cssi/SciSciGPT-SciSciNet huggingface dataset:
Efficient parameters of vagus nerve stimulation to enhance extinction learning in an extinction-resistant rat model of PTSD.

Abstract Vagus nerve stimulation (VNS) has shown promise as an adjuvant treatment for posttraumatic stress disorder (PTSD), as it enhances fear extinction and reduces anxiety symptoms in multiple rat models of this condition. Yet, identification of the optimal stimulation paradigm is needed to facilitate clinical translation of this potential therapy. Using an extinction-resistant rat model of PTSD, we tested whether varying VNS intensity and duration could maximize extinction learning while minimizing the total amount of stimulation. We confirmed that sham rats failed to extinguish after a week of extinction training. Delivery of the standard LONG VNS trains (30 s) at 0.4 mA enhanced extinction and reduced anxiety but did not prevent fear return. Increasing the intensity of LONG VNS trains to 0.8 mA prevented fear return and attenuated anxiety symptoms. Interestingly, delivering 1, 4 or 16 SHORT VNS bursts (0.5 s) at 0.8 mA during each cue presentation in extinction training also enhanced extinction. LONG VNS trains or multiple SHORT VNS bursts at 0.8 mA attenuated fear renewal and reinstatement, promoted extinction generalization and reduced generalized anxiety. Delivering 16 SHORT VNS bursts also facilitated extinction in fewer trials. This study provides the first evidence that brief bursts of VNS can enhance extinction training, reduce relapse and support symptom remission using much less VNS than previous protocols. These findings suggest that VNS parameters can be adjusted in order to minimize total charge delivery and maximize therapeutic effectiveness.
Abstract P186: Position Effects Blood Pressure Measurement During Pregnancy

Hypertension in pregnancy is a leading cause of maternal morbidity and mortality. Studies demonstrate that body positions affect the blood pressure (BP) measurements and have led to guidelines for ...
Parent-Mediated Music Interventions with Children with ASD: a Systematic Review

Parent-mediated interventions complement professional services and empower parents. In music therapy, this treatment modality is emerging. A systematic review was conducted to assess the existence of parent-mediated music interventions with children with ASD, identify the characteristics of parent coaching used, and summarize results. Thirteen studies were selected. Framework analyses were performed on descriptions of “parent-mediated,” “parent coaching,” outcomes, measures, and findings. Quality of the research and of the training programs varied substantially. Salient findings include emerging interest in involving parents in treatment, limited conceptual frameworks for parent coaching, and limited development of this modality. High attrition, parental effort, and mixed populations limit the internal and social validity of studies. Music therapists may consider investigating parent-mediated interventions, while considering parental effort.
Multiscale modeling of cruciform dwell tests with the uncertainty-quantified parametrically homogenized constitutive model

Abstract This paper presents a novel multiscale approach for analyzing multi-axial stress-strain evolution in Ti-7Al cruciform specimens under dwell loading, through the use of an uncertainty-quantified, parametrically homogenized constitutive model (UQ-PHCM). The thermodynamically-consistent UQ-PHCM is built from rigorous upscaling of crystal plasticity FE models (CPFEM) using machine learning and uncertainty quantification. They explicitly incorporate microstructural information in the form of representative aggregated microstructural parameters (RAMPs). Uncertainty quantification accounts for uncertainty in model reduction, data sparsity and microstructural descriptors. This paper integrates advanced multiscale, multi-axial experiments with computational modeling at multiple scales to establish the UQ-PHCM as an effective tool for bridging the gap between laboratory specimen-scale experimental observations and micro-scale stresses and strains using CPFEM. The CPFEM is calibrated and validated by experimental data from surface strain measurements using digital image correlation (DIC) and grain-by-grain lattice strain measurements with in-situ far field high energy diffraction microscopy (ff-HEDM). A computational method is developed in CPFEM, to incorporate initial residual stresses consistent with measured lattice strains. The UQ-PHCM is validated with biaxial tensile dwell test results performed on the cruciform specimen with satisfactory prediction of gauge strain evolution in DIC measurements. Uncertainty in the strain field due to microstructural variability is also corroborated by the DIC measurements.
“Such business will be impossible”: Mitsubishi Trading Company and the roles of design and tariff policy in the American bicycle market (1933–1938):

During the 1930s Mitsubishi Shoji Kaisha, a Japanese trading conglomerate, attempted to foster a market for adult bicycles in America. They promoted bikes manufactured by Nichibei Shoten (including...
The use of automated data extraction tools to develop a solid organ transplant registry: Proof of concept study of bloodstream infections.

Summary Background We created an electronic health record-based registry using automated data extraction tools to study the epidemiology of bloodstream infections (BSI) in solid organ transplant recipients. The overarching goal was to determine the usefulness of an electronic health record-based registry using data extraction tools for clinical research in solid organ transplantation. Methods We performed a retrospective single-center cohort study of adult solid organ transplant recipients from 2010 to 2015. Extraction tools were used to retrieve data from the electronic health record, which was integrated with national data sources. Electronic health records of subjects with positive blood cultures were manually adjudicated using consensus definitions. One-year cumulative incidence, risk factors for BSI acquisition, and 1-year mortality were analyzed by Kaplan–Meier method and Cox modeling, and 30-day mortality with logistic regression. Results In 917 solid organ transplant recipients the cumulative incidence of BSI was 8.4% (95% confidence interval 6.8–10.4) with central line-associated BSI as the most common source. The proportion of multidrug-resistant isolates increased from 0% in 2010 to 47% in 2015 (p = 0.03). BSI was the strongest risk factor for 1-year mortality (HR=8.44; 4.99–14.27; p Conclusions Our study illustrates the usefulness of an electronic health record-based registry using automated extraction tools for clinical research in the field of solid organ transplantation. A BSI reduces the 1-year survival of solid organ transplant recipients. The most common sources of BSIs in our studies are preventable.
A Deep Learning–Based Unsupervised Method to Impute Missing Values in Patient Records for Improved Management of Cardiovascular Patients

Physicians increasingly depend on electronic health records (EHRs) to manage their patients. However, many patient records have substantial missing values that pose a fundamental challenge to their clinical use. To address this prevailing challenge, we propose an unsupervised deep learning–based method that can facilitate physicians’ use of EHRs to improve their management of cardiovascular patients. By building on the deep autoencoder framework, we develop a novel method to impute missing values in patient records. To demonstrate its clinical applicability and values, we use data from cardiovascular patients and evaluate the proposed method's imputation effectiveness and predictive efficacy, in comparison with six prevalent benchmark techniques. The proposed method can impute missing values and predict important patient outcomes more effectively than all the benchmark techniques. This study reinforces the importance of adequately addressing missing values in patient records. It further illustrates how effective imputations can enable greater predictive efficacy with regard to important patient outcomes, which are crucial to the use of EHRs and health analytics for improved patient management. Supported by the complete data imputed by the proposed method, physicians can make timely patient outcome estimations (predictions) and therapeutic treatment assessments.
Development and performance of timber REITs in the United States: A review and some prospects

Timber real estate investment trusts (REITs) are companies that own and manage timberland and generate revenue by harvesting and selling timber or other forest-related products. Due to their popula...
Health Greeter Kiosk: Tech-Enabled Signage to Encourage Face Mask Use and Social Distancing

COVID-19 has been the cause of a global health crisis over the last year. High transmission rates of the virus threaten to cause a wave of infections which have the potential to overwhelm hospitals, leaving infected individuals without treatment. The World Health Organization (WHO) endorses two primary preventative measures for reducing transmission rates: the usage of face masks and adherence to social distancing [World Health Organization 2021]. In order to increase population adherence to these measures, we designed the Health Greeter Kiosk: a form of digital signage. Traditional physical signage has been used throughout the pandemic to enforce COVID-19 mandates, but lack population engagement and can easily go unnoticed. We designed this kiosk with the intent to reinforce these COVID-19 prevention mandates while also considering the necessity of population engagement. Our kiosk encourages engagement by providing visual feedback which is based on analysis from our kiosk’s computer vision software. This software integrates real-time face mask and social distance detection on a low-budget computer, without the need of a GPU. Our kiosk also collects statistics, relevant to the WHO mandates, which can be used to develop well-informed reopening strategies.
Abiogenic Syntheses of Lipoamino Acids and Lipopeptides and their Prebiotic Significance

Researchers have formed peptide bonds under a variety of presumed prebiotic conditions. Here it is proposed that these same conditions would have also formed amide bonds between fatty acids and amino acids, producing phosphate-free amphipathic lipoamino acids and lipopeptides. These compounds are known to form vesicles and are ubiquitous in living organisms. They could represent molecules that provided protection by membranes as well as possibilities for proto-life metabolism . It is here demonstrated that when a fatty acid is heated with various amino acids, optimally in the presence of suitable salts or minerals, lipoamino acids are formed. Magnesium and potassium carbonates as well as iron (II) sulfide are found to be particularly useful in these reactions. In this manner N-lauroylglycine, N-lauroylalanine, N-stearoylalanine and several other lipoamino acids have been synthesized. Similarly, when glycylglycine was heated with lauric acid in the presence of magnesium carbonate, the lipopeptide N-lauroylglycylglycine was formed. Such compounds are proposed to have been critical precursors to the development of life.
New 40Ar/39Ar age progression for the Louisville hot spot trail and implications for inter–hot spot motion

[1] In this study we present 42 new 40Ar/39Ar incremental heating age determinations that contribute to an updated age progression for the Louisville seamount trail. Louisville is the South Pacific counterpart to the Hawaiian-Emperor seamount trail, both trails representing intraplate volcanism over the same time interval (∼80 Ma to present) and being examples of primary hot spot lineaments. Our data provide evidence for an age-progressive trend from 71 to 21 Ma. Assuming fixed hot spots, this makes possible a direct comparison to the Hawaiian-Emperor age progression and the most recent absolute plate motion (APM) model (WK08G) of Wessel and Kroenke (2008). We observe that for the Louisville seamount trail the measured ages are systematically older relative to both the WK08G model predictions and Hawaiian seamount ages, with offsets ranging up to 6 Myr. Taking into account the uncertainty about the duration of eruption and magmatic succession at individual Louisville volcanoes, these age offsets should be considered minimum estimates, as our sampling probably tended to recover the youngest lava flows. These large deviations point to either a contribution of inter–hot spot motion between the Louisville and Hawaiian hot spots or to a more easterly location of the Louisville hot spot than the one inferred in the WK08G model. Both scenarios are investigated in this paper, whereby the more eastern hot spot location (52.0°S, 134.5°W versus 52.4°S, 137.2°W) reduces the average age offset, but still results in a relatively large maximum offset of 3.7 Myr. When comparing the new ages to the APM models (S04P, S04G) by Steinberger et al. (2004) that attempt to compensate for the motion of hot spots in the Pacific (Hawaii) or globally (Hawaii, Louisville, Reunion and Walvis), the measured and predicted ages are more in agreement, showing only a maximum offset of 2.3 Myr with respect to the S04G model. At face value these more advanced APM models, which consider both plate and hot spot motions, therefore provide a better fit to the new Louisville age data. The fit is particularly good for seamounts younger than 50 Ma, a period for which there is little predicted motion for the Louisville hot spot and little inter–hot spot motion with Hawaii. However, discrepancies in the Louisville age-distance record prior to 50 Ma indicate there is an extra source of inter–hot spot motion between Louisville and the other Pacific hot spots that was not corrected for in the global S04G model. Finally, based on six new 40Ar/39Ar age dates, the 169°W bend in the Louisville seamount trail seems to have formed at least 3 Myr before the formation of the Hawaiian-Emperor bend. The timing of the most acute parts of both bends thus appears to be asynchronous, which would require other processes (e.g., plume motions) than a global plate motion change between 50 and 47 Ma to explain these two observations.
Engineering and mathematical modelling of a microbial swimmer based biosensor

Our goal here was to develop an Escherichia coli based sensing and actuation system. Here we divided the genetic circuitry required for actuation and sensing into two strains of E. coli and linked the two strains via a cell-cell communication signal. We targeted a quorum-sensing (QS) signaling molecule to control the motility response of our actuator strain. We demonstrated that the actuator cells showed signaling molecule dependent motility. Further, we developed a mathematical model that describes our engineered actuator system to provide insight into the key parameters controlling behavior of the system. As a model sensing system, we built an isopropyl s-D-1-thiogalactopyranoside (IPTG) sensor in E. coli. The sensor was designed to produce the QS signaling molecule in response to IPTG. We then demonstrated that the actuator cells respond to signaling molecule produced by this sensor strain. The sensing and actuation system engineered here can be used to build synthetic networks where motility is tightly regulated and controlled by cell-cell communication.
Biological Nitrile Reduction - Structure and Mechanism (LB136)

The enzyme QueF catalyzes the NADPH-dependent reduction of the nitrile group of 7-cyano-7-deazaguanine (preQ0) to 7-aminomethyl-7-deazaguanine (preQ1) in the biosynthesis pathway to the tRNA modified nucleoside Queuosine. The only nitrile reductase known in biology, QueF is a potential new candidate for industrial biocatalysis of nitrile transformations to amines. QueF belongs to the tunneling fold (T-fold) structural superfamily built around a small ββααββ protein domain that oligomerizes to form a β2nαn barrel and facilitates interfacial catalysis of a variety of chemical reactions. In recent years, several crystal structures have been determined of unimodular and bimodular QueF enzymes, and of active site mutants and complexes with substrate and cofactor. Here we present crystal structures and biochemical and transient kinetic data that elucidate the mechanism of biological nitrile reduction and provide insight into the molecular evolution of T-fold mediated interfacial catalysis. Structures of substra...
Mimickers of Corporate Insiders Who Make Large-Volume Trades

Most prior research shows that corporate insiders can systematically earn abnormal returns by buying or selling their own securities. Also, several studies have investigated whether outsiders can earn abnormal returns by mimicking the trades of insiders after the latter report their trades. The findings of these studies suggest that they cannot. In contrast, this study's results indicate that outsiders can earn significant abnormal returns by mimicking such trades. This conclusion is consistent with a growing body of empirical literature that suggests that the market is not efficient in the semistrong form (i.e., is not efficient with respect to all publicly available information).
The PHOA and PHOB Cyclin-Dependent Kinases Perform an Essential Function in Aspergillus nidulans

Unlike Pho85 of Saccharomyces cerevisiae, the highly related PHOA cyclin-dependent kinase (CDK) of Aspergillus nidulans plays no role in regulation of enzymes involved in phosphorous acquisition but instead modulates differentiation in response to environmental conditions, including limited phosphorous. Like PHO85, Aspergillus phoA is a nonessential gene. However, we find that expression of dominant-negative PHOA inhibits growth, suggesting it may have an essential but redundant function. Supporting this we have identified another cyclin-dependent kinase, PHOB, which is 77% identical to PHOA. Deletion of phoB causes no phenotype, even under phosphorous-limited growth conditions. To investigate the function of phoA/phoB, double mutants were selected from a cross of strains containing null alleles and by generating a temperature-sensitive allele of phoA in a deltaphoB background. Double-deleted ascospores were able to germinate but had a limited capacity for nuclear division, suggesting a cell cycle defect. Longer germination revealed morphological defects. The temperature-sensitive phoA allele caused both nuclear division and polarity defects at restrictive temperature, which could be complemented by expression of mammalian CDK5. Therefore, an essential function exists in A. nidulans for the Pho85-like kinase pair PHOA and PHOB, which may involve cell cycle control and morphogenesis.
Integration of Genomics in Primary Care

Primary care is changing rapidly. The wide-scale expansion of electronic medical records is redefining the way we approach chronic disease management, and automated decision support is increasingly being leveraged to reduce risk and optimize quality. Many of these interventions are now beginning to integrate genomic data. We explore the convergence of these 2 forces (expansion of clinical informatics and integration of translational genomics), and we highlight several applications where these forces are helping our patients avoid potentially preventable events. Because gene-environment interactions are dynamic, the utility of gene-based decision support varies over time. Primary care providers will serve a key role as our patients navigate these changes.
Phonological Assessment as an Integral Part of Language Assessment

Research indicates that preschool children presenting delayed phonological development are also likely to show delayed development of morphology, syntax, and discourse structure. Moreover, a child's phonological performance is typically better when labeling pictures and speaking individual words than when organizing syntactically more complex utterances as parts of narratives or when speaking in conversations. Such findings motivate us to assess children's speech sound development as an integral part of their abilities to organize language within realistic communication situations. To this end, we engage the preschool child in play and storybook topics that represent every day events. We use oral language scaffolding techniques to prompt the child to talk about sequences of acts within these events. We then describe the child's ability to (a) organize their discourse structure with respect to temporal, causal, and intentional links; (b) express semantic complexity; and (c) utilize conventions of syntax, m...
Intracellular distribution of 8-14C-puromycin aminonucleoside in ultraviolet irradiated Escherichia coli

Abstract The uptake of 8- 14 C-puromycin aminonucleoside (8- 14 C0PAN) was studied in ultraviolet (UV) irradiated strains of E. coli B/r hcr + and hcr − . The cells took up only 0.1–0.3% of the 8- 14 C-PAN present in the medium when grown in minimal (M9) containing 8- 14 C-PAN. When ethylenedinitrilotetra-acetic acid (EDTA) treated E. coli cells are placed in a medium containing 8- 14 C-PAN, the total concentration of 8- 14 C-PAN in the cells reaches 43–54% of the medium within 30 min of incubation. Almost all 8- 14 C-PAN can be dialyzed from cells exposed in the absence of an energy source, but cells metabolizing in M9 medium during exposure can retain up to 30% of their internal concentration. Bacteria grown in the presence of 8- 14 C-PAN, accumulated the radioactive material intracellularly in three forms, namely, unbound, reversibly bound (dialyzable) and irreversibly bound to the protein (nondialyzable). Approx. 70–77% of the irreversibly bound radioactive material linked with the protein fraction was released by treatment with a protease. Addition of PAN into the post-irradiation medium of EDTA-treated hcr + cells, increased UV induced mutation rates. Antimutagenic purine ribosides decreased the final level of 8- 14 C-PAN accumulated by the cells. Decreases in 8- 14 C-PAN uptake in the presence of antimutagens correspond to reductions in the rate of mutation to streptomycin resistance induced by UV light. Therefore, protein bound PAN appears to be the relevant component in the enhancement of UV induced mutation by this drug.
Projections from behaviorally-defined sectors of the prefrontal cortex to the basal ganglia, septum, and diencephalon of the monkey

Abstract Subcortical fiber degeneration in Macaca mulatta was traced by means of Nauta's technique following lesions of behaviorally-defined prefrontal sectors: dorsal, principalis, lateral orbital and medial orbital. All lesions led to degeneration in parts of the anterior basal ganglia, hippocampus, medial, ventral and intralaminar thalamic nuclei, and subthalamic region. Within most of these structures, however, at least two different patterns of degeneration could be distinguished: an “orbital” pattern which differed from a “dorsolateral” one mainly in being more ventral and caudal in the basal ganglia, and more medial and denser in the thalamus and subthalamus. In addition, only orbital lesions sent fibers to the septum, or, in any substantial number, to the lateral hypothalamus. The finest differentiation among the projections was observed in the head of the caudate nucleus where each type of prefrontal lesion distributed fibers to a different locus. An attempt was made to relate the anatomical findings to behavioral studies of prefrontal-subcortical functions.
The regulation of insulin-induced and sleep-related human growth hormone secretion: a review.

Abstract (1) A series of studies evaluating pharmacological alterations of insulin-induced and sleep-related GH secretion are presented. (2) In several cases, the effects of the same pharmacological agent on the two forms of secretion were very different. (3) It may be, then, that the neurotransmitter pathways which mediate the GH response to insulin differ from those that regulate sleep-related secretion.
Post fire regeneration of southern California chaparral

Succession of chaparral shrubs was studied for the first 4 years after fire on the four major slope faces at three elevations in southern California. Although total cover fluctuated from year to year, shrub cover increased annually through the third year. There was little or no increase in shrub cover between the third and fourth years. Four years after fire the shrubs covered 55% ground suiface at the highest elevation site but only 28% at the lowest elevation site. Shrub cover was similar between slope faces with one exception; at the lowest elevation site shrub cover was twice as great on the north and east-facing slopes as on the south and west-facing
A Pastoral Analysis of the Three Pillars of U.S. Hegemony—“Free Market” Capitalism, Militarism, and Exceptionalism

In this article, I offer a pastoral analysis of the three interrelated pillars of U.S. hegemony, namely, “free market” capitalism, militarism, and exceptionalism. My claims are that these pillars 1) were and are integral to the rise and maintenance of the U.S. Empire or the U.S. as hyperpower, 2) while beneficial to some U.S. citizens (as well as Western Europeans) and accidentally to other peoples, have significant and extensive detrimental and long-term consequences for other peoples, and 3) represent fundamentally and profoundly flawed symbol systems vis-a-vis creating social policies and programs that involve the common good or foster community. I argue further that the fusion of these symbol systems—free market capitalism, militarism, and exceptionalism—gives rise to the interpretation of the Other as functional and is inherently flawed and dangerous, because these systems lead to controlling, manipulating, using, or destroying the Other. If the notion of the common good is to expand beyond the narrow confines of corporations or a nation and if we seek a good enough society that fosters diverse communities, then these semiotic systems must be subordinate to religious or humanistic symbol systems that elevate the personhood of the Other.
A preliminary study of the effect of a diagnosis of concussion on PTSD symptoms and other psychiatric variables at the time of treatment seeking among veterans.

ABSTRACTThe aim of this study was to assess whether a diagnosis of concussion given at a Veterans Healthcare Administration secondary traumatic brain injury assessment impacted either posttraumatic stress disorder (PTSD) symptomatology or other variables at the time veterans sought treatment for PTSD. This retrospective study compared 61 male veterans with a history of military-related concussion and military-related PTSD to 83 male veterans with military-related PTSD but without a diagnosis of military-related concussion. There were no significant between-group differences in PTSD symptomatology. However, the cohort with a history of military concussion endorsed decreased ability to cope with PTSD symptoms, increased problems with physical health, and more pain complaints. If replicated, these results may guide the design of more effective interventions for veterans who receive diagnoses of PTSD and concussion.
A new toxic fluorescent metabolite derived from the interaction of rat liver and aflatoxin B1

Abstract A new metabolite of aflatoxin B1 which may represent one or more compounds with similar thin-layer chromatographic characteristics, was shown to be produced in vitro from the incubation of aflatoxin B1 and nonmicrosomal preparations of rat liver. This metabolite shows aflatoxin-like toxicity in the fertile chicken egg.
Hypoxia-induced alveolar epithelial-mesenchymal transition requires mitochondrial ROS and hypoxia-inducible factor 1

Patients with acute lung injury develop hypoxia, which may lead to lung dysfunction and aberrant tissue repair. Recent studies have suggested that epithelial-mesenchymal transition (EMT) contribute...
Temporal vs. spatial information as a reinforcer of observing

Conditioned reinforcement interpretations of observing behavior predict that certain kinds of temporal information, but not spatial information, will reinforce observing. In a free operant observing experiment, pigeons pecked the left and right keys of a three-key panel to produce intermittent food deliveries. Pecks to the center key (observing responses) produced stimulus displays providing some birds with spatial information (which side key to peck) and other birds with temporal information (which component of a mixed variable-interval/extinction schedule was operating). Four of the six birds that could produce temporal information did so, whereas none of the six birds that could produce spatial information did so. The “information hypothesis” of observing apparently cannot explain this result.
Noradrenaline neuron plasticity in developing rat brain: effects of neonatal 6-hydroxydopamine demonstrated by dopamine-β- hydroxylase immunocytochemistry

Abstract The present study was conducted to assess the morphological changes produced by neonatal administration of 6-hydroxydopamine (6-OHDA) in the noradrenergic innervation of the developing and adult rat brain. As demonstrated by dopamine-β-hydroxylase (DBH) immunohistochemistry, the major alterations are the following. First, neocortical and hippocampal noradrenergic innervation is permanently eliminated by the treatment, with lesser effects on other telencephalic structures. These changes appear by postnatal day 5 and are permanent in nature. In adult treated animals, most thalamic nuclei are hyperinnervated by DBH-immunoreactive axons as are the cerebellum and a number of brainstem nuclei. The hyperinnervation of these structures occurs after postnatal day 20, and is extremely specific, with the pattern of organization and distribution of noradrenergic axons in treated animals identical to that of controls. In contrast, the noradrenergic innervation of the hypothalamus is relatively unaffected by 6-OHDA treatment. The principal exception is the development of an anomalous plexus of DBH immunoreactive axons in the lateral hypothalamus. The timing and organization of the changes produced by neonatal 6-OHDA administration are consistent with the hypothesis that noradrenergic neurons, and particularly those of the locus coeruleus, are programmed to produce a defined amount of axon and terminal field, with any developmental loss resulting in a ‘pruning effect’ such that the total terminal field appears conserved. Given the specificity of the hyperinnervation, inductive influences from the target nuclei probably play a major role in determining the pattern of the noradrenergic innervation.
Transportable natural language database update

Natural language database access requires support of both query and update capabilities. Although a great deal of research effort has gone to support natural language database query, little effort has gone to support update. We describe a model of action that supports natural language database update, as well as query, and the implementation of a system that supports the model. A major goal of this research is to design a system that is easily transportable both to different database domains and different database management systems.
Overview of acyclovir pharmacokinetic disposition in adults and children

The metabolic disposition and pharmacokinetics of acyclovir have been studied as part of the clinical evaluation of the drug in humans. Data from 10 studies have been summarized and, when appropriate, pooled across studies for further analysis. The principal findings are as follows: Renal excretion is the major route of elimination of acyclovir and is dependent, in part, on active tubular secretion. Total body clearance (Cltot) and half-life are dependent on renal function as evaluated by estimated creatinine clearance (Clcr). Cltot is markedly reduced in the anuric patient. Plasma protein binding is low and drug interactions involving binding displacement are not anticipated. Acyclovir levels in cerebrospinal fluid are approximately 50 percent of corresponding plasma levels. Dose-independent pharmacokinetics is observed in the range of 0.5 to 15 mg/kg. Proportionality between dose and plasma levels is seen after single doses or at steady state after multiple dosing. Similar plasma levels are achieved in adults and pediatric patients (greater than 1 year) when equivalent doses are given based on body surface area. Intrasubject variability of acyclovir disposition is low. Much but not all intersubject variability in Cltot can be explained by differences in renal function. Dosage adjustment for various stages of renal impairment are proposed based on the observed relationship between Cltot and Clcr.
Decline in Homicide Victimization and the Changing Share of Homicide Victimization in Rural Areas During the 1990s: A Research Note

From approximately 1993 to 2000, the overall homicide rate in the USA declined dramatically. This decline reflected not only a drop in the rate of homicide itself, but also a substantial decline in the raw volume of homicide in terms of the number of people being killed. Our analysis of Supplementary Homicide Report data provides evidence that the decline in the raw volume of homicide in the USA during the second half of the 1990s was mostly driven by decreasing numbers of homicide victims in large cities and suburban areas. Two consequences of this are that the proportional share of homicide occurring in rural areas increased, and that the ratio of the volume of homicide in rural areas to large cities also increased. The implications of these changes for public perceptions of crime and the relative risk of victimization in rural areas are discussed.
THE SELECTIVITY OF DIFFERENT EXTERNAL BINDING SITES FOR QUATERNARY AMMONIUM IONS IN CLONED POTASSIUM CHANNELS

Tetraethylammonium (TEA) is thought to be the most effective quaternary ammonium (QA) ion blocker at the external site of K+ channels, and small changes to the TEA ion reduce its potency. To examine the properties of the external QA receptor, we applied a variety of QA ions to excised patches from human embryonic kidney cells or Xenopus oocytes transfected with the delayed rectifying K+ channels Kv 2.1 and Kv 3.1. In outside-out patches of Kv 3.1, the relative potencies were TEA > tetrapropylammonium (TPA) > tetrabutylammonium (TBA). In contrast to Kv 3.1, the relative potencies in Kv 2.1 were TBA > TEA > TPA. In Kv 3.1 and Kv 2.1, external tetrapentylammonium (TPeA) blocked K+ currents in a fast, reversible and, in contrast to TEA, time-dependent manner. The external binding of TPeA appeared to be voltage independent, unlike the effects of TPeA applied to inside-out patches. External n-alkyl-triethylammonium compounds (C8, C10 chain length) had a lower affinity than TEA in Kv 3.1, but a higher affinity than TEA in Kv 2.1. In Kv 3.1, the decrease in QA affinity was large when one or two methyl groups were substituted for ethyl groups in TEA, but minor when propyl groups replaced ethyl groups. Changes in the free energy of binding could be correlated to changes in the free energy of hydration of TEA derivatives calculated by continuum methodology. These results reveal a substantial hydrophobic component of external QA ion binding to Kv 2.1, and to a lesser degree to Kv 3.1, in addition to the generally accepted electrostatic interactions. The chain length of hydrophobic TEA derivatives affects the affinity for the hydrophobic binding site, whereas the hydropathy of QA ions determines the electrostatic interaction energy.
A long-term evaluation of the juvenile diabetic.

Summary In the regulation of diabetes mellitus in children, control is of the utmost importance when prevention of serious vascular complications is considered. Retinopathy and albuminuria were the most frequently encountered vascular complications. Complications of this sort first became detectable at an average of eleven years eight months after the initial diagnosis. There is an increased need for insulin and calories as growth progresses. A peak is reached at puberty, followed by a drop and then stabilization of both insulin and caloric requirements.
Abstract 4742: BCG in combination with anti-IL-10R1 monoclonal antibody induces specific antitumor immunity in an orthotopic bladder cancer model.

Introduction and Objective: We previously demonstrated that combination therapy with BCG and anti-IL-10 receptor 1 monoclonal antibody (anti-IL-10R1 mAb) effectively prevented bladder cancer metastasis in a murine MB49 orthotopic tumor model. MB49 cells express the male minor histocompatibility (HY) antigen that, although is immunogenic, induces no tumor rejection in female mice. Here we investigated whether the combination therapy could enhance HY-specific immune responses and whether this HY-specific immunity contributed to the prevention of bladder cancer metastasis in this model. Methods: Four groups of female mice (n = 5) were inoculated intravesically (i.b.) with 1 X 106 luciferase–expressing MB49 (MB49-Luc) cells and treated intraperitoneally (i.p.) with PBS, control IgG (200μg), or anti-IL-10R1 mAb (200μg) at day 0. Starting at day 1, mice were treated twice weekly with i.b. PBS plus i.p. PBS (Group 1), i.b. PBS plus i.p. anti-IL-10R1 mAb (Group 2), i.b. BCG plus i.p. control IgG (Group 3), or i.b. BCG plus i.p. anti-IL-10R1 mAb (Group 4) for a total of 6 treatments. Tumor growth was monitored using the IVIS luminescence system. Mice were sacrificed for analysis at day 21. Splenocytes were prepared, pooled and cultured in the presence of a HY antigen peptide or a control ovalbumin (OVA) peptide. After 3 days culture supernatants were collected and analyzed for IFN-γ production by ELISA. After 5 days splenocytes were used as effector cells in a cytotoxicity assay. Results: Tumor implantation was confirmed for all groups. Splenocytes produced no IFNγ in response to OVA peptide stimulation. Splenocytes from Groups 1 and 3 (treated with no anti-IL-10R1 mAb) produced no IFN-γ in response to HY peptide stimulation. In contrast, splenocytes from Groups 2 and 4 (treated with anti-IL-10R1 mAb) produced significantly increased IFN-γ in a dose-dependent manner in response to HY peptide stimulation, with Group 4 (combination therapy) splenocytes being more potent. Accordingly, Group 4 splenocytes exhibited profound cytotoxicity against MB49-Luc cells with 69.8%, 51.2% and 25.6% killing at an E:T ratio of 50:1, 25:1 and 12.5:1, respectively. However, splenocytes from Group 2 (anti-IL-10R1 mAb monotherapy) showed marginal killing of MB49-Luc cells. Conclusions: BCG in combination with anti-IL-10R1 mAb induced HY-specific effector cells cytotoxic to MB49-Luc bladder cancer cells. Anti-IL-10R1 mAb may prove useful in clinical practice for the prevention of metastatic bladder cancer in high-risk patients. Citation Format: Eric J. Askeland, Mark R. Newton, Xu Wang, Xiaohong Chen, Ryan W. Askeland, Michael A. O9Donnell, Yi Luo. BCG in combination with anti-IL-10R1 monoclonal antibody induces specific antitumor immunity in an orthotopic bladder cancer model. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4742. doi:10.1158/1538-7445.AM2013-4742
The release of Bβ 1–42 from fibrinogen and fibrin by plasmin

Abstract The balance between thrombin and plasmin action has been postulated to be an important determinant of thrombosis. Measurement of plasma concentrations of fibrinopeptide A (FPA), which reflect thrombin action on the NH2-terminal end of the Aα chain, and of Bβ 1–42 (thrombin-increasable fibrinopeptide B immunoreactivity - TIFPB) which reflect plasmin action on the NH2-terminal end of the Bβ chain have shown systematic changes in the relative concentrations of the two peptides in thrombotic states. This paper reports kinetic data for TIFPB release by plasmin using fibrinogen, fibrin I monomer, and fibrin I polymer as substrates. For fibrinogen and fibrin I monomer the data fit the Michaelis-Menten equation. Experiments were performed with human proteins in 0.15M Trisbuffered saline at pH 7.4 and at 37°C. With fibrinogen as substrate the Km was calculated to be 0.87 μM and the Vmax 3.75 × 10−5 M/min/unit of plasmin. With fibrin I monomer as the substrate the Km was calculated to be 1.25 μM and the Vmax 5.5 × 10−5 M/min/unit of plasmin. With fibrin I polymer as substrate the data did not fit the Michaelis-Menten equation but there appeared to be no dramatic differences in rates from those obtained with the other two substrates. The influence of factor XIIIa-induced cross-linking of fibrin was not examined. It is concluded from these findings that fibrinogen and non-cross-linked fibrin I are equally good substrates for plasmin cleavage of the NH2-terminal end of the Bβ chain.
Naloxone antagonism of conditioned hyperthermia: an evidence for release of endogenous opioid.

Abstract Morphine-induced hyperthermia was conditioned to environmental stimuli by pairing each injection (10 mg/kg) with the smell of anise oil. After 39 pairings the smell itself acquired a conditional property of eliciting hyperthermia which was antagonized by naloxone.
Absentee herd owners and part-time pastoralists: the political economy of resource use in northern Kenya

The prevalence of absentee herd ownership in Africa's pastoral areas is increasing. Its presence has important implications both for local resource management systems and for research programs that address pastoral ecology and related topics. This paper examines patterns of absentee herd ownership in the Baringo District of northern Kenya. This region has been the source of much debate regarding herder “mismanagement” of range lands. Three categories of absentee herd owners are discussed in the paper: (1) ranchers, (2) livestock traders, and (3) townsmen. It is suggested that the blame for some of the apparent resource mismanagement in the region may lie more with actors in these categories than with the pastoralists themselves. Data collected during an 18-month period in 1980–1981 on pastoral ecology, grazing patterns, and tenure institutions are presented in support of the argument. The paper concludes with a comparative analysis of contemporary resource management strategies in pastoral Africa, emphasizing that: (1) the Baringo case is not an isolated anomaly, and (2) a new orientation toward pastoral studies is warranted.
Reactive oxygen species-caspase-3 relationship in mediating blood-brain barrier endothelial cell hyperpermeability following oxygen-glucose deprivation and reoxygenation.

Objective Microvascular hyperpermeability that occurs due to breakdown of the BBB is a major contributor of brain vasogenic edema, following IR injury. In microvascular endothelial cells, increased ROS formation leads to caspase-3 activation following IR injury. The specific mechanisms, by which ROS mediates microvascular hyperpermeability following IR, are not clearly known. We utilized an OGD-R in vitro model of IR injury to study this. Methods RBMEC were subjected to OGD-R in presence of a caspase-3 inhibitor Z-DEVD, caspase-3 siRNA or an ROS inhibitor L-AA. Cytochrome c levels were measured by ELISA and caspase-3 activity was measured fluorometrically. TJ integrity and cytoskeletal assembly were studied using ZO-1 immunofluorescence and rhodamine phalloidin staining for f-actin, respectively. Results OGD-R significantly increased monolayer permeability, ROS formation, cytochrome c levels, and caspase-3 activity (p < 0.05) and induced TJ disruption and actin stress fiber formation. Z-DEVD, L-AA and caspase-3 siRNA significantly attenuated OGD-R-induced hyperpermeability (p < 0.05) while only L-AA decreased cytochrome c levels. Z-DEVD and L-AA protected TJ integrity and actin cytoskeletal assembly. Conclusions These results suggest that OGD-R-induced hyperpermeability is ROS and caspase-3 dependent and can be regulated by their inhibitors.
Molecular second hyperpolarizability measured in cumulene-containing polymers

Abstract Nonlinear optical susceptibilities were measured in a cumulene-containing polymer using the Z-scan technique at 1064 780 and 590 nm, respectively. At off resonance conditions we obtained real (Re) and imaginary (Im) orientationally averaged second hyperpolarizability γ from a straightforward Z-scan analysis using CS 2 as our standard; we got Rey=−6.2 × 10 −30 esu at 1064 nm and γ=(−2 + 0.261) × 10 −30 esu at 780 nm. Measurements at 590 nm were accompanied by one-photon absorption saturation, which could be mathematically extracted from the overall γ, leaving only the nonresonant terms. We thus obtained at 590 nm γ=(−1.4 + 2.21) × 10 −29 esu. The two orders of magnitude increase in Imγ from 780 to 590 nm is discussed within the summation of states model.
Perturbation of Wreath Products and Quasi-Isometric Rigidity 1

We extend the notion of perturbation of wreath products, and by the methods similar to [3], prove that certain perturbations are still quasi-isometric to the original wreath product. As an application, we show that a property of containing free subgroup or free subsemigroup, and many other algebraic properties of groups are not quasi-isometrically rigid.
Supporting Family Choice

Supporting family choice in the decision-making process is recommended practice in the field of early childhood and early childhood special education. These decisions may relate to the medical, educational, social, recreational, therapeutic/rehabilitative, and community aspects of the child's disability. Although this practice conveys the message that families are the primary decision-makers for their children, families are not always adequately supported by professionals through the decision-making process. This manuscript calls for a renewed focus on family choice from the parents’ perspective by offering vignettes from parents who have had both positive and negative experiences with parent choice. To explore family choice, this manuscript includes discussions of (a) ethical, societal, and legislative rationales for families making choices, (b) benefits and challenges of family informed choice in practice, and (c) clarification of the professionals’ roles. This manuscript provides recommendations and strategies for assisting professionals in facilitating and optimizing the choice process for families.
c-Fos and ΔFosB expression are differentially altered in distinct subregions of the nucleus accumbens shell in cocaine-sensitized rats

Repeated cocaine administration in rats can lead to sensitization as evidenced by an increased locomotor response to a subsequent exposure (challenge) dose of cocaine even after a drug-free period. Expression of the immediate early gene product, c-Fos, differs among distinct subregions of the nucleus accumbens shell. This would suggest that these subregions may be differentially involved in sensitization. The present study quantified c-Fos- and deltaFosB-immunoreactive nuclei in subterritories of the nucleus accumbens in animals behaviorally sensitized to cocaine. Rats received a sensitization-inducing regimen of cocaine (twice-daily injections of 15 mg/kg i.p. for five consecutive days). Fourteen days following the last injection, rats were given a challenge injection of cocaine (15 mg/kg i.p.), and killed 2 h later. Sections through the nucleus accumbens were processed for tyrosine hydroxylase and either c-Fos or deltaFosB. The number of immunoreactive nuclei was quantified in five subregions of the nucleus accumbens shell: the vertex, arch, cone, intermediate zone and ventrolateral zone, which can be identified by differential histological staining for tyrosine hydroxylase. Repeated cocaine administration resulted in robust sensitization that was associated with more deltaFosB in the vertex, arch, and cone compared with saline-treated controls. As previously reported, c-Fos immunoreactivity was increased in the intermediate zone in cocaine-sensitized rats. deltaFosB was significantly elevated in rats that did not receive a cocaine challenge, attesting to the long half-life of this transcription factor. These results provide further evidence suggesting distinct anatomical neuroadaptations within the nucleus accumbens shell that may play a functional role in psychomotor-stimulant sensitization.