cssi/SciSciGPT-SciSciNet huggingface dataset:
Smooth-Muscle Myosin II

The major motor protein in all hollow organs, except the heart, is smooth-muscle myosin II (SmM) and the emphasis of this chapter is on the function of SmM in differentiated smooth muscle. A sliding-filament mechanism is assumed for smooth muscle, as in striated muscle, but there are differences in smooth-muscle thick filaments with respect to assembly and stability. Various isoforms of SmM are expressed and are discussed. SmM differs from its striated muscle counterparts in the requirement for phosphorylation of the regulatory light chains to regulate motor activity. The components of myosin structure required for phosphorylation dependence are outlined. The level of SmM phosphorylation is controlled by opposing actions of the Ca2+-calmodulin-dependent myosin-light-chain kinase and myosin phosphatase. Both are subject to regulation and putative mechanisms are presented. The focus of recent research has been on regulation of myosin phosphatase and inhibition and activation are proposed. Several signaling pathways converge at the myosin phosphatase target subunit to regulate activity. Two pathways that work in opposition are inhibition via the RhoA/Rho-kinase couple and activation by cyclic nucleotides, particularly cGMP. Each is vital in smooth-muscle function and both pathways have important clinical application and are argeted bypharmacological intervention in treatment of smooth-muscle disorders.
Summation of Findings and Conclusion

This project to study the effectiveness of methadone maintenance treatment was jointly planned by the senior author and staff at the National Institute on Drug Abuse in 1984. In response to earlier expert reviews of the status of drug abuse treatment in the United States, it was held that large-scale intensive studies of particular types of treatment, or modalities, were warranted. The reasons advanced for supporting more intensive research about treatment effectiveness were various but emphasized such issues as matching drug abusing patients to appropriate treatment and determining the extent of psychiatric impairment in this population. At that time there was little or no interest in studying drug abuse treatment programs; the emphasis was on studying patients.
7.10 Conceptualization in Catchment Modeling

In both hydrology and geomorphology, conceptualization plays an important role in interpreting existing data, guiding future data collection, and developing models. Concept-development simulation can be a useful tool for understanding how hydrogeomorphic systems work. Here, model classification, the issues of scale, and model performance testing are discussed. Concept-development examples, based upon ‘what if’ simulation with the integrated hydrology model (InHM), are given for a small rangeland catchment in Oklahoma (i.e., runoff generation), a dammed watershed in California (i.e., hydrologically driven erosion), and the Hawaiian island of Kaho'olawe (i.e., hydrologically driven erosion). The reductionist approach to concept-development simulation is fully demonstrated in the comprehensive InHM simulations for the data-rich Coos Bay experimental catchment (i.e., pore–water pressure development related to slope instability). The various calls for detailed, long-duration field-monitoring programs at selected experimental catchments are renewed, as the search for a comprehensive understanding of hydrologically driven landscape evolution begs data-intensive discovery.
Relationship between diagnostic interval and pancreatic ductal adenocarcinoma (PDAC) resectability: A single-center retrospective analysis.

e15738Background: PDAC often presents with nonspecific symptoms and the workup for suspected PDAC is not standardized. While surgery remains the only curative therapy, only 20% of PDAC is resectabl...
The Impact of Low-Dose Cranial Boost on the Long-Term Outcomes of Adult Patients with High-Risk Acute Lymphoblastic Leukemia Undergoing Total Body Irradiation and Allogeneic Hematopoietic Stem Cell Transplantation.

Abstract Purpose Total body irradiation (TBI) is an integral part of the conditioning regimen for patients with acute lymphoblastic leukemia (ALL) undergoing allogeneic, hematopoietic, cell transplantation (allo-HCT). There are conflicting data in the literature regarding the utility of a cranial irradiation boost in high-risk adult ALL without evidence of preexisting central nervous system (CNS) involvement. This study investigates the posttransplant clinical outcomes of patients with high-risk adult ALL undergoing TBI conditioning for allo-HCT with or without a whole-brain boost, without overt CNS involvement at the time of diagnosis. Methods and materials A retrospective cohort study was conducted using a medical record analysis. We identified 58 patients who were treated between January 1998 and December 2016, and met our preset inclusion criteria of adults (age >18 years old) who carried a pathologically confirmed diagnosis of CNS-negative, high-risk ALL, who underwent hematopoietic stem cell transplantation with TBI conditioning. A multivariate analysis of correlation between patient outcomes and collected categorical variables was assessed with stepwise Cox logistic regression. Survival analyses were assessed using the Kaplan-Meier technique with a log-rank test. Results With a median follow-up time of 5.3 years, there was a statistically significant improvement in actuarial 7-year CNS relapse-free survival (100% vs 76.4%; P = .043) in favor of patients undergoing a cranial boost. There was no statistically significant improvement in 7-year progression-free survival (78.3% vs 62.5%; P = .076) or overall survival (49.4% vs 43.5%; P = .921) with versus without a cranial boost. On multivariate analysis, the presence of a cranial boost was the only identified variable with an independent relationship to CNS relapse-free survival. Conclusions Adult patients with high-risk, CNS-negative ALL were found to have a statistically significant improvement in CNS relapse-free survival and a trend toward improved progression-free survival with the inclusion of a cranial boost with TBI pretransplant conditioning. Our data indicate that further investigation into the use of cranial boost in this patient population is warranted.
Analyzing ring moiety additions to the A-ring of camptothecin

e13529 Background: Two camptothecin (CPT) analogues, irinotecan and topotecan, are currently approved by the FDA for the treatment of several advanced cancers. Over the last decade, interest in CPT...
The genetics of resistance to lettuce drop (Sclerotinia spp.) in lettuce in a recombinant inbred line population from Reine des Glaces × Eruption

Two QTLs for resistance to lettuce drop, qLDR1.1 and qLDR5.1, were identified. Associated SNPs will be useful in breeding for lettuce drop and provide the foundation for future molecular analysis. Lettuce drop, caused by Sclerotinia minor and S. sclerotiorum, is an economically important disease of lettuce. The association of resistance to lettuce drop with the commercially undesirable trait of fast bolting has hindered the integration of host resistance in control of this disease. Eruption is a slow-bolting cultivar that exhibits a high level of resistance to lettuce drop. Eruption also is completely resistant to Verticillium wilt caused by race 1 of Verticillium dahliae. A recombinant inbred line population from the cross Reine des Glaces × Eruption was genotyped by sequencing and evaluated for lettuce drop and bolting in separate fields infested with either S. minor or V. dahliae. Two quantitative trait loci (QTLs) for lettuce drop resistance were consistently detected in at least two experiments, and two other QTLs were identified in another experiment; the alleles for resistance at all four QTLs originated from Eruption. A QTL for lettuce drop resistance on linkage group (LG) 5, qLDR5.1, was consistently detected in all experiments and explained 11 to 25% of phenotypic variation. On LG1, qLDR1.1 was detected in two experiments explaining 9 to 12% of the phenotypic variation. Three out of four resistance QTLs are distinct from QTLs for bolting; qLDR5.1 is pleiotropic or closely linked with a QTL for early bolting; however, the rate of bolting shows only a small effect on the variance in resistance observed at this locus. The SNP markers linked with these QTLs will be useful in breeding for resistance through marker-assisted selection.
CoPPer: Soft Real-Time Application Performance Using Hardware Power Capping

Dynamic voltage and frequency scaling (DVFS) has been the cornerstone of innumerable software approaches to meeting application timing requirements with minimal energy. However, recent trends in technology—e.g., moving voltage converters on chip—favor hardware control of DVFS, as hardware can both react faster to external events and perform fine-grained power management across a device. We respond to these trends with CoPPer, which instead uses hardware power capping to meet application performance requirements with high energy efficiency. We find that meeting performance requirements with power capping is more challenging than using DVFS because the relationship between power and performance is non-linear and has diminishing returns at high power values. CoPPer overcomes these difficulties by using adaptive control to approximate non-linearities and a novel gain limit to avoid over-allocating power when it is no longer beneficial. We evaluate CoPPer with 20 parallel applications and compare it to both a classic linear DVFS controller and to a sophisticated control-theoretic, model-driven software DVFS manager. CoPPer provides all the functionality of the sophisticated DVFS-based approach, without requiring a user-specified model or time-consuming, exhaustive application/system pre-characterization. Compared to DVFS, CoPPer's gain limit reduces energy by 6% on average and by 12% for memory-bound applications. For high performance requirements, the energy savings are even greater: 8% on average and 18% for memory-bound applications.
Quantitative Fundus Autofluorescence in Rhesus Macaques in Aging and Age-Related Drusen.

Author(s): Tran, Tu M; Kim, Soohyun; Lin, Kira H; Chung, Sook Hyun; Park, Sangwan; Sazhnyev, Yevgeniy; Wang, Yinwen; Cunefare, David; Farsiu, Sina; Thomasy, Sara M; Moshiri, Ala; Yiu, Glenn | Abstract: PurposeTo employ quantitative fundus autofluorescence (qAF) imaging in rhesus macaques to noninvasively assess retinal pigment epithelial (RPE) lipofuscin in nonhuman primates (NHPs) as a model of aging and age-related macular degeneration (AMD).MethodsThe qAF imaging was performed on eyes of 26 rhesus macaques (mean age 18.8 ± 8.2 years, range 4-27 years) with normal-appearing fundus or with age-related soft drusen using a confocal scanning laser ophthalmoscope with 488 nm excitation and an internal fluorescence reference. Eyes with soft drusen also underwent spectral-domain optical coherence tomography imaging to measure drusen volume and height of individual drusen lesions. The qAF levels were measured from the perifoveal annular ring (quantitative autofluorescence 8 [qAF8]) using the Delori grid, as well as focally over individual drusen lesions in this region. The association between qAF levels and age, sex, and drusen presence and volume were determined using multivariable regression analysis.ResultsMean qAF levels increased with age (P l 0.001) and were higher in females (P = 0.047). Eyes with soft drusen exhibited reduced mean qAF compared with age-matched normal eyes (P = 0.003), with greater drusen volume showing a trend toward decreased qAF levels. However, qAF levels are focally increased over most individual drusen (P l 0.001), with larger drusen appearing more hyperautofluorescent (R2 = 0.391, P l 0.001).ConclusionsIn rhesus macaques, qAF levels are increased with age and female sex, but decreased in eyes with soft drusen, similar to human AMD. However, drusen lesions appear hyperautofluorescent unlike those in humans, suggesting similarities and differences in RPE lipofuscin between humans and NHPs that may provide insight into drusen biogenesis and AMD pathogenesis.
Idiosyncratic epistasis creates universals in mutational effects and evolutionary trajectories.

Patterns of epistasis and shapes of fitness landscapes are of wide interest because of their bearings on a number of evolutionary theories. The common phenomena of slowing fitness increases during adaptations and diminishing returns from beneficial mutations are believed to reflect a concave fitness landscape and a preponderance of negative epistasis. Paradoxically, fitness decreases tend to decelerate and harm from deleterious mutations shrinks during the accumulation of random mutations—patterns thought to indicate a convex fitness landscape and a predominance of positive epistasis. Current theories cannot resolve this apparent contradiction. Here, we show that the phenotypic effect of a mutation varies substantially depending on the specific genetic background and that this idiosyncrasy in epistasis creates all of the above trends without requiring a biased distribution of epistasis. The idiosyncratic epistasis theory explains the universalities in mutational effects and evolutionary trajectories as emerging from randomness due to biological complexity. Theory, simulations and empirical data are used to show that the phenotypic effect of a mutation varies substantially depending on the specific genetic background, thereby resolving an apparent contradiction between predictions of convex and concave fitness landscapes.
Syllabus Sanctions: Controlling Language and Fairness as Antecedents to Students’ Psychological Reactance and Intent to Comply

Psychological reactance theory (PRT) has helped explain students’ resistant behavior. Additionally, several studies have explored resistant student behaviors as a product of an instructor’s syllabu...
"Stress taper" fixation increases torsional failure strength in a cadaveric femur model.

Abstract Background To potentially limit peri-implant fractures our institution commonly implements a “stress-taper” fixation construct in which the screw lengths towards the proximal end of a construct are incrementally decreased, in order to avoid a focal stress-riser when loaded. To assess this construct, we asked: 1) Does the stress taper strategy increase torsional strength than the bicortical locking construct when biomechanically tested in a cadaveric femur model? 2) Does it fail in a less comminuted fracture pattern? Methods Seven matched pairs of cadaveric femora were randomly assigned to one of two distal femur fixation groups: plating with stress taper strategy or bicortical fixation. Specimens were first cyclically loaded, then axially rotated to failure under 800 N of compression. Peak torque at failure, degrees of rotation at failure, and energy to failure were calculated and compared using paired t-tests. Fractures were categorized with the assistance of fluoroscopy according to the Orthopedic Trauma Association classification, 32. Findings There was significantly greater peak torque (110.6 ± 49.7 Nm vs. 80.6 ± 35.2 Nm), rotation at failure (23.8 ± 5.3° vs 18.9 ± 4.5°) and energy to failure (25.3 ± 15.7 J vs. 14.1 ± 8.3 J) in the stress-taper group as compared to the bicortical group (p = 0.0424), (p = 0.0213) and (p = 0.0460), respectively. 6/7 fractures in the stress-taper group were classified 32 A1 with 1/7 classified A2. 5/7 fractures in the bicortical group were classified B1 and 2/7 classified A2. Interpretation ‘Stress taper fixation’ in distal femurs may be protective against peri-implant fractures compared to traditional bicortical fixation. The ‘stress taper’ concept can increase torsional failure strength in an in vitro model.
A very present help: The role of religious support for Black adolescent girls' mental well-being.

This study explored religious emotional support as a mediator of the association between organized religious involvement (ORI) and mental well-being among African American and Caribbean Black girls. Data are drawn from a nationally representative survey of Black adolescents. The sample was composed of African American (n = 412) and Caribbean Black (n = 165) girls, aged 13-17. Structural equation modeling tested direct and indirect effects of ORI on mental well-being, through religious emotional support. For African American girls, ORI was not directly related to any of the mental well-being outcomes. Religious emotional support mediated the association between ORI and self-esteem, mastery, and life satisfaction. For Caribbean Black girls, ORI was negatively associated with mastery and life satisfaction. Religious emotional support mediated the association between ORI and life satisfaction. Results suggest that the well-being benefits of ORI for Black girls only remain significant in the presence of religious emotional support and are different for ethnic subgroups.
Lapatinib and poziotinib overcome ABCB1-mediated paclitaxel resistance in ovarian cancer

Conventional frontline treatment for ovarian cancer consists of successive chemotherapy cycles of paclitaxel and platinum. Despite the initial favorable responses for most patients, chemotherapy resistance frequently leads to recurrent or refractory disease. New treatment strategies that circumvent or prevent mechanisms of resistance are needed to improve ovarian cancer therapy. We established in vitro paclitaxel-resistant ovarian cancer cell line and organoid models. Gene expression differences in resistant and sensitive lines were analyzed by RNA sequencing. We manipulated candidate genes associated with paclitaxel resistance using siRNA or small molecule inhibitors, and then screened the cells for paclitaxel sensitivity using cell viability assays. We used the Bliss independence model to evaluate the anti-proliferative synergy for drug combinations. ABCB1 expression was upregulated in paclitaxel-resistant TOV-21G (q < 1x10-300), OVCAR3 (q = 7.4x10-156) and novel ovarian tumor organoid (p = 2.4x10-4) models. Previous reports have shown some tyrosine kinase inhibitors can inhibit ABCB1 function. We tested a panel of tyrosine kinase inhibitors for the ability to sensitize resistant ABCB1-overexpressing ovarian cancer cell lines to paclitaxel. We observed synergy when we combined poziotinib or lapatinib with paclitaxel in resistant TOV-21G and OVCAR3 cells. Silencing ABCB1 expression in paclitaxel-resistant TOV-21G and OVCAR3 cells reduced paclitaxel IC50 by 20.7 and 6.2-fold, respectively. Furthermore, we demonstrated direct inhibition of paclitaxel-induced ABCB1 transporter activity by both lapatinib and poziotinib. In conclusion, lapatinib and poziotinib combined with paclitaxel synergizes to inhibit the proliferation of ABCB1-overexpressing ovarian cancer cells in vitro. The addition of FDA-approved lapatinib to second-line paclitaxel therapy is a promising strategy for patients with recurrent ovarian cancer.
Are gastroenterologists willing to implement imaging-guided surveillance for Barrett's esophagus? Results from a national survey.

Introduction: The American Society for Gastrointestinal Endoscopy (ASGE) has published a Preservation and Incorporation of Valuable Endoscopic Innovations (PIVI) statement on incorporating an imaging-guided surveillance protocol to replace the current practice of four-quadrant biopsies every two centimeters for Barrett’s esophagus (BE) surveillance. We sought to determine if current gastroenterologists would be willing to apply these changes to their practice and identify any barriers to implementation. Methods: We collected data using surveys that were distributed at two national meetings and using a random selection process emailed surveys to members listed in the American Gastroenterological Association directory. Physicians from a variety of practice settings participated. Primary outcomes of our study included determining whether clinicians would be willing to accept an imaging-based surveillance protocol, their reasons for not doing so, and whether a financial incentive would be persuade them to implement the protocol. Continuous variables were reported as mean ± standard deviation. Categorical variables were summarized with percentages and 95 % confidence intervals. Results: Gastroenterologists (172) completed the survey; and 140 (81.4 %) of them stated they would implemented the PIVI recommendations into practice. Using a multivariate analysis of the data, physicians who reported a financial incentive for submitting biopsy specimens to pathology were less likely to implement the PIVI recommendations. The two main barriers to implementation of the protocol were medical-legal and financial reasons. Of the 32 gastroenterologists who were not willing to implement the imaging-guided surveillance protocol, 20 (62.5 %) stated that they would implement it if there were a financial incentive. Discussion: The PIVI statement focuses on re-evaluating our current method of surveillance for BE. The results of our survey show that gastroenterologists may be willing to implement an imaging-guided surveillance program, but concerns regarding financial compensation and proper training in advanced imaging techniques remain.
Contrasting visions of science in ecological restoration: Expert-lay dynamics between professional practitioners and volunteers

Abstract Ecological restoration as a popular form of volunteer participation has been praised as an example of democratic natural resource management. However, the involvement of volunteers in projects guided by professionals does not necessarily ensure democratic knowledge exchange and production. Drawing insights from citizen science and political ecology, this paper investigates the role of science in mediating the dynamics between professional practitioners and volunteers. Using case studies of ecological restoration programs at two university arboreta in the American Midwest, this paper argues that the contrasting visions of science between professional practitioners and volunteers led to conflicts and presented challenges for the institutions to genuinely engage the public in contributing local knowledge and framing management priorities. While both groups emphasized the practical aspect of science in guiding restoration work, they differed in how they conceptualized the role of humans in restoration, work priorities, and how to apply scientific theories and methods in restoration. Moreover, at the university arboreta, science defined institutional identity and claims to scientific authority further delineated boundaries between professional practitioners and volunteers. As a result, distrust, tensions, lack of engagement, and different levels of desired public participation existed in these seemingly participatory programs. Theoretically, this paper contributes to the cross-fertilization between citizen science and political ecology by underscoring the politics of participation and the role of science (and its interpretations) in challenging expert-lay dynamics in environmental volunteering programs. Practical recommendations are included for deconstructing the expert-lay hierarchy and moving restoration toward a democratic practice.
Wide-complex tachycardia.

To the Editor: The Images in Cardiovascular Medicine section of the August 29, 2000 issue of Circulation presented a case of wide-complex tachycardia (WCT) that reportedly required placement of a transesophageal lead to diagnose ventricular tachycardia (VT).1 Pharmacological trials of adenosine, diltiazem, lidocaine, and procainamide were noted to be unhelpful. In our view, the diagnosis of VT can be firmly established from the 12-lead ECG alone without the use of the …
Metabolism of pipecolic acid in a Pseudomonas species: VI. Precursors of glutamate☆

Abstract The terminal metabolite in pipecolic acid catabolism by Pseudomonas putida is glutamic acid. The specific conversion of carbon 6 of pipecolate to carbon 5 of glutamate suggests that no symmetrical intermediates are involved. Cell extracts are capable of converting α-aminoadipate to glutamate.
Low-Overhead, high-speed multi-core barrier synchronization

Whereas efficient barrier implementations were once a concern only in high-performance computing, recent trends in core integration make the topic relevant even for general-purpose CMPs. While the nature of CMP applications requires low-latency, the cost of low-latency barrier implementations using hardware-based techniques can be prohibitive for CMPs, where die area represents opportunities for throughput and yield. Similarly, whereas traditional multiprocessor barrier implementations were developed primarily for dedicated environments, scheduling and multi-programming on CMPs require more adaptable barrier implementations. In this paper, we present and evaluate three barrier implementations that are hybrids of software and dedicated hardware barriers and are specifically tailored for CMPs. The implementations leverage the unique characteristics of CMPs and provide low latency comparable to that of dedicated hardware networks at a fraction of the cost. The implementations also support adaptability, enabling efficient multi-programming and dynamic remapping of the barrier network.
Reaction of lecithin cholesterol acyltransferase with water-soluble substrates.

Abstract To separate the interfacial and catalytic reactions of lecithin cholesterol acyltransferase (LCAT), we carried out the first investigation of its reaction with water-soluble substrates. We used a continuous spectrophotometric assay for the hydrolysis of p-nitrophenyl esters of fatty acids to determine the chain length specificity of the enzyme and its modulation by anions and apolipoproteins in solution. By chemical modification of amino acid residues, we demonstrated that the active site serine and histidine residues participate in both the esterase and acyltransferase reactions but that cysteine residues are not involved in the esterase reaction. The kinetics of the LCAT reaction were measured for p-nitrophenyl esters of fatty acids having up to six (C-6) carbons in length. With increasing acyl chain lengths the optimal reaction rates occurred for the C-5 ester and Km and Vmax values decreased progressively, while the specificity constant, kcat/Km, increased. The same series of substrates and longer chain esters, up to C-16, were also reacted with LCAT in the presence of Triton X-100 in order to determine the general trends for the reaction rates as a function of chain length. The observed trends for the reaction rates and kinetic constants were attributed to an increasing binding affinity for the longer acyl chains in a large hydrophobic cavity, with a concomitant restriction in the motions of the substrates and a decreased probability for the correct positioning of the ester bond for hydrolysis, resulting in a decreased substrate turnover. Since the kinetics of the interfacial reactions of LCAT are very sensitive to the presence of anions and apolipoproteins, in particular apoA-I, we investigated the effects of these modulators on the reactions of LCAT in solution. Unlike the interfacial reactions, the hydrolysis of the p-nitrophenyl esters was not affected by 0.1 M concentrations of anions nor by water-soluble apolipoproteins (apoA-I, apoA-II, and apoCs). Thus the regulation of the activity of LCAT is mediated largely by the interfaces on which it acts.
Rap1 activators are novel anti-angiogenic agents induced by Anthrax Edema Toxin

Proc Amer Assoc Cancer Res, Volume 47, 2006 249 Angiogenesis, the formation of new blood vessels from a pre-existing vasculature, is a tightly regulated process required for embryonic development and tissue regeneration. Since abnormal angiogenesis can promote diseases including blindness, heart disease and cancer, it is critical to find factors that control the angiogenic process. Anthrax edema toxin (ET) is a highly active calmodulin-dependent adenylyl cyclase toxin that can potently raise intracellular cAMP levels and causes a broad range of tissue damage upon host cell entry. We now show that 1) ET activates Rap1 in primary vascular endothelial cells by cAMP stimulation of Epac, a guanine nucleotide-exchange protein (RAP1-GEF), and 2) Epac/Rap activators are anti-angiogenic. ET causes cytoskeletal changes and inhibits chemotaxis and tube formation by human primary vascular endothelial cells. ET also induces transcription of Epac-related activators of Rap1, Epac2 (RapGEF4) and RapGEF5. Like ET, Epac activators induce cytoskeletal changes and block chemotaxis in human endothelial cells. Finally, injection of an Epac activator into mice blocks microvessel development from implanted human microvascular endothelial cells. These results identify activators of Epac and Rap1 as inhibitors of angiogenesis, reveal a novel mechanism for angiogenic regulation and provide an additional target for the toxic action of anthrax.
Teacher education pedagogy: disrupting the apprenticeship of observation

Teacher educators are challenged to enact a pedagogy that helps facilitate conceptual transitions in preservice teachers away from the naive notions formed during their long apprenticeships of observation. This study examines one ‘educative experience purposefully embedded in meaningful pedagogical experiences’ using the three-level model of teacher learning. Findings indicate preservice teachers derived a range of learning from the educative experience, and most were found to be surfacing, confronting, and beginning to replace naive notions of teaching, learning, and assessment. Findings also suggest several characteristics of teacher education pedagogy that disrupt the apprenticeship of observation, including the presentation of dramatically new ideas to elicit the awareness of unexamined assumptions about teaching and learning; the usefulness of affect in awakening that awareness; and opportunities to develop metacognition and process reactions through writing that surfaces prior ideas and articulates ...
Midbrain Microstructural Atrophy Associated with Parkinson’s Disease Motor and Cognitive Symptoms Using 7-Tesla MRI (S57.004)

OBJECTIVE: Using ultra-high field 7 Tesla (T) MRI, we investigated the relationship between midbrain microstructural atrophy and symptom severity in Parkinson9s disease (PD). BACKGROUND: Midbrain pathology is the hallmark of PD; however, midbrain nuclei are difficult to distinguish on conventional MRI, therefore correlation between microstructural volumes and motor symptoms can only be performed at autopsy. Further, the role of midbrain pathology in the development of PD cognitive symptoms remains unclear. DESIGN/METHODS: We used susceptibility-weighted 3D 7T MRI to identify midbrain nuclei in 15 PD patients (MDS-UPDRS-III 29.85±13.02), who completed motor and neuropsychological testing. The substantia nigra (SN), subthalamic nucleus (STN), and red nucleus (RN) were segmented both manually and semi-automatically using ITK-SNAP software. We calculated volumetric measurements for each nuclei and performed correlation analysis between these volumes and measures of motor and cognitive performance. RESULTS: Twelve PD patients tolerated 7T MRI without significant movement-related artifact, including 6 tremor-dominant patients (MDS-UPDRS tremor range 0-16). PD-MCI diagnostic criteria (Litvan 2012, Level-II) were used to categorize 7 no-MCI and 5 MCI. We found higher (worse) MDS-UPDRS-III scores correlated with smaller SN volume (r=-0.56, p=0.04). Further, higher akinesia/rigidity subscores correlated with smaller SN volume (r=-0.65, p=0.01). When considering the more- versus less-affected side, we found higher motor subscores on the less-affected body-side trended toward correlation with smaller contralateral SN volume (r=-0.51, p=0.07). Poorer performance on the Hooper Visual Organization Test correlated with smaller SN volume (r=0.65, p=0.04). No correlations were found between motor or cognitive tests and STN or RN volumes. CONCLUSIONS: Ultra-high field 7T MRI with midbrain microstructural visualization and segmentation is feasible in PD patients, even with moderate to severe limb tremor. Correlations with the less-affected body-side suggest SN volume changes may be sensitive to early motor symptoms, particularly bradykinesia and rigidity. In addition, SN pathology could directly contribute to visuo-spatial cognitive deficits in PD. Study Supported by: NIH/NINDS, NIH/NIA, MJFF Disclosure: Dr. Poston has nothing to disclose. Dr. Santoso has nothing to disclose. Dr. Bernstein has nothing to disclose. Dr. Cruadhlaoich has nothing to disclose. Dr. Everling has nothing to disclose. Dr. YorkWilliams has nothing to disclose. Dr. Fenesy has nothing to disclose. Dr. Zeineh has nothing to disclose. Dr. Kerchner has received personal compensation for activities with Phloronol, Inc. as an advisory board member.
Mitochondrial structure in sites of steroid secretion.

1. Mitochondria of the adrenal gland, corpus luteum, theca interna and granulosa of the graafian follicle, interstitial cells of the testis, and placenta of the rat have been studied with the electron microscope. 2. In most sites of steroid secretion, the internal structure of the mitochondria is in the form of tubular reflections of the internal mitochondrial membrane, rather than plate-like cristae. 3. The mitochondria of the adrenal gland have a highly variable size, even within a single cell; they may reach 2 to 3 µ in diameter, and are nearly filled with tubules. 4. It is suggested that while mitochondria in many places have a tubular component, those in the adrenal gland are highly specialized by virtue of their giant size and their internal structure.
Mapping of Io's thermal radiation by the Galileo photopolarimeter-radiometer (PPR) instrument

Abstract Between 1999 and 2002, the Galileo spacecraft made 6 close flybys of Io during which many observations of Io's thermal radiation were made with the photopolarimeter–radiometer (PPR). While the NIMS instrument could measure thermal emission from hot spots with T>200 K, PPR was the only Galileo instrument capable of mapping the lower temperatures of older, cooling lava flows, and the passive background. We tabulate all data taken by PPR of Io during these flybys and describe some scientific highlights revealed by the data. The data include almost complete coverage of Io at better than 250 km resolution, with extensive regional coverage at higher resolutions. We found a modest poleward drop in nighttime background temperatures and evidence of thermal inertia variations across the surface. Comparison of high spatial resolution temperature measurements with observed daytime SO2 gas pressures on Io provides evidence for local cold trapping of SO2 frost on scales smaller than the 60 km resolution of the PPR data. We also calculated the power output from several hot spots and estimated total global heat flow to be about 2.0–2.6 W m−2. The low-latitude diurnal temperature variations for the regions between obvious hot spots are well matched by a laterally-inhomogeneous thermal model with less than 1 W m−2 endogenic heat flow.
Development and elimination of presynaptic elements on polylysine-coated beads implanted in neonatal rat cerebellum.

Polylysine-coated sepharose beads were implanted in the cerebellum of neonatal rats and examined at 3 hr, 3 days, 14 days, and 21 days after surgery. Previous studies at 5 or 8 days after implantation showed that axons formed neuronal swellings that appeared to be presynaptic elements, with the bead surface in the position of a postsynaptic element. Results reported here show that no beads at 3 hr had presynaptic elements, whereas the number of beads with presynaptic elements increased to high levels at 3 and 7 days but dropped to low values at 14 and 21 days after implantation. Presynaptic elements were seen on beads regard less of their distance from cerebellar tissue except at 3 hr, when no axons were seen in the implant, indicating that axons first grew into the implant and then formed presynaptic elements. The morphological measurements of presynaptic elements on beads at 3 to 7 days after implantation showed increases in area and number of synaptic vesicles, which then decreased at 14 and 21 days after implantation. These results show that axons can grow into implants of polylysine-coated beads and form presynaptic elements that do not survive with increased time after implantation. The survival of presynaptic elements on beads can be used as a model for investigations into regeneration of axons and presynaptic elements in the injured brain.
Resource management in power‐controlled cellular wireless systems

The efficient management of wireless resource is essential to the success of wireless systems. While power control is traditionally considered as a means to counteract the detrimental effects of channel fading, it is also a flexible mechanism to provide Quality of Service to individual users, and can be used as a platform for radio resource management. In this paper, we review the developments of distributed power control and related resource management problems in cellular wireless systems. We highlight the feasibility issue in a power-controlled system, which enables us to push the system toward high efficiency, and prevent the system from collapsing at the same time. Considering the unique features of multimedia traffic to be supported in future wireless systems, we also review power and rate control schemes proposed for wireless data, and present a framework for utility-based power control as a possible candidate for distributed power control of multimedia wireless systems. Copyright © 2001 John Wiley & Sons, Ltd.
Competition and physician-enabled demand: The role of managed care ☆

Abstract Recent organizational changes in the health care sector promote greater patient participation in their treatment decisions. How physicians respond to patient-initiated requests for treatment is an issue of considerable policy interest. To study this phenomenon, we introduce the notion of physician-enabled demand and examine empirically whether this behavior responds to competitive pressures in the market and financial incentives associated with different physician payment mechanisms. We find that physician-enabled demand increases with more competition under fee-for-service reimbursement, but decreases with greater competition under managed care. This asymmetric response is quite consistent with our conceptual framework and at odds with alternative interpretations.
The Effects of Thyroid Hormone on Insulin-Like Growth Factor (IGF) and IGF-Binding Protein (IGFBP) Expression in the Neonatal Rat: Prolonged High Expression of IGFBP-2 in Methimazole- Induced Congenital Hypothyroidism*

In the rat a developmental switch in the serum insulin-like growth factor (IGF) and IGF-binding protein (IGFBP) profile takes place during the first 3 postnatal weeks. The fetal expression pattern of high IGF-II and IGFBP-2 is replaced by the adult pattern of low levels of IGF-II and IGFBP-2 and high levels of IGF-I and IGFBP-3. The regulatory mechanisms mediating these changes are unknown, but may include perinatal changes in endocrine function. To study the effects of thyroid function and the perinatal thyroid secretory burst on IGF and IGFBP expression, we established a rat model of congenital hypothyroidism, leading to marked postnatal growth retardation during the perinatal period. The hypothyroid animals lacked the steep rise in serum IGF-I levels normally occurring during the third week of life, showing only a modest rise to approximately 50% of control levels. The pattern of serum IGF-II decline in hypothyroid animals was slightly different from that in controls, with lower IGF-II levels during the second week of life and a slower decline down to the very low final levels. The hypothyroid pups continued to express high levels of IGFBP-2 up to the age of 19 days, while the control animals, after a slow initial decline, showed an abrupt fall of IGFBP-2 serum levels during the third week of life. Liver IGFBP-2 mRNA levels reflected the serum changes, with elevated IGFBP-2 mRNA in hypothyroid animals. The expression of other IGFBPs did not differ from that in the control group. At the age of 18 days, serum GH levels in the hypothyroid animals were approximately one third of control GH levels, which suggests a role for GH as a possible mediator of thyroid hormone actions on the IGF system. The changes in growth parameters and in the IGF and IGFBP profile of hypothyroid pups could be abolished by thyroid hormone replacement from birth. We conclude that thyroid hormone is, directly or indirectly, essential for some of the neonatal changes in IGF and IGFBP profiles.
Preliminary investigation of Cu-containing proteins in seeds of Brazil nuts by ICPMS and MALDI-MS methods

Abstract Metalloproteomics (studying metal-containing proteins by proteomics approach) is an important subset of any proteomics study. Metals existing in different isotopes in nature impart a “finger-print” isotope pattern to the metal-containing polypeptide, which is different from the normal isotope pattern of a polypeptide. This study was directed to identify Cu-containing polypeptide generated by tryptic digestion of Cu-containing protein in Brazil nuts (a real-world sample) using characteristic isotope pattern of Cu-containing polypeptides under acidic conditions by MALDI MS. A Cu-containing polypeptide at m / z 1438.12 and its protonated apopeptide at m / z 1376.21 were identified and a tentative formula for the Cu-containing polypeptide, [M+Cu(I)] + , was proposed based on MALDI spectral characteristics. Presence of Cu-containing polypeptides in tryptic digest was further supported by SEC-ICPMS (size-exclusion chromatography coupled with inductively coupled plasma mass spectrometry) profiling of tryptic digests of Cu-containing proteins. Cytochrome C was used as a model protein to investigate the feasibility of using characteristic isotope pattern in identifying metal-containing polypeptides under standard experimental conditions (denaturing, reduction, alkylation and acidic matrix) employed in proteomics. Additionally, Cu-containing proteins in water-soluble protein fraction of Brazil nuts was profiled by SEC-ICPMS.
Dynamic hysteresis loop measuring equipment

WITHIN the past 2 or 3 years many scientists and engineers working on research and development projects in the magnetic amplifier field have come to realize that the dynamic hysteresis loop of a magnetic material plays an important role in determining the amplification and control characteristics of high-gain magnetic amplifiers. Figure 1 shows a block diagram of an excitation and test circuit which often has been used to display the dynamic hysteresis loop of a core material upon the screen of a cathode-ray oscilloscope tube.
Novel use of polymer brushes in colloidal lithography to overcome lateral capillary force.

A general method has been developed for transferring interfacially trapped, submonolayer hexagonal arrays of silica particles for nano- and mesoscopic surface patterning. Poly(n-butyl acrylate) and poly(n-butyl acrylate-random-N,N-diethylaminoethyl acrylate) brushes were grafted on the substrates via the “graft-from” method using atom transfer radical polymerization. The polymer brush served as an adhesive promoter between the particles and the substrate and proved to be effective for locking the particles in the hexagonal lattice against the lateral capillary force arising from a thin layer of water attached to the surface of the substrate. Several parameters that influence preservation of the order of the particle arrays were examined. These include brush thickness, brush composition, interparticle distance, and particle diameter.
Applications and limitations of laser-assisted angioplasty.

Laser-assisted angioplasty is rapidly evolving into a promising adjunct to or replacement for standard vascular procedures. A protocol was devised to evaluate the technique in a non-selected, consecutive patient population to define the applications and limitations of the technique. In a 12-month period, 358 lower-limb atherosclerotic lesions were treated with laser/balloon angioplasty [percutaneously (52%) or open (48%)] in 206 consecutive patients. Overall, the laser/balloon technique recanalised 234 lesions (65% laser success), judged clinically effective by a >0.15 improvement in the ankle/brachial index and elimination of symptoms. Operative complications included: perforation (15, 4.2%); thrombosis (16, 4.5%); spasm (5, 1.4%); and false aneurysm at the puncture site (7, 2.0%). Of the 124 failures (35%) categorised for analysis, the most common cause was inability to cross the lesion in 20 cases. This experience has identified three significant clinical limitations to successful laser recanalisation: calcification, inadequate distal circulation, and inability to control restenosis/reocclusion (collapsible lesions and accelerated plaque deposition). Further research is needed to determine if thermal injury seriously compromises the safety and long-term outcome of laser-assisted angioplasty.
The challenge behind brain death organ transplantation in liver ischemia and reperfusion injury.

* Corresponding author. Michigan State Univ Tel.: +1 269 226 6896; fax: +1 269 226 6735. E-mail address: toledo@kcms.msu.edu (L 0022-4804/$ e see front matter a 2013 Elsev doi:10.1016/j.jss.2012.01.009 Organs from brain death (BD) donors have reduced quality, higher immunogenicity, and subsequently reduced function compared with those from living donors. Danobeitia et al. [1] demonstrated the early innate immune response induced by BD in liver and peripheral blood of non-human primates in a recently published article in the Journal of Surgical Research. The highlights of the research measured the up-regulation of systemic inflammatorymarkers such as cortisol, epinephrine, norepinephrine, and interleukin-6; innate immune system cellular markers such as neutrophils and monocytes; and genes regulating inflammatory processes such as Toll-like receptor (TLR) signaling, cell deaths, and stress pathways. On the contrary, pathways regulating metabolism of glucose, protein, and lipid in the liver were noted to be downregulated. Danobeitia et al also examined results consistent with previous studies showing that donor BD triggers a systemic inflammatory response and increased immunogenicity of the graft that could potentially lead to reduced organ function [2e5].
The effect of ACTH on the distribution of eosinophils in blood and peribronchial tissue of guinea pigs

Abstract 1.1. Guinea pigs are of limited usefulness for the study of the response of eosinophils to the injection of ACTH adrenal cortical stroids. 2.2. One single dose of ACTH failed to produce significant changes in the eosinophils in blood and peribronchial tissue of guinea pigs which have been sensitized and reinjected with a homologous antigen. 3.3. Repeated injection of ACTH in sensitized but not reinjected guinea pigs produced a marked depression of the peripheral eosinophil count without proportionate reduction of the number of eosinophils in the peribronchial tissue. 4.4. The production of anaphylactic shock in guinea pigs whose peripheral eosinophil count has been depressed by the administration of ACTH caused a return of eosinophils into the circulation. The distribution of eosinophils in the peribronchial tissue of these animals is similar to the distribution found in shocked animals which had not received ACTH.