cssi/SciSciGPT-SciSciNet huggingface dataset:
Digital information support for domestic violence victims: Research Articles

With domestic violence directly impacting over 5 million victims in the United States annually, the growing e-health and e-government networks are developing digitally based resources for both victims and those who aid them. The well-established community information and referral role of public libraries dovetails with this digital referral network model; however, no study of the actual service provided by public libraries is available. This examination of e-mail reference responses to requests for safe-house contact information revealed major gaps in cyber-safety awareness and uneven implementation of professional standards for virtual reference service. Implications for information system design, professional standards, education, and future research are discussed. © 2007 Wiley Periodicals, Inc.
EVALUATION OF CYCLAMATE AND SACCHARIN

Publisher Summary After about 20 years of the widespread use of the cyclamates, and more than 80 years of the extensive worldwide use of saccharin, during which millions of people have consumed these agents for long periods of time, no evidence of adverse effects on human health has come to light. This fact does not prove that one or the other of these substances has not produced some subtle, insidious, harmful effect. The specific causes of long-delayed effects are often very difficult to identify. In the investigations of the toxicity and assessment of safety of the cyclamates and saccharin, the greatest attention has been directed toward the question of their possible carcinogenicity, especially for the urinary bladder. In the case of the cyclamates, the problems of possible cardiovascular damage and testicular atrophy have yet to be settled, though these issues do not appear to be critical. In the case of saccharin, the only remaining uncertainty seems to be the question whether it can produce malignant tumors in the urinary bladder. Numerous studies of the possible teratogenic, mutagenic, or other reproductive effects of these agents have not shown cause for undue concern in these respects.
Evaluation of Computed Tomography Scanners for Feasibility of Using Averaged Hounsfield Unit–to–Stopping Power Ratio Calibration Curve

Abstract Purpose: The purpose of this study was to quantify the variability of stoichiometric calibration curves for different computed tomography (CT) scanners and determine whether an averaged Ho...
Predicting Site-Binding Modes of Ions and Water to Nucleic Acids Using Molecular Solvation Theory

Site binding of ions and water shapes nucleic acids folding, dynamics, and biological function, complementing the more diffuse, nonspecific “territorial” ion binding. Unlike territorial binding, pr...
Abstract SY36-01: Decoding the biochemical, regulatory, and clinical impact of genomic mutations

A key challenge in precision medicine lies in decoding the complexity of the functional effects of genome variation to determine which mutations are functional and what are their biochemical and phenotypic consequences. This question is especially difficult for the 98% of the genome that is outside of exomes. To address this challenge we developed deep learning-based methods, DeepSEA and SeqWeaver, that predict the transcriptional and post-transcriptional effects of noncoding variants with single-nucleotide sensitivity. These methods not only classify mutations as likely to be associated with disease, they also provide specific biochemical consequences of each mutation, including on transcription factor and RBP binding, histone modification, and DNA accessibility. Building upon these findings, we created a deep learning-based framework, ExPecto, that can accurately predict, ab initio from DNA sequence alone, the tissue-specific transcriptional effects of mutations. These methods thus provide a platform for predicting and characterizing specific mutational impact for any genomic mutation, including those that are rare or that have not been observed. Applying these methods (available at hb.flatironinstitute.org) to whole genomes in a number of diseases, including cancer, autism, and heart disease, we demonstrate the contribution of de novo noncoding mutations and analyze the functional landscape of noncoding cancer-associated mutations. Citation Format: Olga Troyanskaya. Decoding the biochemical, regulatory, and clinical impact of genomic mutations [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr SY36-01.
Mediating Human-Robot Interactions with Virtual, Augmented, and Mixed Reality

Effective human-robot interaction (HRI) remains a critical barrier to the successful and widespread deployment of robotic technologies. Fundamentally, HRI problems represent breakdowns in communication, where poor information exchange between people and robots leads to disfluencies, incorrect mental models, poorly calibrated trust, inadequate situational awareness, etc. In this paper, I argue that the emergence of a new generation of virtual, augmented, and mixed reality (VAMR) technologies is creating an exciting new design space in which to address these problems in communication. To support this argument, I present the results of three experiments demonstrating the value in using modern VAMR technologies to mediate human-robot interactions and discuss various challenges and opportunities in this emerging space at the intersection of several communities, including robotics, VR, graphics, and human-computer interaction.
Healthcare 4.0

Healthcare is shifting from traditional hospital-centric care to a more virtual, distributed care that heavily leverages the latest technologies around artificial intelligence, deep learning, data analytics, genomics, home-based healthcare, robotics, and three-dimensional printing of tissue and implants. In the future, fundamental shifts will reshape the healthcare industry. Healthcare will be delivered as a seamless continuum of care, away from the clinic-centered point-of-care model and with a greater focus on prevention and early intervention.
Preface for focused issue: ambulatory spine surgery.

Spine surgery has been increasingly transitioning from the inpatient to outpatient setting in ambulatory surgery centers (ASC). The drivers for this paradigm shift include potential for significant cost reductions in the current value-based healthcare climate; ability to perform minimally invasive procedures due to technological advances; and patient preference to spend their postoperative recovery period at home. The development of refined protocols such as multimodal analgesic regimens are enabling more ASC-based spinal procedures to take place, with increasing evidence demonstrating their safety and efficacy.
Impaired hippocampus-dependent associative learning as a mechanism underlying PTSD: A meta-analysis.

Abstract Smaller hippocampal volume is associated with increased risk for PTSD following trauma, but the hippocampal functions involved remain unknown. We propose a conceptual model that identifies broad impairment in hippocampus-dependent associative learning as a vulnerability factor for PTSD. Associative learning of foreground cues and background context is required to form an integrated representation of an event. People with poor associative learning may have difficulty remembering who or what was present during a trauma, where the trauma occurred, or the sequence of events, which may contribute to PTSD symptoms. We argue that associative learning difficulties in PTSD exist for cues and context, regardless of the emotional nature of the information. This contrasts with PTSD models that focus exclusively on threat-processing or contextual-processing. In a meta-analysis, people with PTSD exhibited poor associative learning of multiple information types compared to those without PTSD. Differences were of medium effect size and similar magnitude for neutral and negative/trauma-related stimuli. We provide evidence for associative learning difficulties as a neurocognitive pathway that may contribute to PTSD.
Differential response of four Californian native plants to worldwide Phytophthora cinnamomi genotypes: implications for the modeling of disease spread in California

Multiple introductions in California of Phytophthora cinnamomi are severely threatening its native ecosystems. However, little is known about the consequences of outbreaks caused by different genotypes on endemic hosts. Virulence of 10 genotypes representative of the California and worldwide genetic variability of P. cinnamomi was studied on roots and stems of four native California plant hosts. Hosts differed in type of response and susceptibility level, and individual pathogen genotypes differed in virulence. Pathogen variability was clear when testing hosts of moderate susceptibility (Pseudotsuga menziesii and Umbellularia californica), but not so on highly susceptible hosts. Some genotypes are better adapted as root rather than stem pathogens, causing a different disease. Arbutus menziesii and Arctostaphylos viscida are hosts with aerial and root susceptibility, while U. californica acts mainly as root host. Four isolates representing three genotypes caused the highest level of disease: two of them were from a genetic lineage only recently identified in California and Mexico, but nowhere else. The results presented here are preliminary, however if confirmed, they would suggest that novel invasive genotypes of P. cinnamomi may require regulatory action to prevent their further spread. It also proves that highly susceptible hosts should not be used to identify phenotypic variability in pathogens.
Assessment of Acute Hospital Use and Transfers for Management of Pediatric Seizures

Importance The availability of pediatric hospital care for common conditions is decreasing across the US. The consequences of this decrease on access to care for specific conditions need to be evaluated. Objective To evaluate the degree of regionalization of pediatric seizure care in the US by characterizing the activity of hospital systems in 6 diverse states. Design, Setting, and Participants This retrospective cross-sectional study used inpatient and emergency department administrative data sets from all acute care hospitals in Arkansas, Florida, Kentucky, Maryland, Massachusetts, and New York from 2014. All patients younger than 18 years who visited a hospital and had a primary diagnosis of seizures were included. Data were analyzed between January and June 2019. Main Outcomes and Measures Characteristics of hospital encounters and pediatric Hospital Capability Index scores of transferring and admitting hospitals. Results Among 57 930 encounters with pediatric patients with seizures (median [range] age, 4 [1-11] years; 31 968 [55.2%] boys) identified in 621 acute care hospitals, 15 467 patients (26.7%) were admitted as inpatients and 3748 patients (6.5%) were transferred between acute care hospitals. Among encounters that resulted in transfers between hospitals, seizure was the only diagnosis in 1554 patients (41.5%). A total of 42 463 encounters began as emergency department visits, of which 38 173 encounters (90.0%) resulted in routine discharge. While 536 hospitals (86.3%) transferred children with seizures, only 232 hospitals (37.4%) ever admitted them and only 63 hospitals (10.1%) ever received a pediatric seizure transfer. The median (interquartile range) pediatric Hospital Capability Index score of all hospitals was 0.10 (0.02-0.28), while that of hospitals occasionally admitting pediatric seizure patients was 0.34 (0.22-0.55). However, although most patients who were admitted had brief stays (ie, ≤2 days) and no comorbidities, three-quarters of all admissions (12 002 admissions [77.6%]) were to very highly capable centers (ie, hospitals with pediatric Hospital Capability Index scores >0.75). Across all states, the number of referral hospitals for pediatric seizures was less than the number of Dartmouth Atlas Hospital Referral Regions (47 referral hospitals vs 63 hospital referral regions). Conclusions and Relevance These findings suggest that although children with seizures are seen in almost all acute care hospital emergency departments, most hospitals transfer children who require admission. Condition-specific interhospital dependency challenges standard definitions of network adequacy and should be accounted for in emergency medical service planning, access to care policies, and health services research.
The Psychology of Hope: A Diagnostic and Prescriptive Account

In this chapter, I review psychology’s contributions to the study of hope. To close potential gaps in this interdisciplinary volume, I include work in psychiatry and nursing. The nearly 400-year history of psychological reflections on hope reveals extended stretches of neglect, alternating with brief flashes of interest. Shifting scientific paradigms are partly to blame. However, I suggest that the greatest challenge for investigators seeking scientific consensus on the topic may be cultural and sociopolitical. I begin with a review of the most significant writings and research on hope, dating back to the seventeenth century. I examine goal-related approaches in greater depth, due to their strong influence on the field of psychology. The latter half of this chapter is more critical and prescriptive. For a deeper commentary, I rely on Markus’s (Meas Interdisciplinary Res Perspect 6:54–77, 2008) distinction between constructs and concepts as well as Danziger’s (Naming the mind: How psychology found its language. Sage Publications, 1997) observation on how psychology found its lexicon. This middle, diagnostic section includes a review of philosophy of science criteria for evaluating theories. I transition to general prescriptions for achieving a better understanding of hope, organized around Bacon’s “four idols” of the mind, and add specific suggestions for future research. I conclude with a summary of recent work within our hope lab.
Simulation testbed for railway infrastructure security and resilience evaluation

The last decade has seen an influx of digital connectivity, operation automation, and remote sensing and control mechanisms in the railway domain. The management of the railway operations through the use of distributed sensors and controllers and with programmable and remotely controllable railway signals and switches has led to gains in system efficiency as well as operational flexibility. However, the network connectivity has opened up the railway cyber communication networks to cyber-attacks. These are a class of cyber-physical systems (CPS) with interconnected physical, computational, and communication components. The cyber-attacks on these systems could potentially cascade through these inter-connection and result into significant damage. These systems are safety-critical owing to their large-scale monetary and, more importantly, human life safety concerns. Therefore, it is better to incorporate security and resilience requirements right from the design time. In this paper, we describe a domain-specific framework for simulations in the railway domain. The framework allows analyzing the resilience of railway operations in the presence of cyber-attacks. In particular, our simulation framework allows modeling the railway network as well as the railway transportation. It provides an online graphical modeling environment that allows multiple users to collaborate, through a web-based interface, over the same model for the railway infrastructure as well as network attacks. The framework also allows the user to configure and run experiments through the web-interface and also to visualize the key operational metrics from the railway domain as the experiment is running. The framework also supports executing large simulations in the cloud. In addition, it supports hardware-in-the-loop (HIL) simulation for incorporating physical effects and network attacks that can only be realized realistically in the hardware. A detailed case study is provided to demonstrate the framework's capabilities.
The day-to-day impact of nighttime noise disturbances on college students' psychological functioning.

OBJECTIVE To understand environmental predictors (i.e., nighttime noise disturbance) of sleep health (i.e., restedness) in residential college students and its potential mental health consequences, this study examined daily variation in restedness upon awakening as a potential mediator between nightly environmental noise disturbances and daily fluctuations in depressive and anxiety symptoms. Participants: The sample was comprised of 283 college students (Mage = 19.9, SD = 1.9; 79% female). Methods: Multilevel structural equation modeling was conducted based on an initial self-report, online questionnaire and an online 7-day daily sleep (morning) and mood (evening) diary. Results: Daily fluctuations in college students' reports of restedness (morning diary) mediated the association between the nighttime presence of noise disturbances (morning diary) and depressive and anxiety symptoms (evening diary). Conclusions: Given the high prevalence of mental health problems in college students, creating more conducive sleep environments may help to prevent depressive and anxiety symptoms in this population.
Wave redirection, localization, and non-reciprocity in a dissipative nonlinear lattice by macroscopic Landau–Zener tunneling: Theoretical results

We consider an asymmetric dissipative network of two semi-infinite nonlinear lattices with weak linear inter-lattice coupling and study its capacity for passive wave redirection and non-reciprocity. Each lattice is composed of linearly grounded oscillators with essentially nonlinear (i.e., non-linearizable) next-neighbor intra-lattice coupling, and it supports breather propagation. Irreversible breather redirection between lattices is governed by a macroscopic analog of the quantum Landau–Zener tunneling (LZT) effect, whereby impulsive energy initially induced to the “excited lattice” is passively and irreversibly redirected to the “absorbing lattice.” Moreover, this wave redirection is realized only in a specific range of impulse intensity (energy), otherwise motion localization occurs. In this work, we show that LZT breather redirection in the dissipative network occurs only when the normalized linear inter-coupling stiffness is larger than the viscous damping ratio of the individual lattice oscillators, with breather arrest and localization occurring otherwise. Then, through a reduced-order model, we provide guidance for selecting the system parameters of the lattice network for robust breather redirection despite the presence of dissipation. To this end, we study the acoustic non-reciprocity and formulate a quantitative measure for studying it based on measured time-series responses at the four free boundaries of the finite network. Then, we show the dependence of non-reciprocity in this system on the intensity (energy) of the applied impulse. These results pave the way for conceiving practical nonlinear lattice networks with inherent capacities for passive wave redirection and acoustic non-reciprocity that are tunable (self-adaptive) to the applied impulsive excitations.
Junction Design and Complementary Capacitance Matching for NCFET CMOS Logic

Negative capacitance field effect transistors (NCFETs) are modeled in this study, with an emphasis on junction design, implications of complementary logic, and device $V_{t}$ menu enablement. Contrary to conventional MOSFET design, increased junction overlap is beneficial to NCFETs, provided the remnant polarization ( $P_{r}$ ) is high enough. Combining broad junctions with complementary capacitance matching (CCM) in MFMIS (metal/ferroelectric/metal/insulator/semiconductor) NCFETs, it is shown that super-steep and non-hysteretic switching are not mutually exclusive, and that it is theoretically possible to achieve non-hysteretic sub-5 mV/dec SS over >6 decades. In a CMOS circuit, due to CCM, low- $V_{t}$ pairs provide steeper subthreshold swing ( SS ) than high- $V_{t}$ pairs. Transient power/performance is also modeled, and it is shown that a DC-optimal NCFET design, employing broad junctions, CCM, and a low- $V_{t}$ NFET/PFET pair, does not translate to improved AC power/performance in unloaded circuits compared to a conventional FET reference. It is also shown that the same non-hysteretic DC design point is hysteretic in AC and may also lead to full polarization switching at higher voltages. Thus, a usable voltage window for AC NCFET operation forces a retreat from the DC-optimal design point.
When plants brace for the emerging pathogens

Abstract Emerging phytopathogens ranging from viruses, bacteria, oomycetes, and fungi to nematodes have seriously threatened global crop productivity and food security, mostly owing to changing demographic dynamics and geographical movements of crops brought by human beings. An understanding of these new pathogens would allow timely intervention in biological control, phytosanitation, and biosecurity of crops and plants. With the flooding of information in the genomic era and with ensuing advances in other related ‘omics’, technologies would pave the path to improvement of plants to protect against the pathogens. We introduce the recently reported, emerging repertoire of phytopathogens, from diverse taxa such as fungi, oomycetes, bacteria, viruses, and nematodes, to the re-emerging ones and the cross-kingdom host jumping pathogens.
NIH Translational Programs for Assisting Pre-Clinical Drug Discovery and Development

Publisher Summary This chapter provides an overview of current and major National Institutes of Health (NIH) translational programs. In addition to supporting basic medical research, the NIH also supports and had re-emphasized, as part of the NIH Roadmap for Medical Research, a number of translational medicine initiatives including the pre-clinical development of agents for the diagnosis and treatment of disease. The goals of these programs are to resurrect fallow pipelines and stimulate the discovery of new agents by providing critical resources that can overcome translational roadblocks on the route to clinical evaluation. These programs are often the only bridge forward for investigators, especially in the costly late preclinical stages of the development process. Support to investigators from the cited programs is generally provided as pre-clinical services at no charge, rather than as direct funding grants. Small Business Innovation Research and Small Business Technology Transfer (SBIR/STTR) programs are available, which can provide direct funding.
Nonlinearity tuning and its effects on the performance of a MEMS gyroscope

A three-fold symmetric SOI-MEMS gyroscope having parasitic softening nonlinearity from the drive comb and frequency tune fingers is successfully linearized through the use of shaped comb fingers that introduce a tuned cubic hardening compensation. The nonlinearity compensated gyroscope achieves high drive displacement (>10µm) while maintaining linear magnitude and phase frequency responses. The proposed tuning method also minimizes the amplitude-frequency (A-f) effects on the drive mode. Cancelling the drive nonlinearities leads to a better bias instability compared to the high displacement with nonlinear characteristics.
Habitat use and movements of shovelnose sturgeon in Pool 13 of the upper Mississippi River during extreme low flow conditions

We monitored habitat use and movement of 27 adult shovelnose sturgeon in Pool 13 of the upper Mississippi River, Iowa-Illinois, by radio-telemetry in April through August 1988. Our objective was to determine the response of this species to unusually low water conditions in the upper Mississippi River in 1988. Most (94%) telemetry contacts were made in 3 habitat types: main channel (50%), main channel border where wing dams were present (29%), and tailwaters of Lock and Dam 12 (15%). Habitat use in spring was affected by the extreme low flows. We often found tagged shovelnose sturgeon in the main channel and tailwaters during the spring period (11 March–20 May) where water velocities were highest. This was in contrast to other studies where shovelnose sturgeon did not occupy those areas during years with normal spring flows. Shovelnose sturgeon were typically found in areas with a sand bottom, mean water depth of 5.8 m, and mean bottom current velocity of 0.23 m sec-1. They occupied areas of swifter current but were not always found in the fastest current in their immediate vicinity. Tagged shovelnose sturgeon tended to remain in the upper, more riverine portion of the pool, and we observed no emigration from the study pool. Linear total range of movement from the tagging site ranged from 1.9 to 54.6 km during the study period.
Polarization Diversity for Detecting Targets in Heavy Inhomogeneous Clutter

Polarization diversity has proved to be a useful tool for radar detection, especially when discrimination by Doppler effect is not possible. In this paper, we address the problem of improving the performance of polarimetric detectors for targets in heavy inhomogeneous clutter. First, we develop a polarimetric detection test that is robust to inhomogeneous clutter. We run this polarimetric test against synthetic and real data to assess its performance in comparison with existing polarimetric detectors. Then, we propose a polarimetric waveform-design algorithm to further improve the target-detection performance. A numerical analysis is presented to demonstrate the potential performance improvement that can be achieved with this algorithm.
Low-Enriched Uranium Fuel Conversion Activities for the High Flux Isotope Reactor, Annual Report for FY 2011

This report describes progress made during FY11 in ORNL activities to support converting the High Flux Isotope Reactor (HFIR) from high-enriched uranium (HEU) fuel to low-enriched uranium (LEU) fuel. Conversion from HEU to LEU will require a change in fuel form from uranium oxide to a uranium-molybdenum (UMo) alloy. With both radial and axial contouring of the fuel foil and an increase in reactor power to 100 MW, calculations indicate that the HFIR can be operated with LEU fuel with no degradation in performance to users from the current levels achieved with HEU fuel. Studies are continuing to demonstrate that the fuel thermal safety margins can be preserved following conversion. Studies are also continuing to update other aspects of the reactor steady state operation and accident response for the effects of fuel conversion. Technical input has been provided to Oregon State University in support of their hydraulic testing program. The HFIR conversion schedule was revised and provided to the GTRI program. In addition to HFIR conversion activities, technical support was provided directly to the Fuel Fabrication Capability program manager.
Experiences in molecular-based prenatal screening for Ashkenazi Jewish genetic diseases.

Abstract Multiple-option prenatal carrier testing in the Ashkenazi Jewish community for three and now eight disorders has been readily accepted in this prenatal, health-oriented and knowledgeable population. Counseling of screenees concerning the nature (severity, treatability, etc.), inheritance, and frequencies of each disorder was essential for informed test choices and future reproductive decision making. The value of couple testing for a group of disorders when 1 in about 6 would be found to be a carrier of at least one disease emphasized. These studies identified issues of education, confidentiality, posttest anxiety, and self-esteem that must be continuously addressed in the Ashkenazi population. However, an important value of these studies is that they provide a framework for the development of mass carrier screening programs in the general population or in specific segments of the population with similar demographic characteristics and in more diverse prenatal populations.
Evaluation of histologic cutpoints for treatment response in eosinophilic esophagitis

Aim: No consensus exists on the definition of successful treatment in eosinophilic esophagitis (EoE). The aim of this study was to identify the optimal histologic cutpoint to define successful treatment of EoE by assessing rates of symptomatic and endoscopic improvement. Materials and Methods: We performed a retrospective cohort study utilizing the University of North Carolina EoE Clinicopathologic Database between 2006 and 2013. Rates of symptomatic and endoscopic improvement were determined, as were post-treatment eosinophil counts. The area under the receiver operator characteristic curve (AUC) was calculated for symptomatic and endoscopic response at several possible eosinophil count cutpoints (eos/hpf). Predictors of response were also assessed. Results: Of 224 treatments in 199 patients, 76% were associated with symptomatic improvement, 68% with endoscopic improvement, and 60% with both. Of treatments that resulted in a post-treatment count of <15 eos/hpf, 90% were associated with an endoscopic response, 88% with a symptomatic response, and 81% with both symptomatic and endoscopic responses. Using a <15 eos/hpf threshold, the area under the curves (AUCs) were 0.70, 0.78, and 0.75 for symptomatic, endoscopic, and symptomatic/endoscopic responses, respectively. Lower histologic cut-points did not result in a substantial gain in response, but decreased the AUC. Conclusion: In this large cohort of EoE patients, rates of symptomatic and endoscopic improvement were generally associated with histologic improvement. A histologic cutoff for treatment response of <15 eos/hpf may balance clinical outcomes and test performance.
Expression of mRNA electroporated into plant and animal cells

A general method to introduce RNA molecules into plant protoplasts and animal cells is described. This technique utilizes the ability of electric pulses of high field strength to form pores in biomembranes. RNA molecules containing the coding region for the bacterial enzyme chloramphenicol acetyltransferase (CAT) were used as a model system. The presence of CAT activity as a result of the in vivo translation of the introduced RNA is entirely dependent on the presence of a 5' cap and greatly increased by the presence of a poly A tail at the 3' end. The introduction of RNA into eukaryotic cells has broad applicability both as an assay for the uptake of nucleic acids into cells independent of transcriptional activity and as a tool to study eukaryotic mRNA translation.
A comparison of three packaging techniques using two extenders for the cryopreservation of canine semen

Abstract The progressive motility of frozen-thawed canine semen was used as a criterion to compare methods of semen cryopreservation. Twenty-one ejaculates from 7 dogs were frozen in 2 extenders, Tris-citrate (TC) and BES-lactose (BL), in each of 3 packaging techniques (pellets, 0.5-ml, and 2.5-ml straws). Duplicate samples were frozen on dry ice (pellets) or in liquid nitrogen vapor (straws). Least squares means for the percentage of post-thaw progressive motility (PTPM) were greater for TC (33.2 ± 1.7) than for BL (20.9 ± 1.7; P
Garlic compounds generate reactive oxygen species leading to activation of stress kinases and cysteine proteases for apoptosis in human glioblastoma T98G and U87MG cells.

BACKGROUND. Garlic-derived organosulfur compounds such as diallyl sulfide (DAS), diallyl disulfide (DADS), and diallyl trisulfide (DATS) provide significant protection against carcinogenesis. METHODS. Dose-dependent cytotoxic effects of the garlic compounds (DAS, DADS, and DATS) were tested in human glioblastoma T98G and U87MG cells. Wright staining and ApopTag assay confirmed induction of apoptosis. Measurements showed that production of reactive oxygen species (ROS) and an increase in intracellular free [Ca2+] promoted apoptosis. Western blot analysis indicated that increased expression and activities of the stress kinases and cysteine proteases caused apoptosis. Use of JC-1 showed changes in mitochondrial membrane potential (Δψm) for mediation of apoptosis. Use of the specific inhibitors monitored the activation of different kinases and proteases in apoptosis. RESULTS. Treatment of glioblastoma cells with garlic compounds triggered production of ROS that induced apoptosis with the phosphorylation of p38 MAPK and activation of the redox-sensitive JNK1 pathway. Pretreatment of cells with ascorbic acid attenuated ROS production, p38 MAPK phosphorylation, and JNK1 activation. Pretreatment with JNK1 inhibitor I also significantly reduced cell death. Increases in intracellular free [Ca2+], expression of calreticulin, and activation of caspase-4 indicated involvement of endoplasmic reticulum (ER) stress in apoptosis. Other events in apoptosis included overexpression of Bax, down-regulation of Bcl-2 and some BIRC proteins, mitochondrial release of cytochrome c and Smac into the cytosol, and activation of calpain, caspase-9, and caspase-3. CONCLUSIONS. Garlic compounds induced apoptosis in glioblastoma cells due toproduction of ROS, increase in ER stress, decrease in Δψm, and activation of stress kinases and cysteine proteases. Cancer 2007. © 2007 American Cancer Society.
Reduced eticlopride-induced fos expression in caudate–putamen and globus pallidus after unilateral frontal cortex injury: relation to neglect

Unilateral ablation of medial agranular cortex in rats results in neglect of contralateral stimuli and reductions in amphetamine-induced expression of the immediate early gene, c-fos, in both caudate-putamen and globus pallidus. Both unilateral neglect and the reductions in dopamine agonist induction of subcortical Fos immunoreactivity dissipate over a matter of weeks. Dopamine agonism induces Fos predominantly in striatonigral cells and in globus pallidus via striatopallidal disinhibition, whereas Fos is induced in striatopallidal cells by administration of antagonists of the D2 dopamine receptor subfamily. To examine more directly effects of cortical injury on striatopallidal function, induction of striatal Fos by the D2 antagonist eticlopride (0.1 mg/kg, s.c.) was examined in rats with medial agranular cortex ablation. In the same animals, eticlopride-induced Fos in globus pallidus was also examined. Five days after unilateral cortex injury, in rats showing neglect, the numbers of Fos immunoreactive nuclei induced by eticlopride were reduced by 50% in caudate-putamen and 25% in globus pallidus of the ipsilateral hemisphere. These lesion effects were restricted to dorsolateral caudate-putamen and dorsal pallidum. Three or more weeks after cortical injury, in rats recovered from neglect, eticlopride-induced Fos was normalized in caudate-putamen, but still decreased by 20% in globus pallidus. Along with previous findings, these results suggest that behavioral recovery from neglect produced by cortical injury may be at least partially mediated by normalizations of function of both striatopallidal and striatonigral neurons. In addition, the present findings suggest that normalization of function of pallidal cells activated by eticlopride is not necessary for behavioral recovery from frontal cortex ablation. Lingering reductions in excitatory cortico-subthalamo-pallidal input may be responsible for the longer-lasting dysfunctions of these pallidal cells.
Expression of activins and activin receptors in human retinoblastoma cell line Y-79

Abstract Activin is a member of TGFβ family and is known to inhibit neuronal differentiation in certain tumor cell lines. In this study, the messenger RNA expression of activin subunits and activin receptors was characterized in retinoblastoma cell line Y-79 using the reverse transcription-polymerase chain reaction as well as in situ hybridization. The identity of the RT-PCR products was confirmed by DNA sequencing of PCR products. The activin protein production was determined by immunocytochemistry. We found that Y-79 cells transcribe mRNAs coding activin subunits and activin receptors and produce activin proteins. Our results imply that activin may have autocrine functions in these cells.
Central mechanisms of cranial nerve stimulation for epilepsy

Stimulation of peripheral cranial nerves has been shown to exert anticonvulsant effects in animal models as well as in human patients. Specifically, stimulation of both the trigeminal and vagus nerves has been shown in multiple clinical trials to be anticonvulsant, and stimulation of these nerves at therapeutic levels does not cause pain or negatively affect brain function. However, the neuronal mechanisms by which such stimulation exerts therapeutic effects are not well understood. In this review, the possible locations of action for trigeminal nerve stimulation (TNS) and vagus nerve stimulation (VNS) are explored. Additionally, the multiple time scales on which TNS and VNS function are discussed.
Mn2+-uncoupling of the catecholamine-sensitive adenylate cyclase system of rat reticulocytes. Parallel effects on cholera toxin-catalyzed ADP-ribosylation of the system.

High concentrations of Mn2+ interfere with functional interactions between the GTP-binding regulatory protein (G) and the catalytic moiety (C) of adenylate cyclase without perturbing interactions between receptor (R) and component G in rat reticulocyte membranes. The ability of cholera toxin to ADP-ribosylate component G and to enhance GTP-stimulated adenylate cyclase activity also appears to be correlated with the efficacy of the communication of component G with the adenylate cyclase system. Thus, increasing the concentration of Mn2+ in rat reticulocyte membrane during in vitro incubations causes a parallel loss of Gpp(NH)p-stimulated adenylate cyclase activity, cholera toxin-catalyzed [32P]ADP-ribosylation of the 42 000 Mr subunit of component G and cholera toxin-catalyzed enhancement of GTP-sensitive adenylate cyclase activity. Removal of Mn2+ by washing the membranes completely restores the sensitivity of adenylate cyclase activity. Removal of Mn2+ by washing the membranes completely restores the sensitivity of adenylate cyclase to all effectors, including cholera toxin. The data suggest that exposure of membranes to Mn2+ provides a useful tool for reversibly uncoupling catecholamine-sensitive adenylate cyclase systems. The data also suggest that the extent of cholera toxin-catalyzed ADP.-ribosylation of membrane substrates, i.e., the G component may rely on functional communication among the various components of the adenylate cyclase system. A corollary of the latter is that the amount of [32P]ADP-ribose-product detected in a membrane may reflect both the quantity and coupling efficiency of component G.
Metabolism of inositol-1,3,4,6-tetrakisphosphate to inositol pentakisphosphate in adrenal glomerulosa cells.

Summary Angiotensin II stimulates rapid formation of inositol-1,4,5-triphosphate (Ins-1,4,5-P 3 ) in bovine adrenal glomerulosa cells. In addition to being rapidly metabolized to lower inositol phosphates, Ins-1,4,5-P 3 is converted to Ins-1,3,4,5-tetrakisphosphate (Ins-1,3,4,5-P 4 ) and Ins-1,3,4-P 3 which is in turn phosphorylated to a further Ins-P 4 isomer, namely Ins-1,3,4,6-P 4 . In bovine adrenocortical cytosol [ 3 H]Ins-1,3,4,5-P 4 and [ 3 H]Ins-1,3,4-P 3 were converted to Ins-1,3,4,6-P 4 and inositol pentakisphosphate (Ins-P 5 ) in a metabolic sequence suggesting that unlike Ins-1,3,4,5-P 4 , Ins-1,3,4,6-P 4 is a direct precursor of Ins-P 5 . Consistent with this assumption, [ 3 H]Ins-1,3,4,6-P 4 was converted to Ins-P 5 in electropermeabilized adrenal glomerulosa cells. These findings demonstrate that Ins-1,3,4,6-P 4 is an intermediate link between InsP 3 metabolism and the higher inositol phosphates detected in several tissues.
Optimal timing in the problem of family farm transfer from parent to child: an option value approach

Abstract The optimal time for transferring the family farm from parent to child is modeled in an option value framework. It is assumed that parents have the ability to wait and enrich their information set before making the decision when to transfer the farm to a succeeding child rather than making a prompt decision. The results indicate that the optimal timing depends on the wedge between the parents' critical level of utility and disutility from the farm transfer to a succeeding child. The arguments of parents' utility function are country/culture and family-specific.
An Exploratory Factor Analysis of Coping Styles and Relationship to Depression Among a Sample of Homeless Youth

The extent to which measures of coping adequately capture the ways that homeless youth cope with challenges, and the influence these coping styles have on mental health outcomes, is largely absent from the literature. This study tests the factor structure of the Coping Scale using Exploratory Factor Analysis (EFA) and then investigates the relationship between coping styles and depression using hierarchical logistic regression with data from 201 homeless youth. Results of the EFA indicate a 3-factor structure of coping, which includes active, avoidant, and social coping styles. Results of the hierarchical logistic regression show that homeless youth who engage in greater avoidant coping are at increased risk of meeting criteria for major depressive disorder. Findings provide insight into the utility of a preliminary tool for assessing homeless youths' coping styles. Such assessment may identify malleable risk factors that could be addressed by service providers to help prevent mental health problems.
10 000 yr record of extreme hydrologic events

Well-dated lacustrine sediments provide a hydrologic record indicating that the frequency and magnitude of runoff events, and by inference, storms, have varied over the past 10 k.y. in northern New England. We used five sediment cores and radiocarbon dating to develop a chronology of Holocene hydrologic events for the Ritterbush Pond basin, northern Vermont. Chemical and physical analyses allow us to identify 52 distinct layers of predominately inorganic sediment that represent terrestrially derived material delivered to the pond by runoff events. The thickness of some layers suggests hydrologic events at least equal in size to, and probably much larger than, any storm or flood recorded during nearly 300 yr of written regional history. Layer thickness and frequency and, by analogy, storm size and recurrence, change through the Holocene. The largest events occurred 2620, 6840, and 9440 calibrated 14C years before present (cal 14C yr B.P.). The most frequent hydrologic events occurred in three periods: 1750 to 2620, 6330 to 6840, and >8600 cal yr B.P. The recurrence interval of layer deposition during stormy periods averages 130 ± 100 cal yr, whereas the recurrence interval during less stormy periods is longer, 270 ±170 cal yr. The Ritterbush Pond event record illustrates the potential of inorganic lacustrine sediment to serve as a proxy record for estimating paleoflood frequency and deciphering climate change.
Systematic integration of design methods

As software becomes more complex, designers are attempting to integrate design methods so they can start with a clear and accurate specification. Although designers typically commit to one method, they often find that its notation is not rich enough to express semantic concepts such as data persistence or that it lacks the guidance needed to choose design entities, such as objects or classes. Consequently, they attempt to borrow useful ideas and notations from other methods. Design method integration has many benefits, but designers lack a framework to make such efforts more systematic and cost effective. The author describes a possible framework and uses it to guide the integration of the Booch and OMT design methods.
Human aldehyde dehydrogenase: chromosomal assignment of the gene for the isozyme that metabolizes γ-aminobutyraldehyde

A cDNA clone of the E3 isozyme of human liver aldehyde dehydrogenase consisting of a 1320-base pair (bp) coding region and a 180-bp non-coding region at the 3′ end was used for chromosomal localization of the E3 gene. Using a panel of human/hamster somatic cell hybrids we have localized, the gene coding for the E3 isozyme to human chromosome 1.
The dopamine hypothesis of schizophrenia: limbic interactions with serotonin and norepinephrine.

The "dopamine hypothesis" of schizophrenia has been the predominant guiding theoretical construct for driving studies of the neurobiology of schizophrenia. There has, however, been much interest in the contributions of non-dopamine systems to the clinical symptoms of schizophrenia, in particular, norepinephrine and serotonin. However, direct evidence for altered transmission in monoamine systems has been quite limited. In part this reflects a focus on specific brain regions for different transmitters, in contrast to a "neural systems" approach. Thus, evidence for the dopamine hypothesis has been derived from studies of the basal ganglia in schizophrenic cases and infrequently from other (e.g. cortical) regions. Recent studies have suggested that disturbances in the organization or development of the temporal lobe may underlie certain aspects of the symptoms of schizophrenia In particular, the hippocampus may show cellular loss or disturbances in cell orientation. These results are supported by the work that has identified neuropsychological and in vivo brain disturbances in schizophrenia specific to the medial temporal lobe. However, not all cases show such pathology and it is likely that these disorders could, in addition, involve an important afferent and/or efferent system associated with the temporal lobe. This model is based on the currently held view that parallel cortico-striatal-pallidal-thalamo circuits form an important basis for information processing in the brain. One such circuit involves the primary efferent of the hippocampus, the subiculum, and associated cortical regions that project onto the ventral striatum. Many of the cortical regions that project directly to the ventral striatum also project to the hippocampus via the entorhinal cortex. These include the anterior cingulate, posterior cingulate, superior temporal cortex, and inferior temporal cortex. The ventral striatum, made up of the nucleus accumbens, olfactory tubercle, and ventral putamen, has as its target the ventral pallidum. The ventral pallidum projects to the medial dorsal nuclei of the thalamus, which, in turn, projects to the anterior prefrontal cortical area. This loop has been referred to as the limbic loop. The patterns of innervation and expression of monoamine receptors in the brain have been delineated for the non-human primate and are being unraveled in the human. We, and other, have described the patterns of receptor expression in the limbic circuit. However, few studies have been published to date that detail what the neurochemical counterparts of the neuronal and neuropsychological disturbances in the limbic circuit might be. We have explored the possibility that monoamine systems are altered at more than one synaptic station in this circuit.(ABSTRACT TRUNCATED AT 400 WORDS)
Ultrastructure of matrix vesicles and mineral in unfixed embryonic bone

Abstract Femurs of seven-day-old chick embryos were prepared by frozen thin-sectioning and conventional embedding methods and examined by electron microscopy. A collar of bone mineral on the cartilage anlage and a layer of osteoid containing mineral deposits were observed in the frozen thin-sections but not in conventionally prepared tissue. Numerous vesicles and nodules were present in the osteoid and they contained mineral in both the amorphous and crystalline forms. Vesicles and nodules in many stages of mineralization were present and it was possible to arrange them in a sequence of maturation from early, slightly mineralized matrix vesicles to heavily mineralized nodules. This may reflect the sequence of events which occurs in vivo . Crystals within vesicles were frequently found in parallel arrangement. There was no evidence of crystal formation along collagen fibers at this early stage or mineralization. Qualitative electron microprobe analysis of nodules revealed the presence of sodium, magnesium, phosphorus, chlorine, potassium and calcium while adjacent regions of matrix contained the same elements but were deficient in phosphorus.