites, characterizing treatment outcomes data for patients with metastatic NSCLC with or without BRAF V600E mutations. The treatment effect of dabrafenib 150 mg twice daily was evaluated in 78 patients with previously treated BRAF mutant NSCLC, yielding an ORR of 27% (95% CI 18%-38%), establishing that dabrafenib alone is active, but that the addition of trametinib is necessary to achieve an ORR of >40%. The most common adverse reactions (≥20%) were pyrexia, fatigue, nausea, vomiting, diarrhea, dry skin, decreased appetite, edema, rash, chills, hemorrhage, cough, and dyspnea. Implications for practice The approvals of dabrafenib and trametinib, administered concurrently, provide a new regimen for the treatment of a rare subset of non-small cell lung cancer (NSCLC) and demonstrate how drugs active for treatment of BRAF-mutant tumors in one setting predict efficacy and can provide supportive evidence for approval in another setting. The FDA also approved the first next-generation sequencing oncology panel test for simultaneous assessment of multiple actionable mutations, which will facilitate selection of optimal, personalized therapy. The test was shown to accurately and reliably select patients with NSCLC with the BRAF V600E mutation for whom treatment with dabrafenib and trametinib is the optimal treatment.
A severe and consistent deficit in marrow and circulating primitive hematopoietic cells (long-term culture-initiating cells) in acquired aplastic anemia

We examined the stem cell compartment of patients with acquired aplastic anemia (AA) using the long-term culture-initiating cell assay (LTC-IC), in parallel with measurements of CD34+ cells and mature hematopoietic progenitors. Secondary colonies from cells surviving 5 weeks of long-term bone marrow culture (LTBMC) were determined for the peripheral blood (PB) of 68 AA patients and 13 normal controls and for BM of 49 AA patients and 14 controls; because of low cell numbers, formal limiting dilution analysis could only be performed in 10 patients. The relationship of cell input in LTBMC and the output of secondary colonies was linear, allowing quantification of LTC-IC number from bulk cultures. Secondary colony formation was markedly abnormal in severe AA. In contrast to 7.8 colony-forming cells (CFC)/10(5) mononuclear cells in normal BM and 0.14 CFC/10(5) normal PB mononuclear cells, patients with severe disease showed 0.024 CFC/10(5) in BM and 0.0068 CFC/10(5) in PB. Under limiting dilution conditions, patients' cells also showed markedly lower colony-forming ability. In contrast to 4.3 +/- 1 colonies/normal LTC-IC, we obtained only 1.27 +/- 0.09 and 2.0 +/- 0.35 colonies from BM of acute and recovered cases, respectively. These values were used to extrapolate LTC-IC numbers from secondary colony formation in suspension cultures. In PB, calculated LTC-IC were decreased 7.4-fold in new and relapsed severe AA and 2.8- fold in recovered AA. In BM, LTC-IC were decreased 10-fold in new and relapsed AA and sixfold in recovered cases. Compared with measurements obtained on presentation, LTC-IC were lower in post-treatment samples from patients who had failed to recover after intensive immunosuppression and relatively higher in cases at relapse. In recovered patients, LTC-IC number increased but remained below the normal range in 20 of 25. In patients studied serially for 3 to 12 months after treatment, LTC-IC numbers remained stable but low. LTC-IC number correlated with concurrently determined CD34+ cell number and primary hematopoietic colony formation. These results indicate that stem cell numbers, as quantitated by the LTC-IC assay, are markedly diminished in number in all severe AA. Additionally, the function of the stem cell or the stem cell compartment in AA is also abnormal, as inferred from the low clonogenic potential in secondary colony assays. Early hematologic improvement in some patients occurs without increasing numbers of LTC-IC, and a minority of recovered cases show apparent repopulation of the LTC-IC compartment years after treatment.
Examining Distributed Leadership Practices by School Grade Configuration.

In this study, we apply a distributed leadership framework to better understand the nature of leadership practices distributed in schools by grade configuration. In this analysis we examine the fol...
Digital Data, Virtual Tours, and 3D Models Integration Using an Open-Source Platform

The site of the ‘Balsignano village’ in Modugno (Italy), for some years has been the object of attention by scholars. Recently renovated, its valuation is nowadays the main objective for that Municipality. The aim of this article is describing our approach in integrating digital data, virtual tours and 3d models of the village elements to produce an interactive tool available on the internet, stimulating the desire to physically visit the settings. Our findings can be generalized to any context in which a link between a website and a physical site represent a challenge for low-budgeted Administrations.
Immigration and Economic Freedom of the US States: Does the Institutional Quality of Immigrants’ Origin Countries Matter?

This paper examines whether the institutional quality of immigrants’ origin countries matters when testing the relationship between immigration and the US states’ economic freedom scores. Our results show that, in the short run, the relationship between economic freedom and immigrants from countries ranked in the second quartile of the Fraser Institute’s Economic Freedom of the World report is negative and statistically significant, but it is not economically significant. In the long run, the relationship between economic freedom and immigrants from countries ranked in the bottom quartile of the EFW report is positive and statistically significant, but it is not economically significant. For other immigrant groups coming from countries that rank higher in terms of economic freedom, the relationship is negative but is not statistically significant or is weakly significant. Our results are robust to various specifications.
Improved design of aluminum test cell to study the thermal resistance of Salmonella enterica and Enterococcus faecium in low-water activity foods

Abstract Salmonella enterica is a major cause of foodborne pathogen contamination in the United States. The heat resistance of Salmonella increases as aw decreases, leading to a significant challenge in the design of thermal processes. The aluminum thermal death time (TDT) cell is a common experimental tool to study the isothermal resistance of Salmonella and other pathogenic bacteria in foods. However, the TDT cell has the problem of a relatively long come-up time, and it is difficult to seal. This research improved the previous design of aluminum TDT cells and evaluated the performance of the improved design by using the thermal inactivation data of Salmonella enterica cocktail and Enterococcus faecium in brown rice flour. The come-up time of brown rice flour was reduced significantly, from 2.33 min in the previous design to 0.67 min (40 s) in the improved design of test cells when immersed in an 85 °C glycol bath. With the increase of the cavity diameter of the cell, it was easy to load and unload food samples. Additional new features of the improved design included the wrench flats on the outer surface of cell wall. The D-values for Salmonella in the aw 0.45 (measured at 25 °C) brown rice flour were 42.70, 17.51, 8.11, and 2.27 min at 70, 75, 80, and 85 °C, respectively. The D-values for Enterococcus faecium were 65.82, 22.28, 6.05, and 1.86 min at 70, 75, 80, and 85 °C, respectively. This research shows that the improved design of test cells is a reliable experimental tool to study the thermal resistance of microorganisms in low-aw foods. Accurate detection of microbial survival under isothermal conditions will provide reliable data for modeling and pathogen control during thermal processing to help ensure food safety and quality.
The Addictions Neuroclinical Assessment Negative Emotionality Domain Among Treatment-Seekers with Alcohol Use Disorder: Construct Validity and Measurement Invariance.

Background The Addictions Neuroclinical Assessment (ANA), a framework for measuring heterogeneity in alcohol use disorder (AUD), focuses on 3 domains that reflect neurobiological dysfunction in addiction and correspond to the cycles of addiction: executive function, incentive salience, and negative emotionality. Kwako and colleagues (Am J Psychiatry 176:744, 2019) validated a 3-factor model of the ANA with neuropsychological and self-report indicators among treatment-seekers and non-treatment-seekers with and without AUD. The present analysis replicated and extended these findings in a treatment-seeking sample, focusing on the negative emotionality domain. Methods Participants (n = 563; 58.8% male; mean age = 34.3) were part of a multisite prospective study of individuals entering AUD treatment. We examined the factor structure of the negative emotionality domain at the baseline, 6-month follow-up, and 12-month follow-up assessments. The Beck Depression Inventory, Beck Anxiety Inventory, State-Trait Anger Expression Inventory-Trait Anger Subscale, and 3 Drinker Inventory of Consequences items assessing negative affective consequences were indicators in the model. Results Results indicated that a 1-factor model was an excellent fit at all assessments and that the negative emotionality domain was time and gender invariant. Furthermore, negative emotionality was associated with drinking patterns and reasons for alcohol use (i.e., drinking because of negative emotions and urges/withdrawal) at all assessments. Conclusions This analysis provides evidence for the construct validity and measurement invariance of the ANA negative emotionality domain among AUD treatment-seekers. Future studies are needed to evaluate prospective associations between negative emotionality and specific treatment modalities, and whether individuals with greater negative emotionality are more likely to respond to treatment that targets drinking to relieve negative affective states.
Numerical Studies on Concrete Barriers Subject to MASH Truck Impact

Abstract In January 2016, the FHWA and AASHTO announced a joint agreement that only bridge railing and longitudinal barriers evaluated using the 2016 edition of Manual for Assessing Safety Hardware...
Beyond the eye: Cortical differences in primary visual processing in children with cerebral palsy.

Abstract Despite the growing clinical recognition of visual impairments among people with cerebral palsy (CP), very few studies have evaluated the neurophysiology of the visual circuitry. To this end, the primary aim of this investigation was to use magnetoencephalography and beamforming methods to image the relative change in the alpha–beta and gamma occipital cortical oscillations induced by a spatial grating stimulus (e.g., visual contrast) that was viewed by a cohort of children with CP and typically-developing (TD) children. Our results showed that the high-contrast, visual gratings stimuli induced a decrease in alpha–beta (10 – 20 Hz) activity, and an increase in both low (40 – 56 Hz) and high (60 – 72 Hz) gamma oscillations in the occipital cortices. Compared with the TD children, the strength of the frequency specific cortical oscillations were significantly weaker in the children with CP, suggesting that they had deficient processing of the contrast stimulus. Although CP is largely perceived as a musculoskeletal centric disorder, our results fuel the growing impression that there may also be prominent visual processing deficiencies. These visual processing deficits likely impact the ability to perceive visual changes in the environment.
Few-shot link prediction via graph neural networks for Covid-19 drug-repurposing

Predicting interactions among heterogenous graph structured data has numerous applications such as knowledge graph completion, recommendation systems and drug discovery. Often times, the links to be predicted belong to rare types such as the case in repurposing drugs for novel diseases. This motivates the task of few-shot link prediction. Typically, GCNs are ill-equipped in learning such rare link types since the relation embedding is not learned in an inductive fashion. This paper proposes an inductive RGCN for learning informative relation embeddings even in the few-shot learning regime. The proposed inductive model significantly outperforms the RGCN and state-of-the-art KGE models in few-shot learning tasks. Furthermore, we apply our method on the drug-repurposing knowledge graph (DRKG) for discovering drugs for Covid-19. We pose the drug discovery task as link prediction and learn embeddings for the biological entities that partake in the DRKG. Our initial results corroborate that several drugs used in clinical trials were identified as possible drug candidates. The method in this paper are implemented using the efficient deep graph learning (DGL)
Collective Action, Foreign Fighting, and the Global Struggle for the Islamic State

This project examines the global “foreign fighter” phenomenon, in which individuals fight in a foreign conflict. We explore the question – “Why do ordinary people travel abroad to fight and potenti...
A systematic review of measures of implementation players and processes: Summarizing the dearth of psychometric evidence:

Background:Measurement is a critical component for any field. Systematic reviews are a way to locate measures and uncover gaps in current measurement practices. The present study identified measure...
HEMATOLOGICAL MANIFESTATIONS OF CELIAC DISEASE AMONG CHILDREN: A SINGLE CENTER STUDY FROM SOUTH PUNJAB, PAKISTAN

OBJECTIVE: To find out various hematological manifestations among children from South Punjab, having confirmed celiac disease (CD). METHODS: This case-control study was done at The Institute of Child Health, Multan, Pakistan, from 1st February 2019 to 31st July 2019. We enrolled 139 children having CD, ranging in age from 1-12 years. An equal number of age and gender matched controls were also enrolled. Haematological parameters were compared between cases and controls. RESULTS: Majority (n=83/139; 59.7%) of children with CD were male. Mean age was 8.78±2.4 years. The common hematological manifestations among children with CD were anemia (n=127; 91.4%), thrombocytosis (n=104; 74.8%); leucopenia (n=10; 7.2%) and coagulopathy (n=13; 9.4%). Anemia alone was present in 20 (14.4%) children, anemia plus thrombocytosis in 91 (65.5%) cases, anemia plus leucopenia in 7 (5.0%) cases and anemia along with thrombocytosis and coagulopathy in 9 (6.5%) cases. Out of 127 cases of anemia, iron deficiency anemia (IDA) was noted in 96 (75.6%) cases, vitamin B12 and folate deficiency anemia in 14 (10.1%) cases whereas double deficiency anemia was seen in 17 (13.4%) cases. According to Modified Marsh Scoring, majority (n=46; 33.1%) of children had Type 3a CD. When compared to controls, CD cases had significantly lower haemoglobin, raised platelet count, lower mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) levels (p value<0.0001). CONCLUSION: In children having CD, hematological manifestations are common. IDA is the most frequent hematological abnormality observed along with thrombocytosis in children with CD. Hematological parameters were significantly impaired among children with CD.
Regional and temporal variations affect the accuracy of variant-specific SARS-CoV-2 PCR assays

Monitoring the prevalence of SARS-CoV-2 variants is necessary to make informed public health decisions during the COVID-19 pandemic. PCR assays have received global attention, facilitating rapid understanding of variant dynamics because they are more accessible and scalable than genome sequencing. However, as PCR assays target only a few mutations, their accuracy could be compromised when these mutations are not exclusive to target variants. Here we show how to design variant-specific PCR assays with high sensitivity and specificity across different geographical regions by incorporating sequences deposited in the GISAID database. Furthermore, we demonstrate that several previously developed PCR assays have decreased accuracy outside their study areas. We introduce PRIMES, an algorithm that enables the design of reliable PCR assays, as demonstrated in our experiments that enabled tracking of dominant SARS-CoV-2 variants in local sewage samples. Our findings will contribute to improving PCR assays for SARS-CoV-2 variant surveillance.
Liquid Crystals as Nonlinear Optical Materials

Liquid crystals materials form a special class of nonlinear optical materials. They are generally composed of highly nonlinear and anisotropie molecules, and possess a number of structurally different fluid phases in a readily accessible temperature range [1]. The optical properties of such media are easily modified by external perturbations because of the high molecular anisotropy, low viscosity of molecular motion, and strong correlation between molecules. The fact that even a weak laser field is strong enough to cause a significant change in the optical properties makes liquid crystals most unusual as nonlinear optical materials. Many nonlinear optical effects, including a few highly nonlinear ones, can be easily observed in thin films of such materials [2]. In this paper, we shall focus our discussion on the nonlinear optical properties of liquid crystals.
E14. Squares in Square: The 1932 Erdős Conjecture

I will take you here on a journey through problems, conjectures, and results. My goal is to present a live fragment of mathematics and to show how mathematical train of thought travels. I hope you will enjoy the ride!
Detecting Very Early Stages of Dementia from Normal Aging with Machine Learning Methods

We used Machine Learning (ML) methods to learn the best decision rules to distinguish normal brain aging from the earliest stages of dementia using subsamples of 198 normal and 244 cognitively impaired or very mildly demented (Clinical Dementia Rating Scale=0.5) persons. Subjects were represented by their age, education and gender, plus their responses on the Functional Activities Questionnaire (FAQ), the Mini-Mental Status Exam (MMSE), and the Ishihara Color Plate (ICP) tasks. The ML algorithms applied to these data contained within the electronic patient records of a medical relational database, learned rule sets that were as good as or better than any rules derived from either the literature or from domain specific knowledge provided by expert clinicians. All ML algorithms for all runs found that a single question from the FAQ, the forgetting rule, (“Do you require assistance remembering appointments, family occasions, holidays, or taking medications?”) was the only attribute included in all rule sets. CART's tree simplification procedure always found that just the forgetting rule gave the best pruned decision tree rule set with classification accuracy (93% sensitivity and 80% specificity) as high as or better than any other decision tree rule-set. Comparison with published classification accuracies for the FAQ and MMSE revealed that including some of the additional attributes in these tests actually worsen classification accuracy. Stepwise logistic regression using the FAQ attributes to classify dementia status confirmed that the forgetting rule gave a much larger odds ratio than any other attribute and was the only attribute included in all of the stepwise logistic regressions performed on 33 random samples of the data. Stepwise logistic regression using the MMSE attributes identified two attributes which occurred in all 33 runs and had by far the highest odds ratio. In summary, ML methods have discovered that the simplest and most sensitive screening test for the earliest clinical stages of dementia consists of a single question, the forgetting rule.
The use of Fourier reverse transforms in crystallographic phase refinement

Often a crystallographer obtains an electron density map which shows only part of the structure. In such cases, the phasing of the trial model is poor enough that the electron density map may show peaks in some of the atomic positions, but other atomic positions are not visible. There may also be extraneous peaks present which are not due to atomic positions. A method for determination of crystal structures that have resisted solution through normal crystallographic methods has been developed. PHASER is a series of FORTRAN programs which aids in the structure solution of poorly phased electron density maps by refining the crystallographic phases. It facilitates the refinement of such poorly phased electron density maps for difficult structures which might otherwise not be solvable. The trial model, which serves as the starting point for the phase refinement, may be acquired by several routes such as direct methods or Patterson methods. Modifications are made to the reverse transform process based on several assumptions. First, the starting electron density map is modified based on the fact that physically the electron density map must be non-negative at all points. In practice a small positive cutoff is used. A reverse Fourier transform is computed based on the modified electron density map. Secondly, the authors assume that a better electron density map will result by using the observed magnitudes of the structure factors combined with the phases calculated in the reverse transform. After convergence has been reached, more atomic positions and less extraneous peaks are observed in the refined electron density map. The starting model need not be very large to achieve success with PHASER; successful phase refinement has been achieved with a starting model that consists of only 5% of the total scattering power of the full molecule. The second part of the thesis discusses three crystal structure determinations.
Determination of littlest Higgs model parameters at the International Linear Collider

We examine the effects of the extended gauge sector of the Littlest Higgs model in high energy e{sup +}e{sup -} collisions. We find that the search reach in e{sup +}e{sup -} {yields} f{bar f} at a {radical}s = 500 GeV International Linear Collider covers essentially the entire parameter region where the Littlest Higgs model is relevant to the gauge hierarchy problem. In addition, we show that this channel provides an accurate determination of the fundamental model parameters, to the precision of a few percent, provided that the LHC measures the mass of the heavy neutral gauge .eld. Additionally, we show that the couplings of the extra gauge bosons to the light Higgs can be observed from the process e{sup +}e{sup -} {yields} Zh for a significant region of the parameter space. This allows for confirmation of the structure of the cancellation of the Higgs mass quadratic divergence and would verify the little Higgs mechanism.
Silicon Photonic Microring Resonator-Based Transceivers for Compact WDM Optical Interconnects

This paper examines the potential of silicon photonic microring resonator-based optical transceivers for compact wavelength-division multiplexing (WDM) optical interconnects. An overview of the photonic devices typically found in a ring resonator optical interconnect platform is provided and the design of transceiver circuits which address key challenges related to the modulators and drop filters is described. The possibility of further improvements in bandwidth density via efficient implementations of &#62;50Gb/s PAM4 modulation with the microring modulators is detailed.
The Death of Death Row Clemency and the Evolving Politics of Unequal Grace

While America’s appetite for capital punishment continues to wane over time, clemency for death row inmates is all but extinct. Moreover, what little clemency activity that persists continues to distribute unevenly across gender, racial and ethnic groups, geography, governors’ political affiliation, and over time. Insofar as courts appear extremely reluctant to review – let alone interfere with – clemency activity, little, if any, formal legal recourse exists. Results from this study of clemency activity on state death rows (1973-2010) suggest that potential problems arise, however, to the extent that our criminal justice system relies on clemency to function as coherent extrajudicial check.
Correlation between mass transfer and operating parameters in zinc electrowinning

The effects of antimony additions, acid concentration, and current density on mass transfer and deposition morphology were examined. The mass transfer coefficients of zinc were calculated using a codeposition method with cadmium as a tracer. The experiments were carried out for vertical electrodes in a Hull cell. The results indicate that the mass transfer coefficients increase with increasing antimony additions, acid concentration, and current density. Zinc dissolution is more severe at low current density and higher antimony levels than at higher current densities and lower antimony levels. A mass transfer correlation for pure zinc electrolyte data is $$Sh = 12.47\left( {ReSc} \right)^{0.45} $$ whereSh, Re, andSc are the Sherwood, Reynolds, and Schmidt numbers, respectively. The correlation fits very well with the experimental data. A correlation for electrolytes containing antimony was also obtained and has an exponent of 0.42. The correlations cover a wide range of operating parameters and provide a fast quantitative estimation of the change in mass transfer in zinc electrowinning.
Computerized manufacturing of transparent face masks for the treatment of facial scarring

In this work an integrated system of computer-aided design and computer-aided manufacturing specifically designed to fabricate affordable transparent face masks is discussed. FaceScan, a custom-designed software system, integrates shape capture, mask design, and pattern fabrication. The software controls a linear scan noncontact laser imager for facial topography acquisition and a milling machine for pattern fabrication. Compared with conventional methods of mask fabrication, this system is faster, more accurate, and less stressful for the patient and allows for greater control of the finished product. Masks for two subjects have been successfully fabricated using this system.
Periods of ordinary abelian varieties in characteristic p

For ordinary abelian varieties in characteristicp>0, we define an analogue of the period lattice and of the parametrization by ℂg and give some applications.
Synthesis and in vivo validation of [O-methyl-11C]2-{4-[4-(7-methoxynaphthalen-1-yl)piperazin- 1-yl]butyl}-4-methyl-2H-[1,2,4]triazine-3,5-dione: a novel 5-HT1A receptor agonist positron emission tomography ligand.

Antagonist 5-HT1A PET ligands are available, but an agonist ligand would give more information about signal transduction capacity. Synthesis and in vivo evaluation of [O-methyl-11C]2-{4-[4-(7-metho...
Why propene is not polymerized by (Cp*2YH)2: reactions of yttrium alkyl complexes with alkenes produce allyl and vinyl yttrium complexes

Abstract Yttrium alkyl complexes Cp* 2 YR react with CH bonds of alkenes to form either yttrium allyl complexes or yttrium vinyl complexes. Less substituted alkenes react faster, consistent with prior alkene coordination. The selectivity of the reaction of Cp* 2 YR with CH bonds is allylic CH 3 ≫vinyl CH≫allylic CH 2 . Propene is readily metallated by Cp* 2 YR giving the η 3 -allyl complex Cp* 2 Y(η 3 -CH 2 ⋯ CH  CH 2 ) which does not react further with propene. This explains why Cp* 2 YR (R=alkyl, H) complexes make poor propene polymerization catalysts.
Drug safety evaluation of vemurafenib in the treatment of melanoma

Introduction: Nearly 50% of melanomas harbor a BRAF mutation, and vemurafenib has shown a clinical response rate of approximately 50% and a median progression-free survival duration of ∼ 6 – 7 months in patients with V600 BRAF-mutant advanced melanoma. Based on a Phase III study demonstrating a survival advantage over dacarbazine, vemurafenib was approved by the regulatory agencies for the treatment of V600 BRAF-mutant advanced melanoma in 2011. Although vemurafenib does not induce life-threatening toxicity frequently associated with conventional chemotherapy. It is associated with other adverse events, particularly skin toxicities. Areas covered: We discuss the mechanism of action, pharmacokinetics and pharmacodynamics, clinical efficacy, and safety profile of vemurafenib in patients with metastatic melanoma harboring a BRAF mutation. In particular, we describe in detail the skin toxicity of vemurafenib, including the development of keratoacanthoma and squamous cell carcinoma of the skin. Expert opinion:...
Age-dependent predation is not a simple process. I. Continuous time models

Abstract The stability of models of age-dependent predation in continuous time with predators exhibiting a functional response are analyzed. A number of new features of biological importance emerge that are not present in simpler models. These include limits to the length of juvenile periods (both upper and lower) for stability, and the possibility that increases or decreases in any of the model parameters can be stabilizing or destabilizing. Hence, increased delays are not necessarily destabilizing. The variance in the length of the juvenile period is shown to be an important factor determining stability. Additionally, the relative stability of predation only on juveniles or only on adults is compared.
Thermal Expansion of Rocksalt

The microscopic Grueneisen parameters and the temperature dependence of the thermal Grueneisen parameter of NaCl are calculated from a shell model with six parameters, five of which are taken as pressure dependent. All parameters are determined from experimental elastic, optical, and dielectric data at absolute-zero temperature. The results agree within 6-8% with experimental data. The discrepancy is primarily attributed to the experimental error of the input data that are used to determine the parameters of the model. Calculations have also been made for two versions of the rigid-ion model (RIM) which indicate that the apparent success previously attributed to the Kellermann model is mainly due to cancellation of errors arising from omitting second-nearest-neighbor interaction and electronic polarizability.
From the Editor in Chief: Pet Peeves

From spam to bad security, Internet pet peeves are common. EIC Fred Douglis shares some of his, and invites readers to share some of their own - as well as any solutions they've come up with.
The notch sensitivity of polymeric materials

Stress–strain tests were made on about five dozen polymeric materials using unnotched and notched specimens containing six different types of notches. Notches decrease the strength, but they decrease the elongation to break even more drastically in general. Notch sensitivity factors are defined for strength and for energy to fracture in such a manner that the greater the notch sensitivity factor, the greater is the effect of a notch relative to the unnotched material. The notch sensitivity factor for breaking (or yield) strength is not the same as the notch sensitivity factor for energy to fracture as measured by the area under the stress–strain curve. Brittle polymers and composites tend to have greater notch sensitivity factors for strength than ductile polymers. For brittle polymers, the notch sensitivity factor for energy to fracture tends to increase with the elongation to break of the unnotched polymer. Notches generally are more detrimental to ductile polymers than to brittle ones as far as the energy to fracture is concerned. For ductile polymers, the shape of the stress–strain curve is important in determining the sensitivity to notches. The ratio of the upper to lower yield strengths should be small for low notch sensitivity. It is desirable to have the breaking strength greater than the yield strength. Glass fibers and filler in ductile matrices increase the notch sensitivity for strength but decrease the sensitivity for energy to fracture relative to the unfilled polymer. Rubber–filled polymers have a reduced notch sensitivity for strength relative to the unfilled polymer, but the notch sensitivity for energy to fracture may be either increased or decreased, depending upon the system. The energy to fracture for notched specimens correlates better with Izod impact strength than does the energy to fracture for unnotched specimens. It is recommended that notched stress–strain specimens be routinely measured along with unnotched specimens.
Insights into the heterogeneity of human B cells: diverse functions, roles in autoimmunity, and use as therapeutic targets

B cells are critical players in the orchestration of properly regulated immune responses, providing protection against infectious agents without inflicting autoinflammatory damage. A balanced B cell compartment is also essential to create protective immunity in response to vaccines. This difficult compromise is achieved through the finely regulated participation of multiple B cell populations with different antibody-dependent and independent functions. Both types of functions allow B cells to powerfully modulate other components of the innate and adaptive immune system. For the most part, however, the necessary division of labor among different B cell populations is poorly understood. B cell dysfunction has been implicated in multiple autoimmune conditions. The physiological importance and complexity of B cell functions has been brought to the fore in recent years by the success of rituximab-based B cell depletion therapy (BCDT) in multiple autoimmune diseases including rheumatoid arthritis (RA) and multiple sclerosis (MS) which are conventionally viewed as T-cell mediated conditions. Given the widespread utilization of BCDT in malignant and autoimmune diseases and the key role of B cells in both protective immunity and pathogenic autoimmunity, a better understanding of B cell functions is of the essence and a focus of the research in our division. We are investigating these issues through a variety of approaches, including the study of the phenotype and function of human B cell populations in health, their perturbation in autoimmune disease states, the effects of targeted biologic therapies, and the study of relevant murine models.
The open field as a test of emotionality

According to Broadhurst (1969), the open field "has now reached the status of one of the few widely used, relatively standardized instruments in animal psychology." Although the open field is the most commonly used test of emotionality, a review of the literature indicates that neither the apparatus nor the test procedures have been standardized. Thus, the purpose of this study was to determine the effect of variations in the size and shape of the field apparatus on behavioral indicants of emotionality. In order to examine the relative sensitivity of the fields to different levels of emotionality, half of the animals received 4 days' experience in Anderson's (1941) water wader. Watson (reported by Broadhurst, 1958) found that any previous experience reduced emotionality in the open field. Since there have been numerous attacks on the validity of the open-field emotionality test (see Tobach & Schneirla, 1962; Becker, 1969), it seems appropriate that the effects of manipulating characteristics of the field be evaluated.
Evidence for cAMP-dependent protein kinase in the dinoflagellate, Amphidinium operculatum.

A cAMP dependent protein kinase (PKA) was identified in the dinoflagellate Amphidinium operculum. In vitro kinase activity towards kemptide, a PKA-specific substrate, was not detectable in crude lysates. However, fractionation of dinoflagellate extracts by gel filtration chromatography showed PKA-like activity toward kemptide at approximately 66 kDa. These findings suggest that possible low molecular mass inhibitors in crude lysates were removed by the gel filtration chromatography. Pre-incubation of extracts with cAMP prior to chromatography resulted in an apparent molecular mass shift in the in vitro kinase assay to 40 kDa. An in-gel kinase assay reflected activity of the free catalytic subunit at approximately 40 kDa. Furthermore, western blotting with an antibody to the human PKA catalytic subunit confirmed a catalytic subunit with a mass of approximately 40 kDa. Results from this study indicate that the PKA in A. operculatum has a catalytic subunit of similar size to that in higher eukaryotes, but with a holoenzyme of a size suggesting a dimeric, rather than tetrameric structure.
Electron impact excitation cross sections for N(V)

Abstract Generalized oscillator strengths and integrated cross sections from threshold to 1 keV are calculated in the Born approximation for the electron impact excitation of N(V).
A framework for assessing and rewarding a scientist's research productivity

A contest for world leadership in science and technology exists. New ways to motivate scientists seem as important to contest outcome as new sources of funds. A framework formed by cross-tabulating question difficulty and answer generality should help to identify the contribution of a research scientist. A reward relationship based on this framework should help to ensure that scientists will work on the most difficult research problems, a necessity for a high quality research program.
Successful Treatment of Diplopia With Prism Improves Health-Related Quality of Life

Purpose To report change in strabismus-specific health-related quality of life (HRQOL) following treatment with prism. Design Retrospective cross-sectional study. Methods Thirty-four patients with diplopia (median age 63, range 14-84 years) completed the Adult Strabismus-20 questionnaire (100-0, best to worst HRQOL) and a diplopia questionnaire in a clinical practice before prism and in prism correction. Before prism, diplopia was "sometimes" or worse for reading and/or straight-ahead distance. Prism treatment success was defined as diplopia rated "never" or "rarely" on the diplopia questionnaire for reading and straight-ahead distance. Failure was defined as worsening or no change in diplopia. For both successes and failures, mean Adult Strabismus-20 scores were compared before prism and in prism correction. Each of the 4 Adult Strabismus-20 domains (self-perception, interactions, reading function, and general function) was analyzed separately. Results Twenty-three of 34 (68%) were successes and 11 (32%) were failures. For successes, reading function improved from 57 ± 27 (SD) before prism to 69 ± 27 in-prism correction (difference 12 ± 20, 95% CI 3.2-20.8, P = .02) and general function improved from 66 ± 25 to 80 ± 18 (difference 14 ± 22, 95% CI 5.0-23.6, P = .003). Self-perception and interaction domains remained unchanged ( P > .2). For failures there was no significant change in Adult Strabismus-20 score on any domain ( P > .4). Conclusions Successful correction of diplopia with prism is associated with improvement in strabismus-specific HRQOL, specifically reading function and general function.
Induction of endochondral bone by demineralized bone matrix from diabetic rats.

In this investigation we examined the osteoinductive potential of demineralized bone matrix derived from chronically diabetic (streptozotocin-induced) rats. Long-Evans rats (28–31 days) were made diabetic with a single injection of streptozotocin (65 mg/kg) and provided food and waterad lib for 2 months. Diaphyseal shafts of femurs and tibias removed from the diabetic rats and their sibling controls were dehydrated, pulverized, sieved to 74–420 μm particles, and demineralized Matrix was then bioassayed for its ability to induce endochondral bone on day 11 following subcutaneous implantation over the thorax of Long-Evans rats. The resulting plaques of tissue were subjected to histological analysis, determination of alkaline phosphatase activity, and calcium content. Bone matrix derived from diabetic animals proved to be a significantly better inducer of endochondral bone than did control matrix.
Secondary activities of diverse inhibitors potentiate the response of hamster embryo cultures to a mitotic stimulus.

The reversal of the density dependent inhibition of replication (DDIR) of Syrian hamster embryo cultures by fresh medium containing 30–50% fetal bovine serum was poorly synchronized. There were two waves of DNA synthesis eight to nine hours apart, which by examination of autoradiograms of cultures pulse-labeled with 3H-thymidine, were found to involve 55% and 45% of the cell population. The second wave was found to be due to a subpopulation of epithelioid cells set in the predominantly fibroblastic cell cultures. Pretreatment of the DDIR cultures with hydroxyurea (HU) or arabinosyl cytosine (ara-C), followed by serum stimulation in the absence of the drugs, led to an enhancement of the synchrony. The effect increased with lengthening of the contact with antimetabolites, to a maximum after 20 hours' pre-exposure, and was in part due to the shortening of the G1 phase of the epithelioid elements, and in part to increasing the synchrony of the fibroblastic cells. The resulting synchrony involved some 95% of the cells in simultaneous DNA synthesis after a median G1 period of 12 hours. The effect had no relationship to the role of HU and ara-C as specific inhibitors of DNA synthesis since the cultures were mitotically quiescent, and a similar enhanced response could be induced in DDIR cultures by prestimulation exposure lasting only two hours to cycloheximide (cyx), an inhibitor of protein synthesis. Pre-exposure of DDIR cultures to actinomycin D did not potentiate the cell response. A survey of the known secondary inhibitions caused by these three antimetabolites suggests that they all may cause deficiencies in the glycolipid or glycoprotein moieties of the cell surface. These observations provide a useful, simple means of improving synchrony in these systems and may prove to be a useful probe for investigating the role of the cell surface in regulating cell replication.
Highway to the inner nuclear membrane: rules for the road

To enter the nucleus a protein must be chaperoned by a transport factor through the nuclear pore complex or it must be small enough to pass through by diffusion. Although these principles have long described the nuclear import of soluble proteins, recent evidence indicates that they also apply to the import of integral inner nuclear membrane proteins. Here we develop a set of rules that might govern the transport of proteins to the inner nuclear membrane.
The occurrence and distribution of Mo and molybdenite in unaltered peralkaline rhyolites from Pantelleria, Italy

Small hexagonal and triangular platelets of molybdenite (MoS2), 5 to 25 μm in diameter, were identified in phenocrysts and matrix glass of unaltered felsic volcanic rocks from Pantelleria, Italy. The MoS2 occurs commonly in pantellerites (peralkaline rhyolites), rarely in pantelleritic trachytes, and never in trachytes. The occurrence of euhedral MoS2 platelets in all phenocryst phases, in matrix glass, and even in some melt inclusions indicates that MoS2 precipitated directly from the peralkaline melt. Despite MoS2 saturation, the melt (glass) contains greater than 95% of the Mo in Pantellerian rocks: X-ray fluorescence analyses of 20 whole rocks and separated glasses show that whole rocks consistently contain less Mo than corresponding matrix glasses, the differences being in proportion to phenocryst abundances. The Mo contents increase with differentiation from trachytes (2–12 ppm) to pantellerites (15–25 ppm) and correlate positively with incompatible elements such as Th, Y, and Nb. The Mo concentrations, as determined by secondary ion mass spectrometry, are essentially the same in matrix glasses and melt inclusions, showing that Mo did not partition strongly into a volatile fluid phase during outgassing. The high Mo contents of the pantellerites (relative to metaluminous magmas with 1–5 ppm) may be due to several factors: (1) the enhanced stability of highly charged cations (such as Mo6+, U4+, and Zr4+) in peralkaline melts; (2) the rarity of Fe-Ti oxides and litanite into which Mo might normally partition; (3) reduced volatility of Mo in low fO2, H2O-poor (1–2 wt%) peralkaline magmas. Geochemical modeling indicates that the precipitation of MoS2 can be explained simply by the drop in temperature during magmatic differentiation. The occurrence of MoS2 in pantellerites may result from their high Mo concentrations and low redox state (▵Ni/NiO=-2.5) relative to metaluminous magmas, causing them to reach MoS2 saturation at magmatic temperatures. The apparent absence of MoS2 microphenocrysts in more oxidized, metaluminous rhyolites may indicate that Mo is dissolved primarily as a hexavalent ion in those magmas.
The extent of saltwater intrusion in southern Baldwin County, Alabama

Contamination of groundwater due to saltwater intrusion has become a major concern for coastal communities which rely on groundwater as their principal source of drinking water. The protection of groundwater resources from saltwater intrusion and groundwater overdraft is a critical concern in these areas as both groundwater resources and environmentally sensitive areas such as coastal wetlands and ecological coastal habitats may be at risk. A regional-scale study was conducted to assess the extent of saltwater intrusion for Baldwin County, Alabama. Groundwater wells were sampled and analyzed for salinity, chloride (Cl−), total dissolved solids (TDS), and other parameters to determine the extent of saltwater intrusion, and the location of the freshwater/saltwater interface in the region. Spatial iso-concentration maps (i.e. salinity, Cl−, and TDS) were constructed using ArcGIS software to determine the extent and severity of saltwater intrusion for the aquifers underlying southern Baldwin County. Concentration data show relatively low salinity levels in the central and northern extent of the study area. Elevated levels of salinity, Cl−, and TDS were observed in the local aquifers A1 and A2 along the coastal areas adjacent to the Gulf of Mexico. The study provides an initial current data set of areas impacted or most vulnerable to saltwater intrusion and provides a scientific basis for effective management of the coastal aquifers in the study region.
Inflammatory fibroid polyp of the stomach in a child

A large inflammatory fibroid polyp of the stomach with endo-exophylic growth is described in a 5-year-old. CT and UGI demonstrate the lesion.