cssi/SciSciGPT-SciSciNet huggingface dataset:
Measures of Glutamate Using Chemical Exchange Saturation Transfer (CEST) MRI Related to Cognition (P4.135)

Objective: Quantitatively evaluate the metabolic abnormalities in cortical gray matter (cGM) of Multiple Sclerosis (MS) patients using chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) and assess the relation of CEST-derived indices sensitive to glutamate (GluCEST) with cognitive measures. Background: Use of MRI in the diagnosis and evaluation of disease progression assumes close association between MRI abnormalities and clinical disability. Although data are conflicting, there is an overall lack of correlation between radiological findings and clinical symptoms of MS. Cognitive dysfunction is seen in 40-70[percnt] of MS patients affecting concentration, attention, speed of processing, and executive function. CEST effect is highly dependent on magnetic field strength, and 7 Tesla (7T) allows greater sensitivity to exchangeable amine protons associated with glutamate within cGM and has potential sensitivity to the pathophysiology driving cognitive dysfunction. Methods: Subjects (41 healthy, 13 MS) provided informed consent and were scanned at 7T using a 32-channel head coil. MP-RAGE anatomical images were obtained for registration and segmentation. CEST MRI was acquired (2D gradient echo: TR/TE/flip = 5.6ms/2.7ms/10°) at 0.94mm² resolution in a 5mm slice. CEST saturation: ten 10-ms pulses at 4.25μT amplitude and a 90[percnt] duty cycle pulse train with offset frequencies swept between -5.0ppm and 5.0ppm plus one reference (80.0ppm). cGM was segmented and the GluCEST asymmetry was calculated and compared to a battery of cognitive tests. Results: Repeatability was evaluated in 8 healthy subjects. Healthy subjects demonstrated more normally distributed GluCEST asymmetry histograms at 3.0ppm, but the medians were not significantly different between healthy and MS patients. However, GluCEST asymmetry was significantly correlated with visuospatial memory test (R=0.70, p=0.014) and trended towards significance with the global deterioration scale (R=0.54, p=0.067). Conclusions: GluCEST-MRI at 7T in the cGM of MS patients shows relationship to measures of cognition. Disclosure: Dr. Dula has nothing to disclose. Dr. Pawate has nothing to disclose. Dr. Lyttle has nothing to disclose. Dr. Conrad has nothing to disclose. Dr. Smith has nothing to disclose.
Exosomes: Origins and Therapeutic Potential for Neurodegenerative Disease

Abstract: Exosomes, small lipid bilayer vesicles, are part of the transportable cell secretome that can be taken up by nearby recipient cells or can travel through the bloodstream to cells in distant organs. Selected cellular cytoplasm containing proteins, RNAs, and other macromolecules is packaged into secreted exosomes. This cargo has the potential to affect cellular function in either healthy or pathological ways. Exosomal content has been increasingly shown to assist in promoting pathways of neurodegeneration such as β-amyloid peptide (Aβ) accumulation forming amyloid plaques in the brains of patients with Alzheimer’s disease, and pathological aggregates of proteins containing α-synuclein in Parkinson’s disease transferred to the central nervous system via exosomes. In attempting to address such debilitating neuropathologies, one promising utility of exosomes lies in the development of methodology to use exosomes as natural delivery vehicles for therapeutics. Because exosomes are capable of penetrating the blood-brain barrier, they can be strategically engineered to carry drugs or other treatments, and possess a suitable half-life and stability for this purpose. Overall, analyses of the roles that exosomes play between diverse cellular sites will refine our understanding of how cells communicate. This mini-review introduces the origin and biogenesis of exosomes, their roles in neurodegenerative processes in the central nervous system, and their potential utility to deliver therapeutic drugs to cellular sites.
The S2 glycoprotein subunit of porcine epidemic diarrhea virus contains immunodominant neutralizing epitopes

The porcine epidemic diarrhea virus (PEDV) spike (S) protein is the major target of neutralizing antibodies against PEDV. Here immunodominant neutralizing epitopes of PEDV were identified using a panel of S-specific monoclonal antibodies (mAbs). Ten of eleven S-specific mAbs successfully neutralized PEDV infectivity in vitro. Notably, epitope mapping by peptide ELISAs revealed that nine of these mAbs recognized linear neutralizing epitopes located in the N-terminus of the S2 glycoprotein subunit (amino acids [aa] 744-759, 747-774 and/or 756-771). Additionally, one mAb recognized a neutralizing epitope located in the C-terminus of S2 (aa 1371-1377), while only one neutralizing mAb reacted against a region of the S1 glycoprotein subunit (aa 499-600). Notably, mAbs that recognized epitopes within the S2 subunit presented the highest neutralizing activity against PEDV. Together these results indicate that the S2 glycoprotein subunit contains major antigenic determinants and, perhaps, the immunodominant neutralizing epitopes of PEDV.
Utilization of Organs From Donors According to Hepatitis C Antibody and Nucleic Acid Testing Status: Time for Change

Previous studies have grouped all HCV antibody (Ab) positive donors. Only recently has testing for donor hepatitis C virus (HCV) nucleic acid (NAT) become routine and the impact of Ab and NAT status on organ utilization is unknown. Using the United Network for Organ Sharing (UNOS) database, we identified 9290 donors from 2015 to 2016 for whom both HCV Ab and NAT data were available, and compared organ utilization by HCV status. 93.8% of donors were Ab- NAT-, 0.15% were Ab- NAT+, 1.8% were Ab+ NAT- and 4.2% were Ab+ NAT+. Ab- NAT- donors donated at the highest rate for all organs except livers, where Ab+ NAT- donors donated at a higher rate (81.2% vs 73.2%, p=0.03). Livers were discarded for reasons related to abnormal biopsies in Ab+ NAT+ donors, whereas kidneys from Ab or NAT positive donors were discarded for reasons related to HCV status. Using a propensity-matched model, we estimated that using Ab+ NAT- donors at the same rate as Ab- NAT- donors could result in 48 more kidney donors, 37 more heart donors and 15 more lung donors annually. We urge use of HCV Ab+ NAT- donors into appropriately selected and consenting recipients. This article is protected by copyright. All rights reserved.
Neurontin and Off-Label Marketing

The drug Neurontin is used as an example of why it is permissible for physicians to engage in off-label prescribing, but off-label marketing by pharmaceutical companies is prohibited by the FDA. Virtual Mentor is a monthly bioethics journal published by the American Medical Association.
Paired agent imaging enables rapid assessment of therapeutic efficacy for personalized therapy (Conference Presentation)

Tools for rapid therapeutic selection for pancreatic ductal adenocarcinoma (PDAC) patients are vital to improved survival as PDAC is the third leading cause of cancer death, with an average life expectancy of 5-7 months post diagnosis. Treatment options are limited to surgery and chemotherapy, where Gemcitabine has been the cornerstone of therapy since 1997. However, Gemcitabine resistance prevents PDAC cure and mechanisms of resistance are not fully understood. Yet, with average survival times still <1 year, improved treatment selection and early assessment of response are urgently needed. Our group has recently developed a promising imaging based technology that will improve patient specific treatment selection and provide a platform for assessment of newly developed therapeutics with improved efficacy prediction compared to drug distribution alone. We have established a spatially-resolved, quantitative imaging methodology termed paired agent imaging (PAI), that enables quantification of drug target sites at the single cell level, allowing direct visualization of drug target availability (DTA) in situ, a parameter directly related to therapeutic efficacy. Using PAI, we examined the mechanisms of cancer therapy resistance on a cell-by-cell basis with the goal of utilizing explants for rapid, patient-specific therapy selection as they can predict treatment response in <5 days. As proof of concept we have studied Erlotinib, synthesizing paired targeted and untargeted fluorescently labeled derivatives. Overall, we anticipate that our spatially resolved maps of DTA will be predictive of therapeutic efficacy in patient PDAC explants, providing a platform technology for patient specific therapy selection <1 week after resection or biopsy.
Isothermal heating: purist and utilitarian views

The common thermodynamics example of reversible isothermal heating at temperature T requires the gas to maintain contact with a constant temperature reservoir at the same temperature as the gas. This is inconsistent with the often used view that heat is an energy transfer from higher to lower temperature. We discuss two ways to deal with this dichotomy, using what we call purist and utilitarian views, emphasizing the roles of language and logic in each. We suggest a way for teachers to address this issue in the classroom, and end with a review of related challenges to physics teachers associated with the terms heat and heating.
Nonlinear Programming: Theory, Algorithms and Applications

BASICS. The Nature of Optimization Problems. Analytical Background. Factorable Functions. UNCONSTRAINED PROBLEMS. Unconstrained Optimization Models. Minimizing a Function of a Single Variable. General Convergence Theory for Unconstrained Minimization Algorithms. Newton's Method With Variations. Conjugate Direction Algorithms. Quasi-Newton Methods. OPTIMALITY CONDITIONS FOR CONSTRAINED PROBLEMS. First- and Second-Order Optimality Conditions. Applications of Optimality Conditions. LINEARLY CONSTRAINED PROBLEMS. Models with Linear Constraints. Variable-Reduction Algorithms. NONLINEARLY CONSTRAINED PROBLEMS. Models with Nonlinear Constraints. Direct Algorithms for Nonlinearly Constrained Problems. Sequential Unconstrained Minimization Techniques. Sequential Constraint Linearization Techniques. OTHER TOPICS. Obtaining Global Solutions. Geometric Programming. References. Author and Subject Indexes.
Metternich, the Police and Hapsburg Censorship

Late the afternoon of Tuesday, 14 March 1848, the Austrian government let it be known in the streets of Vienna that Emperor Ferdinand had deigned to abolish censorship and to promise a law concerning the press. Jubilant crowds decorated the statue of Joseph II with garlands and, undisturbed by historical knowledge, placed in the hand of the “People’s Emperor” a banner with the words “Freedom of the Press.” A Patent of the All Highest Emperor Ferdinand I the next day recognized the wishes of loyal subjects and proclaimed, “By our declaration abolishing censorship, freedom of the press is granted just as in all states where it exists.” But this late concession followed the revolutionary outbreak in Vienna and did not appease the passions that burst forth then.2 Too long the objections to Hapsburg censorship had been disregarded.
Lymphocyte migration to the brain

Lymphocyte migration to the CNS is a tightly regulated process, which involves many cellular signaling cascades and molecules. Under normal conditions, lymphocyte migration to the CNS is limited and restricted to the perivascular spaces and CSF, but is thought to be important for CNS immunosurveillance. Here, the CP is most likely the “port of entry” for CD4+ central-memory T cells. Under pathological conditions, traffic signals are altered and expression of many adhesion molecules and chemokines permit lymphocytes to enter the CNS parenchyma where they need interaction with APCs to persist. The specific molecular mechanisms differ, depending on CNS site and stimuli, and need further exploration for better understanding and novel treatments of neuroinflammation.
Informed contrarian trades and stock returns

Abstract We develop a novel measure for the probability of informed trading. This measure, termed PCM, captures the adverse selection component of bid-ask spreads, becomes elevated around earnings announcements, and exhibits similar time-series patterns to price impact. Returns in double-sorted portfolios increase in PCM while controlling for liquidity. A long-short portfolio based on PCM generates 18.3% abnormal return annually. PCM significantly explains cross-sectional returns while controlling for other factors. This effect is robust to alternative specifications and remains significant after the decimalization in 2001. In sum, PCM is easy to implement and serves as an effective proxy for informed trading.
Restoration of Medical Images Using Genetic Algorithms

Image restoration is still one of the most important areas of medical image processing. Image restoration concerns about the removal or reduction of degradations in an image that could happen during the acquisition process. Being able to restore a medical image helps providing a better diagnosis and treatment. One of the most common blurring is the motion blur. Many restoration algorithms were proposed to solve the image restoration problem such as Wiener Filter, Lucy-Richardson and Blind Deconvolution Algorithms. These algorithms have varied performance, computational complexity, and abilities to deal with noisy images. They also require the knowledge of the Point Spread function (PSF) such that image deconvolution can be implemented. Restoration of an image is extremely reliant on the quality of the estimation technique used to find an accurate PSF parameters (i.e. motion length and motion angle). In this paper, we adopt Genetic Algorithms (GAs) to find the optimal PSF parameters such that a Wiener filter can be used for image restoration. We adopted number of statistical evaluation criteria to asses the quality of our proposed method. We applied our method on a number of medical images with various additive Gaussian noise. The developed results show that our proposed algorithm, PSF generated by GAs, is showing better results compared to other known methods in the literature in the absence of the real PSF.
Detecting Digital Photo Tampering with Deep Learning

The tools to tamper with digital photographs have become easier to use by the lay person and techniques have evolved that make detection of tampering more difficult, there is a clear need to not only discover novel ways to distinguish the difference between real and fake, but also to make the detection quicker and easier. Using content-aware resizing, which is also known as image retargeting, seam carving, content-aware rescaling, liquid rescaling, or liquid resizing, allows for changing the resolution of an image while keeping the content unchanged in the image. In this paper, the retraining of Inception ResNet v2, one of the best object detection deep learning classifiers, is undertaken to look at classifications of untampered versus tampered photos via seam removal.
Shrinkage Behavior of Cementitious Mortars Mixed with Seawater

The shrinkage behavior of cementitious materials mixed with seawater is investigated. Cement mortar mixtures were prepared with two water-to-cementitious materials ratios (w/cm = 0.36 and 0.45), two binder compositions (namely, ordinary portland cement (OPC) and OPC with 20 % fly ash replacement), and two types of water (tap water and seawater). The autogenous and drying shrinkage behavior of these mixtures are examined using ASTM standard test methods for 65 days. The use of seawater as mixing water increased the autogenous shrinkage. At w/cm 0.36, the ultimate autogenous shrinkage increased from 213 μs in the mixture with tap water to 387 μs in the mixture with seawater; the corresponding values were 149 and 314 μs, respectively, for mixtures with w/cm 0.45. An acceleration of the cement hydration at early ages caused by the seawater is identified as the cause of the increase in autogenous shrinkage in mixtures with seawater. At w/cm 0.36, seawater did not have a strong effect on the drying shrinkage, and tested mixtures had ultimate drying shrinkage values between 543 and 663 μs. At w/cm 0.45, in mixtures without fly ash, ultimate drying shrinkage increased from 838 μs in the mixture with tap water to 1,027 μs in the mixture with seawater. In mixtures with fly ash, the ultimate drying shrinkage increased from 738 μs in the mixture with tap water to 1,370 μs in the mixture with seawater. The drastic increase in the drying shrinkage in mixtures containing fly ash and seawater at w/cm 0.45 seems to be due to changes in mass loss behavior and the development of a finer pore size distribution. In applications where drying shrinkage may be a concern, the use of fly ash in seawater-mixed concrete could be problematic and lead to increased cracking risk. While the trends observed here will also hold in concrete, quantifying drying shrinkage and cracking of concrete based on the drying shrinkage of mortar mixtures is complex and depends on many other factors.
Shock Physics Fundamentals

Important concepts from continuum mechanics and shock physics are described. Plane shock waves are defined and categorized. Governing equations from geometrically nonlinear solid mechanics are presented. Continuum balance laws are discussed first, followed by derivation of the Rankine–Hugoniot jump conditions with emphasis on planar longitudinal shocks. Structured steady waves are analyzed. Supplemental relationships are derived in the context of the frequently used linear shock velocity versus particle velocity model. Material properties pertinent to the shock relations are tabulated for polycrystalline metals.
Glucose-Regulated Protein 78 Autoantibodies Are Associated with Carotid Atherosclerosis in Chronic Obstructive Pulmonary Disease Patients.

Atherosclerosis prevalence is increased in chronic obstructive pulmonary disease (COPD) patients, independent of other risk factors. The etiology of the excess vascular disease in COPD is unknown, although it is presumably related to an underlying (if cryptic) systemic immune response. Autoantibodies with specificity for glucose-regulated protein 78 (GRP78), a multifunctional component of the unfolded protein response, are common in COPD patients and linked to comorbidities of this lung disease. We hypothesized anti-GRP78 autoreactivity might also be a risk factor for atherosclerosis in COPD patients. Carotid intima-medial thickness (cIMT) was measured in 144 current and former smokers by ultrasound. Concentrations of circulating IgG autoantibodies against full-length GRP78, determined by ELISA, were greater among subjects with abnormally increased cIMT (p
Challenges and Opportunities for Virtual Learning in College Geology

We researched virtual strategies that can help engage college geology students in formal and/or informal environments. These virtual strategies were accomplished by using technological advances in photogrammetry, unmanned aircraft systems (UASs), panoramic photography, gigapixel imagery, 360° imagery, 3D mapping, 3D rendering, 3D game programming, and virtual reality. The core part of our virtual strategies is the Virtual Geology Learning Toolbox which contains virtual tools such as virtual specimens in a traditional laboratory, virtual roadcut, virtual overlook, virtual helicopter tour in 3D map platforms, and virtual field trips in 3D game worlds. We developed a virtual reality application as well and brought those tools into a more immersive virtual world. In addition to the Virtual Geology Learning Toolbox, we exploited technologies to promote active participation in traditional field trips by introducing UAS and an outdoor media sharing platform. Feedback from students and instructors is very positive, although we have faced limitations in some aspects of the technology. We predict that these limitations can be addressed as the technology develops, resulting in more powerful tools to leverage active learning in college geology.
The Impact of Early Epidural Discontinuation on Pain, Opioid Usage, and Length of Stay After Periacetabular Osteotomy.

BACKGROUND Periacetabular osteotomy (PAO) is the standard of care for treatment of symptomatic acetabular dysplasia. Patients undergoing PAO for acetabular dysplasia have postoperative pain that can be managed with epidural analgesia. The purpose of this study was to evaluate the impact of the timing of the discontinuation of epidural analgesia on pain, opioid usage, and hospital length of stay (LOS). The study hypothesis was that removal of the epidural catheter on postoperative day 1 (POD1) would lead to reduced overall opioid usage and LOS compared with removal on POD2. METHODS This is a retrospective before-and-after observational review of the impact of discontinuing epidural analgesia on POD1 versus POD2 in terms of in-hospital pain, opioid usage, and LOS. Baseline patient factors such as age, sex, and body mass index (BMI) as well as outcomes including mean and median of daily pain, total oral morphine milligram equivalents (MMEs) used per day, and LOS were recorded. Descriptive and comparative statistical analyses including multivariable main-effects linear regression modeling were performed to evaluate the impact of the timing of epidural removal on outcomes. RESULTS Directly comparing outcomes for the day of epidural removal, patients with removal on POD1 had significantly less pain (mean of 4.6 versus 5.1 on the numeric rating scale [NRS], p = 0.033) and opioid usage (130.7 versus 200.4 MMEs, p < 0.001) than patients with removal on POD2. Additionally, LOS (3.3 versus 4.6 days, p < 0.001) and total opioid usage (333.0 versus 674.8 MMEs, p < 0.001) were significantly reduced in patients with epidural removal on POD1. These results persisted in multivariable analyses that were adjusted for age, sex, and BMI. CONCLUSIONS This study demonstrated that patients with epidural removal on POD1 have significantly lower pain and an overall decrease in opioid usage on the date of epidural removal compared with patients undergoing epidural removal on POD2. Additionally, they have a shorter LOS as well as lower total opioid usage. Decreasing the duration of epidural usage may reduce pain, opioid usage, and LOS in patients undergoing PAO. LEVEL OF EVIDENCE Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.
"COVID arm": A reaction to the Moderna vaccine.

The Moderna mRNA-1273 vaccine was authorized by the Food and Drug Administration for emergency use during the ongoing COVID-19 pandemic in December 2020.1 Out of 15,185 participants in the phase III Coronavirus Efficacy (COVE) trials who received at least one dose of the Moderna vaccine, 228 (1.5%) reported hypersensitivity adverse events, including injection site rash and urticaria.2 Although we have seen an eruptive, morbilliform rash that manifests 48 hours postvaccination that is similar to a drug rash (Fig 1), we report 4 cases of “COVID arm”: a localized erythematous rash surrounding the injection site that manifests days after the first dose of the Moderna COVID-19 vaccine. Open in a separate window Fig 1 Generalized erythrodermic reaction observed 48 hours after the first dose of the Moderna vaccine in an 82-year-old man. A, Torso, anterior view. B Bilateral lower extremity involvement. C Right upper extremity.
Average Dwell-Time Minimization of Switched Systems via Sequential Convex Programming

This work finds a lower bound on the average dwell-time (ADT) of switching signals such that a continuous-time, graph-based, switched system is globally asymptotically stable, input-to-state stable, or integral input-to-state stable. We first formulate the lower bound on the ADT as a nonconvex optimization problem with bilinear matrix inequality constraints. Because this formulation is independent of the choice of Lyapunov functions, its solution gives a less conservative lower bound than previous Lyapunov-function-based approaches. We then design a numerical iterative algorithm to solve the optimization based on sequential convex programming with a convex-concave decomposition of the constraints. We analyze the convergence properties of the proposed algorithm, establishing the monotonic evolution of the estimates of the average dwell-time lower bound. Finally, we demonstrate the benefits of the proposed approach in two examples and compare it against other baseline methods.
Coil Embolization of Wide-Neck Bifurcation Aneurysms Using a Single-Balloon Microcatheter

Background: Coil embolization of wide-neck cerebral aneurysms frequently requires stent or balloon assistance. Such approaches to coil embolization increase the procedural complexity, adding risk and cost. Objective: To describe a series of coil embolization procedures performed using a single-balloon microcatheter to treat wide-neck aneurysms and establish the safety, feasibility and efficacy of this technique. Methods: A retrospective review was performed to identify cases in which the Ascent balloon (Codman Neurovascular, Raynham, Mass., USA) was used as a single-balloon microcatheter for aneurysm coil embolization at two institutions. Clinical, demographic and angiographic data were obtained, and aneurysm volumes as well as packing densities (PD) were calculated. Results: Eight cerebral aneurysms were treated using this technique. Six of these were unruptured. The aneurysms had an average neck diameter of 3.7 mm, and the maximum dimension ranged from 5 to 11 mm, with a mean of 7.5 mm. The mean aspect ratio was 2.07. The mean volume of the aneurysms was 180.38 mm3. The average PD achieved in these 8 aneurysms was 41.79%. Complete occlusion with coil embolization [Raymond-Roy Occlusion Classification (RROC) 1] was achieved in all cases except one, where a small residual was left deliberately and the occlusion grade was RROC 2. There were no intraprocedural complications. Conclusion: This initial experience demonstrates the feasibility and immediate outcomes of a single-balloon microcatheter technique in coil embolization of wide-neck cerebral aneurysms. This technique may be used to achieve a high PD, comparable to that obtained with stent-assisted coiling or coiling alone, while avoiding permanent stent placement and potentially reducing thromboembolic complications.
AN ANALYTICAL STUDY OF VOID GROWTH IN VISCOPLASTIC SOLIDS

Detailed numerical analyses are conducted to examine the effect of material elasticity and non-linear shape changes on void growth in viscoplastic solids. Numerical simulations are carried out under constant stress as well as cyclic loading conditions. The material response is assumed to be elastic-non-linear viscous (power law creep). Analyses of void growth are conducted assuming creep-controlled mechanism. The role of finite geometry changes in understanding cavity growth under balanced strain-controlled cyclic loading is also explored. The results indicate that while elastic accommodation does not influence void growth, non-linear shape changes of the voids significantly affect their growth characteristics. It is also shown that while grain boundary voids can grow under balanced strain cyclic loading when the accompanying shape changes are accounted for, they can either shrink or grow under load-controlled cycling depending on the loading frequency.
Sociotropic and Autonomous Personality Styles: Contributions to Chronic Life Stress

Sociotropy and autonomy are personality styles that are believed to moderate the effects of stressors on depression. This study tested the hypothesis that these styles may actually contribute to the occurrence of chronic stress. Specifically, we tested whether the personality styles are associated with increased chronic stress in the domain of vulnerability or in the cross domain. In a longitudinal study of 115 young women followed over 18 months, results indicated that one facet of autonomy, need for control, is a risk factor for increases in chronic interpersonal stress. Sociotropy was a risk factor for increases in future chronic achievement stress when coupled with either poor problem solving or low levels of perceived interpersonal competence. These results are consistent with Hammen's stress generation model, which emphasizes how individuals play a role in the creation of their own stress. Results also suggest that those with highly sociotropic or autonomous personality styles are more likely to create stress in the domain that they value less.
Integrin αvβ5-dependent Serine Phosphorylation of Paxillin in Cultured Human Macrophages Adherent to Vitronectin

The macrophage colony-stimulating factor (M-CSF) is able to induce the expression of the alpha v beta 5 integrin receptor on the surface of cultured human macrophages (De Nichilo, M. O., and Burns, G. F. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 2517-2521). In the present study, we establish that the adhesion of M-CSF-treated macrophages to vitronectin is mediated by the integrin alpha v beta 5, and show by indirect immunofluorescence analysis that alpha v beta 5 and the cytoskeletal protein paxillin localize to focal contacts upon adhesion to vitronectin. Immunoprecipitation and Western blot analysis revealed that M-CSF-treated macrophages do not express focal adhesion kinase (FAK), thereby providing direct evidence for integrin-dependent localization of paxillin to focal contacts in the absence of FAK expression. Investigation of paxillin phosphorylation by two-dimensional phosphoamino acid analysis indicates that paxillin is 99% phosphorylated on serine residue(s) in response to vitronectin adhesion, and only 1% phosphorylated on tyrosine. Stimulation of protein kinase C (PKC) activity with the phorbol ester phorbol 12-myristate 13-acetate enhances paxillin phosphorylation, while two selective inhibitors of PKC, GF109203X and chelerythrine chloride, effectively block the phosphorylation of paxillin induced in response to vitronectin adhesion. Taken together, these data demonstrate that in M-CSF-treated macrophages adherent to vitronectin, paxillin localizes to focal contacts in the absence of FAK expression and is predominantly phosphorylated on serine residue(s) in a PKC-dependent manner.
Ground bounce, what you simulate may not be what you get

Ground bounce is caused by rapid transitions at the input to the last stage of a CMOS output buffer. The noise is relatively independent of the output edge transition time. The critical noise observation point is the output of a nonswitching gate. More realistic ground bounce simulations can be obtained by observing the output of a nonswitching gate instead of the voltage at the package inductance. Ground bounce is shown to be independent of output risetimes, and nonlinear with the number of outputs switching or the inductance. >
Frameless single-isocenter intensity modulated stereotactic radiosurgery for simultaneous treatment of multiple intracranial metastases

Purpose: Stereotactic radiosurgery (SRS) is well accepted treatment for patients with intracranial metastases, but the role of frameless radiosurgery is not well defined. Here, we describe our clinical experience applying a novel single-isocenter technique to frameless intensity modulated stereotactic radiosurgery (IMRS) for simultaneous treatment of multiple intracranial metastases. Methods and materials: Between 2006 and 2012, 100 consecutive patients received frameless IMRS for multiple intracranial metastases using a single, centrally-located isocenter. Among these, 29 patients were treated for progressive or recurrent intracranial disease. A total of 465 metastases (median, 4 per patient, range, 2-18) were treated to a median dose of 20 Gy (range, 15-50 Gy). Follow-up including clinical examination and magnetic resonance imaging (MRI) occurred every 3 months. Results: Median follow-up for all patients was 4.3 months (range, 0.2-58.3 months), with 83 patients (83.0%) followed until their death. For the remaining 17 patients alive at the time of analysis, median followup was 9.2 months (range, 2.2-58.3 months). Overall survival at 6 months was 49.5% [95% confidence interval (CI), 35.3-63.6%]. Local control at 6 and 12 months was 88.9% (95% CI, 79.1-98.6%) and 81.5% (95% CI, 65.2-97.7%), respectively. Regional failure was observed in 39 patients (39%), and 25 patients (25%) received salvage therapy. Grade 3 or greater treatment-related toxicity was observed in 4 patients (4%) and included intracranial hemorrhage, seizure, and radionecrosis. Median total treatment time was 17.2 minutes (range, 2.8-55.3 minutes). Conclusions: Single-isocenter IMRS for multiple intracranial metastases can produce clinical outcomes comparable to those of conventional radiosurgery techniques.
Passive properties of canine left ventricle: diastolic stiffness and restoring forces.

Left ventricular (LV) diastolic pressure-volume (P-V) relations arise from a complex interplay of active decay of force (i.e., relaxation), passive elastic myocardial properties, and time-varying inflow across the mitral orifice. This study was designed to quantify the passive properties of the intact ventricle and the effects of elastic recoil by separating filling from relaxation with a method of LV volume clamping with a remote-controlled mitral valve. Eleven open-chest fentanyl-anesthetized dogs were instrumented with aortic and mitral flow probes, LV and left atrium micromanometers, and a remote-controlled mitral valve. We prevented complete (end-systolic volume clamping) or partial filling at different times in diastole. The ventricle thus relaxed completely at different volumes, and we generated P-V coordinates for the passive ventricle that included negative, as well as positive, values of pressure. We then estimated ventricular volumes from ventricular weight in eight dogs, using regression equations based on data in the literature, to determine the equilibrium volume (V0), that is, volume at zero transmural pressure, in the working ventricle. We abandoned the traditional exponential approach and characterized by the P-V relation with a logarithmic approach that included maximum LV volume (Vm), minimum volume (Vd), and stiffness parameters (Sp and Sn) for the positive (p) and negative (n) phases: Pp = -Sp In[(Vm - V)/(Vm - V0)] and Pn = Sn In[(V - Vd)/(V0 - Vd)]. With this formulation, the chamber compliance, dP/dV, is normalized by the LV operating volume, and Sp and Sn are size-independent chamber stiffness parameters with the units of stress. In eight ventricles with LV weight = 131 +/- 20 g, Vm = 116 +/- 18 ml, V0 = 37 +/- 6 ml, and Vd = 13 +/- 2 ml, stiffness Sp = 14.6 mm Hg and Sn = 5.1 mm Hg were determined from the slopes of the log-linearized equations. Also, the duration of LV relaxation is increased by the process of ventricular filling (161 +/- 31 msec, filling versus 108 +/- 36 msec, nonfilling, measured from dP/dtmin, p less than 0.0001). We conclude that volume clamping is a useful method of studying restoring forces and that the logarithmic approach is conceptually and quantitatively useful in characterizing the passive properties of the intact ventricle.
Persistent pruritic papules and plaques: a characteristic histopathologic presentation seen in a subset of patients with adult-onset and juvenile Still's disease

Background: ‘Persistent pruritic papules and plaques’ of Still’s disease represents a recently described eruption seen in a subset of patients. Most cases reported in the literature to date have been associated with adult-onset Still’s disease. Methods: We present the clinical and histopathologic examinations of three female patients ranging in age from 15 to 54 years. Results: Our three patients each presented with clinical findings consistent with Still’s disease. The youngest patient suffered from the juvenile form of Still’s disease (systemic-onset juvenile rheumatoid arthritis). Each patient had a persistent, pruritic eruption with histopathologic findings of dyskeratosis confined to the upper layers of the epidermis as well as a sparse superficial dermal infiltrate containing scattered neutrophils. Conclusions: These cases confirm the characteristic clinical and histopathologic findings of ‘persistent papules and plaques of Still’s disease’ and show the potential for this eruption in both the adult and juvenile age groups.
A liquid‐metal magnetohydrodynamic acoustic transducer

The properties of a liquid‐metal magnetohydrodynamic acoustic power transducer have been both calculated and measured. The calculations are based on linearized Navier–Stokes and Maxwell’s equations, and include Ohmic and viscous dissipation in the liquid metal. The measurements were made with liquid sodium at frequencies of about 1 kHz in a channel much larger than the viscous penetration depth but comparable in size to the electromagnetic skin depth. Calculated and measured quantities are in good agreement, indicating a quantitative understanding of this transducer. It converts acoustic power to electric power with 45% efficiency; substantially higher efficiencies appear possible with a slightly modified design.
Variable neural adaptive robust output feedback control of uncertain systems

The design of an adaptive robust output feedback controller is presented for a class of multi-input multi-output uncertain systems. The proposed output feedback controller uses a variable-structure radial basis function (RBF) network to approximate unknown system dynamics. The output feedback implementation is realized employing a high-gain observer. The structure variation of the RBF network is taken into account in the stability analysis of the closed-loop system using the piecewise quadratic Lyapunov function. The performance of the proposed variable neural adaptive robust output feedback controller is illustrated with simulations.
Case Series of Behavioral Psychotherapy for Obsessive-Compulsive Symptoms in Youth with Prader-Willi Syndrome

Obsessive-compulsive symptoms among youth with Prader-Willi Syndrome (PWS) are frequently present and associated with considerable problems in the daily functioning of the child and his/her family. Although pharmacological and psychosocial treatments exist that target obsessive-compulsive symptoms among typically developing youth, these treatments have not been systematically adapted and/or evaluated for this population. Furthermore, although psychotropic medications have shown promising support in addressing obsessive-compulsive symptoms in several case reports involving youth with PWS, associated efficacy is modest and potential for side effects is a realistic concern. Given efficacy and tolerability of cognitive-behavioral treatment for obsessive-compulsive symptoms in typically developing youth, an adapted version of this approach may hold promise in treating clinically problematic obsessive-compulsive symptoms in youth with PWS. Thus, we report on a case series of behavioral treatment for obsessive-compulsive symptoms in three youth with PWS. Diagnostic and symptom severity assessments were conducted at screening, pre-treatment, and post-treatment by a trained independent evaluator. All youth were considered treatment responders and exhibited meaningful reductions in compulsion severity, overall obsessive-compulsive severity, and obsessive-compulsive related impairment. These data provide preliminary evidence for the utility of behavioral therapy in treating obsessive-compulsive symptoms in youth with PWS.
Determination of the superconducting penetration depth from coplanar-waveguide measurements

We introduce a novel transmission-line method for determining the penetration depth in thin high-temperature superconducting (HTS) films. The method is based on the accurate measurement of the inductance per unit length of a superconducting coplanar-waveguide (CPW) transmission line fabricated on the HTS sample. Using the experimentally obtained inductance per unit length, we interpolate the penetration depth from a table of numerically determined values of inductance (per unit length) as a function of penetration depth, calculated from a coupled transmission-line model. A novelty of our procedure is the utilization of the multiline thru-reflect-line (TRL) method and the calibration-comparison method to accurately determine the inductance per unit length of the superconducting transmission line. By measuring different CPW geometries patterned onto the same thin-film sample, we can verify our penetration depth values. We demonstrate this technique by extracting the penetration depth for several different HTS films at 76 K. Estimated uncertainties in the extracted penetration depth are also provided.
Dendritic cells as controllers of antigen-specific Foxp3^+ regulatory T cells

Regulatory T cells (Treg) are a subpopulation of CD4(+) lymphocytes that maintain immunological self-tolerance in the periphery. Treg also regulate or suppress other classes of immune response such as allograft rejection, allergy, tumor immunity, and responses to microbes. Treg express the Foxp3 transcription factor and CD25, the high affinity interleukin-2 receptor (IL-2R). Treg are divided into two types: naturally occurring Treg derived from thymus (natural Treg) and Treg induced from Foxp3(-) CD4(+) T cells in the periphery (induced Treg). It would be valuable to understand how to control the generation of antigen-specific Treg, which could also provide a new approach to treat autoimmunity, allergy or allograft rejection without suppressing immune responses to tumor and microbes. In this review, we will discuss the role of dendritic cells (DCs) in controlling antigen-specific natural Treg and induced Treg. Natural Treg are anergic upon T cell receptor stimulation generally, however, we found that the antigen-specific natural Treg can be expanded by antigen-presenting mature bone marrow-derived dendritic cells (BM-DCs). Furthermore, recent studies showed that antigen-specific Treg can be induced from Foxp3(-) CD25(-) CD4(+) T cells by antigen-presenting DCs, particularly select subsets of DCs in the periphery. These findings need to be pursued to develop novel immune suppressive therapies using antigen-specific Treg educated by DCs.
Mast cells in allergy and infection: Versatile effector and regulatory cells in innate and adaptive immunity

Mast cells are widely distributed in tissues, particularly near surfaces exposed to the environment. Mast cells can be activated to secrete diverse mediators and cytokines by IgE and specific Ag and many other stimuli, including products derived from either pathogens or the host during innate immune responses. Although mast cells are best known for their role in IgE-associated allergic disorders, mast cells can also exacerbate models of autoimmunity, enhance the sensitization and/or effector phases of certain cutaneous contact hypersensitivity responses, and increase inflammation and mortality during some severe bacterial infections. In other settings, however, mast cells can limit inflammation and tissue injury: mast cells promote host resistance in certain models of bacterial or parasite infection, limit pathology during some acquired immune responses to environmental Ag, including examples of severe contact hypersensitivity, and have adjuvant-like properties that can enhance the development of protective immunity against pathogens. These and other findings suggest that mast cells occupy a critical niche at the interface of innate and acquired immunity, where, depending on circumstances that remain to be fully understood, mast cells may function to perturb or help to restore homeostasis (or both), with consequences that can either promote health or contribute to disease.
Fraud risk assessments and auditors’ professional skepticism

Purpose – To examine whether planning‐stage fraud risk assessments and audit experience affect the level of professional skepticism displayed by auditors during fieldwork.Design/methodology/approach – The paper presents an experiment using professional auditors.Findings – Overall, auditors predisposed to low fraud risk assessments were less skeptical than those with no knowledge of fraud risk (control group). Also, as expected, auditors in the control group were less skeptical than those predisposed to moderate/high fraud risk assessments. Staff auditors were more skeptical than seniors. Senior auditors showed no differences in skepticism between the control group and high fraud risk assessment group.Research limitations/implications – Professional skepticism in this study is measured as the auditors’ assessment of client truthfulness. There is reasonable disagreement on the exact meaning of professional skepticism and some readers’ interpretation of the term may be different from the authors' own.Practic...
Relationship of restriction fragment length polymorphisms to single-cross hybrid performance of maize.

Isozymes and restriction fragment length polymorphisms (RFLPs) have been proposed for use in varietal identification and selection for agronomic traits. Although the use of isozymes for these purposes has been well documented, evaluation of the efficacy of RFLP technology as applied to crop improvement is far from complete. This investigation was conducted to study the relationship between RFLP-derived genotypes and heterotic patterns of a group of maize (Zea mays L.) inbred lines. A total of 22 inbreds was crossed to four testers (B73, B76, Mo17, and Va26) in combinations that minimized crossing within heterotic groups. Forty-seven single-cross progeny were subsequently evaluated for several agronomic traits (including grain yield and moisture, ear height, and root lodging) over 2–4 consecutive years at two to four Iowa locations in a randomized complete-block design. The inbred lines were subjected to RFLP analysis, which involved 47 genomic clones and the restriction enzymes EcoRI and HindIII. Hybrid RFLP patterns were predicted from their inbred parents. Modified Roger's distances were computed to estimate genetic distance among the inbred lines. Principal component analysis facilitated ascertainment of relative dispersion of the inbreds based on the frequency of variants at specific RFLP loci. Evident associations of variants with genes affecting agronomic traits were identified by principal component regression analysis, in which adjusted hybrid means were regressed on the matrix of hybrid variants frequencies. The hybrid means were adjusted by removing environmental effects, using residuals as dependent variables in the regression analysis. Results from this study suggest that RFLP analysis may be of value in allocating maize inbreds to heterotic groups, but no relationship between RFLP-based genetic distance and hybrid performance was apparent. Principal component regression identified variants potentially linked to genes that control specific agronomic traits.
Near-infrared face recognition utilizing open CV software

Commercially available hardware, freely available algorithms, and authors’ developed software are synergized successfully to detect and recognize subjects in an environment without visible light. This project integrates three major components: an illumination device operating in near infrared (NIR) spectrum, a NIR capable camera and a software algorithm capable of performing image manipulation, facial detection and recognition. Focusing our efforts in the near infrared spectrum allows the low budget system to operate covertly while still allowing for accurate face recognition. In doing so a valuable function has been developed which presents potential benefits in future civilian and military security and surveillance operations.