cssi/SciSciGPT-SciSciNet huggingface dataset:
Inverse Correlation of STAT3 and MEK Signaling Mediates Resistance to RAS Pathway Inhibition in Pancreatic Cancer.

Major contributors to therapeutic resistance in pancreatic ductal adenocarcinoma (PDAC) include Kras mutations, a dense desmoplastic stroma that prevents drug delivery to the tumor, and activation of redundant signaling pathways. We have previously identified a mechanistic rationale for targeting STAT3 signaling to overcome therapeutic resistance in PDAC. In this study, we investigate the molecular mechanisms underlying the heterogeneous response to STAT3 and RAS pathway inhibition in PDAC. Effects of JAK/STAT3 inhibition (STAT3i) or MEK inhibition (MEKi) were established in Ptf1acre/+; LSL-KrasG12D/+ ; and Tgfbr2flox/flox (PKT) mice and patient-derived xenografts (PDX). Amphiregulin (AREG) levels were determined in serum from human patients with PDAC, LSL-KrasG12D/+;Trp53R172H/+;Pdx1Cre/+ (KPC), and PKT mice. MEKi/STAT3i-treated tumors were analyzed for integrity of the pancreas and the presence of cancer stem cells (CSC). We observed an inverse correlation between ERK and STAT3 phosphorylation. MEKi resulted in an immediate activation of STAT3, whereas STAT3i resulted in TACE-induced, AREG-dependent activation of EGFR and ERK. Combined MEKi/STAT3i sustained blockade of ERK, EGFR, and STAT3 signaling, overcoming resistance to individual MEKi or STAT3i. This combined inhibition attenuated tumor growth in PDX and increased survival of PKT mice while reducing serum AREG levels. Furthermore, MEKi/STAT3i altered the PDAC tumor microenvironment by depleting tumor fibrosis, maintaining pancreatic integrity, and downregulating CD44+ and CD133+ CSCs. These results demonstrate that resistance to MEKi is mediated through activation of STAT3, whereas TACE-AREG-EGFR-dependent activation of RAS pathway signaling confers resistance to STAT3 inhibition. Combined MEKi/STAT3i overcomes these resistances and provides a novel therapeutic strategy to target the RAS and STAT3 pathway in PDAC.Significance: This report describes an inverse correlation between MEK and STAT3 signaling as key mechanisms of resistance in PDAC and shows that combined inhibition of MEK and STAT3 overcomes this resistance and provides an improved therapeutic strategy to target the RAS pathway in PDAC.Graphical Abstract: http://cancerres.aacrjournals.org/content/canres/78/21/6235/F1.large.jpg Cancer Res; 78(21); 6235-46. ©2018 AACR.
Terror by Any Other Name

Definitions matter. As scholars, we traffic in conceptualizations, seeking nuance and clarity in our terminology; these debates are central to our pursuit of knowledge. Definitions have theoretical...
Face-to-Face Documentation Using the FACE-2-FACE Method

Nurse practitioners play an integral part of the face-to-face visit. The face-to-face visit requirement came into effect on January 11, 2011, for hospice patients entering their third or later benefit period. The face-to-face requirement was created because of concerns regarding high numbers of hospice patients with lengths of stay greater than 180 days, in addition to concerns the physician was not as active in the care of the hospice patient as required. Face-to-face visits can be completed by the hospice physician or nurse practitioner employed by the hospice agency. The face-to-face narrative includes a clear title, date, clinical findings demonstrating continued hospice eligibility and a signature of the individual completing the face-to-face visit. In addition, an attestation statement stating that the encounter was completed with the patient and the clinical findings were provided to the certifying physician is also a requirement of the narrative. Documenting clinical findings that demonstrate hospice eligibility can be challenging. Using the FACE-2-FACE method can help clarify the clinical findings necessary to demonstrate the patient's continued hospice eligibility.
Solution-processable electrochromic materials and devices: roadblocks and strategies towards large-scale applications

Electrochromic devices (ECDs) that modulate optical transmission or reflection in a controllable manner are attractive in energy-saving and colour-tuning applications. In this review, we discuss the key components, fundamental working principles and performance metrics of ECDs using layman's terms. We also highlight recent materials development of each component and illustrate how the structure–property relationships impact their processability, device performance and stability. We further introduce emerging materials that exhibit electrochromic properties, and discuss the transition from laboratory-scale, half-cell-based characterisations of electrochromic materials to the fabrication of solid-state electrochromic devices and evaluation of their performances. Finally, we lay out major challenges for fabricating large-scale and cost-effective ECDs, particularly the materials design and fabrication strategies for achieving chemically and electrochemically stable, high performance ECDs that can be produced by roll-to-roll techniques.
Percutaneous Image-guided Core Needle Biopsy for Upper Tract Urothelial Carcinoma.

Abstract OBJECTIVE To better understand the safety and diagnostic yield of percutaneous core-needle biopsy (PCNB) for upper tract urothelial carcinoma (UTUC). METHODS Of 444 patients undergoing radical nephroureterectomy (RNU) for UTUC between 2009 and 2017 at our institution, 42 who had PCNB prior to RNU were identified for analysis. Endpoints included safety, diagnostic yield, and concordance with RNU pathology. PCNB specimens were deemed histologically concordant with RNU specimens for cases when cytologic evaluation of biopsy specimen and corresponding pathologic evaluation of RNU specimen both made a histologic diagnosis of urothelial carcinoma. RESULTS Median tumor size was 3.8 cm (1.2-10.2 cm). All lesions arose from the pelvicalyceal system. CT-guidance was utilized in 52% (n = 22), and ultrasound-guidance in 48% (n = 20). Relative to RNU pathology, 95% of PCNBs demonstrated histologic concordance. Histologic grade was provided in 69% (n = 29) of PCNBs, with a 90% (n = 26) concordance with surgical pathology. Grades 1-2 and 3 complications occurred in 14.3% (n = 6) and 2.4% (n = 1), respectively. At a median follow-up of 28.2 months (range, 1.2-97.1 months) after biopsy, no cases of radiographic tract seeding were identified. CONCLUSION In our cohort of 42 patients undergoing RNU for UTUC, PCNB appeared a safe diagnostic tool with high histologic yield and grade concordance. With greater than 2 years of follow-up, no cases of tract seeding were identified.
EEG Recording Method for Quantitative Analysis

정량적 뇌파는 연구와 임상적 분야에서 활발하게 이용되어 다양한 임상적 증상과 인지기능의 자극 및 과제에 따른 대뇌의 생물학적인 바이오 마커를 규명하는 등 대뇌의 변화를 객관적으로 증명하는데 지속적으로 사용되고 있다. 뇌파에서 정량적 분석과 정성적 분석은 분석하는 방법이 다르기 때문에 측정 방법과 환경이 비슷하지만 한편으론 다르다. 정성적 분석은 뇌파를 판독하는 사람이 잡파를 제외시키고 볼 수 있지만 정량적 분석은 수학적 모델링을 기반으로 데이터의 모든 것을 포함하여 분석을 실시하고 있기 때문에 잡파가 결과에 영향을 준다. 병원에서 임상생리학적 검사인 뇌파를 담당하는 임상병리사들이 뇌파를 이용한 연구는 다른 분야에 비해서 아주 드물다. 이러한 현상은 임상검사과학 분야 중에 임상생리학적 검사에서 두드러지게 나타난다. 왜냐하면 현재 대학에서 임상생리학을 연구하는 실험실이 많지 않기 때문이다. 본 저자의 목적은 정량적 분석을 하고자 하는 임상병리사, 대학원생, 연구자들이 쉽게 접근하여 앞으로 뇌파의 많은 연구가 이루어 질 수 있는 기초자료로 활용되기를 기대하고, 앞으로 많은 대학에서 임상생리학 실험실이 생겨 많은 연구들이 이루어져 좋은 논문들이 많이 나오기를 기대해 본다
Numerical Investigation of Decomposed Full Magneto-Fluid-Dynamics Equations

In addition to the two commonly used formulations for magnetofluid dynamics, a third formulation based on the decomposition of the magnetic field for solving full magnetofluid dynamics equations is explored. The governing equations are transformed to a generalized computational domain and discretized using a finite difference technique. A time-explicit multistage Runge―Kutta scheme augmented with total variation diminishing limiters for time integration is implemented. The developed codes have been validated with the existing closed-form solution of the magnetic Rayleigh problem. Results obtained from the decomposed magnetofluid dynamics equations compare well with results obtained by solving the classical full magnetofluid dynamics equations for a wide range of magnetic Reynolds numbers. It is shown that the decomposed magnetofluid dynamics technique requires substantially less computation time compared with classical full magnetofluid dynamics equations for the solution involving flowfields with high imposed magnetic fields.
Lassa virus, but not highly pathogenic new world arenaviruses, restricts immunostimulatory double-stranded RNA accumulation during infection

The arenaviruses Lassa virus (LASV), Junin virus (JUNV), and Machupo virus (MACV) can cause severe and fatal diseases in humans. Although these pathogens are closely related, the host immune responses to these virus infections differ remarkably, with direct implications for viral pathogenesis. LASV infection is immunosuppressive, with a very low-level interferon response. In contrast, JUNV and MACV infections stimulate a robust interferon (IFN) response in a retinoic acid-inducible gene I (RIG-I)-dependent manner and readily activate protein kinase R (PKR), a known host double-stranded RNA (dsRNA) sensor. In response to infection with RNA viruses, host nonself RNA sensors recognize virus-derived dsRNA as danger signals and initiate innate immune responses. Arenavirus nucleoproteins (NPs) contain a highly conserved exoribonuclease (ExoN) motif, through which LASV NP has been shown to degrade virus-derived immunostimulatory dsRNA in biochemical assays. In this study, we for the first time present evidence that LASV restricts dsRNA accumulation during infection. Although JUNV and MACV NPs also have the ExoN motif, dsRNA readily accumulated in infected cells and often colocalized with dsRNA sensors. Moreover, LASV coinfection diminished the accumulation of dsRNA and the IFN response in JUNV-infected cells. The disruption of LASV NP ExoN with a mutation led to dsRNA accumulation and impaired LASV replication in minigenome systems. Importantly, both LASV NP and RNA polymerase L protein were required to diminish the accumulation of dsRNA and the IFN response in JUNV infection. For the first time, we discovered a collaboration between LASV NP ExoN and L protein in limiting dsRNA accumulation. Our new findings provide mechanistic insights into the differential host innate immune responses to highly pathogenic arenavirus infections.IMPORTANCE Arenavirus NPs contain a highly conserved DEDDh ExoN motif, through which LASV NP degrades virus-derived, immunostimulatory dsRNA in biochemical assays to eliminate the danger signal and inhibit the innate immune response. Nevertheless, the function of NP ExoN in arenavirus infection remains to be defined. In this study, we discovered that LASV potently restricts dsRNA accumulation during infection and minigenome replication. In contrast, although the NPs of JUNV and MACV also harbor the ExoN motif, dsRNA readily formed during JUNV and MACV infections, accompanied by IFN and PKR responses. Interestingly, LASV NP alone was not sufficient to limit dsRNA accumulation. Instead, both LASV NP and L protein were required to restrict immunostimulatory dsRNA accumulation. Our findings provide novel and important insights into the mechanism for the distinct innate immune response to these highly pathogenic arenaviruses and open new directions for future studies.
Other Ultrasound-Guided Interventional Procedures

Various percutaneous interventional procedures can benefit from ultrasound (US) guidance. These include (but are not limited to) ductography, the injection of radionuclide for lymphoscintigraphy or contrast agents for sentinel lymph node biopsy, and the insertion of brachytherapy devices in the postoperative cavity after lumpectomy.
Angle Fixability and Angle-Based Sensor Network Localization

This paper introduces the concept of "angle fixability" and applies it to angle-based sensor network localization (ASNL). Generally speaking, a framework is said to be angle fixable if it can be uniquely determined by angles between edges up to translation, rotation, scaling, and reflection. It is shown that any framework with a "non-degenerate bilateration ordering" is angle fixable in the plane. The ASNL problem is to determine locations of all sensors, given locations of partial sensors (called anchors) and angle constraints based on bearings measured in the local coordinate frame of each sensor. By establishing connections between angle fixability and angle localizability, it is proved that if a sensor network in the plane has a non-degenerate bilateration ordering and anchors are not all collinear, then the ASNL has a unique solution. If the network also contains an acute-triangulated sub-framework, then the ASNL can be equivalently formulated as a linear semi-definite programming (SDP) to be solved within polynomial time. Simulation examples are provided to validate effectiveness of the theoretical findings.
Improving trainee engagement in science: Lessons from a virtual seminar series

To be a successful researcher, you are expected to have important skills beyond the bench such as being able to ask questions, talk about science with your peers, and organize scientific events. However, there is frequently little to no training or emphasis on these skills at the student and postdoc level. The virtual Aging Science Talks seminar series and Slack group have benefitted the scientific community in many ways amidst the chaos of coronavirus quarantines and lab shutdowns, but as a 2nd year PhD student, I was particularly excited about how this format was able to engage trainees. We should end the era of trainees sitting at the back of the room while PIs dominate discussions and Q&A sessions with speakers. Reflecting on the advantages of Aging Science Talks can show us how to make future scientific events more engaging and inclusive for everyone.
Differences in influenza-specific CD4 T cell mediated immunity following acute infection versus inactivated vaccination in children

BACKGROUND Early childhood influenza infections imprint influenza-specific immune memory, with most studies evaluating antibody specificity. In this study, we examined how infection versus inactivated influenza vaccination (IIV) establish pediatric CD4 T-cell mediated immunity to influenza and whether this poises the immune system to respond differently to IIV the following year. METHODS We tracked influenza-specific CD4 T-cell responses in 16 H3N2 infected and 28 IIV immunized children following both initial exposure and after cohorts were revaccinated with IIV the following fall. PBMCs were stimulated with peptide pools encompassing the translated regions of the H3 HA and NP proteins and were then stained to assess CD4 T-cell specificity and function. RESULTS Compared to IIV, infection primed a greater magnitude CD4 T-cell response specific for the infecting HA and NP proteins, with more robust NP-specific immunity persisting through year 2. Post infection, CD4 T cells preferentially produced combinations of cytokines that included interferon-γ. Interestingly, age-specific patterns in CD4 T-cell reactivity demonstrated the impact of multiple influenza exposures over time. CONCLUSIONS These data indicate that infection and vaccination differentially prime influenza-specific CD4 T-cell responses in early childhood, with these differences contributing to the lasting immunologic imprinting established following early influenza infection. CLINICAL TRIALS REGISTRATION NCT02559505.
Dynamics of Wing Structures

This chapter deals with the dynamics of elastic structures: unswept fixed-wing and free-free wings, modeled as beams of zero thickness, linear as well as nonlinear. The main concern is with spectral analysis, modes and mode shapes as a means to study stability. The language is that of abstract functional analysis: Hilbert spaces and semigroup theory of operators for time domain description.
[carbonyl-11C]4-Fluoro-N-methyl-N-(4-(6-(methylamino)pyrimidin-4-yl)thiazol-2-yl)benzamide ([11C]FIMX) is an effective radioligand for PET imaging of metabotropic glutamate receptor 1 (mGluR1) in monkey brain.

Abstract Introduction Metabotropic glutamate subtype receptor 1 (mGluR1) is implicated in several neuropsychiatric disorders and is a target for drug development. [ 18 F]FIMX ([ 18 F]4-fluoro-- N -methyl- N --(4-(6-(methylamino)pyrimidin-4-yl)thiazol-2-yl)benzamide) is an effective radioligand for imaging brain mGluR1 with PET. A similarly effective radioligand with a shorter half-life would usefully allow PET studies of mGluR1 at baseline and after pharmacological or other challenge on the same day. Here we describe the preparation of [ 11 C]FIMX for evaluation in monkey with PET. Methods [ 11 C]FIMX was prepared via Pd-promoted carbonylation of 1-fluoro-4-iodobenzene with [ 11 C]carbon monoxide, aminolysis of the [ 11 C]acyl-palladium complex with the requisite Boc-protected amine, and deprotection with HCl in THF. PET scans of [ 11 C]FIMX injected into a monkey were performed at baseline and after preblock of mGluR1 with measurement of the arterial input function. Results The radiosynthesis required 42min and gave [ 11 C]FIMX in about 5% overall decay-corrected radiochemical yield and with a specific activity of about 100GBq/μmol. PET in rhesus monkey at baseline showed that radioactivity peaked high in receptor-rich cerebellum and much lower in receptor-poor occipital cortex. Radioactivity in cerebellum declined to 32% of peak at 85min. V T at baseline appeared stable in all brain regions after 60min. Under mGluR1 pre-blocked condition, radioactivity uptake in all regions declined more rapidly to a low level. Receptor pre-block reduced V T from 13.0 to 1.5 in cerebellum and from 2.9 to 1.4 in occipital cortex. Conclusion [ 11 C]FIMX is an effective radioligand for imaging mGluR1 in monkey with PET.
Genomics of Aspergillus flavus Mycotoxin Production

Food microbiologists often overlook the importance of fungi as a threat to food safety and security even though fungi produce a wide array of toxic compounds. Aspergillus flavus is known to produce over 14 described mycotoxins. It is common for strains of A. flavus to produce both aflatoxin and cyclopiazonic acid (CPA) and for commodities to contain both mycotoxins. Other than A. flavus and A. minisclerotigenes, no other fungal genera are known to produce aflatrem; however, structurally related tremorgenic mycotoxins, such as penitrem from Penicillium spp., are prevalent in other fungi and likely share common enzymes. Fungi have the capacity to produce many diverse secondary metabolites, and over 300 fungal secondary metabolites are described as mycotoxins. It is now possible to predict whether potential toxins produced by secondary metabolism clusters may be present in food. With respect to the regulation of aflatrem biosynthesis, researchers have shown that the gene called veA, previously shown to control aflatoxin and sclerotial production in A. parasiticus was found to not only be necessary for the production of aflatoxins B1 and B2 and sclerotia, but also regulated the synthesis of the mycotoxins cyclopiazonic acid and aflatrem. New tools for genomewide gene profiling and functional analysis will surely reveal additional information on aflatoxin production and the regulation of the process. This knowledge will empower researchers to find effective strategies for controlling aflatoxin contamination of food and feed. Gradually, newly developed next-generation sequencing technologies will become common research tools for functional genomics studies.
Fluid inking: augmenting the medium of free-form inking with gestures

We present Fluid Inking, a generally applicable approach to augmenting the fluid medium of free-form inking with gestural commands. Our approach is characterized by four design criteria, including: 1) pen-based hardware impartiality: all interactions can be performed with a button-free stylus, the minimal input hardware requirement for inking, and the least common denominator device for pen-based systems ranging from PDAs to whiteboards; 2) performability: gestures use short sequences of simple and familiar inking interactions that require minimal targeting; 3) extensibility: gestures are a regular pattern of optional shortcuts for commands in an arbitrarily scalable menu system; and 4) discoverability: gesture shortcuts (analogous to modifier keys) are displayed in the interactive menu and are suggested with dynamic feedback during inking. This paper presents the Fluid Inking techniques in the unified context of a prototype notetaking application and emphasizes how post-fix terminal punctuation and prefix flicks can disambiguate gestures from regular inking. We also discuss how user feedback influenced the Fluid Inking design.
Racial Constructions of Africans on ChinaSMACK

Cheng (2011) identified the comments and discussions on Chinese blogs and news websites as the location of a new kind of cyber-racism focusing on black people that is emerging from Chinese netizens. This paper seeks to explore the way black people are discussed in these websites by examining the content and comments on translated blogs and news websites provided by ChinaSMACK.com. Content was grouped into themes focusing on what the use of stereotypes revealed about how Chinese netizens view both the self and the other.
Diagnosis of endogenous depression ☆: Comparison of clinical, research and neuroendocrine criteria

Eighty-nine depressed outpatients were studied by clinical criteria, Research Diagnostic Criteria (RDC), and the dexamethasone suppression test (DST) of neuroendocrine regulation. A simple outpatient version of the DST, requiring only one blood sample, correctly identified 40% of patients diagnosed clinically as endogenous depression (ED), with a specificity of 98% and a diagnostic confidence of 95%. Differences in age, sex, or severity of symptoms between endogenous and non-endogenous depressives did not account for these results. By comparison, the diagnostic performance of the DST was weaker for the RDC categories Major Depressive Disorder (MDD) and primary MDD. These were less selective and more heterogeneous than the clinical category ED. The clinical diagnoses of ED were supported in 98% of cases by the RDC, but 22% of RDC endogenous MDD diagnoses were not supported by the clinical diagnoses. Abnormal DST results were found only in patients with both the clinical diagnosis of ED and the RDC diagnosis of endogenous MDD. Patients with definite endogenous MDD had a significantly higher frequency of abnormal DST results (42%) than those with probable endogenous MDD (14%), or those with other RDC diagnoses (3%). A significant association was found between positive DST results and a positive family history of depression. These results support other evidence for use of a positive DST result as an external validating criterion for ED. The category MDD contained all cases diagnosed clinically as ED, but was diluted by cases diagnosed clinically as non-endogenous depression who had no neuroendocrine disturbance. The results also confirmed that the endogenous/non-endogenous and primary/secondary classifications of depression are not identical. We conclude: (1) that the DST can be used in the differential diagnosis of depressed outpatients as well as inpatients; (2) that the RDC category primary MDD and the Washington University category primary depression are more heterogeneous and probably less valid than the clinical category ED; (3) that the RDC for endogenous MDD have only moderate validity; (4) that RDC diagnoses cannot substitute for careful clinical diagnoses in research studies; (5) that the best use of the RDC is to support clinical diagnoses, but not to generate diagnoses independently as a free-standing system; (6) that the concept of endogenous or endogenomorphic depression has validity and should be retained in research studies of depression.
Formation of ohmic contacts to n-GaAs via heterojunction by using indium and gold

Ohmic contacts with contact resistivity of the order of M Omega -cm/sup 2/, have been successfully fabricated by deposition of a thin film of gold and indium on a clean GaAs surface followed by annealing. An annealing temperature as low as 280 degrees C can be used to achieve this result. Increasing the annealing temperature to 350 degrees C reduces the required annealing time to only 12 seconds. >
ERK signaling leads to mitochondrial dysfunction in extracellular zinc-induced neurotoxicity

A zinc-induced signaling pathway leading to extracellular signal-regulated kinase 1/2 (ERK1/2) activation and subsequent neuronal death has been investigated. We find that an extracellular zinc application stimulates biphasic phosphorylation of ERK1/2 and p38 MAPK in rat cultured neurons. The activation of ERK1/2, but not p38, is responsible for zinc neurotoxicity as only U0126, a MEK inhibitor that blocks ERK1/2 phosphorylation, significantly protects cortical neurons from zinc exposure. Over-expression of a dominant negative Ras mutant blocks zinc-induced Elk1-dependent gene expression in neurons, indicating the involvement of Ras activation in the zinc pathway leading to ERK phosphorylation and Elk1 signaling. We also find that zinc treatment results in neuronal mitochondrial hyperpolarization. Importantly, both U0126 and bongkrekic acid, an inhibitor of the mitochondrial adenine nucleotide translocase, effectively reduce zinc-triggered mitochondrial changes. As bongkrekic acid also prevents zinc-triggered neuronal death but not ERK1/2 phosphorylation, activation of MAPK signaling precedes and is required for mitochondrial dysfunction and cell death. These results provide new insight on the mechanism of extracellular zinc-induced toxicity in which the regulation of mitochondrial function by the Ras/MEK/ERK pathway is closely associated with neuronal viability.
Management of Acquired Adult Dropfoot

Dropfoot is a catchall term for ankle equinus, equinovarus, and equinovalgus. The deformity can be flexible or rigid and may be associated with other pathology. In the adult, dropfoot may be congenital or acquired. Acquired dropfoot results from weakness of the ankle dorsiflexors, overpull of the plantarflexors, contracture of the soft tissues, bony deformity, or any combination of these factors. Appropriate treatment includes observation, orthotic devices, bracing, tendon transfers, arthrodesis, and neurolysis. The purpose of this paper is to review the pathophysiology and treatment of acquired dropfoot.
Concept mapping for planning and evaluation of a big brother/big sister program

This paper describes how concept mapping was used to organize a conceptual framework from which a questionnaire was constructed, in order to evaluate the One-to-One Big Brother/Big Sister youth program. The evaluation results derived from this questionnaire support the claim that the program effectively meets its goals: program participants scored significantly higher on the questionnaire than a comparable group of youth who had not participated in the program. Furthermore, the pattern of results was consistent with the staff's expectations of the program's outcomes as indicated through the concept mapping process.
The Shadow of Physical Harm? Examining the Unique and Gendered Relationship Between Fear of Murder Versus Fear of Sexual Assault on Fear of Violent Crime

The shadow hypothesis regarding the impact of fear of sexual assault on fear of violent crime suggests that female fear of crime is characterized by concern about sexual assault as a contemporaneous victimization event during a violent crime event. Recent research has found that other types of crime, namely physical assault, may also be feared as a contemporaneous offense. We know of no research that has examined the unique impact of fear of murder versus fear of sexual assault on fear of violent crime. There is also a lack of research that explores how these two types of fear uniquely affect men and women. In addition to gender, we examine factors that have been suggested in previous research to correlate with fear of crime: race, victimization, vicarious victimization, and perceived risk. Through survey methodology, this research examines the unique relationship between both fear of murder and fear of sexual assault and fear of three types of violent crime for men and women. Results suggest differences ...
Novel Atomic Force Microscopy Based Biopanning for Isolation of Morphology Specific Reagents against TDP-43 Variants in Amyotrophic Lateral Sclerosis

Because protein variants play critical roles in many diseases including TDP-43 in Amyotrophic Lateral Sclerosis (ALS), alpha-synuclein in Parkinson's disease and beta-amyloid and tau in Alzheimer's disease, it is critically important to develop morphology specific reagents that can selectively target these disease-specific protein variants to study the role of these variants in disease pathology and for potential diagnostic and therapeutic applications. We have developed novel atomic force microscopy (AFM) based biopanning techniques that enable isolation of reagents that selectively recognize disease-specific protein variants. There are two key phases involved in the process, the negative and positive panning phases. During the negative panning phase, phages that are reactive to off-target antigens are eliminated through multiple rounds of subtractive panning utilizing a series of carefully selected off-target antigens. A key feature in the negative panning phase is utilizing AFM imaging to monitor the process and confirm that all undesired phage particles are removed. For the positive panning phase, the target antigen of interest is fixed on a mica surface and bound phages are eluted and screened to identify phages that selectively bind the target antigen. The target protein variant does not need to be purified providing the appropriate negative panning controls have been used. Even target protein variants that are only present at very low concentrations in complex biological material can be utilized in the positive panning step. Through application of this technology, we acquired antibodies to protein variants of TDP-43 that are selectively found in human ALS brain tissue. We expect that this protocol should be applicable to generating reagents that selectively bind protein variants present in a wide variety of different biological processes and diseases.
Marketing research in the new millennium: emerging issues and trends

Given the focus of the special issue, the present paper combines both the academic and the practitioner perspectives to highlight several issues and emerging trends that will shape the role of marketing research in the new millennium. These include a redefinition of the marketing researcher, the on‐going nature of marketing research, qualitative research, quantitative research, international marketing research, Internet marketing research, and ethical issues in marketing research.
Enhancement of sympathetic nerve activity by single premature ventricular beats in humans.

Abstract This is the first systematic study of the effects of ventricular premature beats on sympathetic nerve activity in humans. Microneurographic techniques were used to record efferent sympathetic activity from the peroneal nerve, and an intracardiac electrode catheter was used to introduce ventricular premature beats after every 6 to 10 sinus heartbeats. Studies were performed in eight patients, aged 22 to 74 years (mean 57), undergoing cardiac electrophysiologic studies. Three patients did not have apparent heart disease and five had coronary artery disease. During sinus rhythm, 19 to 93% (mean 42%) of heartbeats were followed by a pulse-synchronous burst of sympathetic activity. Provoked ventricular premature beats had obvious effects on this activity. Premature beats with coupling intervals It is concluded that single ventricular premature beats provoke fluxes of muscle sympathetic nerve activity in humans, comprising surges of sympathetic activity larger than those occurring during sinus rhythm, followed by neural silence.
The effect of cold as a stressor agent upon the periodontium of albino rats.

Abstract Exposure of male albino rats to temperatures of 0 to 2° C. for two weeks resulted in osteoporosis of alveolar bone, characterized by decreased osteoblastic activity and periodontal membrane changes consisting of decreased cellularity and granularity of the collagen. With continued exposure, the changes in the periodontium diminished in severity. There was evidence of changes after four weeks, but after four months the periodontium returned to normal.
Goliath: A Configurable Approach for Network Testing

When testing a network environment and/or application many aspects need to be taken into consideration. For example, different software needs to be deployed at different nodes and different topologies may also need to be tested. The manual execution of these tasks are very time consuming and a configurable environment to facilitate these tasks and consequently improve testing performance is desired. In this paper a virtual network environment that can be easily reconfigured is presented to address this problem. Also presented is a case study with the results of deployment and containing a worm propagation attack.
Coronary heart disease in black Americans: Suggestions for research on psychosocial factors

Despite the fact that coronary heart disease (CHD) is the leading cause of death among U.S. blacks, virtually no information exists on the contribution of psychosocial factors to CHD risk in this population. Studies conducted on U.S. whites suggest that type A behavior may be positively associated with risk for CHD. Other studies on whites suggest that occupational stressors, socioeconomic status, and social mobility may also be important. Studies that examine the contribution of these factors to CHD risk in the black population are needed. Moreover, recent changes in the socioeconomic profile of the U.S. black population present an unusual opportunity to study the role of psychosocial variables in CHD among black Americans. Some of the theoretical and measurement issues that investigators may face in conducting such research are discussed, and some specific suggestions for research are offered.
Primary sensory and forebrain motor systems in the newborn brain are preferentially damaged by hypoxia-ischemia

Cerebral hypoxia-ischemia causes encephalopathy and neurologic disabilities in newborns by unclear mechanisms. We tested the hypothesis that hypoxia-ischemia causes brain damage in newborns that is system-preferential and related to regional oxidative metabolism. One-week-old piglets were subjected to 30 minutes of hypoxia and then seven minutes of airway occlusion, producing asphyxic cardiac arrest, followed by cardiopulmonary resuscitation and four-day recovery. Brain injury in hypoxic-ischemia piglets (n = 6) compared to controls (n = 5) was analyzed by hematoxylin-eosin, Nissl, and silver staining, relationships between regional vulnerability and oxidative metabolism were evaluated by cytochrome oxidase histochemistry. Profile counting-based estimates showed that 13% and 27% of neurons in layers II/III and layers of somatosensory cortex had ischemic cytopathology, respectively; CA1 neuronal perikarya appeared undamaged, and < 10% of CA3 and CA4 neurons were injured; and neuronal damage was 79% in putamen, 17% in caudate, but nucleus accumbens was undamaged. Injury was found preferentially in primary sensory neocortices (particularly somatosensory cortex), basal ganglia (predominantly putamen, subthalamic nucleus, and substantia nigra reticulata), ventral thalamus, geniculate nuclei, and tectal nuclei. In sham piglets, vulnerable region generally had higher cytochrome oxidase levels than less vulnerable areas. Postischemic alterations in cytochrome oxidase were regional and laminar, with reductions (31-66%) occurring in vulnerable regions and increases (20%) in less vulnerable areas. We conclude that neonatal hypoxia-ischemia causes highly organized, system-preferential and topographic encephalopathy, targeting regions that function in sensorimotor integration and movement control. This distribution of neonatal encephalopathy is dictated possibly by regional function, mitochondrial activity, and connectivity.
Guided ion-beam determination of the Co+-H2 bond dissociation energy

Abstract A guided ion-beam tandem mass spectrometer with a flow tube ion source is used to determine the 0 K bond dissociation energy of Co + -H 2 from ligand exchange of CoCH 4 + with D 2 and from collision-induced dissociation (CID) of CoH 2 + + Xe. Given D 0 (Co + -CH 4 ) = 0.93 ± 0.06 eV determined in our labs, the endothermicity of the ligand exchange reaction provides D 0 (Co + -D 2 ) = 0.74 ± 0.07 eV. The direct CID kof CoH 2 + process yields D 0 (Co + -H 2 ) = 0.82 ± 0.11 eV. After zero-point energy corrections, the average of these two results yields 0.76 ± 0.10 eV. This values agrees nicely with those determined by equilibrium methods and theory.
On the Origin of Cosmic Rays

The presence of heavy particles in cosmic rays makes it plausible that cosmic radiation is generated by the acceleration of charged particles in extended electromagnetic fields. The energy density of cosmic rays ($3\ifmmode\times\else\texttimes\fi{}{10}^{\ensuremath{-}10}\frac{M{c}^{2}}{{\mathrm{cm}}^{3}}$) would lead to very great total amounts of energy if one assumes that cosmic radiation extends throughout intergalactic or throughout interstellar space. This would require very efficient methods of cosmic-ray production. It is therefore of interest to investigate the possibility that cosmic rays are generated in the vicinity of the sun and are confined to the solar system by extended magnetic fields. The strength of these fields is estimated to be ${10}^{\ensuremath{-}5}$ gauss. According to this picture, cosmic rays circulate in the neighborhood of the planetary system for thousands of years, during which time the radiation becomes isotropic. The electron component of the radiation is eliminated by collisions with solar light quanta.
Evidence for Phenotypic Mixing with Reovirus in Cell Culture

Abstract From pairwise mixed infections of different reovirus wild-type isolates (T3 Dearing plus T1 Lang or plus T2 Jones) the progeny virus is phenotypically mixed, i.e., progeny viral particles contain proteins derived from both parents but the corresponding genes derived from only one parent. Experiments with differential inactivation of virus progeny of mixed infections by monoclonal antibodies or by 33% ethanol reveal phenotypic mixing of two outer shell proteins, σ1 and probably μ1. Phenotypic mixing of the μ1 protein, the product of the M2 gene, is a possible explanation for the recent observation of M2 gene-linked dominant interference between reovirus isolates (M. N. Rozinov and B. N. Fields. 1994. J. Virol. 68, 6667–6671).
Descriptive and experimental analysis of teacher and peer attention and the use of assessment-based intervention to improve pro-social behavior

This study examined the inclusion of peer attention within a functional assessment and the effectiveness of an assessment based intervention with an elementary student without disabilities who displayed high rates of inappropriate behavior in the classroom. A multiple assessment strategy was employed to generate hypotheses regarding the possible function of the problem behavior. An experimental manipulation was conducted to confirm the hypotheses. Assessment based interventions were also implemented. Data from the descriptive and experimental assessment and interventions supported the hypothesis that the subject's behavior was maintained by peer attention. Procedures and results from this research extend current functional analysis research by conducting experimental manipulation of identified variables, including the use of peer attention, in applied settings, providing additional evidence for the necessary consideration of response efficiency during intervention, and the use of a multiple assessment strategy.
Larval RNA interference in the red flour beetle, Tribolium castaneum.

The red flour beetle, Tribolium castaneum, offers a repertoire of experimental tools for genetic and developmental studies, including a fully annotated genome sequence, transposon-based transgenesis, and effective RNA interference (RNAi). Among these advantages, RNAi-based gene knockdown techniques are at the core of Tribolium research. T. castaneum show a robust systemic RNAi response, making it possible to perform RNAi at any life stage by simply injecting double-stranded RNA (dsRNA) into the beetle’s body cavity. In this report, we provide an overview of our larval RNAi technique in T. castaneum. The protocol includes (i) isolation of the proper stage of T. castaneum larvae for injection, (ii) preparation for the injection setting, and (iii) dsRNA injection. Larval RNAi is a simple, but powerful technique that provides us with quick access to loss-of-function phenotypes, including multiple gene knockdown phenotypes as well as a series of hypomorphic phenotypes. Since virtually all T. castaneum tissues are susceptible to extracellular dsRNA, the larval RNAi technique allows researchers to study a wide variety of tissues in diverse contexts, including the genetic basis of organismal responses to the outside environment. In addition, the simplicity of this technique stimulates more student involvement in research, making T. castaneum an ideal genetic system for use in a classroom setting.
Factors Affecting Survival of Channel Catfish after Surgical Removal of Testes

Abstract Testes from adult male channel catfish (Ictalurus punctatus; N= 73) and blue catfish (I. furcatus; N= 16) were surgically removed, and the incisions closed. Variables evaluated for their effect on survival of fish were method of anesthesia (tricaine [MS–222] at 12 and at 23°C, and metomidate at 23°C), suturing procedure (suture, adhesive, and adhesive plus suture), and treatment with antibiotic (erythromycin) or without antibiotic. Postsurgery survival was determined 8–10 weeks later. Observed survival was 61 and 53% among fish treated with MS-222 at 12 and 23°C, respectively. The lower temperature decreased bleeding and increased the efficacy of MS-222. Metomidate-treated fish had significantly higher (P < 0.05) survival (74%) than MS-222-treated fish. Fewer of the metomidate-treated fish had incisions reopen because their swimming behavior in the recovery tank was more normal than that of MS-222-treated fish. Closure of incisions with adhesive alone resulted in 100% mortality. No difference (P ...
The Molecular Ecology of Fundulus heteroclitus Hemoglobin-Oxygen Affinity

Animals faced with environmental perturbations must adapt or face extinction. The respiratory complex, specifically hemoglobins, is perhaps the best system to study such adaptation because it exists at the organism—environment interface. Fish are particularly useful models because they respond directly to such environmental variables as temperature, oxygen, pH, carbon dioxide, and salinity. Our experiments have addressed the molecular, cellular, and physiological mechanisms employed by fish to maintain respiratory homeostasis in the wake of changing temperature and oxygen. Immediate, intermediate, and long-term adaptation can only be understood when the hemoglobin's ligand binding properties and the cellular and hormonal regulation of various ligands are considered simultaneously. We describe a detailed thermodynamic model for the binding of oxygen, protons, and organic phosphates to hemoglobin; discuss the role of multiple hemoglobins; and present evidence for physiological and genetic regulation of hemoglobin's major allosteric modifiers in response to environmental stress in the mummichog, Fundulus heteroclitus
Integrating perception and problem solving to predict complex object behaviours

One of the objectives of Cognitive Robotics is to construct robot systems that can be directed to achieve realworld goals by high-level directions rather than complex, low-level robot programming. Such a system must have the ability to represent, problem-solve and learn about its environment as well as communicate with other agents. In previous work, we have proposed ADAPT, a Cognitive Architecture that views perception as top-down and goaloriented and part of the problem solving process. Our approach is linked to a SOAR-based problem-solving and learning framework. In this paper, we present an architecture for the perceptive and world modelling components of ADAPT and report on experimental results using this architecture to predict complex object behaviour. A novel aspect of our approach is a 'mirror system' that ensures that the modelled background and foreground objects are synchronized with observations and task-based expectations. This is based on our prior work on comparing real and synthetic images. We show results for a moving object that collides and rebounds from its environment, hence showing that this perception-based problem solving approach has the potential to be used to predict complex object motions.
Glauconitic peloids and chamositic ooids - favorable factors, constraints, and problems

Abstract Glauconitic minerals constitute a family ranging from green smectite to a 10Adioctahedral mica (glauconite). Chamositic minerals include a 7Atrioctahedral serpentine (berthierine) and a 14Atrioctahedral chlorite (chamosite). These green iron-rich, neoformed or transformed clay minerals are most commonly concentrated in sand-size granules. Recent berthierine and Recent and ancient glauconitic minerals occur mainly in structureless peloids, most of which are believed to have been fecal pellets. In contrast, most of the ancient chamositic minerals are in multi-coated ooids generally assumed to have been made by gentle rolling on the sea floor. Glauconitic and chamositic granules accumulated most commonly in marine shelf environments during episodes of reduced influx of sediment. In modern deposits chamositic peloids predominate on the inner shelf, whereas glauconitic peloids are most abundant on the middle and outer shelf. In general, ancient glauconitic and chamositic deposits had a rather similar environmental distribution; in detail, however, they reflect more varied and overlapping marine habitats. Glauconitic greensands and chamositic ironstones commonly occur above a coarsening- or shoaling-upward facies sequence. Many of them are cross-bedded and burrowed, and some are interbedded with a ferruginized or phosphatized hardground. Although differing in detail, their temporal distributions throughout Phanerozoic time were rather similar. Both attained a maximum when cratonic blocks were widely dispersed and sea level was high in Early Paleozoic and Late Mesozoic time. In addition, recurring development of chamositic ooids commonly coincided with repeated regional transgressions. This review of current information and differing interpretations leads to significant questions that are essential subjects for future research. Moreover, some of these relate to unsolved problems of phosphorite genesis.