cssi/SciSciGPT-SciSciNet huggingface dataset:
A Preliminary Assessment of HeterozygousCFHR3-CFHR1Deletion As a Permissive Mutation in Carfilzomib-Induced Atypical Hemolytic Uremic Syndrome

Carfilzomib is a critical chemotherapy medication used to treat patients with relapsed or refractory multiple myeloma. Unfortunately, drug-induced atypical hemolytic uremic syndrome (aHUS) has been established as a devastating and unpredictable side-effect of carfilzomib. Loss-of-function mutations in alternative complement pathway regulatory genes, such as complement factor H (CFH) and its related proteins (CFHRs), are the most frequently identified genetic abnormalities seen with aHUS. In our recently published work, two of three patients treated at the University of Rochester Medical Center for carfilzomib-induced aHUS were found to harbor the heterozygousCFHR3-CFHR1deletion, a genetic variant that is generally considered benign, implicating it in development of disease. We sought to further characterize the relationship between the heterozygousCFHR3-CFHR1deletion and development of carfilzomib-induced aHUS by conducting a case-control study. We screened banked frozen peripheral blood mononuclear cell (PBMC) samples from subjects treated with carfilzomib-based regimens at Washington University. Criteria for aHUS case selection were defined as all of the following: elevated LDH, decreased haptoglobin or elevated total bilirubin, evidence of schistocytes on peripheral blood smear, de novo anemia and thrombocytopenia, acute kidney injury, no evidence of infectious diarrhea (if tested), and active carfilzomib treatment at the time of disease. To ensure that controls had adequate exposure to carfilzomib, controls were selected from subjects who received ≥20 treatment cycles. Additional control selection criteria included: age >40 years, no evidence of hemolysis (LDH 9 g/dL and platelets >100 x 109/L), and no chronic or acute kidney disease (creatinine We found that two of three case samples (4 of 6 total [67%], including the previously published cases), and two of four control samples (50%) harbored the heterozygousCFHR3-CFHR1mutation. No otherCFH-CFHR5genomic region mutations were detected. The frequency of heterozygousCFHR3-CFHR1deletion was not found to be significantly different between case and control groups. Given the large amount of carfilzomib exposure among the control group, this result suggests that the heterozygousCFHR3-CFHR1deletion is likely not a predisposing mutation in the development carfilzomib-induced aHUS. However, an adequately powered case-control study would be required to statistically rule-out the association. Disclosures Wildes:Seattle Genetics:Consultancy;Janssen:Research Funding;Carevive Systems:Consultancy.Lipe:Janssen:Membership on an entity's Board of Directors or advisory committees;GlaxoSmithKline:Membership on an entity's Board of Directors or advisory committees;Celgene:Membership on an entity's Board of Directors or advisory committees;Amgen:Membership on an entity's Board of Directors or advisory committees.
From conflicts and confusion to doubts: Examining review inconsistency for fake review detection

Abstract Inconsistency in online consumer reviews (OCRs) may cause uncertainty and confusion to consumers when they make purchase decisions. However, there is a lack of a systematic and empirical investigation of review inconsistency in the literature. This research characterizes review inconsistency from multiple aspects, including rating-sentiment, content, and language, and proposes hypotheses about their effects on fake OCR detection by drawing upon deception and attitude-behavior consistency theories. We characterize review inconsistency with 22 features, and test the hypotheses with machine learning models developed for fake OCR detection. Our empirical evaluation results using real OCRs not only confirm the presence of review inconsistency, but also demonstrate significant positive effects of review inconsistency on the performance of fake OCR detection. The research findings have important implications for improving the effectiveness of consumer decision making and the trustworthiness of OCRs.
Mitigation of deleterious phenotypes in chloroplast-engineered plants accumulating high levels of foreign proteins

The global demand for functional proteins is extensive, diverse, and constantly increasing. Medicine, agriculture, and industrial manufacturing all rely on high-quality proteins as major active components or process additives. Historically, these demands have been met by microbial bioreactors that are expensive to operate and maintain, prone to contamination, and relatively inflexible to changing market demands. Well-established crop cultivation techniques coupled with new advancements in genetic engineering may offer a cheaper and more versatile protein production platform. Chloroplast-engineered plants, like tobacco, have the potential to produce large quantities of high-value proteins, but often result in engineered plants with mutant phenotypes. This technology needs to be fine-tuned for commercial applications to maximize target protein yield while maintaining robust plant growth. Here, we show that a previously developed Nicotiana tabacum line, TetC-cel6A, can produce an industrial cellulase at levels of up to 28% of total soluble protein (TSP) with a slight dwarf phenotype but no loss in biomass. In seedlings, the dwarf phenotype is recovered by exogenous application of gibberellic acid. We also demonstrate that accumulating foreign protein represents an added burden to the plants’ metabolism that can make them more sensitive to limiting growth conditions such as low nitrogen. The biomass of nitrogen-limited TetC-cel6A plants was found to be as much as 40% lower than wildtype (WT) tobacco, although heterologous cellulase production was not greatly reduced compared to well-fertilized TetC-cel6A plants. Furthermore, cultivation at elevated carbon dioxide (1600 ppm CO2) restored biomass accumulation in TetC-cel6A plants to that of WT, while also increasing total heterologous protein yield (mg Cel6A plant−1) by 50–70%. The work reported here demonstrates that well-fertilized tobacco plants have a substantial degree of flexibility in protein metabolism and can accommodate considerable levels of some recombinant proteins without exhibiting deleterious mutant phenotypes. Furthermore, we show that the alterations to protein expression triggered by growth at elevated CO2 can help rebalance endogenous protein expression and/or increase foreign protein production in chloroplast-engineered tobacco.
Does hitting the window break it?: Investigating effects of discourse-level and verb-level information in guiding object state representations

During language comprehension, comprehenders form mental representations of the described events. We investigate discourse-level and verb-level cues that guide this process. In particular, we inves...
Key Factors Influencing the Rise of Current Ransomware Attacks on Industrial Control Systems

Ransomware is a malware type whose purpose is to lock and deny access to vital resources and services in the system. Like any other system, ransomware targets Supervisory Control and Data Acquisition (SCADA) and denies access to many components and data these systems collect. This represents a major threat to the systems that rely on SCADA to control the operational process. Although several studies have been conducted to address the issue of ransomware and mitigate the effect of its attacks, they approach the problem from the traditional systems perspective. That is, these solutions treat the ransomware attack on SCADA systems similar to those attacking conventional systems. This is not realistic because of the unique characteristics of SCADA systems, which are reflected in the nature and capability of ransomware attacks. Not only are data stored in SCADA nodes vulnerable to the ransomware attack, but also the data collected and shared with the other nodes. As such, traditional measures for ransomware detection become unable to deal with the attack as they assume that ransomware attacks the data at rest only. In SCADA systems, the attack model, success factors, and infection vectors of ransomware attacks are different. As such it is important to explore and understand the unique characteristics of ransomware that target SCADA systems as a prerequisite to thwart it. Therefore, this study is devoted to investigating the unique characteristics and main factors for successful ransomware attacks.
Two-Level Multi-Level Modeling

With the introduction and conceptualization of multi-level modeling (MLM) in Chap. 2, we will focus on the detailed model building and implementation in R in this chapter.
The Climate Emergency and Solar Geoengineering

This Article examines the climate emergency and solar geoengineering—proposals to intentionally alter Earth’s reflectivity to cool the planet. It first defends climate emergency as a concept and possible mode of doing government while also warning against its hasty declaration. It then surveys the science and public language that gives shape to the climate emergency and examines how climate emergency-necessity frameworks are already interacting with the U.S. legal system and beyond. Next it reintroduces solar geoengineering as a potential climate emergency response and its research as an emergency measure. It closes by reviewing the legal theory on emergency measures within constitutional democracies and under international law, using those lessons to suggest governance principles for solar geoengineering research and, potentially, its development and deployment.
Loneliness and psychological distress in everyday life among Latinx college students.

OBJECTIVE Changes in surroundings and social relationships may heighten feelings of loneliness, suggesting the need to measure as a state. This study tested whether loneliness fluctuates within and across days and the resultant associations with psychological distress. Further it tested familism as a moderator as endorsing this cultural value may buffer the negative effects of state loneliness. PARTICIPANTS Participants (n = 220) were Latinx undergraduate students. METHODS Students reported their loneliness levels and psychological distress twice a day for two weeks using an ecological momentary assessment approach. RESULTS Results showed that experiencing a higher than usual level of loneliness predicted greater sadness, stress, and anxiety at both the moment-to-moment and day-to-day level. Familism, measured at baseline, only moderated the relationship between loneliness and sadness. CONCLUSIONS The findings suggest being in a lonely moment may lead to the initiation or amplification of psychological distress immediately and the effects may linger over the day.Supplemental data for this article can be accessed online at https://doi.org/10.1080/07448481.2021.1927051.
Outcomes of SARS-CoV-2 infection in patients with pulmonary sarcoidosis: A multicenter retrospective research network study.

Abstract Background Analyses of COVID-19 infection outcomes in patients with preexisting pulmonary sarcoidosis are lacking and are limited to case reports or small case series with the largest study reporting outcomes of 37 patients. Research question Retrospective cohort study to assess clinical outcomes of 945 patients with pulmonary sarcoidosis, presenting with COVID 19, compared to a propensity matched cohort of patients without sarcoidosis. Study design and methods Analysis of a multi-center research network TriNETX was performed including patients more than 16 years of age diagnosed with COVID-19. Outcomes in COVID-19 positive patients with concurrent pulmonary sarcoidosis were compared with a propensity score matched cohort of patients without pulmonary sarcoidosis. Results A total of 278,271 patients with COVID-19 on the research network were identified, 954 patients (0.34 %) carried a diagnosis of pulmonary sarcoidosis. Mean age of patients with sarcoidosis was 56.3 ± 13.2 years, with female predominance (n = 619, 64.89 %). 49.69 % of the participants were African American (n = 474). Co-morbidities including hypertension, chronic lower respiratory diseases, diabetes mellitus, ischemic heart disease, nicotine dependence, and chronic kidney disease were more common in patients with pulmonary sarcoidosis when compared to the non-pulmonary sarcoidosis cohort (all p values Interpretation Crude COVID-19 mortality and other clinical outcome measures are poor in pulmonary sarcoidosis cohort; however, propensity-matched analyses revealed no difference in outcomes, showing that higher mortality is driven by higher burden of comorbidities.
A Case Series: Acute ACA Stroke Presenting With Spasticity (720)

Objective: Demonstrate cases of acute anterior cerebral artery (ACA) stroke presenting with spasticity Background: Given the importance of time in stroke treatment, prompt recognition of unusual syndromes is essential. Spasticity, a well-known post-stroke phenomenon, is not a common presentation of acute ACA stroke. We illustrate three patients presenting with acute spasticity, all diagnosed with ACA stroke. Design/Methods: Three cases of acute ACA stroke were identified at the authors’ institution and associated hospitals. Data analysis included age, sex, symptoms, risk factors, treatment, and imaging findings. Results: Case 1: 48 year old healthy female presented with right leg weakness. Exam demonstrated increased tone with spasticity, hyperextension, plegia and loss of sensation in the right leg. NIHSS 5. Patient was treated with tPA. MRI demonstrated acute left paracentral lobule stroke. Etiology cryptogenic. Case 2: 67 year old male with prior atheroembolic strokes presented after a fall. Exam demonstrated left arm flexion contracture and left leg flaccid plegia. NIHSS 11. Neurological change was not recognized in time for tPA. MRI demonstrated right ACA stroke involving the frontal, parasagittal, and cingulate gyrus. Etiology atheroembolic vs cardioembolic from cardiac thrombus. Case 3: 49 year old healthy female presented with right sided weakness. Exam demonstrated right arm contracture and right leg spastic extension. NIHSS 8. tPA was not given due to unfamiliar presentation. MRI demonstrated left parasagittal and anterior cingulate gyrus stroke. Etiology cryptogenic. Conclusions: Damage to the corticospinal tract commonly results in negative symptoms (weakness, hyporeflexia) but can also result in positive symptoms (spasticity, hyperreflexia, and rigidity) as in these cases. In patients with sudden onset of symptoms, focal weakness and increased tone, ACA and anterior cingulate gyrus stroke and tPA should be considered if there are no contraindications. Differential diagnosis may include medication or illicit drug induced dystonia, musculoskeletal injury or functional presentation. Disclosure: Dr. Yu has nothing to disclose. Dr. Selvadurai has nothing to disclose. Dr. Amin has nothing to disclose.
Preventing perinatal transmission of HIV--costs and effectiveness of a recommended intervention.

Objective To calculate the national costs of reducing perinatal transmission of human immunodeficiency virus through counseling and voluntary testing of pregnant women and zidovudine treatment of infected women and their infants, as recommended by the Public Health Service, and to compare these costs with the savings from reducing the number of pediatric infections. Method The authors analyzed the estimated costs of the intervention and the estimated cost savings from reducing the number of pediatric infections. The outcome measures are the number of infections prevented by the intervention and the net cost (cost of intervention minus the savings from a reduced number of pediatric HIV infections). The base model assumed that intervention participation and outcomes would resemble those found in the AIDS Clinical Trials Group Protocol 076. Assumptions were varied regarding maternal seroprevalence, participation by HIV-infected women, the proportion of infected women who accepted and completed the treatment, and the efficacy of zidovudine to illustrate the effect of these assumptions on infections prevented and net cost. Results Without the intervention, a perinatal HIV transmission rate of 25% would result in 1750 HIV-infected infants born annually in the United States, with lifetime medical-care costs estimated at $282 million. The cost of the intervention (counseling, testing, and zidovudine treatment) was estimated to be $ 67.6 million. In the base model, the intervention would prevent 656 pediatric HIV infections with a medical care cost saving of $105.6 million. The net cost saving of the intervention was $38.1 million. Conclusion Voluntary HIV screening of pregnant women and ziovudine treatment for infected women and their infants resulted in cost savings under most of the assumptions used in this analysis. These results strongly support implementation of the Public Health Service recommendations for this intervention.
Integrated Frequency Allocation and User Assignment in Multimodal Transit Networks: Methodology and Application to Large-Scale Urban Systems

This paper presents an integrated solution method to the frequency-setting problem using optimization and assignment simulation. With a bilevel solution framework, an optimization problem is run at the upper level under the assumption that the total transit demand is fixed. The objective is to maximize wait time savings under the budget, fleet size, vehicle load, and policy headway constraints. At the lower level, an assignment and simulation algorithm is run; the algorithm models the demand response to the new frequency setting and transmits updated ridership and flow values to the upper level. The procedure is repeated until the improvement in the wait time savings converges. The platform is tested on the Chicago Transit Authority network in Illinois for the morning peak. The wait time savings in this experiment are converging and are found to be comparable with the results of a stand-alone frequency-setting algorithm that finds optimal solutions. Results are comparable with the optimal results of a sta...
Chapter 19 The economics of strikes

Publisher Summary This chapter discusses the prospects for constructing a theoretical explanation of strike activity and reviews the evidence that strikes are systematically related to other economic variables. The economic analysis of strikes begins with the “Hicks Paradox”: it is impossible to build a bargaining model in which each side behaves optimally but the outcome is not Pareto optimal. This paradox can be circumvented in several ways. It is assumed that only one side behaves optimally. The joint cost theory treats bargaining as a black box, and it is assumed that there is a tendency toward Pareto optimal outcomes, which is stronger when strikes are more expensive. The private information theory is based on the idea that strikes are Pareto optimal after all, when incentive-compatibility constraints are taken into account. It is difficult to assess the extent of empirical knowledge on economic aspects of strikes.
Nucleic Acid and Protein Synthesis During Thymineless Death in Lysogenic and Nonlysogenic Thymine Auxotrophs

Thymine deprivation causes the non-phage-associated component of thymineless death in Escherichia coli 15T(-). Addition of thymine causes the phage-associated component to occur.
Two-dimensional polysilicon quantum-mechanical effects in double-gate SOI

Important quantum-mechanical poly quantization effects are demonstrated that reduce inversion capacitance and accentuate short-channel (DIBL) effects in fully depleted double gate SOI devices. Without considering the polysilicon quantization effects, /spl sim/20% over-estimated gate capacitance is predicted with L/sub g/ = 20 nm, t/sub si/ = 5 nm and t/sub ox/ = 1 nm. The polysilicon quantization effect is shown to be enhanced by the drain bias, which implies that DIBL of double-gate SOI is significant due to these effects. The QM effects become worse with increased gate doping, implying ultimate limitations in using polysilicon gates for sub-20 nm DG/FD SOI. Even highly-doped polysilicon gates degrade device performance for sub-20 nm DG/FD SOI due to the polysilicon quantization effects, just as low-doped polysilicon gates degrade performance due to polydepletion effects.
An exploratory investigation of cumulative shock fatigue

A simple device for producing cumulative shock loading in solids is described. The device uses a ballistic-impact-driven projectile to introduce high-stress waves into a solid. The impact time and load amplitude can be varied to produce fracture in one or several impacts in PMMA rods. The wavefront approached a square wave shape. Materials other than PMMA were loaded to failure to demonstrate the versatility of the device. Fracture morphologies observed with optical and scanning-electron microscopy are described.
IDS rainStorm: visualizing IDS alarms

The massive amount of alarm data generated from intrusion detection systems is cumbersome for network system administrators to analyze. Often, important details are overlooked and it is difficult to get an overall picture of what is occurring in the network by manually traversing textual alarm logs. We have designed a novel visualization to address this problem by showing alarm activity within a network. Alarm data is presented in an overview where system administrators can get a general sense of network activity and easily detect anomalies. They then have the option of zooming and drilling down for details. The information is presented with local network IP (Internet Protocol) addresses plotted over multiple yaxes to represent the location of alarms. Time on the x-axis is used to show the pattern of the alarms and variations in color encode the severity and amount of alarms. Based on our system administrator requirements study, this graphical layout addresses what system administrators need to see, is faster and easier than analyzing text logs, and uses visualization techniques to effectively scale and display the data. With this design, we have built a tool that effectively uses operational alarm log data generated on the Georgia Tech campus network. The motivation and background of our design is presented along with examples that illustrate its usefulness.
Enabling scalable social group analytics via hypergraph analysis systems

With the rapid growth of large online social networks, the ability to analyze large-scale social structure and behavior has become critically important, and this has led to the development of several scalable graph processing systems. In reality, social interaction takes place not just between pairs of individuals as in the common graph model, but rather in the context of multi-user groups. Research has shown that such group dynamics can be better modeled through hypergraphs: a generalization of graphs. There are not yet, however, scalable systems to support hypergraph computation, and several challenges and opportunities arise in their design and implementation. In this paper, we present an initial attempt at building a scalable hypergraph analysis framework based on the GraphX/Spark framework. We use this prototype to examine several programmability and implementation issues through experiments with two real-world datasets on a 6-node cluster.
99mTechnetium Pyridoxylidene Glutamate Imaging I 'n Visceral Heterotaxy (Ivemark's Syndrome)

A two and one-half year old boy with complex congenital heart disease had Howell-Jolly bodies in his blood raising the possibility of the asplenia syndrome. A 99mTc-sulfur colloid liver-spleen scan was reported normal, but the right lobe of the abnormally reversed liver was mistaken for the spleen. The diagnosis of visceral heterotaxy (Ivemark's syndrome) was established after scanning the patient with a new radiopharmaceutical, 99m-Technetium pyridoxylideine glutamate. The agent clearly demonstrated a left-sided gall bladder, and on comparison with the sulfur colloid scan it was established that asplenia was present. Radionuclide imaging with the new generation of hepatobiliary agents is a reliable method to document asplenia and is useful in studying patients with visceral heterotaxy.
Correlates of Postmenopausal Estrogen Use and Trends through the 1980s in Two Southeastern New England Communities

Correlates and prevalence of current postmenopausal estrogen use were examined in two southeastern New England communities for the period 1981 through 1990. Data were obtained from five biennial cross-sectional household health surveys, with current use of postmenopausal estrogen determined by inspection of medication bottles. Analysis included 3,279 women aged 40-64 years, of whom 2,215 (67.6%) were postmenopausal. The prevalence of estrogen use among all postmenopausal women increased from 5.3% (95% confidence interval (CI) 3.2-7.4) in 1981-1982 to 10.9% (95% CI 7.5-14.4) in 1989-1990. Among women with surgical menopause, prevalence increased from 11.4% (95% CI 6.6-16.2) to 20.3% (95% CI 13.6-27.0), while use among women with natural menopause increased from 1.5% (95% CI 0.04-2.9) to 3.5% (95% CI 0.74-6.2). Logistic regression was used to compute age-adjusted prevalence of estrogen use according to demographic characteristics and cardiovascular risk factors. Postmenopausal estrogen use was positively associated with income, and a positive trend with education was suggested. Estrogen use was positively associated with high density lipoprotein cholesterol and was inversely associated with body mass index. Nonsmokers, women who exercised at least once per week, and women who reported having their cholesterol checked in the past year were more likely to use estrogen. These findings suggest that estrogen users have a more healthy profile than do nonusers. In addition, the prevalence of postmenopausal estrogen use appears to be substantially lower in women with natural versus surgical menopause throughout the period studied.
ARCHEAN AND EARLY PROTEROZOIC SEDIMENTATION STYLES IN THE KAAPVAAL PROVINCE, SOUTH AFRICA AND PILBARA BLOCK, AUSTRALIA

Archean sediments intercalated within the lower volcanic interval in the Barberton Mountain Land and Pilbara Block accumulated in an anorogenic, shallow-oceanic environment distant from a continental influence. Overlying terrigenous sediments represent continental margin deposits: in South Africa, terrigenous influx across oceanic crust was in response to crustal shortening and uplift of gneisses to the south. Both steep and shelf-rimmed continental margins are recognized. In South Africa, sedimentation was terminated by ocean closure through the northward advance of the zone of crustal shortening. The late-Archean Pongola Supergroup is interpreted as a response 10 this closure with sedimentation taking place in a cratonic shelf basin to the south. The lower Proterozoic witwatersrand and Transvaal Supergroups likewise accumulated in cratonic shelf basins with sediment derived from the north. Terrigenous sediment was supplied by fluvial systems but the dominant mode of sedimentation in lhe pericratonic seas was tida I and took place during prolonged periods of submergence of the Kaapvaal Province. Offshelf basinal equivalents are not recognized for these cratonic sequences. Intracratonic rift basins are represented by the Ventersdorp Supergroup and Soutpansberg Group and are also developed at the base of the Hamersley basin. A third style of lower Proterozoic sedimentation is represented by the chemical sedimentary unit in the Transvaal basin. A basal ramp margin developed after initial drowning of the Kaapvaal Province and evolved into a rimmed shelf margin. ln the latter, platform tidal flat and subtidal stromatolitic assemblages pass laterally into high-energy oolitic and stromatolitic plutform-edge facies. Basinal equivalents are present and consist of non-stromatolitic, ferruginous dolomite and limestone, mudstone, chert and finely-laminated iron-formation. The Hamersley Group is a lithologic equivalent of the basinal facies. Platform fades are poorly-represented in Australia, and comprise the thin Carawine Dolomite in the eastern Pilbara Block.
Future of immunotherapy: a call for comparative immunology.

the potentials of immunotherapy are many, but much is left to learn about fundamental principles of human immunology before they can be realized. The strategy to identify common immunologic themes relevant to human pathology include comparisons of immunologic events necessary for the occurrence of distinct immune-mediated diseases, and we contend that this is most effectively studied following a bottom-up, inductive approach using high-throughput t echnology [5].
Detecting phase transitions in phosphatidylcholine vesicles by Raman microscopy and self-modeling curve resolution.

The study of phospholipid phase transitions is important for understanding drug− and protein−membrane interactions as well as other phenomena such as trans-membrane diffusion and vesicle fusion. A temperature-controlled stage on a confocal Raman microscope has allowed phase transitions in optically trapped phospholipid vesicles to be monitored. Raman spectra were acquired and analyzed using self-modeling curve resolution, a multivariate statistical analysis technique. This method revealed the subtle spectral changes indicative of sub- and pretransitions and main transitions in vesicles composed of 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC). The Raman scattering results were compared to differential scanning calorimetry (DSC) experiments and found to be in good agreement. This method of observing lipid phase transition profiles requires little sample preparation and a minimal amount of lipid (≤0.1 nmol) for an experiment. The conformational changes of the phospholipid molecules occurring during pha...
The genetics of alcoholism : identifying specific genes through family studies

Alcoholism is a complex disorder with both genetic and environmental risk factors. Studies in humans have begun to elucidate the genetic underpinnings of the risk for alcoholism. Here we briefly review strategies for identifying individual genes in which variations affect the risk for alcoholism and related phenotypes, in the context of one large study that has successfully identified such genes. The Collaborative Study on the Genetics of Alcoholism (COGA) is a family-based study that has collected detailed phenotypic data on individuals in families with multiple alcoholic members. A genome-wide linkage approach led to the identification of chromosomal regions containing genes that influenced alcoholism risk and related phenotypes. Subsequently, single nucleotide polymorphisms (SNPs) were genotyped in positional candidate genes located within the linked chromosomal regions, and analyzed for association with these phenotypes. Using this sequential approach, COGA has detected association with GABRA2, CHRM2 and ADH4; these associations have all been replicated by other researchers. COGA has detected association to additional genes including GABRG3, TAS2R16, SNCA, OPRK1 and PDYN, results that are awaiting confirmation. These successes demonstrate that genes contributing to the risk for alcoholism can be reliably identified using human subjects.
Role of a membrane glycoprotein in Friend virus-induced erythroleukemia: studies of mutant and revertant viruses.

We previously reported the isolation and characterization of spontaneous, transmissible mutants of Friend spleen focus-forming virus (SFFV) that are nonpathogenic in adult NIH/Swiss mice and that contain abnormalities in nonoverlapping regions of their envelope glycoprotein (env) genes (M. Ruta, R. Bestwick, C. Machida, and D. Kabat, 1983,Proc. Natl. Acad. Sci. USA 80, 4704–4708). In newborn NIH/Swiss mice, these mutant SFFVs form revertants that are pathogenic in mice of all ages. At least two of three studied revertants contain second site env mutations which affect the sizes and proteolytic fragmentation patterns of their encoded glycoproteins. A variety of structural and genetic evidence suggests that the xenotropic- and ecotropic-related regions of the SFFV glycoprotein fold into separate globular domains that are connected by a flexible proline-rich joint. A glutamyl peptide bond within this joint is exceptionally susceptible to cleavage with Staphylococcus aureus V8 protease. Moreover, disulfide bonds occur within the xenotropic-related domain, but not between the globular domains. These results provide strong additional evidence that the env gene is required for SFFV pathogenesis, and they provide a new system for identifying the features of glycoprotein structure and localization which are essential for its leukemogenic activity.
The Relationship between Real-Time and Time-Integrated Coarse (2.5–10 μm), Intermodal (1–2.5 μm), and Fine (<2.5 μm) Particulate Matter in the Los Angeles Basin

A periodic review of the National Ambient Air Quality Standards for Particulate Matter by the U.S. Environmental Protection Agency (EPA) will assess the standards with respect to levels, particle size, and averaging times. Some members of the scientific community in the United States and Europe have suggested the use of PM1 instead of PM2.5 as the fine particle measurement standard. This proposed standard is intended to reduce the influence of coarse particle sources on PM2.5, because some evidence suggests that PM1-2.5 is dominated by coarse particulate matter (PM) sources. In this study, coarse (PM2.5-10), intermodal (PM1-2.5), and fine (PM2.5) mass concentrations at four different sites are measured with continuous and time-integrated sampling devices. The main objective is to compare variations in these three size ranges while considering the effects of location, sources, weather, wind speed, and wind direction. Results show strong correlations between PM1 and intermodal PM in receptor sites. The contribution of PM1-2.5 to PM2.5 is highest in the summer months, most likely due to enhanced long-range transport. Coarse PM is poorly correlated with intermodal PM. Continuous data suggest that PM1 is growing into PM1-2.5 via complex processes involving stagnation of the aerosol during high relative humidity conditions, followed by advection during daytime hours.
Consecutive GA Pairs Stabilize Medium-Size RNA Internal Loops†

Internal loops in RNA are important for folding and function. Consecutive noncanonical pairs can form in internal loops having at least two nucleotides on each side. Thermodynamic and structural insights into such internal loops should improve approximations for their stabilities and predictions of secondary and three-dimensional structures. Most natural internal loops are purine rich. A series of oligoribonucleotides that form purine-rich internal loops of 5-10 nucleotides, including kink-turn loops, were studied by UV melting, exchangeable proton and phosphorus NMR. Three consecutive GA pairs with the motif 5' Y GGA/3' R AAG or GGA R 3'/AAG Y 5' (i.e., 5' GGA 3'/3' AAG 5' closed on at least one side with a CG, UA, or UG pair with Y representing C or U and R representing A or G) stabilize internal loops having 6-10 nucleotides. Certain motifs with two consecutive GA pairs are also stabilizing. In internal loops with three or more nucleotides on each side, the motif 5' U G/3' G A has stability similar to 5' C G/3' G A. A revised model for predicting stabilities of internal loops with 6-10 nucleotides is derived by multiple linear regression. Loops with 2 x 3 nucleotides are predicted well by a previous thermodynamic model.
Effect of irradiation on cell division and nucleic acid synthesis in strain U-12 fibroblasts.

Abstract The sequence of events following an irradiation of 500 R was investigated in strain U-12 fibroblasts. The irradiation caused a rapid and almost complete inhibition of cell multiplication, as measured by nuclear counts, the mitotic index, and the number of colonies produced from single cells. Although mitotic figures reappeared and increased in frequency to abnormally high levels 13–20 h after irradiation, a recovery in cell multiplication did not occur. Time-lapse cinematography showed that the increased incidence in mitotic figures was very probably caused by the increased time spent by these cells in abortive mitoses. In contrast to the immediate inhibition of mitosis, DNA synthesis was reduced at a later time, falling to less than 50% of the control 18–24 h after irradiation. In this system, therefore, the immediate inhibition of mitosis cannot be the result of a deficiency in DNA synthesis, as measured by the number of individual cells incorporating [ 3 H]thymidine or by the specific activity of DNA after incorporation of 32 P. On the other hand, it is possible that the reduction in the number of cells synthesizing DNA results entirely from the inhibition of mitosis and subsequent failure of the orderly progression of cells through the mitotic cycle.
Female red-winged blackbirds accrue material benefits from copulating with extra-pair males

This study tested whether female red-winged blackbirds,Agelaius phoeniceusacquire non-genetic, material benefits from copulating with multiple males. In this population, females solicit extra-pair copulations, primarily from males defending adjacent territories on the same breeding marsh. Results of a feeder experiment revealed that females that copulated with an extra-pair male were allowed to feed on his territory, but females that remained faithful to their social mates were actively excluded from foraging on neighbouring territories. Males discriminated between faithful and unfaithful social mates. Females that engaged in extra-pair copulations were prevented from foraging on their social mate's territory significantly more often than females that did not. Measurement of neighbouring male responses to a mounted nest predator, a black-billed magpie,Pica picarevealed that males were also significantly more aggressive towards a predator at a nest on a neighbouring territory if they had copulated with the breeding female than if they had not. These findings provide a possible explanation for results of Gray (1997,Anim. Behav.53, 605–623), which showed that fledging success was significantly higher for females that engaged in extra-pair copulations than for females that did not, because depredation rates were significantly lower in clutches laid by females that had engaged in extra-pair copulations, and starvation rates tended to be lower in broods containing extra-pair young. This study is the first to demonstrate that females can benefit materially as well as genetically by copulating outside their pair bond and illustrates the need for manipulative tests to understand fully the reproductive strategies of individuals in populations where social relationships often do not reflect genetic relationships.
Observation of the continuous transformation of a four level laser into a two level system

A longstanding and fundamental question of laser and maser physics concerns the energy separation (Δϵ) required between the pumped and lasing states of a three (or four) level system. We observe a four level laser gradually transform into a two level (nonlasing) system by photoassociating Cs-Ar thermal atomic pairs and monitoring subsequent stimulated emission on the 6p2P3/2 → 6s2S1/2 (D2) transition of Cs at 852.1 nm. Laser excitation spectra demonstrate that the value of Δϵ below which the system rapidly assumes the form of a two level structure and lasing ceases is ∼0.7kT which corresponds to a Boltzmann factor (exp[−Δϵ/kT]) of 0.5.
Time-dependent cluster distribution in nucleation

Abstract The time-dependent size distribution function of clusters, as well as the relaxation and lag times, are calculated numerically in the framework of the recently developed kinetic theories of nucleation in liquids (E. Ruckenstein and B. Nowakowski, J. Colloid Interface Sci.137, 583 (1990)), and gases (B. Nowakowski and E. Ruckenstein, J. Chem. Phys.94, 1397 (1991)). The basic approach used in the calculation is the same as that employed for the classical theory. Differences in the treatment occur as a result of the fact that, in contrast to the classical theory, the rates of condensation and evaporation are calculated independently. The size distribution function of clusters approaches monotonically the steadystate distribution. The nucleation rate relaxes monotonically to the steady-state value for clusters greater than the critical cluster x ∗ ; for x ∗ the nucleation rate exhibits an initial overshoot that exceeds the stationary value and then tapers to the steady-state rate from above. The relaxation times calculated for typical systems are of the order of 1 μs both in liquids and gases. The time lags were found to be of the order of, but larger than, the relaxation time and were found to increase with the size of the cluster. In contrast to the steady-state nucleation rates, which differ by orders of magnitude, the relaxation and lag times calculated in the framework of the kinetic theories are comparable to those obtained on the basis of the classical theory.
APJM's first Best Paper Award

At the Asia Academy of Management conference in Taipei in December 2008, the winner of the first APJM Best Paper Award was announced. As part of the celebrations for APJM’s successful entry into the Social Sciences Citation Index (SSCI), Springer, our publisher, graciously agreed upon my urging to sponsor an annual Best Paper Award, starting in 2008. The recipient would receive a plaque and a US$1,000 award. The Selection Committee consisted of two Senior Editors (David Ahlstrom and Garry D. Bruton) and me. After going through 25 years of APJM publications, we decided to present the Best Paper Award to the following paper and author:
Transition rates for lithium-like ions, sodium-like ions, and neutral alkali-metal atoms

Abstract Third-order many-body perturbation theory is used to obtainE1 transition amplitudes for ions of the lithium and sodium isoelectronic sequences and for the neutral alkali-metal atoms potassium, rubidium, cesium, and francium. Complete angular reductions of the first-, second-, and third-order amplitudes are given. Tables of transition energies and rates are given for the 2p1/2→ 2s1/2, 2p3/2→ 2s1/2, 3s1/2→ 2p1/2, and 3s1/2→ 2p3/2transitions in the lithium isoelectronic sequence and for the corresponding 3p1/2→ 3s1/2, 3p3/2→ 3s1/2, 4s1/2→ 3p1/2, and 4s1/2→ 3p3/2transitions in the sodium sequence. For neutral alkali atoms, amplitudes ofnp1/2→ ns1/2,np3/2→ ns1/2, (n+ 1)s1/2→ np1/2, and (n+ 1)s1/2→ np3/2transitions are evaluated, wherenis the principal quantum number of the valence electron in the atomic ground state. Semi-empirical corrections for the omitted fourth- and higher-order terms in perturbation theory are given for the neutral alkali-metal atoms. Comparisons with previous high-precision calculations and with experiment are made.
(Na + , K + )-ATPase activity of embryonic chick heart and skeletal muscles as a function of age.

Abstract The specific activity of the membrane (Na+,K+)-ATPase of intact chick embryonic hearts (ventricles) was measured as a function of embryonic age. The membranes were prepared by a NaI extraction method of the 100 000 × g fraction which selectively removes much of the ouabain-insensitive Mg2+-ATPase. The specific activity of the myocardial (Na+, K+)-ATPase increased markedly during embryonic development from mean levels of about 3.0 μmoles Pi per h per mg protein at day 6 to 7.4 at day 16 and 11.0 at day 20 (1 day prior to hatching); the adult level was about the same as that of the 16-day-old chick. The relative activities with respect to that at day 16 (from paired experiments) averaged 43 % (day 6), 56 % (day 9), 73 % (day 13), 140 % (day 20), 115 % (day 23), 126 % (day 30) and 96 % (adult). There was a similar increase in relative activity of the (Na+,K+)-ATPase from chick skeletal (leg) muscles during development. If the total protein content per unit membrane area and the turnover number remain constant, the data indicate that the surface density of the (Na+,K+)-ATPase molecules increases during embryonic development; thus, the cation pumping capabilities of the cells should be enhanced if the surface area/volum ratio of the myocardial cells remains unchanged. However, the pumping capabilities of the very young cells must be sufficient to maintain the known high [K+]i and low [Na+]i already present; their internal activities actually change only to a small extent during development. Since there is a known increase in K+ permeability during embryonic development, thereby increasing the demand on the cation pump, the observed increase in activity of the (Na+,K+)-ATPase tends to compensate for this.
The heat of the moment: the effect of sexual arousal on sexual decision making

Despite the social importance of decisions taken in the “heat of the moment,” very little research has examined the effect of sexual arousal on judgment and decision making. Here we examine the effect of sexual arousal, induced by self-stimulation, on judgments and hypothetical decisions made by male college students. Students were assigned to be in either a state of sexual arousal or a neutral state and were asked to: (1) indicate how appealing they find a wide range of sexual stimuli and activities, (2) report their willingness to engage in morally questionable behavior in order to obtain sexual gratification, and (3) describe their willingness to engage in unsafe sex when sexually aroused. The results show that sexual arousal had a strong impact on all three areas of judgment and decision making, demonstrating the importance of situational forces on preferences, as well as subjects' inability to predict these influences on their own behavior. Copyright © 2005 John Wiley & Sons, Ltd.
Inhibition of RNA polymerase by captan at both DNA and substrate binding sites

Abstract RNA synthesis carried out in vitro by Escherichia coli RNA polymerase was inhibited irreversibly by captan when T7 DNA was used as template. An earlier report and this one show that captan blocks the DNA binding site on the enzyme. Herein, it is also revealed that captan acts at the nucleoside triphosphate (NTP) binding site, and kinetic relationships of the action of captan at the two sites are detailed. The inhibition by captan via the DNA binding site of the enzyme was confirmed by kinetic studies and it was further shown that [14C]captan bound to the β' subunit of RNA polymerase. This subunit contains the DNA binding site. Competitive-like inhibition by captan versus UTP led to the conclusion that captan also blocked the NTP binding site. In support of this conclusion, [14C]captan was observed to bind to the β subunit which contains the NTP binding site. Whereas, preincubation of RNA polymerase with both DNA and NTPs prevented captan inhibition, preincubation with either DNA or NTPs alone was insufficient to protect the enzyme from the action of captan. Furthermore, the interaction of [14C]captan with the β and β' subunits was not prevented by a similar preincubation. Captan also bound, to a lesser extent, to the α and σ subunits. Therefore, captan binding appears to involve interaction with RNA polymerase at sites in addition to those for DNA and NTP; however, this action does not inhibit the polymerase activity.
Horizontally propagating quasi-sinusoidal tropospheric waves observed in the lee of the Andes

VHF profiler observations of the troposphere obtained over a flat desert in northern Peru show the presence of strong, quasi-sinusoidal oscillations in the vertical wind velocity with periods of around 8–18 minutes. These oscillations are a very consistent feature of the vertical velocities over Piura, and are also observed at other profiler locations. This paper presents an overview of the wave characteristics obtained at Piura until this point, including results obtained using a second antenna built a few hundreds meters to the west of the main antenna to measure horizontal wavelengths and phase velocities. Briefly, the Piura waves appear to have horizontal wavelengths in the zonal direction of 5–10 m, with either westward or eastward phase velocities (in a ground-based reference frame) of 5–15 m s−1. Their occurrence appears to be causally related to the magnitude of the easterly wind, which blows over the Andean Cordillera some 60 km to the east of the site.