cssi/SciSciGPT-SciSciNet huggingface dataset:
GABA Levels are Reduced in the Thalamus of Patients with Cervical Dystonia (P6.031)

Objective: Determine if gamma-aminobutyric acid (GABA) levels are abnormal in the thalamus and insula of patients with cervical dystonia (CD) compared to healthy controls (HC), and whether GABA levels in these brain regions are linked to dystonia severity. Background: A growing body of research supports that a key pathogenic mechanism underlying adult-onset focal dystonia is a reduction in inhibitory control over the sensorimotor network. We recently found GABA A receptor binding was reduced in the thalamus of patients with CD, and that levels of GABA A binding in the insula correlated with dystonia severity. Whether these GABA A binding changes in CD are associated with abnormal GABA levels is not known. Design/Methods: Ten CD patients (7F; 66.4±8.0 yrs) and six HC (5F; 66±8.3 yrs) underwent magnetic resonance spectrosopy on a 3T MRI. GABA levels and the ratio of GABA to levels of glutamate were calculated from single voxels placed in the right thalamus and left insula, and then compared using two-sample two-tailed t-tests. Pearson’s coefficient was used to test for correlations between GABA levels and dystonia severity as measured by the Toronto Western Spasmodic Torticollis Rating Scale. Significance was defined as a p Results: Compared to HC, GABA levels were decreased in the thalamus of CD patients (1.11±0.26 vs. 1.42±0.22, p =0.028), but not in the insula (0.64±0.19 vs. 0.72±0.16, p =0.40). GABA/glutamate ratios were also decreased in the thalamus of CD patients (0.23±0.06 vs. 0.30±0.05, p =0.027), but not in the insula (0.11±0.03 vs. 0.13±0.04, p =0.22). No significant correlations were found between GABA levels and dystonia severity. Conclusions: Decreased thalamic GABA levels and GABA/glutamate ratio in the thalamus provide further evidence of reduced inhibitory control over sensorimotor network function in CD. In combination with our finding of reduced thalamic GABA A binding in CD, the pathogenesis of dystonia may involve an abnormal regulation of GABA signaling. Disclosure: Dr. Groth has nothing to disclose. Dr. Brown has nothing to disclose. Dr. Shelton has nothing to disclose. Dr. Berman has nothing to disclose.
Optimized TEM Horn Impulse Receiving Antenna

Impulse receiving antennas are usually designed for ultra-wideband applications involving high-fidelity sensing of incident impulsive electromagnetic fields. These antennas may be utilized in advanced radar and information warfare systems, such as in the receive portion of impulse radar systems, or as stand-alone sensors for ultra-wideband direction finding. Impulse receiving antennas can also be used for measurement of field strength and waveform type being produced by high-power microwave sources or by natural and man-made EMP generators.
Anti-mutagenic activity of Methyl Sulfonyl Methane (MSM) in ICR mice

4814 Inhibiting mutagenicity in experimental animals can provide an end point to evaluate the anti-mutagenic activity and safety of chemopreventive agents, and to predict their protective efficacy in humans. In this study, we studied the inhibitory ability of Methyl Sulfonyl Methane (MSM) on micronuclei (MN) formation of erythrocytes (ETCs) in bone marrow, induced by cyclophosphamide (CPA), a well-known anticancer drug that is mutagenic. MSM is a nutritional supplement used for pain relief. It is naturally found in food and in the human body. Our previous study has demonstrated that MSM possesses a cancer preventive activity in DMBA-induced mammary gland tumors of female SD rats. In this study, the inhibitory effect of MSM on MN formation induced by CPA was analyzed. Thirty 22-24g ICR mice were divided into 5 groups: control, 6.25, 12.5, 25, and 50 mg of CPA, 3 males and 3 females in each group. The control group was given 0.1ml/10 g body weight of saline by i.p. The other groups were given 6.25, 12.5, 25, and 50 mg/kg of CPA in saline by i.p. All animals were sacrificed by cervical dislocation at the 24th hour after CPA administration. The frequency of MN in bone marrow erythrocytes was determined under the light microscope (LM) at 1000X. The frequency of MN was 0.85 in the control group, 5.8, 9.4, 15.3, and 28.5 per 1000 ETC corresponding to the four doses of CPA respectively. The result indicated that 25 mg/kg CPA provided the optimum level of mutagenicity, which was chosen to be used for next experiment. Thirty 22-24 g ICR mice were divided into 5 groups: 2 untreated controls, and 3%, 5%, and 8% MSM groups. Each group contained 3 males and 3 females. MSM was supplied for 1 week in drinking water. On the 7th day, 25 mg/kg CPA was given by i.p. to all animals except the negative control group. All animals were sacrificed by cervical dislocation at the 24th hour after CPA administration. The frequency of MN was assessed under LM. MN in the negative control, positive CPA control, and 3%, 5%, and 8% MSM group were 0.85±1.03, 15.3±6.6, and 4.2±1.9, 4.6±1.5, and 2.3±1.5 per 1000 ETCs, respectively. The data indicated in an extremely significant manner that there was a 73%, 70%, and 85% inhibition of MN formation in the three doses of MSM compared to that of the positive controls. In conclusion, MSM is able to inhibit MN formation in bone marrow erythrocytes of ICR mice. Therefore, MSM may strongly protect the bone marrow from the toxicity of anticancer drugs and is safe for long-term preventive purposes. This data provides evidence, for the first time, of in vivo anti-mutagenicity of MSM on mammalian cells.
Do Experts and Novices Agree? A Qualitative Review of the 2016 INACSL Standards of Best Practice: SimulationSM Reviewer Feedback

Abstract Background The International Nursing Association for Clinical Simulation and Learning published Standards of Best Practice: SimulationSM for the purpose of advancing the science of simulation and sharing best practices. Methods This study used a qualitative description to answer the primary research question, how does the type of feedback given by the expert reviewers differ compared with the novice reviewers? Results There were five main themes identified from the reviews: consistency, theory/objectives, reliability/validity, clearly defining expectations, and excellence. Novices and experts had similar themes but differences in details. Conclusions Both types of feedback are important to obtain because users of the standards are both experts and novices.
Occupational Groups and Environmental Justice: A Case Study in the Bronx, New York

We used spatial analyses to examine exposure of people in vulnerable occupational groups to neighborhood-level environmental pollutants in the Bronx borough of New York City. Five-year estimates of environmental ambient exposures (derived from land use regression models for PM2.5 [particulate matter with an aerodynamic diameter ≤2.5 µm] and black carbon) and demographic and occupational variables were harmonized at the census tract level. Correlations revealed that areas with high environmental exposures also had high proportions of people in service industries and manufacturing and high proportions of socioeconomically vulnerable populations. This combination of vulnerabilities may be cumulative, suggesting residents could have high occupational and residential exposures in addition to sociodemographic-related inequity.
Secure Attachment and Career Indecision: The Mediating Role of Emotional Intelligence:

Over the past few decades, researchers have been trying to understand the career decision-making process from interpersonal and affective perspectives. Previous findings suggest that secure attachm...
Changes in marrow adipose tissue with short-term changes in weight in premenopausal women with anorexia nervosa.

Objective In anorexia nervosa, a psychiatric disease characterized by self-induced starvation and a model of chronic undernutrition, levels of subcutaneous (SAT) and visceral (VAT) adipose tissue are low, whereas marrow adipose tissue (MAT) levels are elevated compared to normal-weight women. The reason for this paradoxical elevation of an adipose tissue depot in starvation is not known. We sought to understand changes in MAT in response to subacute changes in weight and to compare these changes with those of other fat depots and body composition parameters. Design and methods We conducted a 12-month longitudinal study including 46 premenopausal women (n = 26 with anorexia nervosa and n = 20 normal-weight controls) with a mean (s.e.m.) age of 28.2 ± 0.8 years. We measured MAT, SAT, VAT and bone mineral density (BMD) at baseline and after 12 months. Results At baseline, SAT (P < 0.0001), VAT (P < 0.02) and BMD of the spine and hip (P ≤ 0.0002) were significantly lower and vertebral and metaphyseal MAT (P ≤ 0.001) significantly higher in anorexia nervosa compared to controls. Weight gain over 12 months was associated with increases not only in SAT and VAT, but also epiphyseal MAT (P < 0.03). Changes in epiphyseal MAT were positively associated with changes in BMD (P < 0.03). Conclusions In contrast to the steady state, in which MAT levels are higher in anorexia nervosa and MAT and BMD are inversely associated, short-term weight gain is associated with increases in both MAT and BMD. These longitudinal data demonstrate the dynamic nature of this fat depot and provide further evidence of its possible role in mineral metabolism.
The effect of homologous marrow transplantation on the survival of monkeys following sublethal whole-body radiation.

Homologous bone marrow given to the rhesus monkey 30 hours after LD 10 radiation dose of 550r increased the mortality rate expected from the radiation alone. The symptoms produced resembled those obtained at higher doses of radiation. The effects of marrow given 48 hours after radiation differed little from those produced by the radiation alone. It is suggested that the 30-hour injection elicited a more violent reaction or that the reaction occurred during a more decisive time in the process of recovery.
'We've Been Thinking You Were Stupid All This Time:' Racial Microinsults and Microinvalidations in a Rural Southern High School.

Racial microaggressions in school have gained increasing attention in recent years. However, scholars often neglect students’ experiences of racial microaggressions in rural schools. To fill this g...
An Accelerated Latent Class Growth Curve Analysis of Adolescent Bonds and Trajectories of Depressive Symptoms

Relationships during adolescence are relevant predictors of depressive symptoms. This project studied how adolescent bonds and connectedness predict the likelihood of latent class membership on various depressive symptoms trajectories. From the restricted use National Longitudinal Study of Adolescent to Adult Health dataset (N = 7196), this study examined a nationally representative sample ranging from ages 11–31 (50.5% female, 42.2% non-white), using a latent class growth analysis with an accelerated design. Measures included the CES-D for tracking depressive symptoms longitudinally, “parent-child bond questions” from the Relations with Parents scale, and “school connectedness” questions and “time spent with friends” questions created by Add Health. Findings show two trajectories of depressive symptoms: one characterized (83%) relatively low, stable depressive symptoms over time, and the other (17%), moderate, fluctuating symptoms. Higher parent-child bond and higher school connectedness were related to a greater likelihood of being on the low-level stable trajectory. Time spent with friends was not significantly related to the likelihood of being on either trajectory. Clinical implications include the necessity of targeting adolescent bond relationships that could affect the trajectory of depression over time. Specifically, capitalizing on adolescents’ school connectedness and parent-child bond is essential for both short-term and long-term mood health. Implications for research indicate a need for longitudinal data collection to target the level of connectedness adolescents feel with their friends to examine whether the strength of the relationship influences depressive symptoms trajectories where time spent with friends did not.
A Multi-Stakeholder Co-Design Approach to Making Strategies for Community Development Harnessing Emerging Technologies

Emerging technologies will be key drivers of the global economy in the upcoming decades and fundamentally shape how people live and work in the future world. It is imperative that local communities can, based on their respective realities, identify priorities and make effective strategies to direct the community development harnessing emerging technologies. This work studies the case of Kingsville, a medium-sized city in South Texas without a technology-intensive current economy or a technology-attracting cultural tradition. Kingsville2050 initiative has been launched to generate future-oriented, out-of-box-thinking ideas and to build innovation capacity within the community. The first and foremost problem is how to reach synergy among community stakeholders and link them to selected emerging technologies with the best fit. This work proposes a workshop design using multi-stakeholder co-design approach to making community development strategies that aim to take full advantage of emergent technologies. During a workshop, which is typically a one-day event, stakeholders from different backgrounds discuss and present their opinions on the challenges of bridging the gap between community realities and emergent technologies. Following the co-design methodology, the workshop planning process also integrates other tools, i.e., design-thinking and strategic visualization, to promote the emergence of creative solutions to address the above challenges. These proposed solutions can later be a valuable reference for policymakers, city planners, educators, local businesses, and other stakeholders.
Reliability estimation considering multi-stress monotonic degradation test data with non-constant scale parameter

The accelerated degradation testing (ADT) has been proven to be effective in quickly assessing the reliability of a highly reliable product, especially during product design and development stage. ...
Postictal stertor: Associations with focal and bilateral seizure types.

Abstract Objective The objective of the present study was to determine the association between respiratory stertor and focal and bilateral seizure types. Methods We characterized ictal and postictal behaviors during symmetric bilateral tonic–clonic (TC) and asymmetric TC seizures in the Johns Hopkins University (JHU) epilepsy monitoring unit, comparing these to focal unaware seizures. We measured the presence and duration of postictal stertorous respirations, postictal generalized electroencephalographic suppression (PGES), immobility/motor dysfunction, and encephalopathy and determined their associations and relationship to seizure types. Results In initial seizures recorded in 80 consecutive patients, bilateral symmetric TC seizures (N = 35) were strongly associated with PGES (97%, p Conclusion Bilateral symmetric TC seizures, but not focal unaware seizures, have postictal stertor during PGES. Severe postictal encephalopathy, however, is also associated with motor dysfunction and stertor. Stertor appears to be a compensatory postictal respiratory pattern for ictal/postictal hypoxemia and occurs with PGES or postictal encephalopathy.
Prospective isolation of human fibroadipogenic progenitors with CD73

Skeletal muscle relies on coordination between myogenic and non-myogenic interstitial cells for homeostasis and for regeneration and response to injury. Fibroadipogenic progenitors (FAPs) have recently been recognized as key modulators of signaling to promote myogenesis following injury. FAPs are also responsible for the fibrosis and fatty replacement of muscle tissue seen in many diseased states. While extensive use of surface markers to purify FAPs has been undertaken in the mouse system, in particular PDGFRA, markers for human FAPs are less well understood. Here, we show that CD73 can be used as a single positive marker to purify FAPs from the lineage-negative (CD45-neg, CD31-neg) fraction of skeletal muscle mononuclear cells. Although CD73 was previously found to be expressed in cultured myogenic cells, we find that this marker is only acquired upon culture and that the CD73+ fraction of human skeletal muscle has no myogenic activity. We show that Lin-neg CD73+ cells from human muscle undergo fat differentiation as well as fibrogenesis when exposed to appropriate activating signals in vitro. This simple single positive marker approach effectively enables isolation of human FAPs from fresh human skeletal muscle biopsies.
Solar-Blind Ultraviolet Photodetectors Based on Vertical Graphene-Hexagonal Boron Nitride Heterostructures

Photodetectors operating in the ultraviolet (UV) play a pivotal role in applications such as ozone monitoring and biosensing. One key factor to successfully implementing such photodetectors is that they must be solar-blind to avoid detecting ambient visible and infrared light. Unfortunately, UV photodetectors based on silicon and other typical semiconductors are not natively solar-blind, since their band gap energies are in the visible range. Hexagonal boron nitride (h-BN) is an example of a wide band gap semiconductor which shows promise for use as the absorbing medium in a UV photodetector device, since its band gap is wide enough to make it inherently insensitive to light in the visible range and above. Here we report on the fabrication and characterization of a graphene-h-BN-heterostructure photodetector which utilizes a vertical geometry, in principle allowing for highly scalable production. We find that our device shows a finite photoresponse to illumination by a 254nm light source, but not to a 365nm source, thus suggesting that our device is solar-blind.
Nietzsche's Dawn: Philosophy, Ethics, and the Passion of Knowledge

The first focused study of Nietzsche's Dawn, offering a close reading of the text by two of the leading scholars on the philosophy of Nietzsche Published in 1881, Dawn: Thoughts on the Presumptions of Morality represents a significant moment in the development of Nietzsche’s philosophy and his break with German philosophic thought. Though groundbreaking in many ways, Dawn remains the least studied of Nietzsche's work. In Nietzsche's Dawn: Philosophy, Ethics, and the Passion of Knowledge, authors Keith Ansell-Pearson and Rebecca Bamford present a thorough treatment of the second of Nietzsche’s so-called “free spirit” trilogy. This unique book explores Nietzsche’s philosophy at the time of Dawn's writing and discusses the modern relevance of themes such as fear, superstition, terror, and moral and religious fanaticism. The authors highlight Dawn's links with key areas of philosophical inquiry, such as "the art of living well," skepticism, and naturalism. The book begins by introducing Dawn and discussing how to read Nietzsche, his literary and philosophical influences, his relation to German philosophy, and his efforts to advance his "free spirit" philosophy. Subsequent discussions address a wide range of topics relevant to Dawn, including presumptions of customary morality, hatred of the self, free-minded thinking, and embracing science and the passion of knowledge. Providing a lively and imaginative engagement with Nietzsche's text, this book: -Highlights the importance of an often-neglected text from Nietzsche's middle writings -Examines Nietzsche's campaign against customary morality -Discusses Nietzsche's responsiveness to key Enlightenment ideas -Offers insights on Nietzsche's philosophical practice and influences -Contextualizes a long-overlooked work by Nietzsche within the philosopher's life of writing Like no other book on the subject, Nietzsche's Dawn: Philosophy, Ethics, and the Passion of Knowledge is a must-read for advanced undergraduate and graduate students, instructors, and scholars in philosophy, as well as general readers with interest in Nietzsche, particularly his middle writings.
Minimally Invasive Removal of a Lipoleiomyoma from a Reproductive-Age Woman

Background: A lipoleiomyoma is a rare benign tumor that is comprised of both smooth-muscle and adipose tissue. Case: A 26-year-old nulligravida presented with pelvic pain, bloating, constipation, u...
Does Service Provider Matter During a Pandemic? COVID-19 Cases and Deaths Among Nonprofit vs. For-Profit Assisted Living Facilities in Florida

When COVID-19 hit the U.S. in early 2020, individuals aged 65+ were identified as a higher risk population. In Florida, Governor DeSantis issued Emergency Order 20-006 to prohibit visitation to facilities housing groups of high-risk people, including assisted living facilities (ALFs). Regardless, 672 ALFs of the 3,119 in Florida had reported at least one positive case of COVID-19 by a resident or staff member as of June 30, 2020. Prior research has highlighted the differences in service delivery between nonprofits and for-profits. This manuscript fills the void of minimal research on nonprofit service delivery during a pandemic. We find that nonprofit ALFs have experienced fewer positive cases of COVID-19 among their residents, but there is no difference between nonprofit and for-profit ALFs in terms of resident deaths. We also find evidence that ALF staff are infecting residents, and the provision of nursing services matters for protecting ALF residents from COVID-19.
Agrochemicals-Induced Dopaminergic Neurotoxicity: Role of Mitochondria-Mediated Oxidative Stress and Protein Clearance Mechanisms

Parkinson’s disease (PD) is the second most common progressive neurodegenerative disorder that is characterized by the progressive loss of substantia nigral dopaminergic neurons resulting in the pronounced depletion of striatal DA levels which subsequently leads to the expression of cardinal features of PD including tremor, bradykinesia, rigidity and postural instability. The mechanisms underlying the selective loss of dopaminergic neurons remain poorly understood; however, studies conducted in post mortem PD brains and experimental PD models have implicated oxidative stress and mitochondrial dysfunction in the mechanism of dopaminergic neurodegeneration. In recent years, the etiology of several neurodegenerative diseases including PD has been linked to low dose and chronic exposure to a variety of agrochemicals including paraquat, rotenone and dieldrin. Here we discuss how several of these pesticides share common mechanistic events, including oxidative stress, mitochondrial impairment/complex I inhibition, abnormal protein aggregation and post translational modifications (PTMs) of proteins including α-synuclein, as well as dopaminergic cell death. Furthermore, intersecting and parallel effects of environmental neurotoxicants on protein clearance mechanisms and mitochondrial function are addressed and hence provide novel insights that might be beneficial in the development of targeted therapies for PD.
A New Framework for Spatio-temporal Climate Change Impact Assessment for Terrestrial Wildlife

We describe a first step framework for climate change species’ impact assessments that produces spatially and temporally heterogeneous models of climate impacts. Case study results are provided for great gray owl (Strix nebulosa) in Idaho as an example of framework application. This framework applies species-specific sensitivity weights to spatial and seasonal models of climate exposure to produce spatial and seasonal models of climate impact. We also evaluated three methods of calculating sensitivity by comparing spatial models of combined exposure and sensitivity. We found the methods used to calculated sensitivity showed little difference, except where sensitivity was directional (i.e., more sensitive to an increase in temperature than a decrease). This approach may assist in the development of State Wildlife Action Plans and other wildlife management plans in the face of potential future climate change.
An Empirical Examination of CEO Relative Performance Evaluation Incentives and R&D

I use hand-collected data from 1995-2009 to examine whether long-term RPE incentives for CEOs are associated with investment in R&D and whether compensation committees grant long-term RPE incentives when there is risk of under-investment in R&D. Companies with CEOs who are granted long-term RPE incentives with a stock return performance measure have higher levels of R&D, particularly those at greater risk of under-investment. Long-term RPE incentives are also negatively associated with under-investment in R&D as measured by differences from predicted levels. The results related to compensation committees indicate that grants of long-term RPE incentives are more likely when there are financial constraints and when there are consecutive years for which R&D expenditures are less than the prior year or less than that of industry peers. These results suggest that compensation committees monitor risks of under-investment and their grants of long-term RPE incentives have the desired effect of inducing greater R&D.
Multiechelon Multiproduct Inventory Management

This article summarizes the inventory management literature within the context of multiechelon systems. The optimal inventory policies for the single-installation under discrete-time and continuous-time are described, followed by the optimal inventory policies for the serial multiechelon system, with the interpretation of the associated induced penalty cost functions. The assembly system's optimal policy translation to an “equivalent” serial system is demonstrated and discussed. Although the optimal inventory policies of distribution systems are generally not known, the performance of various simple heuristics are then discussed. Keywords: bill of materials; economic order quantity; discrete-time model; base-stock; induced penalty cost function
Development and Plasticity

Publisher Summary This chapter summarizes new and exciting development and plasticity of catecholaminergic systems that can be summed up by the term neurotrophic factors. There are reports of novel proteins, of new members, and even new gene families of factors. The role of catecholamines in learning and memory promises further insights into their possible function in plasticity responses of the central nervous system. The chapter discusses on the gamut from factors that determine the fate of neural crest cells to factors that determine that of those cells become catecholaminergic. The neural crest arises as a result of inductive interactions between neural and nonneural ectoderm; among the factors involved are sonic hedgehog (SHH), BMP-4 and BMP-7 (bone morphogenetic proteins), and a novel gene cloned in her laboratory, named NP-1. The BMPs, also members of the transforming growth factor- β (TGF β) family, not only affect neural crest cell induction, but also are involved in induction of tyrosine hydroxylase (TH) in the neural crest-derived sympathetic neurons. SHH can act first in the generation of neuronal progenitor cells and then in the differentiation of a population of those cells to become dopaminergic. In culture, those neurons become dependent on a member of the TGF β family, possibly GDNF (glialderived neurotrophic factor), neurturin, or TGF β 2 or - β 3. All of these related proteins can support survival of dopaminergic neurons in culture. The apparent stability of and/or the long-lasting response to a neurotrophic factor such as GDNF, as well as its ability to affect an injured neuron 2-3 wk following injury, have profound implications for the potential of gene therapy. Moreover, catecholamines play a fundamental role in a variety of forms of learning and memory that of course, are the ultimate examples of plasticity responses in the nervous system.
Abstract 5566: Functional new insights into the regulation of the androgen receptor by PMEPA1/NEDD4-1 in prostate cancer

Introduction: Androgen receptor (AR) stability has been shown to be regulated by MDM2 E3 ubiquitin ligase. Our data suggest a role for PMEPA1 and NEDD4-1 in the regulation of AR protein in prostate cancer cells. The AR inducible PMEPA1 recruits NEDD4-1, an E3 ubiquitin ligase, to degrade AR. Decreased or absent PMPEA1 was observed in more than 65% of prostate tumors. PMEPA1 depleted transfectant is established in LNCaP cells with a shRNA lentivirus system and shown elevated AR protein levels, AR signaling and increased cell growth. In the current study, we investigated the growth and AR signaling of PMEPA1 depleted prostate cancer cells in the presence of AR inhibitors. Also we investigated the role of PMEPA1 silencing by DNA methylation in the regulation of AR. Methods: PMEPA1 depleted LNCaP cells were treated with AR inhibitors (MDV3100 or bicalutamide) in the presence or absence of the synthetic androgen R1881. Cell growth was monitored by cell counting, BrdU incorporation, colony plating and soft agar assays. Cell cycle was analyzed with propidium iodide staining based flowcytometry. AR, PMEPA1, PSA proteins were assessed by immunoblot assay. Methylation of the PMEPA1 gene was evaluated in LCM-enriched tumor samples by combing precipitation of methylated-DNA and methylation-sensitive restriction enzyme digestion (COMPARE-MS). The transcript levels of PMEPA1 gene was assessed by qRT-PCR. Results: PMEPA1 depleted LNCaP cells are more resistance to growth inhibition by MDV3100 or bicalutamide in both hormone and hormone-depleted conditions, which demonstrated stronger BrdU incorporation abilities, cell plating efficiency and colony formation capacities in soft agar under MDV3100 or bicalutamid treatment compared to controls. The half life of AR was increased, and more cells in S-phase and less apoptotic cells in PMEPA1 depleted LNCaP cells. Methylation of PMEPA1 gene and mRNA levels showed significant correlation in prostate tumors (n=77, P=0.001). The higher frequency of PMEPA1 gene methylation was noticed in Caucasian American patients. Conclusions: PMEPA1 depleted prostate cancer cells develop increased resistance to AR inhibitors through enhanced AR signaling. Silencing of PMEPA1 may contribute to AR activation in prostate cancer. These data highlight that PMEPA1 deficiency may confer resistance to AR inhibitors during prostate cancer progression. This study is supported by the NIH grant (R01CA106653) to SS. Citation Format: Hua Li, Shashwat Sharad, Lakshmi Ravindranath, Michael Haffner, Daniel Heidenberg, Srinivasan Yegnasubramanian, Yongmei Chen, Ahmed Mohamed, Alagarsamy Srinivasan, Gyorgy Petrovics, Shiv Srivastava. Functional new insights into the regulation of the androgen receptor by PMEPA1/NEDD4-1 in prostate cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5566. doi:10.1158/1538-7445.AM2014-5566
Stepping-stone detection via request-response traffic analysis

In this paper, we develop an algorithm that may be used as a steppingstone detection tool. Our approach is based on analyzing correlations between the cumulative number of packets sent in outgoing connections and that of the incoming connections. We present a study of our method's effectiveness with actual connections as well as simulations of time-jittering (introduction of inter-packet delay) and chaff (introduction of superfluous packets). Experimental results suggest that our algorithm works well in the following scenarios: (1) distinguishing connection chains that go through the same stepping stone host and carry traffic of users who perform similar operations at the same time; and (2) distinguishing a single connection chain from unrelated incoming and outgoing connections even in the presence of chaff. The result suggests that timejittering will not diminish our method's usefulness.
Potassium-Coupled Chloride Cotransport Controls Intracellular Chloride in Rat Neocortical Pyramidal Neurons

Chloride (Cl(-)) homeostasis is critical for many cell functions including cell signaling and volume regulation. The action of GABA at GABA(A) receptors is primarily determined by the concentration of intracellular Cl(-). Developmental regulation of intracellular Cl(-) results in a depolarizing response to GABA in immature neocortical neurons and a hyperpolarizing or shunting response in mature neocortical neurons. One protein that participates in Cl(-) homeostasis is the neuron-specific K(+)-Cl(-) cotransporter (KCC2). Thermodynamic considerations predict that in the physiological ranges of intracellular Cl(-) and extracellular K(+) concentrations, KCC2 can act to either extrude or accumulate Cl(-). To test this hypothesis, we examined KCC2 function in pyramidal cells from rat neocortical slices in mature (18-28 d postnatal) and immature (3-6 d postnatal) rats. Intracellular Cl(-) concentration was estimated from the reversal potential of whole-cell currents evoked by local application of exogenous GABA. Both increasing and decreasing the extracellular K(+) concentration resulted in a concomitant change in intracellular Cl(-) concentration in neurons from mature rats. KCC2 inhibition by furosemide caused a change in the intracellular Cl(-) concentration that depended on the concentration of pipette Cl(-); in recordings with low pipette Cl(-), furosemide lowered intracellular Cl(-), whereas in recordings with elevated pipette Cl(-), furosemide raised intracellular Cl(-). In neurons from neonatal rats, manipulation of extracellular K(+) had no effect on intracellular Cl(-) concentration, consistent with the minimal KCC2 mRNA levels observed in neocortical neurons from immature animals. These data demonstrate a physiologically relevant and developmentally regulated role for KCC2 in Cl(-) homeostasis via both Cl(-) extrusion and accumulation.
Protection and Advocacy for Individuals with Mental Illness Act

Abstract This study explored the perceptions of one state's policy stakeholders toward the implementation of the Protection and Advocacy for Individuals with Mental Illness Act (PAIMI Act). This congressional act established state programs authorized to investigate abuse, neglect, and civil rights violations against individuals with mental illness in residential facilities. A qualitative case study approach was selected to study the perceptions of the impact of this law. Participants were chosen using a maximum variation sampling of four diverse stakeholder groups. In-depth interview responses were developed into a series of proposed assertions regarding the impact of the PAIMI Act.
Impact of current technologies (TOF, PSF, solid state detector) on the quantitative accuracy of PET/CT

2159 Objectives The increasing use of PET/CT as a quantitative imaging tool demands highly accurate and reproducible readouts. Recent advances which improve photon detection, such as Time of flight (TOF), Solid state Detector (SD), and reconstruction with Point Spread Function (PSF), impact quantification in unique ways. We evaluated the impact on accuracy of TOF, PSF, analog and digital detector acquired phantom PET/CT data. Methods Two Jaszczak phantoms with hollow sphere inserts were filled with 18F for simultaneous imaging on current technology PET/CT systems (Siemens Biograph mCT, Philips Gemini TF). The data using the new solid state detector system (Philips Vereos) will also be reported. Acquisition modes were compared between with and without TOF acquisition and with and without PSF correction. The maximum activity concentration of each sphere was measured and the Recovery Coefficient (RC) of each was calculated. Results TOF-acquired data were most accurate when measuring activity concentrations in spheres 2 ml or larger. The average RC in these spheres was 0.98 (ranging 1.16-0.86). In spheres of 1 ml or less the ability to distinguish between varying activity levels greatly diminished, the average RC was 0.61 in 1 ml spheres and 0.44 in 0.5 ml spheres. The acquisitions with a PSF correction tended to overestimate activity concentrations in all but the smallest sphere. These data were however able to distinguish between different concentrations regardless of object size. The average RC for spheres 1 ml and larger was 1.19 (ranging 1.41-0.98). The smallest sphere had an average RC of 0.86. Conclusions Significant differences in quantitative accuracy were revealed in the PET/CT data sets. TOF appears to improve the quantitative accuracy of measurements in larger objects, while PSF correction appears necessary for precision in smaller objects; solid state performed better than conventional photomultiplier detector. Research Support Wright Project TECH 10-012 and OIRAIN TECH 09-028
Noradrenergic blockade stabilizes prefrontal activity and enables fear extinction under stress

Stress-induced impairments in extinction learning are believed to sustain posttraumatic stress disorder (PTSD). Noradrenergic signaling may contribute to extinction impairments by modulating medial prefrontal cortex (mPFC) circuits involved in fear regulation. Here we demonstrate that aversive fear conditioning rapidly and persistently alters spontaneous single-unit activity in the prelimbic and infralimbic subdivisions of the mPFC in behaving rats. These conditioning-induced changes in mPFC firing were mitigated by systemic administration of propranolol (10 mg/kg, i.p.), a β-noradrenergic receptor antagonist. Moreover, propranolol administration dampened the stress-induced impairment in extinction observed when extinction training is delivered shortly after fear conditioning. These findings suggest that β-adrenoceptors mediate stress-induced changes in mPFC spike firing that contribute to extinction impairments. Propranolol may be a helpful adjunct to behavioral therapy for PTSD, particularly in patients who have recently experienced trauma.
Experimental Design Considerations in Pharmacokinetic Studies

Pharmacokinetic studies are conducted in experimental contexts to define pharmacokinetic relationships for new drugs that may be beneficial for patients and to enable the understanding the concentration-effect relationships. For both these purposes, an accurate description of pharmacokinetics is vital, which can be achieved by appropriate experimental design. This article describes some of the issues in the design of experimental models, which enable pharmacokinetic relationships to be established. Keywords: pharmacokinetic studies; experimental design; experimental models; sampling time
Detection of in vivo enzyme activity with CatalyCEST MRI

Purpose CatalyCEST MRI compares the detection of an enzyme-responsive CEST agent with the detection of an unresponsive “control” CEST agent that accounts for other conditions that influence CEST. The purpose of this study was to investigate the feasibility of in vivo catalyCEST MRI.
Get Them to Read, Get Them to Talk: Using Discussion Forums to Enhance Student Learning

Abstract A persistent question in undergraduate education is the question of getting students to prepare adequately prior to coming to class meetings. This article touches on some of the literature related to this “perennial issue” and then discusses the use of the Internet, via Course Management Software systems, as a solution this problem. As opposed to surprise quizzes and other such activities, this article shows that the use of technology can produce better quality preparation and more efficient use of class time. In the assignment, students are asked to post responses to thought questions on an internet discussion forum, which is read by the instructor prior to class and is a graded assignment. Before class, the instructor uses these postings to help prepare specific themes or discussion topics for class meetings. The article includes tabular data on the assignment's “costs and benefits” and a sample Discussion Forum. Alternative formulations of the assignment are also discussed for readers who migh...
Correlates of Daytime Sleepiness in Patients With Posttraumatic Stress Disorder and Sleep Disturbance

The purpose of this study was to describe the types of sleep problems reported and observed in patients with lifetime posttraumatic stress disorder (PTSD) and chronic sleep disturbance not due to apnea or other sleep disorders. Various forms of sleep disturbance can interfere with work, exercise and recreation, interpersonal relationships, and instrumental activities such as driving.1 Sleep-related problems in patients with PTSD and insomnia have included repetitive awakenings, nightmares, difficulties obtaining sufficient sleep, daytime sleepiness, and daytime dysfunction.2–4 Investigators have differed in their opinions regarding sleep disturbance in PTSD. One text on sleep disorders barely mentions PTSD.5 Daytime sleepiness, awakenings, and other forms of sleep disturbance are neither universal concomitants nor core features of PTSD.6,7 Although sleep disturbances are sometimes reported as cardinal symptoms in PTSD,8 2 studies, 1 using polysomnography9 and the other using actigraphy,10 failed to demonstrate objective evidence of sleep disturbance in posttrauma survivors. Despite these reports, most combat veterans and rape victims with PTSD whom we studied for several months to a year with a daily life charting instrument reported sleep disturbances.11 Our actigraphic study demonstrated that most veterans with PTSD and sleep disturbance had shortened sleep times (with prolonged sleep times in some cases) and/or increased awakenings12—factors that could cause daytime sleepiness. In order to study daytime sleepiness in people who had lifetime PTSD with current sleep disturbance, we sampled a mixed group of patients with diverse comorbid disorders and treatment histories, so as to obtain a sample reflecting common clinical practice. Our primary rationale for conducting this study was to assess the sleep problems associated with PTSD in the patient's own environment rather than in a monitored laboratory, which could ameliorate the sleep disturbance. Second, we wanted to observe the patients' sleep over several days or longer, since the sleep disturbance associated with PTSD can vary from day to day. Third, we wanted to employ both objective as well as subjective measures of sleep disturbance. This study tested the following hypotheses: Daytime sleepiness would be directly correlated with subjective and objective measures of sleep awakenings and sleep duration. Daytime sleepiness would be directly correlated with subjective assessment of sleep quality. Daytime sleepiness would be associated with increased depressive symptoms but not posttraumatic symptoms. Clinical Points ♦ Clinicians should inquire about symptoms of daytime sleepiness in patients with posttraumatic stress disorder (PTSD). ♦ In patients with PTSD, it appears that daytime sleepiness is related to a self-perception of daytime dysfunction.
Comparative biochemistry of proteases from a coelenterate.

Abstract 1. 1. An enzyme homologous with mammalian trypsin and chymotrypsin was isolated from Renilla reniformis, a coelenterate. 2. 2. Some of its properties, including amino acid composition, pH profile, temperature of maximum activity, requirements for stability and the effect of inhibitors were determined, and these were compared with those of other well-characterized trypsins. 3. 3. Evidence for a zymogen form was presented. 4. 4. The enzyme was found to be quite unstable, probably as a result of its high number of basic amino acid residues.
The glomerular basement membrane as a barrier to albumin

The glomerular basement membrane (GBM) is the central layer of the glomerular filtration barrier and is situated between endothelial cells and podocyte foot processes. The functional importance of the GBM versus that of podocytes and endothelial cells for establishing the glomerular filtration barrier to albumin is still debated. This Review discusses the proposed mechanisms whereby the GBM serves as the major albumin barrier and describes two genetic kidney diseases that target GBM components. The glomerular basement membrane (GBM) is the central, non-cellular layer of the glomerular filtration barrier that is situated between the two cellular components—fenestrated endothelial cells and interdigitated podocyte foot processes. The GBM is composed primarily of four types of extracellular matrix macromolecule—laminin-521, type IV collagen α3α4α5, the heparan sulphate proteoglycan agrin, and nidogen—which produce an interwoven meshwork thought to impart both size-selective and charge-selective properties. Although the composition and biochemical nature of the GBM have been known for a long time, the functional importance of the GBM versus that of podocytes and endothelial cells for establishing the glomerular filtration barrier to albumin is still debated. Together with findings from genetic studies in mice, the discoveries of four human mutations affecting GBM components in two inherited kidney disorders, Alport syndrome and Pierson syndrome, support essential roles for the GBM in glomerular permselectivity. Here, we explain in detail the proposed mechanisms whereby the GBM can serve as the major albumin barrier and discuss possible approaches to circumvent GBM defects associated with loss of permselectivity.
Towards an integrated land-sea stratigraphy of the Netherlands

Abstract The classification of rocks and sediments may be based on many types of stratigraphy; e.g. litho-, bio-, seismo-, chrono-, chemostratigraphy, and others. The boundaries of the various types of stratigraphy need not at all or seldom coincide. It is especially this last consideration that may cause problems, since this discrepancy in boundaries is very difficult to understand for those not professionally trained as geologists. Since TNO-NITG, as the Dutch Geological Survey, is an organisation for applied geosciences it is necessary that full notice is taken of this problem. A complete revision of the existing late Tertiary and Quaternary lithostratigraphy of the onshore part of the Netherlands, which was a mixture of various types of stratigraphies, was undertaken starting in 1997. At the same time the opportunity was taken to integrate this new scheme with the two other operational stratigraphies used by TNO-NITG. Important solutions in resolving some of the integration problems are outlined. An example of the relation between some of the newly established lithostratigraphic units with some of the seismostratigraphic ones used in the offshore part of the Netherlands is given. Finally an example of the implications of the new approach for the existing geological model is presented.
Microstructure and mechanical strength of snag-based solid liquid inter-diffusion bonds for 3 dimensional integrated circuits

Solid liquid inter-diffusion is a bonding technology that has been proposed at microscale for fabrication of ultrafine interconnects in high density and 3 dimensional integrated circuit packages. Due to very small size, bonds that are formed using this technology are very susceptible to process variations and thus reliability and quality of the bonds may deteriorate by small variations in the process. This study examines the effect of process parameters; temperature, bonding time, and pressure on the bond strength, microstructure, and intermetallic formation at the bonds. A full factorial experiment is designed and implemented on the process. Bonds are characterized using a micro-tester for mechanical strength and ductility. The microstructure of bonds formed under different process conditions are explored using scanning electron microscope, energy dispersive X-ray spectroscopy, and X-ray diffraction pattern to determine the bond thickness, elemental composition, copper concentration, and extent of copper diffusion and intermetallic compound. 1-dimensional phase lag modeling technique was used to estimate the time required for complete bond transformation to intermetallics. Results of these analyses show that temperature plays the strongest role in intermetallics formation and thickness. Bonds formed at higher temperatures and longer bonding time behaved more brittle and had higher strength. Pressure does not show a significant effect, and bonds that are formed under higher pressure show a slight reduction in bond strength with the same brittle behavior. This reduction is associated with formation of e phase of intermetallic and the lower strength between e and η phase. Modeling intermetallics formation for different bond thicknesses show that smaller bond thickness does not translate into much shorter time for complete transformation to intermetallics.