cssi/SciSciGPT-SciSciNet huggingface dataset:
The Externalizing Pathway to Borderline Personality Disorder in Youth

Borderline personality disorder (BPD) is a debilitating psychiatric disorder characterized by the presence of any five of nine symptoms from the Diagnostic and Statistical Manual of Mental Disorders (DSM-V; American Psychiatric Association, 2013). Symptoms include emotional instability and anger, impulsive and suicidal behaviors, interpersonal turmoil, as well as cognitive and identity disturbances. The severe nature of BPD, including a high rate of concurrent comorbid psychiatric disorders and physical health problems, and with suicide rates almost 50 times higher in those with BPD than in the general population, BPD is a major public health concern (Frankenburg & Zanarini, 2006; Grant et al., 2008; Holm & Severinsson, 2011). In light of the serious costs associated with this disorder, elucidating pathways that lead to BPD is of the utmost importance in order to ultimately prevent such suffering.
Constitutional Folk Theories as a Guide to Constitutional Values

Abstract constitutional values often motivate separation of powers doctrine and doctrines in other areas of law. A jurist favors one doctrinal position over another because, under some implicit positive theory, it promotes a consequential value: for example, abstract liberty, rule of law, or democratic values. Yet this jurisprudential posture falters if theory is incomplete or inapt. As an object lesson into the perils of incomplete functionalism, I consider the relationship between the so-called unitary executive and democratic values. I first formalize a theoretical account of the unitary executive along the lines of the one that animates judicial decisions; I then show that, viewed in a more complete setting, judicial decisions seemingly promoting a unitary executive may engender pluralism and undermine the value of accountability. I empirically examine the relationship between electoral accountability and innovations relating to one such offensive institution -- the legislative veto -- in the context of the American states between 1950-2010. I find that the offending institution of the legislative veto is, if anything, associated with stronger, not weaker, executive accountability for administrative actions, questioning the soundness of democratic values as a motivation for pursuing a unitary executive. I conclude with thoughts on the role of courts in managing functionalist constitutional values.
A Modified Mixed Domain Method for Modeling Wave Propagation in Heterogeneous Media

A modified mixed-domain method is presented in this paper to model wave propagation in heterogeneous media. The previous mixed domain method is only accurate for weakly heterogeneous media. Both the phase and amplitude corrections are introduced to the mixed-domain method in order to model wave propagation in more strongly heterogeneous media. Two cases are studied to validate the modified method. A two-layered medium with density and speed of sound variation is first studied. A human skull with density and speed of sound variation is then used to further evaluate the accuracy of this method. Result from the angular spectrum approach is used as the benchmark for the layered medium and result from the MATLAB toolbox k-Wave is used as the benchmark for the case of skull. Simulation results show that the modified mixed-domain method is more accurate for strongly heterogeneous media.
Changing heart failure coding practices and hospital risk-standardized mortality rates

As the most common reason for hospitalization among the elderly, admissions for acute heart failure (HF) are a frequent target for quality measurement and improvement activities. Large scale performance improvement initiatives such as the Centers for Medicare and Medicaid Services (CMS) Value Based Purchasing program use hospital HF mortality measures to determine hospital reimbursement rates.(1,2) To identify patients with a hospitalization for HF, programs use International Classification of Diseases 9th or 10th Edition codes limited to the principal diagnosis position. However, studies in other conditions suggest that there may be limitations to an approach that focuses only on a principal diagnosis to identify hospitalizations tracked for performance measurement. For example, diagnostic coding in pneumonia gradually shifted more severe conditions (e.g., sepsis) that were not targeted for outcome measurement into the principal diagnosis position in place of pneumonia. Hospitals that were more likely to shift the most severely ill patients with pneumonia out of performance surveillance (e.g., by using a principal diagnosis of sepsis) showed lower risk adjusted mortality rates than hospitals that were more likely to code pneumonia as a principal diagnosis, biasing hospital pneumonia mortality performance measures.(3–5) Although hospitalizations for acute HF may plausibly also be coded with alternative principal diagnoses (e.g., acute respiratory failure), it is unknown whether the kind of coding trends observed in pneumonia have carried over to HF, or whether shifts to alternative principal diagnoses have biased estimates of HF outcome performance measures. Among patients hospitalized for acute HF, we evaluated trends in the position of HF diagnosis codes and the association between use of alternative principal diagnosis codes and risk-standardized HF mortality rates.
‘The laws are in charge of the magistrates’: reply to Edelstein, Sullivan and Springborg

I am very grateful that my book is being discussed in this symposium and I much appreciate the fact that Professors Edelstein, Sullivan and Springborg took the time and energy to engage with my sch...
Association Between Rural Residence and Nonfatal Suicidal Behavior Among California Adults: A Population-Based Study.

Objective Suicide mortality rates in rural areas of the United States are twice that of rates in urban areas, and identifying which factors-eg, higher rates of suicidal distress, lower rates of help-seeking behaviors, or greater access to firearms-contribute to this rural/urban disparity could help target interventions. Method Using 2015-2016 data on adult respondents to the California Health Interview Survey (n = 40,041), we examined associations between residence in a rural (vs nonrural) census tract and nonfatal suicidal ideation and attempt. Results We found that living in a rural area was not associated with nonfatal suicidal behavior (OR for past-year suicidal ideation = 0.87, 95% CI: 0.63-1.20; OR for past-year suicide attempt = 0.55, CI: 0.20-1.48). Women living in rural areas had higher odds of lifetime suicidal ideation compared to women living in nonrural areas, but this difference was not significant (OR = 1.17, CI: 0.94-1.44). We also found that, among individuals reporting suicidal behavior, there were few rural/nonrural differences in perceived need for treatment, such as seeing a physician or taking a prescription for mental health problems. Conclusions Our results do not suggest higher suicidal distress or lower treatment-seeking behaviors as explanations for the rural/urban disparity in suicide mortality rates. Further attention is needed to the unique risk factors driving suicidality in rural areas, as well as exploring heterogeneity in these factors across different rural contexts.
Glow Powder: See the Germs? An Innovative Teaching Technique in a Student Sonography Laboratory:

The purpose of this study was to compare the disinfection rate of a laboratory environment before and after glow powder exposure and training of sonography students (n = 23) and establish if glow p...
DIFFERENCE EQUATIONS FOR GRADED CHARACTERS FROM QUANTUM CLUSTER ALGEBRA

We introduce a new set of q-difference operators acting as raising operators on a family of symmetric polynomials which are characters of graded tensor products of current algebra $$ \mathfrak{g}\left[u\right] $$ KR-modules [FL1] for $$ \mathfrak{g}={\mathrm{A}}_r $$ . These operators are generalizations of the Kirillov-Noumi [KN] Macdonald raising operators, in the dual q-Whittaker limit t → ∞. They form a representation of the quantum Q-system of type A, see [DFK3]. This system is a subalgebra of a quantum cluster algebra, and is also a discrete integrable system whose conserved quantities, analogous to the Casimirs of $$ {U}_q\left({\mathfrak{sl}}_{r+1}\right) $$ , act as difference operators on the above family of symmetric polynomials. The characters in the special case of products of fundamental modules are class I q-Whittaker functions, or characters of level-1 Demazure modules or Weyl modules. The action of the conserved quantities on these characters gives the difference quantum Toda equations [E]. For other modules, the action of the conserved quantities is thus a generalization of these difference equations in the case of an arbitrary (higher level) tensor products of KR-modules.
Imaginary quadratic fields with class groups of 3-rank at least 2

In this short note, we construct a family of imaginary quadratic fields whose class group has 3-rank at least 2. We show that, for every large X, there are $$\gg X^{\frac{1}{2}-\epsilon }$$ such fields with the discriminant $$-D$$ satisfying $$D\le X$$ .
Distribution and diversity of squirrels on university and college campuses of the United States and Canada

Squirrels on North American college and university campuses have been the subject of much animated conversation in informal venues, but a systematic assessment of their distribution across this habitat type has not been undertaken until now. We collected reports of squirrel species' presence and absence from faculty experts at 536 campuses in Canada and the continental United States, and found that squirrels are nearly ubiquitous on campuses (95% had at least one species, and 40% had three or more), but that only a select few species are common campus residents. Foremost among these is the eastern gray squirrel (Sciurus carolinensis—on 62% of surveyed campuses), followed by the eastern fox squirrel (Sciurus niger), eastern chipmunk (Tamias striatus), North American red squirrel (Tamiasciurus hudsonicus), and woodchuck (Marmota monax). Eastern gray and fox squirrels partition campuses with one another, both in their shared native/core range and on the West Coast. While these invasive eastern species are present on campuses on the West Coast, notably, contingency analysis did not provide evidence that they are the primary factor discouraging western gray squirrels (Sciurus griseus) from using these habitats. The inventory and analyses presented here can provide a basis for longitudinal studies both within and across campuses and may be productively combined with initiatives that involve students in research.
Selective killing of oncogenic transformed cells through ROS-mediated mechanism by β-phenylethyl isothiocyanates

1368 Therapeutic selectivity is important for anticancer drug development. Understanding the biological differences between normal and cancer cells is essential in designing strategies to preferentially kill cancer cells. Compared to normal cells, most cancer cells exhibit high metabolic activity, generate increased levels of reactive oxygen species (ROS), and are under oxidative stress. Elevated ROS renders the cancer cells more vulnerable to further ROS stress by exogenous ROS-generating agents. Here, we report that immortalization of ovarian epithelial cells with SV40 and hTERT followed by transformation with H-RasV12 oncogene rendered the cells tumorigenic, and exhibited significantly higher ROS generation compared to the non-tumorigenic parental cells. The malignant cells were highly vulnerable to further oxidative stress by β-phenylethyl isothiocyanates (PEITC), a dietary metabolic product of cruciferous vegetables. Treatment with 10 μM PEITC for 5 h preferentially induced ROS generation in (15-19 fold increase) and induced massive cell death (60-80%) within a relatively short period (5-24 h). In contrast, the parental non-tumorigenic cells without ras-transformation exhibited low basal ROS generation and better tolerated PEITC-induced ROS stress, as evidenced by only a modest ROS increase and less cell death (10-20%, 10 μM, 5-24 h). The in vitro therapeutic selectivity of PEITC against ovarian cancer cells was superior to cisplatin. Further studies revealed that PEITC caused a more severe depletion of glutathione in the malignant cells (93%, 5 μM, 3h) compared to the non-tumorigenic cells (52%), which appeared to be a biochemical mechanism for preferential increase of ROS in the malignant cells. Mechanistic studies demonstrated that PEITC induced cell death by causing a striking ROS-mediated oxidative damage to the mitochondrial membranes, and disrupting the redox-sensitive survival pathways such as NF-KB and Ras in the cancer cells. The action of PEITC was reversed by antioxidant N-acetylcysteine and ROS scavenger enzyme catalase. The promising therapeutic activity of PEITC was further demonstrated in animal models bearing the ras-transformed ovarian cancer cells, with an 84% increase in median animal survival time (25 vs 48 days, p
Interhemispheric callosal projections enforce response fidelity and frequency tuning in auditory cortex

Sensory cortical areas receive glutamatergic callosal projections that link information processing between brain hemispheres. However, the role of interhemispheric projections in sensory processing is unclear. Here we use single unit recordings and optogenetic manipulations in awake mice to probe how callosal inputs modulate spontaneous and tone-evoked activity in primary auditory cortex (A1). Although activation of callosal fibers increased firing of some pyramidal cells, the majority of responsive cells were suppressed. In contrast, callosal stimulation consistently increased fast spiking (FS) cell activity and brain slice recordings indicated that parvalbumin (PV)-expressing cells receive stronger callosal input than pyramidal cells or other interneuron subtypes. In vivo silencing of the contralateral cortex revealed that callosal inputs linearly modulate tone-evoked pyramidal cell activity via both multiplicative and subtractive operations. These results suggest that callosal input regulates both the salience and tuning sharpness of tone responses in A1 via PV cell-mediated feedforward inhibition.
The Driftless Oaks: A new network of tree-ring chronologies to improve regional perspectives of drought in the Upper Midwest, USA:

New and updated multi-century tree-ring chronologies from living oak trees, remnants, and archeological beams from across the Driftless Area of southwest Wisconsin and northeast Iowa, USA, were dev...
Surgical Outcomes With Cochlear Implantation in Patients With Enlarged Cochlear Aperture: A Systematic Review.

OBJECTIVE Evaluate surgical outcomes in patients with enlarged cochlear aperture (ECA) after cochlear implantation. DATABASES REVIEWED PubMed, EMBASE, and Scopus. METHODS A systematic review was performed using standardized methodology. Studies were included if they included subjects with ECA who underwent cochlear implantation. Exclusion criteria included non-English articles, abstracts, letters/commentaries, case reports, and reviews. Bias was assessed using the Risk of Bias in Non-randomized Studies of Interventions (ROBINS-I) tool. RESULTS Out of 1,688 identified articles, 7 articles representing 23 subjects with ECA were included. Publication rates increased between the period of study from 2009 to 2018. Four studies were level 4 evidence and three studies were level 3 evidence. In total, 20 subjects underwent cochlear implantation. Cerebrospinal fluid gushers were encountered in the majority of cases that reported complications (16/17, 94.1%); one patient developed postoperative meningitis, and another experienced postimplantation facial nerve stimulation. No study provided measurements on cochlear aperture size or defined size criteria used to identify ECA. Four studies recognized X-linked deafness to be associated with ECA, and the most common mutation was in POU3F4 gene. CONCLUSION An association exists between ECA and cerebrospinal fluid gusher, underscoring the importance of reviewing preoperative imaging. Size criteria are not well defined, and there is a paucity of data with respect to normative measurements. Many cases of ECA may give a genetic link. Although level of evidence of current studies remains modest, ECA reports have increased and will likely continue to expand with advancements in imaging and genetic testing.
Synthesis of CT Imaging and Right Heart Catheterization Enables Single-Beat RV-PA Coupling Estimations in Heart Failure Patients

Purpose Right ventricular-pulmonary arterial (RV-PA) coupling has been shown to predict RV failure in PH patients. However, current clinical approaches require physiological assumptions which may be invalid in heart failure patients. We utilized functional CT and right heart catheterization (RHC) to construct single-beat pressure-volume (PV) loops, assess the impact of coupling assumptions, and compare impact on predicting patient outcomes. Methods Heart failure patients who underwent advanced therapy evaluation between since 9/2017 with ECG-gated contrast-enhanced CT scans and RHC within 14 days were enrolled. PV loops were generated via synchronizing CT-derived volume and RHC-derived pressure waveforms. A model using PV data and RV wall thickness was used to fit RV and PA elastance. We compared our approach to two clinical alternatives: volumetric approach, which estimates coupling as stroke volume / end-systolic volume (SV/ESV), and pressure adjusted approach, estimated as (SV * ESP) / (ESV * mPAP). The prognostic value of the coupling approaches was evaluated using a composite endpoint of heart transplant due to ventricular decompensation, VAD implantation with RV failure, or cardiac related death within 30 days. Results 22 patients met inclusion criteria and within 30 days, 7 had the composite endpoint (3 deaths, 2 RV failure post VAD, 2 transplants), and 15 did not (2 VAD with no RV failure, 13 no events). Compared to the single-beat PV-loop based approach, both the volumetric approach (75.2% reduction) and pressure-adjusted approach (45.6% reduction) underestimated coupling. PV-derived coupling was significantly (p 0.05). Conclusion Functional CT and RHC can be used to derive single-beat measures of coupling and differentiate between patients with and without short-term adverse outcomes.
Bursting the bubble: A molecular understanding of surfactant-water interfaces

Surfactant science has historically emphasized bulk, thermodynamic measurements to understand the microemulsion properties of greatest industrial significance, such as interfacial tensions, phase behavior, and thermal stability. Recently, interest in the molecular properties of surfactants has grown among the physical chemistry community. This has led to the application of cutting-edge spectroscopic methods and advanced simulations to understand the specific interactions that give rise to the previously studied bulk characteristics. In this Perspective, we catalog key findings that describe the surfactant–oil and surfactant–water interfaces in molecular detail. We emphasize the role of ultrafast spectroscopic methods, including two-dimensional infrared spectroscopy and sum-frequency-generation spectroscopy, in conjunction with molecular dynamics simulations, and the role these techniques have played in advancing our understanding of interfacial properties in surfactant microemulsions.
Evaluation of SrAl2O4:Eu, Dy phosphor for potential applications in thermoluminescent dosimetry

PURPOSE To evaluate the use of commercial-grade strontium aluminate phosphorescent powder as a thermoluminescent (TL) dosimeter for clinical radiotherapy beams. MATERIALS AND METHOD Commercially available Eu2+ , Dy3+ co-doped strontium aluminate powder (SrAl2 O4 :Eu, Dy) was annealed and then irradiated using 20 × 20 cm2 field size, with 6-MV (PDD10 = 70.7) and 18-MV (PDD10 = 79.4) photon beams and and 9-MeV (R50 = 3.6), 15 MeV (R50 = 5.9) and 18-MeV (R50 = 7.2) electron beams. To calibrate the relationship between the TL readings and the irradiated doses, TL glow curves were acquired for doses up to 600 cGy at all beam energies. For the percentage depth dose (PDD) measurement, the SrAl2 O4 :Eu, Dy powder was sandwiched by solid water phantoms, with varying thickness of solid water placed above to determine the depth. PDDs were measured at four representative depths and compared against the commissioning depth dose data for each beam energy. RESULTS Linear dose response models of doses up to 200 cGy were created for all beam energies. Superlinearity was observed with doses greater than 200 cGy. The PDD measurement acquired experimentally agrees well with the commissioning data of the medical linear accelerator. Trapping parameters such as order of kinetics, activation energy and frequency factor have been obtained via TL glow curve analysis. CONCLUSION The linear dose response demonstrates that SrAl2 O4 :Eu, Dy is a potential TLD dosimeter for both electron beams and photon beams at different beam energies. The PDD measurements further support its potential use in quality assurance and radiation dosimetry.
Border Carbon Adjustments When Carbon Intensity Varies across Producers: Evidence from California

Governments taxing carbon emissions within their jurisdiction can impose a commensurate tax on emissions embodied in imports in order to mitigate emissions leakage. California offers a rare opportunity to investigate how such a border carbon adjustment (BCA) is working in practice. Experience to date highlights important tensions between greenhouse gas accounting accuracy, market efficiency, and concerns about trade protectionism. We simulate electricity market outcomes under BCA designs that differ in terms of how the carbon intensity of imports is assessed. Simulations suggest significant potential for leakage via resource shuffling. Realized emissions outcomes indicate that this potential has not been fully realized.
The Ultraviolet Structure of Quantum Field Theories. Part 3: Gauge Theories

This paper develops a detailed lattice-continuum correspondence for all common examples of Abelian gauge theories, with and without matter. These rules for extracting a continuum theory out of a lattice one represent an elementary way to rigorously define continuum gauge theories. The focus is on (2+1)D but the techniques developed here work in all dimensions. The first half of this paper is devoted to pure Maxwell theory. It is precisely shown how continuum Maxwell theory emerges at low energies in an appropriate parameter regime of the $\mathbb{Z}_K$ lattice gauge theory at large $K$. The familiar features of this theory -- its OPE structure, the distinction between compact and noncompact degrees of freedom, infrared "particle-vortex" dualities, and the Coulomb law behavior of its Wilson loop -- are all derived directly from the lattice. The rest of the paper studies gauge fields coupled to either bosonic or fermionic matter. Scalar QED is analyzed at the same level of precision as pure Maxwell theory, with new comments on its phase structure and its connections to the topological BF theory. Ordinary QED (Dirac fermions coupled to Maxwell theory) is constructed with an eye toward properly defining spinors and avoiding global anomalies. The conventional continuum QED is shown to arise from a specific restriction of the starting theory to smoothly varying fields. Such smoothing also turns out to be a necessary condition for Chern-Simons theory to arise from integrating out massive fermions in a path integral framework. In an effort to find a canonical origin of Chern-Simons theory that does not rely on path integral smoothing, a simple flux-attached lattice gauge theory is shown to give rise to the Abelian Chern-Simons action with the correct properties.
Transition to Teaching: Lessons Learned by a First-Year Rural Alternative Route Program

This article describes lessons learned from the first-year implementation of a Grow Your Own teacher preparation alternative route program, Transition to Teaching. Implemented in a rural area in Washington State facing significant teacher shortages, the Transition to Teaching program reaches potential teachers who may not have access to a four-year college and a high-quality, competency-based teacher preparation program. The Transition to Teaching program fulfills the priority assigned by the state to recruiting and retaining teachers from underrepresented groups. Beginning with describing the design of the program and the application process, we discuss students’ first-year experiences, lessons learned, and solutions developed. Content, strategies, access, and efficiencies are highlighted and advice for new programs is provided. In the end, we prove programs comparable to Transition to Teaching require clear collaboration and coordination as well as oversight to ensure teacher candidates are successful.
The value of management control systems : evidence on the market reaction to ISO 9000 quality assurance certification

We study the link between firm value and quality management practices by examining stock price reactions to third party attestation that a firm's quality control process complies with ISO 9000 quality assurance standards. We find that ISO 9000 certification is motivated by international sales opportunities for attaining 'preferred supplier' status with manufacturing customers availability of alternatives for disclosing quality and costs of obtaining certification. Our analysis of wealth effects which addresses Lanen and Thompson's (1988) critique by controlling for investors' prior anticipation of certification indicates that factors which explain certification also explain cross-sectional variation in abnormal returns around the certification date. Additionally we find that firms voluntarily disclose information about ISO 9000 certification when certification is initiated by the firm but not when certification is in response to customer demands or regulatory requirements.
Life Expectancy of Highway Bridges to Vehicle Loads

Life expectancy of highway bridges to vehicle loads is studied. Vehicular traffic is represented by the Poisson process and response of bridges is considered as a filtered Poisson process. A method is developed to obtain, numerically, peak probability density function and expected total number of peaks per unit time of stress response of bridges. These quantities are used in conjunction with Palmgren-Miner's theory of cumulative damage to predict the fatigue life of a particular bridge.
USING ASYNCHRONOUS LEARNING IN REDESIGN: REACHING AND RETAINING THE AT-RISK STUDENT

Successful completion of introductory courses is critical for first-year students, but typical failure rates in these courses contribute heavily to overall institutional drop-out rates between the first and second year. Although success rates vary by institutional type and by subject matter, Research I universities commonly cite a 15 percent drop-failure-withdrawal (DFW) rate in introductory courses. Comprehensive universities’ DFW rates range from 22 percent to 45 percent in these courses. Community colleges frequently experience DFW rates of 40 percent to 50 percent or more. Most of the weaknesses attributed to large introductory courses are generic in nature and have as their source the limitations of the predominant form of instruction in U.S. colleges and universities: the didactic lecture. An overwhelming body of research shows that students do not learn effectively from lectures, and testimony from the field corroborates the literature.
Benchmark Employment in Representative Pennsylvania Green Occupations, 2005-2008

Presented in this report are benchmarks that allow assessment of, first, current Pennsylvania worker assets in green occupations and, then, any progress that is made as returns are realized from green economic investment in Pennsylvania.
Subspace learning in non-Gaussian log-concave noise

We consider subspace learning from measurements corrupted by log-concave random noise. The class includes, but is not limited to, generalized Gaussian (GG) noise with shape parameter greater than or equal to unity, log-concave spherically invariant random processes (SIRPs), and their generalizations to norm invariant random processes (NIRPs). The noise properties need not be constant in the independent time and/or space variable. Necessary conditions are derived and they are computationally simpler when factorability properties are applicable, as is the case with GG's, SIRP's, and NIRPs when the signal space is one-dimensional.
Thermally-induced microstructural changes in a three-way automotive catalyst

The use of advanced electron microscopy techniques to characterize both the bulk and near-atomic level microstructural evolution of catalyst materials during different dynamometer/vehicle aging cycles is an integral part of understanding catalyst deactivation. The study described here was undertaken to evaluate thermally-induced microstructural changes which caused the progressive loss of catalyst performance in a three-way automotive catalyst. Several different catalyst processing variables, for example changing the washcoat ceria content, were also evaluated as a function of aging cycle and thermal history. A number of thermally-induced microstructural changes were identified using high resolution electron microscopy techniques that contributed to the deactivation of the catalyst, including sintering of all washcoat constituents, {gamma}-alumina transforming to {alpha}-, {beta}-, and {delta}-alumina, precious metal redistribution, and constituent encapsulation. The data accumulated in this study have been used to correlate microstructural evolution with thermal history and catalyst performance during various aging cycles and to subsequently evaluate different washcoat formulations for increased thermal stability.
Abstract A14: Hyperactivation of RSK1 is a hallmark of metastatic nodular melanoma

It is generally accepted that superficial spreading (SSM) and nodular melanoma (NM), the most common melanoma histologic subtypes, are biologically indistinct once they invade and metastasize. Consequently, targeted therapy is dictated by the mutational profile of metastatic disease, regardless of the histologic subtype of the primary melanoma. Here, we show that p90 ribosomal S6 kinase (RSK1) is constitutively phosphorylated in human melanoma cell lines derived from NM but not SSM. Significantly, metastases from primary NM patients showed p-RSK1 overexpression and a distinct metalloproteinase profile compared with metastases from primary SSM patients. Interestingly, p-RSK1 hyper-activation could not be solely explained by MAPK activation due to BRAF mutations. We show that NM-derived cell lines were more sensitive to genetic and pharmacological RSK1 inhibition than SSM-derived cell lines. Using a zebrafish model, we demonstrate that activated RSK1 significantly accelerates melanoma progression. In addition, RNAseq revealed up-regulation of extracellular matrix degradation, cell migration, and cell proliferation genes in the RSK1 mutant-expressing tumors. Together, our data demonstrate that metastatic melanoma originating from different histologic subtypes might depend on distinct oncogenic pathways. Data also support constitutive RSK1 activation as a driver of nodular metastatic melanoma, a finding that supports the concept of subtype-specific melanoma therapy. Citation Format: Amel Salhi, Joshua A. Farhadian, Keith M. Giles, Eleazar C. Vega-Saenz de Miera, Ines Pires Da Silva, Caitlin Bourque, Karen Yeh, Sagar Chhangawala, Jinhua Wang, Fei Ye, David Y. Zhang, Eva Hernando-Monge, Yariv Houvras, Iman Osman. Hyperactivation of RSK1 is a hallmark of metastatic nodular melanoma. [abstract]. In: Proceedings of the AACR Special Conference on Advances in Melanoma: From Biology to Therapy; Sep 20-23, 2014; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(14 Suppl):Abstract nr A14.
Abstract 3490: Topotecan synergizes with CHEK1 inhibitor to induce apoptosis in ovarian cancer cells

Proceedings: AACR 106th Annual Meeting 2015; April 18-22, 2015; Philadelphia, PA Background Topotecan is a therapeutic option for women with platinum-resistant or -refractory ovarian cancer. However, the dose-limiting toxicity of topotecan is myelosuppression. This led us to seek a combination treatment to augment topotecan anti-cancer activity in a cancer-targeted manner. Ovarian serous cancers, a major subtype, show dysregulated DNA repair pathway and often display a high level of CHEK1, a cell cycle regulator and DNA damage sensor. CHEK1 inhibitors are a novel approach to treatment, and have been used as single agents or in combination chemotherapy in many cancers. Methods We evaluated the cellular effects of topotecan in a panel of high grade serous (HGS) and non-HGS ovarian cancer cells. We then determined IC50s of topotecan in the absence and presence of suboptimal concentrations of CHEK1 inhibitor, PF477736. Synergism between topotecan and PF477736 was calculated based on cellular viability assays. Cytotoxic effect of the combined treatment was compared with apoptotic activities by Caspase3/7 activity assay and Western blotting of cleaved-PARP1 and γH2A.X. Results Non-HGS ovarian cancer cells were generally more sensitive to topotecan treatment compared to HGS ovarian cancer cells. When combined with suboptimal concentrations of CHEK1 inhibitor, topotecan potently and synergistically inhibited the proliferation of HGS ovarian cancer cells. This dramatic synergism in cellular toxicity was consistent with increases in markers of apoptosis. Conclusions Our findings suggest that the addition of CHEK1 inhibitor increases the response of ovarian cancer cells to topotecan. Furthermore, reduced dosages of both drugs achieved maximal cytotoxic effects by combining topotecan with CHEK1 inhibitor. This strategy would potentially minimize side effects of the drugs for extended clinical benefit. Citation Format: Marianne K. H. Kim, Jana James, Christina Annunziata. Topotecan synergizes with CHEK1 inhibitor to induce apoptosis in ovarian cancer cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3490. doi:10.1158/1538-7445.AM2015-3490
Satanism in Contemporary America: Establishment or Underground?

Sociological discourse has generally represented Satanism as a harmless, law-abiding alternative religion. Conversely, the antisocial and criminal aspects of Satanism have been the focus of most la...
Synthesis of a new bisphosphonic acid ligand (SEDP) and preparation of a 188Re-(Sn)SEDP bone seeking radiotracer

Abstract The new bisphosphonate ligand SEDP (2-sulfonato-1,1-ethylidene bisphosphonic acid) has been synthesized and characterized, including the determination of the protonation constants, and used to form 188 Re-(Sn)SEDP from Na 188 ReO 4 . The title compound 188 Re-(Sn)SEDP shows slightly greater bone uptake and less kidney uptake than 188 Re-(Sn)HEDP in rat biodistribution studies.
Antecedent hypoglycemia does not alter increased epinephrine-induced lipolysis in type 1 diabetes mellitus.

Type 1 diabetic subjects have decreased epinephrine responses to hypoglycemia that may be counterbalanced by increased β-adrenergic sensitivity. The goal of this study was to determine whether type 1 diabetic subjects have increased metabolic response to epinephrine and to determine the effect of antecedent hypoglycemia on these responses. Muscular glucose uptake across the forearm (forearm glucose uptake, Fick principle) and lipolysis (free fatty acid and glycerol levels) were studied before and during a 4-hour euglycemic, hyperinsulinemic (40 mU · m−2 · min−1) clamp with epinephrine infusion (0.015 μg · kg−1 · min−1) over 3 hours. Subjects were studied twice, once with antecedent hypoglycemia (2.8 mmol/L for two 2-hour sessions) and once with antecedent euglycemia (5 mmol/L) the day prior. Free fatty acid and glycerol concentrations were higher, and total body glucose utilization and forearm glucose uptake during epinephrine were lower in diabetic than in control subjects (P < .05). Antecedent hypoglycemia had no effect. These results demonstrate that type 1 diabetic subjects have increased lipolysis and decreased glucose utilization in response to epinephrine. These effects are not altered by antecedent hypoglycemia.
A Procedure for Phonetic Transcription by Consensus

A consensus transcription procedure is presented, and representative data are reported. The procedure includes explicit response definitions for mapping narrow phonetic transcription onto dichotomo...
Consumer evaluation of dual focus mutual aid

ABSTRACT Double Trouble in Recovery (DTR) is a “dual focus,” 12 step-based mutual aid program tailored to assist recovery from co-occurring substance use and psychiatric disorders. Objective: To determine consumers' perceptions of DTR's usefulness for their recoveries and the relationships between perceived DTR usefulness and self-help processes, self-efficacy to cope with problems in recovery, and changes in behaviors conducive to dual recovery. Methods: Consumers attending DTR groups, located within a psychiatric day-treatment program, completed anonymous surveys 8 months (N = 19) and 20 months (N = 61) after DTR was implemented. Results: DTR participants rated DTR favorably and length of DTR attendance was significantly associated with increased self-efficacy for recovery and positive changes in recovery-oriented behaviors. Perceived DTR usefulness was significantly associated with greater engagement in three specific self-help processes and increased self-efficacy for recovery; notably, these associat...
Organometal-induced increases in oxygen reactive species: The potential of 2′,7′-dichlorofluorescin diacetate as an index of neurotoxic damage

The effects of the neurotoxic metals methylmercury (MeHg) and trimethyltin (TMT) on oxygen reactive species formation within a crude synaptosomal fraction (P2), using the probe 2',7'-dichlorofluorescin diacetate (DCFH-DA), and intracellular calcium ([Ca2+]i), with the fluorescent indicator fluo-3, have been investigated. Two and seven days after a single injection of MeHg (1 mg/kg) the formation rate of cerebellar oxygen reactive species was significantly increased. Hippocampal and frontocortical oxygen reactive species were elevated 2 days after TMT injection (3 mg/kg). In vitro exposure to MeHg (10-20 microM) increased the formation rate of oxygen reactive species, while TMT (5-40 microM) was without effect. Levels of [Ca2+]i were unaltered in P2 fractions from cerebellum and hippocampus of animals treated with either organometal. The data demonstrate that oxygen reactive species are elevated in brain regions, cerebellum (MeHg) and hippocampus (TMT), believed to be selectively vulnerable to these toxic agents. Findings suggest that oxidative damage may be a mechanism underlying the toxicity of both organometals. The use of DCFH-DA may have potential in the nervous system as an indicator of neurotoxic damage.
Activation of Muscarinic Receptors Inhibits औ-Amyloid Peptide-induced Signaling in Cortical Slices

Deposition of fibrillar aggregates of the औ-amyloid peptide (Aऔ) is a key pathologic feature during the early stage of Alzheimer's disease. The initial neuronal responses to Aऔ in cortical circuits and the regulation of Aऔ-induced signaling remain unclear. In this study, we found that exposure of cortical slices to Aऔ1–42 or Aऔ25–35 induced a marked increase in the activation of protein kinase C (PKC) and Ca2+/calmodulin-dependent kinase II (CaMKII), two enzymes critically involved in a variety of cellular functions. Activation of M1 muscarinic receptors, but not nicotinic receptors, significantly inhibited the Aऔ activation of PKC and CaMKII. Increasing inhibitory transmission mimicked the M1 effect on Aऔ, whereas blocking GABAA receptors eliminated the M1 action. Moreover, electrophysiological evidence shows that application of Aऔ to cortical slices induced action potential firing and enhanced excitatory postsynaptic currents, whereas muscarinic agonists potently increased inhibitory postsynaptic currents. These results suggest that Aऔ activates PKC and CaMKII through enhancing excitatory activity in glutamatergic synaptic networks. Activation of M1 receptors inhibits Aऔ signaling by enhancing the counteracting GABAergic inhibitory transmission. Thus the muscarinic reversal of the Aऔ-induced biochemical and physiological changes provides a potential mechanism for the treatment of Alzheimer's disease with cholinergic enhancers.
Determination by microcoulometric gas chromatography of chlorpromazine metabolites in human urine.

Abstract The application of gas-liquid chromatography to the analysis of chlorpromazine and its metabolites is described. Several new metabolites have been identified in the urine of psychiatric patients with the microcoulometer as a detector. The method, which requires no elaborate extraction or cleanup procedures, is rapid and quantitative for eight metabolites.
Characterization of cell samples from measurements of spectroscopic scattering phase-dispersion

We present spectroscopic swept-source optical coherence tomography (OCT) measurements of the phase-dispersion of cell samples. We have previously demonstrated that the phase of the scattered field is, in general, independent of the intensity, and both must be measured for a complete characterization of the sample. In this paper, we show that, in addition to providing a measurement of the size of the cell nuclei, the phase spectrum provides a very sensitive indication of the separations between the cells. Epithelial cancers are characterized by many factors, including enlarged nuclei and a significant loss in the architectural orientation of the cells. Therefore, an in vivo diagnostic tool that analyzes multiple properties of the sample instead of focusing on cellular nuclei sizes alone could provide a better assessment of tissue health. We show that the phase spectrum of the scattered light appears to be more sensitive to cell spacing than the intensity spectrum. It is possible to determine simultaneously the cell nuclei sizes from the intensity spectrum and the nuclei spacing from the phase spectrum. We measure cell monolayer samples with high and low cell density and compare measured results with histograms of the cell separations calculated from microscope images of the samples. We show qualitative agreement between the predicted histograms and the interferometric results.
Determining the potential to breed for enhanced antioxidant status in Malus: mean inter- and intravarietal fruit vitamin C and glutathione contents at harvest and their evolution during storage.

Vitamin C (l-ascorbate, l-ascorbic acid; L-AA) and glutathione (GSH) are major hydrophilic antioxidants in plants with important roles in stress resistance and nutrition. To evaluate the potential for breeding for enhanced levels of these compounds, a comprehensive screen of the fruit from some 31 apple (Malus) cultivars has been carried out to determine the biodiversity present in the mean inter- and intracultivar concentrations of both the oxidized and reduced forms of these compounds, as well as the impact of storage on their concentrations. It is noted that despite limited variation at harvest, cultivars differed substantially in their ability to maintain L-AA levels during storage, primarily due to the loss of L-AA by “low-vitamin C” cultivars. Generally, cultivars that could maintain their L-AA and GSH pools also had better storage properties. Interestingly, there was also a correlation between fruit vitamin C contents and the harvest date, such that cultivars with the highest vitamin C contents wer...
Mass Spectrometry-Based Quantification of Pseudouridine in RNA

Direct detection of pseudouridine (ψ), an isomer of uridine, in RNA is challenging. The most popular method requires chemical derivatization using N-cyclohexyl-N'-β-(4-methylmorpholinum ethyl) carbodiimide p-tosylate (CMCT) followed by radiolabeled primer extension mediated by reverse transcriptase. More recently, mass spectrometry (MS)-based approaches for sequence placement of pseudouridine in RNA have been developed. Nearly all of these approaches, however, only yield qualitative information regarding the presence or absence of pseudouridine in a given RNA population. Here, we have extended a previously developed liquid chromatography tandem mass spectrometry (LC-MS/MS) method to enable both the qualitative and quantitative analysis of pseudouridine. Quantitative selected reaction monitoring (SRM) assays were developed using synthetic oligonucleotides, with or without pseudouridine, and the results yielded a linear relationship between the ion abundance of the pseudouridine-specific fragment ion and the amount of pseudouridine-containing oligonucleotide present in the original sample. Using this quantitative SRM assay, the extent of pseudouridine hypomodification in the conserved T-loop of tRNA isolated from two different Escherichia coli strains was established.
The Changing Role of Colostomy in the Management of Acute Diverticulitis and Rectal Cancer

The application of colostomy to the treatment of acute diverticulitis and to rectal cancer has decreased with time. A review of contributions that have brought about this trend is presented.
Annotated Bibliography on the Teaching of Psychology: 2005

This bibliography is a continuation of those previously published in Teaching of Psychology (e.g., Berry & Daniel, 1984; Fulkerson & Wise, 1987; Johnson & Schroder, 1997; Wise & Fulkerson,1996). We maintained similar search methods and criteria for inclusion that were used in previous bibliographies. We also continued the cumulative numbering of the items. To help the reader locate relevant articles, we arranged items into a small number of subject categories. Generally, if fewer than 3 items fell into a specific subject category, we relegated them to a category labeled miscellaneous.
Sudden and Unexpected Death-A Late Effect of Occult Intraesophageal Foreign Body

Acute upper airway obstruction in a 4-month-old male infant who presented as sudden infant death syndrome is described. At autopsy external tracheal compression and tracheobronchitis with plugging of the trachea and bronchi by an abundant mucopurulent exudate were found. The source of the inflammation was the adjacent esophagus where previous impaction of a coin had caused pressure necrosis with mucosal erosion and transmural granulation tissue formation. This case is reported to demonstrate that foreign bodies that remain in the esophagus, having by-passed the larynx, may still result in upper airway obstruction and death in early infancy by this unusual mechanism.
Multiple mechanisms of bipA gene regulation by the Bordetella BvgAS phosphorelay system.

I thank Dan Wozniak for critical reading of the manuscript. Research in my laboratory is supported by faculty development funds from Wake Forest University Health Sciences.