cssi/SciSciGPT-SciSciNet huggingface dataset:
Abnormal target detection and novelty processing neural response in posttraumatic stress disorder.

Abstract Attention impairments are common symptoms of posttraumatic stress disorder (PTSD); however, the nature of these impairments remains elusive. Attention impairment may arise as the result of either excessive response to task-irrelevant stimuli or reduced response to task-relevant information. To test the association between PTSD and response to task-relevant and task-irrelevant stimuli, we used a 3-tone novelty auditory oddball task (AOD). We hypothesized that participants with PTSD relative to trauma controls would have less response during novelty processing in the dorsolateral prefrontal cortex (dlPFC) and the anterior cingulate cortex, as well as less response in the dlPFC and the orbitofrontal cortex during target detection. Thirty-one male veterans completed a 3-tone novelty AOD task during functional magnetic resonance imaging. Compared to trauma controls, the PTSD group had reduced response during novelty processing in ventromedial prefrontal cortex, superior/middle frontal gyrus (dlPFC), supplementary motor area/caudate, and in posterior regions including bilateral posterior cingulate cortex. The current results suggest PTSD is associated with a pattern of reduced response to novel stimuli. A disturbed orienting response in these brain regions could theoretically underlie PTSD attention-related symptoms.
The Laguerre Calculus on the Heisenberg Group

The purpose of this article is to derive a multiplicative symbolic calculus for left-invariant convolution operators on the Heisenberg group. We let Hn denote the n-th Heisenberg group with underlying manifold $${R^{2n + 1}} = \left\{ {\left( {{x_0},x'} \right)} \right\} = \left\{ {\left( {{x_0},{x_1},...,{x_{2n}}} \right)} \right\},$$ (1.1) and with the group law $$xy = \left( {{x_0},x'} \right)\left( {{y_0},y'} \right)$$ $$= \left( {{x_0} + {y_0} + \frac{1}{2}\sum\limits_{j = l}^n {{a_j}\left[ {{x_j}{y_{j + n}} - {x_{j + n}}{y_j}} \right]} ,x' + y'} \right).$$ (1.2) .
Military-Industrial Complex

In the councils of government, we must guard against the acquisition of unwarranted influence, whether sought or not sought, by the military-industrial complex. [D. Eisenhower, U.S. News & World Report, January 17, 1961, p. 69.]
Neural Substrates of Remembering – Electroencephalographic Studies

A comprehensive understanding of human memory requires both cognitive and neural descriptions of memory processes along with a conception of how memory processing drives behavioral responses and subjective experiences. The electrophysiological approaches described here are highly suitable for progressing toward these goals. In particular, event-related potentials provide real-time measures of relevant memory processes, including those associated with recollection, familiarity, perceptual priming, and conceptual priming. Many challenges remain in isolating and understanding these different memory functions. Nonetheless, brain potentials can be used effectively in conjunction with other cognitive neuroscience methods to advance our understanding of remembering.
NMR Analysis of a Multi-domain Peptide of the Saccharomyces cerevisiae Alpha Factor Receptor

Introduction Biophysical studies on GPCRs are hampered by difficulty in crystallizing these molecules and conducting NMR on the intact receptor in the presence of vesicles. We have examined the biophysical properties of peptides representing fragments of Ste2p, a GPCR for α-factor, a tridecapeptide from the yeast Saccharomyces cerevisiae. To gain high resolution structural evidence supporting the interaction of the sixth and seventh transmembrane domains of Ste2p [1,2], milligram quantities of multidomain peptides are required for spectroscopic investigation. Receptor fragments were prepared as isotopically labeled fusion proteins by biosynthetic approaches. The N-labeled fusion protein was expressed and purified by HPLC. N-labeled E3-M7-24-T40 fusion protein (N-M7FP) was cleaved with cyanogen bromide (CNBr) to remove the TrpΔLE. The cleaved N-E3-M7-24-T40 was isolated by HPLC, characterized by mass spectrometry and its secondary and tertiary structure was obtained using circular dichroism and nuclear magnetic resonance spectroscopy, respectively.
Systematic review of HIV treatment adherence research among people who inject drugs in the United States and Canada: evidence to inform pre-exposure prophylaxis (PrEP) adherence interventions.

People who inject drugs (PWID) are at increased risk for HIV acquisition and could benefit from antiretroviral pre-exposure prophylaxis (PrEP). However, PrEP has been underutilized in this population, and PrEP adherence intervention needs are understudied. To inform PrEP intervention development, we reviewed evidence on antiretroviral therapy (ART) adherence among HIV-infected PWID. Guided by a behavioral model of healthcare utilization and using the PICOS framework, we conducted a systematic review in four electronic databases to identify original research studies of ART adherence in HIV-infected PWID in the United States and Canada between Jan 1, 2006–Dec 31, 2016. We synthesized and interpreted findings related to developing recommendations for PrEP adherence interventions for PWID. After excluding 618 duplicates and screening 1049 unique records, we retained 20 studies of PWID (mean n = 465) with adherence-related outcomes (via pharmacy records: n = 9; self-report: n = 8; biological markers: n = 5; electronic monitoring: n = 2). Predisposing factors (patient-level barriers to adherence) included younger age, female sex, and structural vulnerability (e.g., incarceration, homelessness). Enabling resources (i.e., facilitators) that could be leveraged or promoted by interventions included self-efficacy, substance use treatment, and high-quality patient-provider relationships. Competing needs that require specific intervention strategies or adaptations included markers of poor physical health, mental health comorbidities (e.g., depression), and engagement in transactional sex. HIV treatment adherence research carries important lessons for efforts to optimize PrEP adherence among PWID. Despite limitations, this systematic review suggests that strategies are needed to engage highly vulnerable and marginalized sub-groups of this underserved population (e.g., younger PWID, women who inject drugs) in PrEP adherence-related research and programming.
Molecular Systematics of Wasp and Polydnavirus Genomes and their Coevolution

Publisher Summary This chapter discusses the molecular systematics of wasp and polydnavirus (PDVs) genomes and their coevolution. Polydnaviruses are integrated, inherited DNA viral endosymbionts of parasitoid wasps found within some lineages of Braconidae and Ichneumonidae that attack caterpillars (larval Lepidoptera). Due to their chromosomal integration and mode of inheritance, phylogenomic relationships among the PDVs are closely tied to phylogenetic relationships among the host wasps that carry them. We have inferred that PDVs must have at least three independent ancient origins in the wasps: bracoviruses (BVs) from ancestral nudiviruses associated with braconid wasps, ichnoviruses, and “banchoviruses” from still unidentified progenitor viruses and associated with unrelated families of Ichneumonidae. Phylogenetic studies of the BV-carrying lineage of braconid wasps are now guiding comparative studies of BV genomes and advancing our understanding of the roles that BV genes may play in the evolution of wasp/caterpillar parasitic relationships.
Is there a rationale for heparin use among severe COVID-19 patients?

The International Society on Thrombosis and Haemostasis (ISTH) has proposed a new category to detect the earlier phase of sepsis-associated disseminated intravascular coagulation (DIC), called sepsis-induced coagulopathy. The criteria included platelet count, prothrombin time and Sequential Organ Failure Assessment (SOFA) score.() Patients with sepsis and extensive forms of DIC may develop overt thromboembolic complications, or clinically less apparent microvascular clot formation that may contribute to multiple organ failure.() Activation of the vascular endothelium, platelets, and leukocytes results in dysregulated thrombin [...]
Electrical Oligomerization of Small Hydrocarbons Activated by Collision with High Energy Electrons at Ambient Conditions

Isomerization and polymerization are two essential chemical processes that produce valuable chemicals and high quality fuels. However, they hardly occur at ambient conditions due to the activation ...
Analysis of the US business cycle with a Vector‐Markov‐switching model

This paper identifies turning points for the US "business cycle" using information from different time series. The model, a multivariate Markov-switching model, assumes that each series is characterized by a mixture of two normal distributions (a high and low mean) with the switching from one to the other determined by a common Markov process. The procedure is applied to the series composing the composite coincident indicator in the USA to obtain business cycle turning points. The business cycle chronology is closer to the NBER reference cycle than the turning points obtained from the individual series using a univariate model. The model is also used to forecast the series with some encouraging results. Copyright © 2001 by John Wiley & Sons, Ltd.
Impact and costs of a hepatitis C virus screening programme for adults hospitalised at an academic medical centre.

Approximately 1.7% of the US population has chronic hepatitis C virus (HCV) infection, but among adults born between 1945 and 1965 prevalence increases to 3.25%, and this birth cohort accounts for almost 75% of the total burden of HCV.1 2 The availability of effective direct-acting antiviral (DAA) therapy for HCV makes screening, linkage to care and treatment a national priority. The Centers for Disease Control and Prevention (CDC) and US Preventative Services Task Force (USPSTF) have recommended one-time HCV screening for persons born between 1945 and 1965,2 3 yet only 14%–17% of this cohort has been screened for HCV.4 5 To improve adherence to HCV screening recommendations for patients hospitalised at our medical centre, the Division of Infectious Diseases (ID) at the University of Vermont Medical Center (UVMMC) undertook a quality improvement (QI) initiative to screen patients born between 1945 and 1965 who were seen by the ID Consultation Service. UVMMC is a 562-bed academic medical centre affiliated with the Robert Larner MD College of Medicine at the University of Vermont (UVM) and serves over 1 million patients in Vermont and New York State. Recognising that the baseline prevalence rate of HCV is 1.45% of adults in Vermont and 1.49% in New York,1 we hypothesised that screening hospitalised patients seen by the ID Consultation Service would increase screening rates, identify undiagnosed HCV infections and link patients to care. We developed a protocol to identify patients born between 1945 and 1965 seen by the ID Consultation Service, perform HCV screening and link patients to outpatient care. All patients receiving a consult were being treated for conditions unrelated to HCV (eg, osteomyelitis, endocarditis, urinary tract infections). ID physicians …
A catalog of tens of thousands of viruses from human metagenomes reveals hidden associations with chronic diseases

Despite remarkable strides in microbiome research, the viral component of the microbiome has generally presented a more challenging target than the bacteriome. This gap persists, even though many thousands of shotgun sequencing runs from human metagenomic samples exist in public databases, and all of them encompass large amounts of viral sequence data. The lack of a comprehensive database for human-associated viruses has historically stymied efforts to interrogate the impact of the virome on human health. This study probes thousands of datasets to uncover sequences from over 45,000 unique virus taxa, with historically high per-genome completeness. Large publicly available case-control studies are reanalyzed, and over 2,200 strong virus–disease associations are found.
Placement Evaluation of Distributed Energy Storage for Integrating EV Charging and PV Solar Infrastructure

The current and future growth in the penetration of the solar photovoltaic (PV) power generation and electric vehicle (EV) charging infrastructure across legacy distribution networks may cause numerous system vulnerabilities. In this paper, an approach is presented to evaluate a distribution system in terms of PV and EV penetration, as well as natural load growth based on a 2025 projection. The system vulnerabilities are identified in worst-case operation scenarios using time-series power flow analysis and load hosting capacity studies. Then, the negative impacts associated with PV and EV penetrations are mitigated using distributed energy storage deployment along the feeders. Finally, a business case and value proposition for the distributed energy storage is developed based on their applications and valuation in a regulated utility environment. The approach and findings of this paper may provide inputs to regulated utilities as they plan for the anticipated growth in PV and EV infrastructure on their legacy distribution networks.
Model-Based Systems

Engineers, who design systems using text specification documents, focus their work upon the completed system to meet Performance, time and budget goals. Consistency and integrity is difficult to maintain within text documents for a single complex system and more difficult to maintain as several systems are combined into higher-level systems, are maintained over decades, and evolve technically and in performance through updates. This system design approach frequently results in major changes during the system integration and test phase, and in time and budget overruns. Engineers who build system specification documents within a model-based systems environment go a step further and aggregate all of the data. They interrelate all of the data to insure consistency and integrity. After the model is constructed, the various system specification documents are prepared, all from the same database. The consistency and integrity of the model is assured, therefore the consistency and integrity of the various specification documents is insured. This article attempts to define model-based systems relative to such an environment. The intent is to expose the complexity of the enabling problem by outlining what is needed, why it is needed and how needs are being addressed by international standards writing teams.
The prevalence of coronary sinus and left circumflex artery overlap in relation to the mitral valve.

Objectives Characterize where the circumflex artery crosses between the coronary sinus and mitral valve in order to minimize the occurrence of coronary compression during percutaneous indirect mitral valve interventions. Background Treatment of mitral valve regurgitation using an indirect percutaneous approach via access through the coronary sinus remains under active research and development. Characterization of anatomical locations where the circumflex artery crosses between the coronary sinus and mitral valve is important for mitigation of serious ischemic complications. Methods Magnetic resonance images were obtained for 65 perfusion-fixed human hearts. Three-dimensional reconstructions of anatomical orientations of the coronary sinus, circumflex artery, and mitral valve annulus were generated. The prevalence and location of sites where the circumflex artery coursed between the coronary sinus and mitral valve were assessed. Results The circumflex artery coursed between the coronary sinus and mitral valve in 88% of specimens. Overlaps between the circumflex artery and coronary sinus were less prevalent more proximal to the coronary sinus ostium. The coronary sinus did not lie in the same plane as the mitral annulus in roughly 20% of the hearts. Conclusion The prevalence of circumflex overlap between the coronary sinus and mitral valve was common across the sample size. The large variability in anatomy confirms the value of imaging individual patient cardiac anatomy prior to performing indirect percutaneous mitral valve annuloplasty to avoid impairment to the circumflex artery. This novel database can be utilized in the development of additional cardiac therapies that require access to the coronary sinus, such as therapeutic ablations. (J Interven Cardiol 2014;27:308–316)
Cholesterol emboli after invasive cardiac procedures.

“Atheromatous emboli” is a general description for embolization of any atheromatous material. The term “atheroemboli” is used to refer to the dislodgement of vascular plaque material that contains cholesterol crystals plus red blood cells and fibrin. These can occlude major systemic vessels
Stimulus Equivalence and The Blocking Effect

The purpose of this experiment was to examine the blocking effect within the context of a stimulus equivalence paradigm. Ten subjects were provided with a prior history of matching unitary sample stimuli to unitary comparisons. Next, the same stimuli appeared as elements of sample stimulus compounds with additional, redundant elements. During the equivalence test, the elements of each compound were separated, and the extent to which the elements had entered separately into equivalence relations with the other stimuli was examined. Five subjects demonstrated the formation of three three-member equivalence classes and showed a strong blocking effect. The other five subjects did not demonstrate the formation of three-member classes, nor did they show a strong blocking effect. The strength of the relations between the elements of each stimulus compound was shown to be consistent with the degree to which the blocking effect was observed. Subjects’ percentage reinforcement estimates were also found to correspond to their performance during the equivalence test. The overt verbal behavior emitted by four subjects who were required to talk aloud during the experiment did not correlate with their nonverbal performance.
The Affordable Care Act: opportunities for collaboration between doctors and lawyers.

Background In 2010, the Affordable Care Act (ACA) was signed into law. The Act seeks to improve the access of Americans to improved quality health care, while controlling the nation's escalating health care expenditures. The Act is scheduled for further implementation in 2014. Objective This article elucidates the opportunities and challenges that the ACA presents for constructive, innovative collaboration between the legal and medical professions in contributing to the quest for a more affordable and accessible high quality health care system. Methods The author analyzed the text of the Act, as well as secondary sources in the areas of law, medicine, and public health. This allowed for the creation of a comprehensive conceptual and empirical framework through which the Act could be properly analyzed and understood. Results The research described the pitfalls inherent in the Act, but demonstrated that the ACA presents more opportunities than challenges if lawyers and doctors are willing to work together to bring about needed social change. Conclusion The article qualified these findings by emphasizing that doctors must learn to advocate on behalf of their profession if the potential benefits of the ACA are to be realized.
Women of Principle: Female Networking in Contemporary Mormon Polygyny

Women of Principle: Female Networking in Contemporary Mormon Polygyny. Janet Bennion. New York: Oxford University Press. 1998. 178 pp.
Comparison of CaMKinase II activation in a dendritic spine computed with deterministic and stochastic models of the NMDA synaptic conductance

Abstract In models of long-term potentiation the NMDA conductance is usually computed deterministically. However, the actual number of open NMDA receptor channels at a synapse is small, so a deterministic representation may not be valid. Here NMDA synaptic conductances computed stochastically with MCell were used in a dentate granule cell model that computed calcium influx and subsequent CaMKinase II activation in a dendritic spine following LTP induction conditions. Spine head calcium concentration and levels of CaMKinase II activation were highly variable with different stochastic simulations of NMDA channel openings. This variability in CaMKinase II activity levels due to stochastic NMDA channel openings may play an important role in LTP induction in individual spines.
A genome-wide association study of total bilirubin and cholelithiasis risk in sickle cell anemia.

Serum bilirubin levels have been associated with polymorphisms in the UGT1A1 promoter in normal populations and in patients with hemolytic anemias, including sickle cell anemia. When hemolysis occurs circulating heme increases, leading to elevated bilirubin levels and an increased incidence of cholelithiasis. We performed the first genome-wide association study (GWAS) of bilirubin levels and cholelithiasis risk in a discovery cohort of 1,117 sickle cell anemia patients. We found 15 single nucleotide polymorphisms (SNPs) associated with total bilirubin levels at the genome-wide significance level (p value <5×10−8). SNPs in UGT1A1, UGT1A3, UGT1A6, UGT1A8 and UGT1A10, different isoforms within the UGT1A locus, were identified (most significant rs887829, p = 9.08×10−25). All of these associations were validated in 4 independent sets of sickle cell anemia patients. We tested the association of the 15 SNPs with cholelithiasis in the discovery cohort and found a significant association (most significant p value 1.15×10−4). These results confirm that the UGT1A region is the major regulator of bilirubin metabolism in African Americans with sickle cell anemia, similar to what is observed in other ethnicities.
New Chemistry of the Triply Bonded Divanadium (V24+) Unit and Reduction to an Unprecedented V23+ Core

We report here the synthesis and characterization of seven new divanadium compounds with the paddlewheel geometry bridged by nitrogen-donating ligands. Five of these contain the diamagnetic V24+ core with short V−V distances of less than 2.0 A, consistent with a formal triple bond. The V−V distances vary with the basicity of the bridging ligands; more basic ligands such as those of the guanidinate type have the shorter metal−metal separations, and those with the less basic formamidinate groups have longer separations. One compound, V2(DPhF)4 (DPhF = the anion of N,N‘-diphenylformamidine), has been reduced by one electron, and two structures, [K(THF)3]V2(DPhF)4 and [K(18-crown-6)(THF)2]V2(DPhF)4, have been obtained. These have an unprecedented V23+ core where the formal oxidation state of each vanadium atom is +1.5. The decrease in V−V bond distance and the multiline EPR spectrum in the reduced species provide evidence that these two molecules contain a bond of order 3.5.
Last-minute bidding in eBay charity auctions

Abstract Relative to typical eBay auctions, bidding in eBay charity auctions occurs earlier and also less frequently in the auctions' final seconds. This suggests that some charity bidders benefit from driving-up others' payments, as when auction revenue is a public good.
Early educational milestones as predictors of lifelong academic achievement, midlife adjustment, and longevity

This study gathered follow-up data from the Terman Life Cycle Study (N = 1,023) to examine how age at first reading and age at school entry relate to grade school academic performance, lifelong educational attainment, midlife health and mental adjustment, and longevity across eight decades. Early reading was associated with early academic success, but less lifelong educational attainment and worse midlife adjustment. Early school entry was associated with less educational attainment, worse midlife adjustment, and most importantly, increased mortality risk. Personality, midlife adjustment, and educational attainment partially mediated the school entry-longevity association (controlling for age, sex, personal characteristics, and home environment factors). Although the sample is limited in some respects and care should be taken in generalizing the results, findings do confirm the importance of lifespan approaches in understanding the effects of education on individual patterns within social contexts.
Clinical and clinical pharmacologic studies of 2-amino-1,3,4-thiadiazole (A-TDA:NSC 4728).

A clinical phase I–II evaluation of 2-amino-1,3,4-thiadiazole (A-TDA) administered daily, twice a week, or weekly was undertaken, in which 71 patients were treated with a range of doses from 2 mg/m2 to 200 mg/m2. Pharmacokinetic studies employing high-performance liquid chromatography (HPLC) demonstrated a terminal (β) serum half-life of 2.19 h.
Eight-color photometry of Hyperion, Iapetus, and Phoebe

The Phoebe, Hyperion and Iapetus Saturn satellites are discussed in light of eight-color spectrophotometry, which together with observed V magnitudes and Voyager spacecraft-derived diameters yields geometric albedos of 0.07 for Iapetus, 0.06 for Phoebe, and maximum- and minimum-dimension based limits of 0.19 and 0.25 respectively for Hyperion. While both Hyperion and Iapetus have similar, very reddish spectra, it is noted that Hyperion has a much higher albedo than the dark side of Iapetus. The mean spectrum of Phoebe is much flatter, with a broad absorption feature near 1 micron. The determination of these optical differences between the surface materials of Phoebe and the dark side of Iapetus constrains the possible interaction modes between Phoebe and the other two satellites.
Improving read performance of Phase Change Memories via Write Cancellation and Write Pausing

Phase Change Memory (PCM) is emerging as a promising technology to build large-scale main memory systems in a cost-effective manner. A characteristic of PCM is that it has write latency much higher than read latency. A higher write latency can typically be tolerated using buffers. However, once a write request is scheduled for service to a bank, it can still cause increased latency for later arriving read requests to the same bank. We show that for the baseline PCM system with read-priority scheduling, the write requests increase the effective read latency to 2.3x (on average), causing significant performance degradation. To reduce the read latency of PCM devices under such scenarios, we propose adaptive Write Cancellation policies. Such policies can abort the processing of a scheduled write requests if a read request arrives to the same bank within a predetermined period. We also propose Write Pausing, which exploits the iterative write algorithms used in PCM to pause at the end of each write iteration to service any pending reads. For the baseline system, the proposed technique removes 75% of the latency increase incurred by read requests and improves overall system performance by 46% (on average), while requiring negligible hardware and simple extensions to PCM controller.
PLUMB: displaying graphs to the blind using an active auditory interface

We present our ongoing research in the communication of graphs and relational information to blind users. We have developed a system called exPLoring graphs at UMB (PLUMB) that displays a drawn graph on a tablet PC and uses auditory cues to help a blind user navigate the graph. This work has applications to assist blind individuals in Computer Science education, navigation and map manipulation.
Screening for natural chemoprevention agents that modify human Keap1

Upregulation of cytoprotective enzymes by therapeutic agents to prevent damage by reactive oxygen species and xenobiotic electrophiles is a strategy for cancer chemoprevention. The Kelch-like ECH-associated protein 1 (Keap1) and its binding partner, transcription factor NF-E2-related factor-2 (NRF2), are chemoprevention targets because of their role in regulating the antioxidant response element (ARE) in response to oxidative stress and exposure to electrophiles. Modification of the sensor protein Keap1 by electrophiles such as the isothiocyanate sulforaphane can direct Nrf2 accumulation in the nucleus and subsequent ARE activation. Since our previous matrix-assisted laser desorption time-of-flight mass spectrometry (MALDI-TOF MS)-based screening method to discover natural products that modify Keap1 does not detect covalent modification of Keap1 by some highly reversible agents such as sulforaphane, a more sensitive screening assay was developed. In this new assay, electrophiles that have reversibly modified Keap1 can be released, trapped, and detected as β-mercaptoethanol adducts by mass spectrometry. Isoliquiritigenin and sulforaphane, known ARE activators that target Keap1, were used to validate the assay. To determine the ability of the assay to identify electrophiles in complex matrixes that modify Keap1, sulforaphane was spiked into a cocoa extract, and LC-MS/MS using high resolution mass spectrometry with accurate mass measurement was used to identify β-mercaptoethanol adducts of sulforaphane that had been released from Keap1. This screening assay permits identification of potential chemoprevention agents in complex natural product mixtures that reversibly modify Keap1 but cannot be detected using MALDI-TOF MS.
Growth inhibition by homofolate in tumor cells utilizing a high-affinity folate binding protein as a means for folate internalization

Abstract A subline (JT-1) of L1210 mouse leukemia cells that contains elevated levels of a high-affinity folate binding protein is sensitive to growth inhibition by homofolate. Inhibition was observed at nanomolar concentrations of folate or 5-fonnyltetrahydrofolate where the high-affinity binding protein is the predominant uptake route for folate compounds. At 1.0 nM folate, inhibition of growth by 50% occurred at 0.7 nM homofolate, and maximal inhibition exceeded 90% at homofolate concentrations above 10 nM. Homofolate also inhibited the uptake of 1.0 nM [ 3 H]folate by L1210/JT-1 cells in 72-hr cultures, and the extent of uptake inhibition by 1.0 and 20 nM homofolate was comparable to the inhibition of cell growth by the same concentrations of homofolate. At a growth-limiting concentration of 5-formyltetrahydrofolate (0.5 nM), half-maximal inhibition of L1210/JT-1 cell growth occurred at 1.0 nM homofolate. When excess concentrations of folate (5 μM) or 5-formyltetrahydrofolate (0.5 μM) were added to the medium, no growth inhibition was observed for homofolate at concentrations up to 100 μM. Parental cells lacking the folate binding protein did not respond to homofolate either at growth-limiting (0.5 μM) or excess (5.0 μM) levels of folate. Binding measurements showed that homofolate has a high affinity for the folate-binding protein ( K i = 0.03 nM) but interacts poorly with the reduced-folate transport system ( K i = 203 μ M). These results indicate that homofolate inhibits the growth of L1210 cells when intracellular folates are acquired via the high-affinity folate binding protein. The basis for this inhibition appears to be competition by homofolate for substrate binding and internalization.
A large-scale in vivo analysis reveals that TALENs are significantly more mutagenic than ZFNs generated using context-dependent assembly

Zinc-finger nucleases (ZFNs) and TAL effector nucleases (TALENs) have been shown to induce targeted mutations, but they have not been extensively tested in any animal model. Here, we describe a large-scale comparison of ZFN and TALEN mutagenicity in zebrafish. Using deep sequencing, we found that TALENs are significantly more likely to be mutagenic and induce an average of 10-fold more mutations than ZFNs. We observed a strong correlation between somatic and germ-line mutagenicity, and identified germ line mutations using ZFNs whose somatic mutations rates are well below the commonly used threshold of 1%. Guidelines that have previously been proposed to predict optimal ZFN and TALEN target sites did not predict mutagenicity in vivo. However, we observed a significant negative correlation between TALEN mutagenicity and the number of CpG repeats in TALEN target sites, suggesting that target site methylation may explain the poor mutagenicity of some TALENs in vivo. The higher mutation rates and ability to target essentially any sequence make TALENs the superior technology for targeted mutagenesis in zebrafish, and likely other animal models.
Review of octopamine in insect nervous systems

Octopamine (OCT) belongs to a group of compounds known as biogenic amines. OCT, a monohydroxylic analog of norepinephrine, is found in both vertebrate and invertebrate nervous systems. OCT is present in relatively high concentrations in the neuronal and non- neuronal tissues of most invertebrate species studied. However, OCT occurs as a trace amine in vertebrates where its physiological significance remains uncertain. OCT acts as a neurotransmit - ter, neuromodulator, and neurohormone in insect nervous systems where it prominently influences multiple physiological events. In the peripheral nervous system, OCT modulates the activity of flight muscles, peripheral organs, and most sense organs. In the central nervous system, OCT is essential for the regulation of motivation, desensitization of sensory inputs, arousal, initiation, and maintenance of various rhythmic behaviors, hygiene behavior, and complex social behaviors, including establishment of labor, as well as learning and memory. As a neurotransmitter, OCT regulates endocrine gland activity and controls the emission of light in the firefly lantern. As a neurohormone, OCT is released into hemolymph, transported to target tissues, and induces mobilization of lipids and carbohydrates, preparing insects for a period of extended activity or assisting recovery from a period of increased energy demand. OCT modulates hemocytic nodulation in nonimmune larvae and enhances phagocytosis as a neurohormone. OCT exerts its effects by binding to specific receptors belonging to the superfamily of G protein-coupled receptors and shares the structural motif of seven transmembrane domains. Activation of octo- paminergic receptor types is coupled with different second messenger pathways depending on the species, tissue source, receptor type, and cell line used for expression of the cloned receptor. OCT-mediated generation of second messengers is associated with changes in cellular response, affecting insect behaviors. This review describes the roles of OCT in insect nervous systems at the behavioral and molecular levels.
Effect of Estrogenic Hormone on Serum Lipids in Patients with Coronary Arteriosclerosis

The oral administration of large amounts of ethinyl estradial daily to patients with coronary arteriosclerosis and to control subjects consistently produced a favorable effect upon the serum lipid pattern. However, toxic effects of the estrogen prohibited its prolonged use. The clinical status of the patient as evidenced by the incidence of chest pain or the electrocardiogram were not altered during the period of the study.
Temperature-induced nanochannel array synthesis in microchannels

An novel on-chip synthesis technique for nanochannel arrays inside microfluidic channels is reported. The microfluidic channels are constructed with etched silicon trenches and a polydimethylsiloxane (PDMS) slab. These silicon microchannels provide a confined environment for highly oriented nanostructure synthesis. Triblock copolymer (SBA-15) is self-assembled inside the microchannel array as template for silica precursor polymerization under an induced temperature gradient. The temperature gradient is maintained by thermoelectric pads and used to control the direction and rate of organic solvent evaporation. This evaporation-induced self-assembly (EISA) process is confined within the microfluidic channels and guided into formation of highly ordered nanochannels with long range alignment. The fabrication and synthesis process is developed and the resultant nanomaterial is characterized. A fluorescent molecule dye, fluorescein, is used to demonstrate the potentials of the integrated device in nanofluidics applications.
Simple connection between covariant Feynman formalism and time-ordered perturbation theory in the infinite-momentum frame

We introduce a parametrization of loop momenta which allows us to perform one of the Feynman integrations in a very transparent way. This leads to expressions which can easily be related to terms resulting from time-ordered perturbation theory in the infinite-momentum frame. To exemplify our method we consider some simple Feynman integrals. As another example we discuss the covariant expressions of Landshoff, Polkinghorne, and Short for the scaling graph and the electromagnetic form factor. We indicate how to substitute the Sudakov parametrization in their work in order to simplify their discussion and to make comparisons with the work of Gunion, Brodsky, and Blankenbecler more convenient. Finally we derive an elegant form of the bound-state Bethe-Salpeter equation in which one of the Feynman integrations is performed.
Systematics in the relative energies of some low-lying electron configurations in the gaseous atoms and free ions of the lanthanide and actinide series

There is a linear characteristic and a common nonlinear characteristic in the energy differences associated with many lanthanide and actinide electronic configurations involving a change of the number of f electrons by one. The differences of energy, ΔdE(q), between the lowest energy levels of the two principal electron configurations in the gaseous atoms of the lanthanide and actinide series exemplify these characteristics. By assuming that the common nonlinear characteristic involves only electrostatic and spin–orbit interaction-energy differences between the parent f-electron core configurations, we obtain linearization functions—one for the lanthanide series and one for the actinide series— which linearize the ΔdE(q) data. These same linearization functions are found to be applicable to the energy differences between most electronic configurations involving the same number of f electrons, including the neutral, the singly, the doubly, and the triply ionized gaseous lanthanides and actinides, independent of the nature or number of valence electrons.
Attention Influences Single Unit and Local Field Potential Response Latencies in Visual Cortical Area V4

Many previous studies have demonstrated that changes in selective attention can alter the response magnitude of visual cortical neurons, but there has been little evidence for attention affecting response latency. Small latency differences, though hard to detect, can potentially be of functional importance, and may also give insight into the mechanisms of neuronal computation. We therefore reexamined the effect of attention on the response latency of both single units and the local field potential (LFP) in primate visual cortical area V4. We find that attention does produce small (1–2 ms) but significant reductions in the latency of both the spiking and LFP responses. Though attention, like contrast elevation, reduces response latencies, we find that the two have different effects on the magnitude of the LFP. Contrast elevations increase and attention decreases the magnitude of the initial deflection of the stimulus-evoked LFP. Both contrast elevation and attention increase the magnitude of the spiking response. We speculate that latencies may be reduced at higher contrast because stronger stimulus inputs drive neurons more rapidly to spiking threshold, while attention may reduce latencies by placing neurons in a more depolarized state closer to threshold before stimulus onset.
Estimating Durbin's approximation

SUMMARY Some statistical procedures involve boundary crossing probabilities for processes that converge weakly to continuous Gaussian limits. When carrying out these procedures, boundary crossing probabilities associated with the limit processes may sometimes be substituted for the probabilities of interest. An approach to estimating Durbin's approximation to boundary crossing probabilities for continuous Gaussian processes is described here. When the covariance of the limit process satisfies a certain condition, the approach may be used to estimate the boundary crossing probabilities associated with the limit processes. Two examples illustrate the applicability of the approach, and the results of some simulation experiments are described.
Highly Selective Olefin Trimerization Catalysis by a Borane-Activated Titanium Trimethyl Complex

Reaction of a trimethyl titanium complex, (FI)TiMe3 (FI = phenoxy-imine), with 1 equiv of B(C6F5)3 gives [(FI)TiMe2][MeB(C6F5)3], an effective precatalyst for the selective trimerization of ethylene. Mechanistic studies indicate that catalyst initiation involves generation of an active TiII species by olefin insertion into a Ti–Me bond, followed by β-H elimination and reductive elimination of methane, and that initiation is slow relative to trimerization. (FI)TiMe3/B(C6F5)3 also leads to a competent catalyst for the oligomerization of α-olefins, displaying high selectivity for trimers (>95%), approximately 85% of which are one regioisomer. This catalyst system thus shows promise for selectively converting light α-olefins into transportation fuels and lubricants.
Negative eugenics and ethical decisions

Negative eugenics, purposive practices to eliminate some trait from our progeny, is a topic that commands discussion today. We have had the ability to practice negative eugenics for many years, perhaps for our entire history in one form or another, but today we have many options, several quite scientifically sophisticated, for such practices. What concerns me is that the easier it becomes to practice negative eugenics, the greater is the need for some consistent criterion of what makes a given trait properly erasable. In this paper, I will argue that there is a need for a criterion of what makes a given trait properly a candidate for elimination through programs and practices of negative eugenics. I will begin by presenting the problem, then will proceed to explore the topic through a series of three questions: First, can we engage in programs of negative eugenics? Second, should we engage in any such programs? Third, which programs should we practice, and how should they be practiced? The paper will conclude with my own suggested criteria.
Photochemistry of 2-mercaptopyridines. Part 2. An EPR and spin-trapping investigation using 2-methyl-2-nitrosopropane and aci-nitromethane as spin traps in aqueous solutions.

Compounds possessing a pyridine-2-thione moiety show antimicrobial, antifungal and anticancer activities. Some of them are also photochemically active and upon UV irradiation generate free radicals. In this work, employing EPR and the spin traps 2-methyl-2-nitrosopropane (MNP) and aci-nitromethane (NM), we investigated the photochemistry in aqueous solutions of N-hydroxypyridine-2-thione (used here as a sodium salt, 2-S-PyrNONa), and pyridine-2-thione (2-S-PryH), as well as photochemistry of the respective disulfides, 2,2'-dithiobis(pyridine N-oxide) [(2-S-PyrN-->O)2] and 2,2'-dithiodipyridine [(2-S-Pyr)2]. We found that UV irradiation of 2-S-PyrNONa and of 2-S-PyrH in the presence of MNP and NM generates EPR signals of reduced spin traps in addition to signals of MNP and NM adducts with aryl-thiyl radicals, 2-.S-PyrN-->O and 2-.S-Pyr. The identification of the aromatic thiyl radicals was based on comparison of EPR spectra of spin adducts generated by irradiation of 2-S-PyrNONa and 2-S-PyrH with those produced by UV photolysis of the respective disulfides (2-S-PyrN-->O)2 and (2-S-Pyr)2. It is concluded that pyridine-2-thione and N-hydroxypyridine-2-thione possess a photoreducing capacity and generate aromatic thiyl radicals upon UV activation. This property may be relevant to biological action of agents containing the pyridine-2-thione moiety.
Differential immune responses and pulmonary pathophysiology are induced by two different strains of respiratory syncytial virus.

In this study we performed comparisons of pulmonary responses between two different respiratory syncytial virus (RSV) antigenic subgroup A strains, A2 and Line 19. Line 19 strain induced significant dose-responsive airway hyperreactivity (AHR) in BALB/c mice at days 6 and 9 after infection, whereas the A2 strain induced no AHR at any dose. Histological examination indicated that A2 induced no goblet cell hyper/metaplasia, whereas the Line 19 induced goblet cell expansion and significant increases in gob5 and MUC5AC mRNA and protein levels in vivo. When examining cytokine responses, A2 strain induced significant interleukin (IL)-10 expression, whereas Line 19 strain induced significant IL-13 expression. When IL-13−/− mice were infected with Line 19 RSV, the AHR responses were abrogated along with gob5 gene expression. There was little difference in viral titer throughout the infection between the line 19- and A2-infected mice. However, the A2 strain grew to significantly higher titers than the Line 19 strain in HEp-2 cells in vitro. Thus, RSV Line 19-induced airway dysfunction does not correlate with viral load in vivo. These data demonstrate that different RSV strains of the same antigenic subgroup can elicit differential immune responses that impact the phenotypic expression of RSV-induced illness.
Electroacupuncture analgesia in naive rats: effects of brainstem and spinal cord lesions, and role of pituitary-adrenal axis.

Recent studies have shown that analgesia is potentiated by naltrexone (NTX) and naloxone (NAL) pretreatment in rats exposed for the first time to electroacupuncture (EA). In the present study, we have investigated the role of the pituitary-adrenal axis and of brainstem and spinal cord structures in EA analgesia and its potentiation by NTX. The pituitary and adrenal glands do not participate in the production of EA analgesia, but may produce a non-opioid substance which interferes with the development of EA analgesia. Spinalization or dorsolateral funiculi lesions blocked EA analgesia, and intrathecal NTX had no effect. These results indicate that supraspinal structures are necessary to produce and potentiate EA analgesia. Contrary to their critical role in morphine and other models of environmentally produced analgesia, nucleus raphe alatus and raphe structures dorsal to it are not necessary for the development of EA analgesia. These structures, however, may contain opiate synapses on which NTX may act as an agonist to potentiate analgesia. The various components which appear to participate in the production of EA analgesia imply a complex circuit of pain modulation systems and indicate that an organism can adapt to distinct environmental conditions with versatile means to avoid pain.
The role of house dust mites and other aeroallergens in atopic dermatitis.

Managing patients with atopic dermatitis (AD) can be a frustrating experience for many clinicians because of the multiplicity of triggers known to exacerbate the condition. The recognized triggers that must be considered include xerosis, sweating, stress, and contactants such as wool and pets. Because of these various nonallergic triggers, many dermatologists tend to refute the important role played by allergens. This misapprehension may also result from their inclination to limit the concept of allergy to essentially an Immunoglobulin (Ig)E-type phenomenon, which implies the immediate hypersensitivity mastcell-effector mechanism—and this we know does not produce an eczematous eruption. However, in the last few years, IgE allergen-reactive type-2 T helper (Th2) cells have been detected in atopic individuals, and these cells are now considered to play a pivotal role in the induction and continuation of the chronic allergic inflammatory cascade.
Discrete polar reciprocal transform for detecting multiple sporadic collineations

Images consisting of dots on a blank background may contain obscure collineations. Transformation of the dots into reciprocal polar lines is effective in detecting sporadically-spaced alignments. The implementation presents polar lines by discrete pixels which compose a cumulative real-valued matrix suited to visual grey-scale presentation.