cssi/SciSciGPT-SciSciNet huggingface dataset:
Targeting the RAS/MAPK pathway with miR-181a in acute myeloid leukemia

// Xiaomeng Huang 1, 2, 3, * , Sebastian Schwind 3, * , Ramasamy Santhanam 3 , Ann-Kathrin Eisfeld 3 , Chi-ling Chiang 2, 3 , Malori Lankenau 3 , Bo Yu 2, 4 , Pia Hoellerbauer 3 , Yan Jin 2 , Somayeh S. Tarighat 1, 3 , Jihane Khalife 1, 3 , Alison Walker 3 , Danilo Perrotti 5 , Clara D. Bloomfield 3 , Hongyan Wang 3 , Robert J. Lee 1, 2, 6 , Ly James Lee 1, 2, 4, #, Guido Marcucci 1, 7, # 1 Molecular Cellular and Developmental Biology, The Ohio State University, Columbus, OH, USA 2 Nanoscale Science and Engineering Center for Affordable Nanoengineering of Polymeric Biomedical Devices, The Ohio State University, Columbus, OH, USA 3 Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA 4 William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH, USA 5 Greenebaum Cancer Center, University of Maryland, Baltimore, MD, USA 6 Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH, USA 7 Gehr Family Leukemia Center, City of Hope Comprehensive Cancer Center, Duarte, CA, USA * These authors contributed equally to this work # Share senior authorship Correspondence to: Guido Marcucci, email: gmarcucci@coh.org Ly James Lee, email: lee.31@osu.edu Keywords: microRNA, nanoparticles, RAS, miR-181a, acute myeloid leukemia Received: March 25, 2016 Accepted: July 19, 2016 Published: August 09, 2016 ABSTRACT Deregulation of microRNAs’ expression frequently occurs in acute myeloid leukemia (AML). Lower miR-181a expression is associated with worse outcomes, but the exact mechanisms by which miR-181a mediates this effect remain elusive. Aberrant activation of the RAS pathway contributes to myeloid leukemogenesis. Here, we report that miR-181a directly binds to 3′-untranslated regions (UTRs); downregulates KRAS, NRAS and MAPK1; and decreases AML growth. The delivery of miR-181a mimics to target AML cells using transferrin-targeting lipopolyplex nanoparticles (NP) increased mature miR-181a ; downregulated KRAS, NRAS and MAPK1; and resulted in decreased phosphorylation of the downstream RAS effectors. NP-mediated upregulation of miR-181a led to reduced proliferation, impaired colony formation and increased sensitivity to chemotherapy. Ectopic expression of KRAS, NRAS and MAPK1 attenuated the anti-leukemic activity of miR-181a mimics, thereby validating the relevance of the deregulated miR-181a -RAS network in AML. Finally, treatment with miR-181a -NP in a murine AML model resulted in longer survival compared to mice treated with scramble-NP control. These data support that targeting the RAS-MAPK-pathway by miR-181a mimics represents a novel promising therapeutic approach for AML and possibly for other RAS-driven cancers.
Risk of lymph node metastases in pathological gleason score≤6 prostate adenocarcinoma: Analysis of institutional and population-based databases.

Abstract Introduction Several institutional studies have suggested that pathological Gleason score≤6 prostate cancer has little or no capacity for metastasis. Materials and methods Using the Surveillance, Epidemiology, and End Results database (SEER, 2004–2011, n = 19,594) and the National Cancer Database (NCDB, 2004–2013, n = 57,540), we identified patients with pathological Gleason score≤6 prostate cancer following radical prostatectomy and lymph node dissection. At the University of Chicago Medicine (UCM, 2003–2014), we considered men with Gleason score≤6 prostate cancer who did ( n = 267) and did not receive ( n = 770) a lymph node dissection at the time of radical prostatectomy. Temporal trends in lymph node dissection and lymph node metastases were determined, and multivariable logistic regressions were used to analyze factors associated with lymph node metastases. In the UCM cohort, we also evaluated secondary endpoints, including biochemical recurrence (BCR), metastatic disease on follow-up imaging, and response to salvage radiation therapy. Results The incidence of lymph node dissection at the time of radical prostatectomy decreased from 60% to 37% in SEER (2004–2011) and from 62% to 45% in NCDB (2004–2013). Positive lymph node metastases were found in 0.2% of SEER and 0.18% of NCDB patients who received a lymph node dissection. Elevated PSA, higher clinical stage, and African American race were associated with lymph node positivity in one or both of these databases ( P Conclusions Our population-based and institutional analyses suggest metastases in cases of Gleason score≤6 prostate cancer to be extremely rare.
The expert interpreter

Comment on Werbner, Richard. 2015. Divination’s grasp: African encounters with the almost said . Bloomington: Indiana University Press.
Antibiotic-Induced Depletion of Anti-inflammatory Clostridia Is Associated with the Development of Graft-versus-Host Disease in Pediatric Stem Cell Transplantation Patients

Abstract Adult stem cell transplantation (SCT) patients with graft-versus-host-disease (GVHD) exhibit significant disruptions in gut microbial communities. These changes are associated with higher overall mortality and appear to be driven by specific antibiotic therapies. It is unclear whether pediatric SCT patients who develop GVHD exhibit similar antibiotic-induced gut microbiota community changes. Here, we show that pediatric SCT patients (from Children's Medical Center Dallas, n = 8, and Cincinnati Children's Hospital, n = 7) who developed GVHD showed a significant decline, up to 10-log fold, in gut anti-inflammatory Clostridia (AIC) compared with those without GVHD. In fact, the development of GVHD is significantly associated with this AIC decline and with cumulative antibiotic exposure, particularly antibiotics effective against anaerobic bacteria (P = .003, Firth logistic regression analysis). Using metagenomic shotgun sequencing analysis, we were able to identify specific commensal bacterial species, including AIC, that were significantly depleted in GVHD patients. We then used a preclinical GVHD model to verify our clinical observations. Clindamycin depleted AIC and exacerbated GVHD in mice, whereas oral AIC supplementation increased gut AIC levels and mitigated GVHD in mice. Together, these data suggest that an antibiotic-induced AIC depletion in the gut microbiota is associated with the development of GVHD in pediatric SCT patients.
A new subspecies of the squirrel Sciurus variegatoides Ogilby from Costa Rica

The addition of S. v. loweryi and S. v. melania to the squirrel fauna of Costa Rica clarifies the distributional hiatus which existed previously. Sciurus v. loweryi is a new subspecies from the Valle de Coto Brus and the Valle del General. It is a very distinctive tawny squirrel with a black dorsal stripe. Sciurus v. melania is now known from as far north as Parrita. It is an inhabitant of the Pacific coastal lowlands. Near the Rio Grande de Tarcoles, S. v. melania intergrades with S. v. rigidus .
Identifying mechanisms of acquired resistance to immunotherapy (TUM2P.1025)

Immunotherapy has demonstrated a remarkable potential to cure established cancer, but many tumors either relapse or fail to respond. The molecular mechanisms which drive these tumor relapses remain unknown. We hypothesize that tumors evolve resistance under immunotherapeutic pressure mediated by changes in gene expression which can be selected and propagated through serial passage and then identified and targeted. We are comparing untreated B16 melanoma tumors to those expanding despite treating with combinations checkpoint blockade (CTLA-4, PD-1, and PD-L1), 4-1BB-agonist antibody, adoptive transfer of TRP-1 specific CD4 T-cells, or growth in MHC-mismatched hosts. Through multiple in vivo passages, we have already selected a B16 melanoma tumor line that has evolved almost 100% resistance to combination blockade of CTLA-4, PD-1, and PD-L1, which could cure nearly 90% of tumor-bearing mice in the first cycle. After each passage under selective pressure of combination blockade, we have observed visible signs of increased angiogenesis correlating with enhanced therapy resistance. By determining the pathways engaged by these tumors to develop resistance to tumor-specific immunity, we hope to discover novel characteristics of the mammalian immune system as well as reveal new targets for immunotherapeutic intervention in melanoma patients.
Reinisch, Simon Leo (1832–1919)

Leo Reinisch began his academic career as an Egyptologist, but had broad interests that encompassed the languages and history of Latin America as well as of North Africa outside of Egypt. In fact, Reinisch was renowned as the father of Cushitic studies and as an editor of Wiener Zeitschrift fur die Kunde des Morgenlandes. Reinisch was not a missionary, which distinguished him from many other Africanist linguists of the period. Nonetheless, he was still a devout Catholic, and translated the Gospels into a variety of North African languages. He spent most of his long career at the University of Vienna, where he studied, taught, and eventually assumed the positions of rector and dean.
Connected Vehicle-Based Lane Selection Assistance Application

Connected vehicle (CV) technology has great potential to improve the performance of today’s advanced driver assistance systems in terms of safety, energy efficiency, and driving comfort. The aim of this paper is to develop a specific CV application that assists with lane selection, i.e., finding the best travel lane in terms of travel time based on predicted lane-level traffic states. In this paper, a spatial-temporal model (ST-model) was developed, which utilizes spatial and temporal information of road cells to predict future traffic states. This information was used by the proposed lane selection assistance application to select an optimal lane sequence for the application-equipped vehicle. A comprehensive simulation-based evaluation was then conducted under various scenarios, e.g., with different traffic volumes, penetration rates of communication-capable vehicles, and information update cycles. The evaluation results reveal several interesting findings, including: 1) the proposed ST-model outperforms the basic estimation model in terms of traffic state prediction accuracy; 2) travel times of application-equipped vehicles can be reduced by up to 8% with the use of the proposed lane selection assistance application when compared with the baseline, under various traffic scenarios; 3) the application can be effective in the early deployment stage of CV technology, where the penetration rate of communication-capable vehicles is still low; and 4) the potential conflict risk of application-equipped vehicles is reduced, although the application is mainly designed for mobility benefits, due to the more strategic and informed lane changes suggested by the proposed application.
A genome-wide screen for ER autophagy highlights key roles of mitochondrial metabolism and ER-resident UFMylation

Summary Selective degradation of organelles via autophagy is critical for cellular differentiation, homeostasis, and organismal health. Autophagy of the ER (ER-phagy) is implicated in human neuropathy but is poorly understood beyond a few specialized autophagosomal receptors and remodelers. Using an ER-phagy reporter and genome-wide CRISPRi screening, we identified 200 high-confidence factors involved in human ER-phagy. We mechanistically investigated two pathways unexpectedly required for ER-phagy. First, reduced mitochondrial metabolism represses ER-phagy, which reverses the logic of general autophagy. Mitochondrial crosstalk with ER-phagy bypasses the energy sensor AMPK, instead directly impacting ULK1. Second, ER-localized UFMylation is required for ER-phagy that represses the unfolded protein response. The UFL1 ligase is brought to the ER surface by DDRGK1, analogous to PINK1-Parkin regulation during mitophagy. Our data provide insight into the unique cellular logic of ER-phagy, reveal parallels between organelle autophagies, and provide an entry point to the relatively unexplored process of degrading the ER network.
Control Method Designs and Comparisons for Tractor-Trailer Vehicle Backward Path Tracking

Tractor-trailer path tracking in backward motion is a challenging nonlinear control problem in automated vehicle development. The control challenges arise from the fact that a backward driving articulated vehicle is an underactuated system with unstable internal dynamics and coupled nonlinear terms. Additionally, there exists a relative body angle margin for saturated steering input beyond which a jackknife accident is unavoidable if backing further. In this work, three different controllers were designed for tractor-trailer reverse motion: a proportional integral controller, a sliding mode controller, and a neural network controller. A generic control safety governor was developed to supervise the tracking control algorithms, which overrides control when necessary to ensure jackknife-free operation. The controllers' path tracking performance was tested on an increasingly rigorous path with introduced discontinuities, and a comparative study of the three controllers was conducted. The performance differences and characteristics of each control algorithm are analyzed for the studied scenario.
Novel PCB Integrated Magnetic Component Design for Reduced AC Power Losses

Inductor design for medium-to-high frequency operation requires special attention to winding ac losses (skin and proximity effect). Integrating novel winding design geometries into the PCB has the potential to provide significant design flexibility to mitigate skin and proximity effect induced winding power losses. This paper will describe three methods to mitigate winding conductor ac losses that are applicable to both core-less and cored magnetic components.
Periphery Plots for Contextualizing Heterogeneous Time-Based Charts

Patterns in temporal data can often be found across different scales, such as days, weeks, and months, making effective visualization of time-based data challenging. Here we propose a new approach for providing focus and context in time-based charts to enable interpretation of patterns across time scales. Our approach employs a focus zone with a time and a second axis, that can either represent quantities or categories, as well as a set of adjacent periphery plots that can aggregate data along the time, value, or both dimensions. We present a framework for periphery plots and describe two use cases that demonstrate the utility of our approach.
Undiagnosed Normocephalic Pancraniosynostosis Presenting as Bilateral Abducens Nerve Palsy.

ABSTRACT Primary pancraniosynostosis is a rare variant of craniosynostosis in which the major cranial sutures prematurely fuse. Single-suture craniosynostosis is often recognized early in life due to an abnormal head shape. In contrast, primary pancraniosynostosis may be diagnosed later in life due to a grossly normal head shape and size. As such, these children can present with symptoms related to chronically elevated intracranial pressure (eg, vision loss or cognitive impairment). This report highlights a patient with primary pancraniosynostosis associated with unique neurologic sequelae-namely, bilateral abducens nerve palsy. A 9-year-old boy presented to the ophthalmologist with a 1-month history of double vision, drifting of his right eye toward the nasal bridge, and intracranial hypertension evident with papilledema. Physical examination was notable for mild bitemporal narrowing. A computed tomography study demonstrated radiologic thumbprinting, diffuse osseous sclerosis, and fusion of the bilateral coronal, sagittal, metopic, and lambdoid sutures. The patient underwent emergent cranial vault expansion with fronto-orbital advancement. Papilledema had resolved 4 months following surgery. At 2-year follow-up, abducens nerve palsy and head shape were significantly improved. This study brings attention to an unreported presenting symptom of pancraniosynostosis (bilateral abducens nerve palsy). This information may lead to quicker diagnosis and treatment of pancraniosynostosis-induced intracranial hypertension, which is critical to prevent long-term sequelae.
Bilateral Auditory Brainstem Implants in Patients With Neurofibromatosis 2.

ObjectiveTo discuss indications for bilateral auditory brainstem implants (ABIs), compare audiometric outcomes of unilateral vs bilateral ABIs, and determine if patients have improved outcomes with...
Institutionalized Organizations: Formal Structure as Myth and Ceremony

Argues that the formal structure of many organizations in post-industrial society dramatically reflect the myths of their institutional environment instead of the demands of their work activities. The authors review prevailing theories of the origins of formal structures and the main problem which those theories confront -- namely, that their assumption that successful coordination and control of activity are responsible for the rise of modern formal organization is not substantiated by empirical evidence. Rather, there is a great gap between the formal structure and the informal practices that govern actual work activities. The authors present an alternative source for formal structures by suggesting that myths embedded in the institutional environment help to explain the adoption of formal structures. Earlier sources understood bureaucratization as emanating from the rationalization of the workplace. Nevertheless, the observation that some formal practices are not followed in favor of other unofficial ones indicates that not all formal structures advance efficiency as a rationalized system would require. Therefore another source of legitimacy is required. This is found in conforming the organization's structure to that of the powerful myths that institutionalized products, services, techniques, policies, and programs become. (CAR)
A high-fat diet, but not haloperidol or olanzapine administration, increases activated microglial expression in the rat brain.

Abstract This study examined the effects of chronic treatment of the antipsychotic drugs, haloperidol and olanzapine, on microglial activation in the brain. In addition, we explored the interaction of these antipsychotic drugs with normal and high-fat diet. In order to measure activated microglial expression, we used [3H] PK11195 in vitro autoradiography. Male Sprague Dawley rats were given a diet of either regular chow diet or a high-fat diet, and assigned either water, haloperidol drinking solution (1.5 mg/kg), or olanzapine drinking solution (10 mg/kg) for four weeks. Following treatment, rats were euthanized and brains extracted for [3H] PK11195 autoradiography. Rats on 4 weeks of a high-fat diet showed increased [3H] PK11195 binding compared to rats on a normal diet in the temporal association cortex (19 %), ectorhinal cortex (17 %), entorhinal cortex (18 %), and perirhinal cortex (18 %), irrespective of drug treatment. These are regions associated with memory, sensory, and visual processing. Rats treated with either haloperidol or olanzapine showed no differences in [3H] PK11195 binding compared to the control group. However, there were differences between the 2 different antipsychotic medications themselves. Haloperidol increased [3H] PK11195 binding in the amygdala (23 %), ectorhinal cortex (24 %), and perihinal cortex (29 %), compared to olanzapine. These results corroborate a known role of a high-fat diet and central inflammatory changes but suggest no role of these antipsychotic drugs in promoting neuroinflammation across 4 weeks compared to normal control rats.
Examining Implementation Outcomes of Sit Down and Play, a Primary Care-Based Intervention, in a Large Urban Primary Care Clinic.

Economical, operational, and employment strains present challenges for widespread implementation of parent-directed interventions. We designed Sit Down and Play (SDP) with the aim of creating a brief primary care-based program that encourages positive parenting practices through take-home play activities. To develop a sustainable model of implementation in real-world settings, we explored the use of university student volunteers as a potential solution for employment strains. Guided by Proctor and colleagues’ implementation outcome framework, this study focused on understanding the following implementation outcomes: acceptability, feasibility, fidelity, and service penetration. Exploratory analysis on the limited-efficacy of the program on parental behavior was also assessed. Student facilitators were trained utilizing a train-the-trainer model. During the study period, facilitators delivered SDP to caregivers attending their well-child visits (WCVs) in a primary care clinic serving predominantly low-income families. Implementation data was gathered from clinic records, student facilitator surveys, and caregiver surveys. Student facilitators delivered SDP interventions to 99/146 (67.8%) eligible families. Caregivers overwhelmingly found the program helpful (M = 4.70, SD = 0.82), enjoyable (M = 4.88, SD = 0.32), and were highly satisfied with individuals who delivered it (M = 4.97, SD = 0.16). Student facilitators successfully delivered the program with high fidelity. Implementation findings suggest that delivery of SDP by student volunteers combined with the use of a train-the-trainer model is a feasible model to integrate strategies that support positive parenting behaviors into existing systems, such as the primary care setting. This study yields promising results that suggest the benefit of utilizing university partnerships with healthcare settings for wider dissemination and adaptations for other subgroups and contexts.
Theory of Deflagration and Fronts of Tunneling in Molecular Magnets

Decay of metastable states in molecular magnets leads to energy release that results in temperature increase that boosts the decay rate. This is the mechanism of the recently discovered magnetic deflagration that is similar to regular chemical burning and can propagate in a form of burning fronts. Near spin-tunneling resonances the decay rate is also affected by the dipolar field that can block or unblock tunneling. There are non-thermal fronts of tunneling in which the magnetization adjusts in such a way that the system is on resonance within the front core. Both dipolar field and temperature control fronts of quantum deflagration. The front speed can reach sonic values if a strong transverse field is applied to boost tunneling.
Transplant options for patients undergoing total pancreatectomy for chronic pancreatitis.

Abstract Background Total pancreatectomy to treat chronic pancreatitis is associated with severe diabetic control problems in 15% to 75% of patients, causing up to 50% of deaths late postoperatively. We report our experience with islet autotransplants at the time of, or with pancreas allotransplants after, total pancreatectomy. Study design Between February 1, 1977, and June 30, 2003, we performed 112 islet autotransplants at the time of total pancreatectomy; we also performed 20 pancreas allotransplants in 13 patients who had already undergone total pancreatectomy months to years earlier. Results Islet autotransplants at the time of total pancreatectomy in patients who had not had previous operations on the body and tail of the pancreas were associated with a high islet yield (>2,500 islet equivalents/kg body weight), and >70% of the recipients achieved complete insulin independence. In contrast, a previous distal pancreatectomy or a Puestow drainage procedure was associated with a low islet yield in 75% of them and with complete insulin independence in A pancreas allotransplant after total pancreatectomy was not associated with any transplant-related mortality at 1 and 3 years posttransplant. The pancreas graft survival rate at 1 year posttransplant was 77% with tacrolimus-based immunosuppression (versus 67% with cyclosporine). Enteric (over bladder) drainage was preferred to manage exocrine graft secretions, to cure pancreatectomy-induced endocrine and exocrine insufficiency. Conclusions Our series shows that pancreas allotransplants can be performed without transplant-related mortality and, when tacrolimus-based immunosuppression is used, with 1-year pancreas graft survival rates >75%. In contrast to a simultaneous islet autotransplant, a pancreas allotransplant has the disadvantage of requiring lifelong immunosuppression, but the advantage of not only curing endocrine but also exocrine insufficiency. Both transplant options, if successful, improve the recipient's quality of life.
Comparison of high frequency, high temperature core loss and B-H loop characteristics of an 80 Ni-Fe crystalline alloy and two iron-based amorphous alloys

Limited experimental data exists for the specific core loss and dynamic B‐H loops for soft magnetic materials for the combined conditions of high frequency and high temperature. This experimental study investigates the specific core loss and dynamic B‐H characteristics of a nickel‐iron crystalline magnetic alloy (Supermalloy) and two‐iron‐based amorphous magnetic materials (Metglas 2605S‐3A and Metglas 2605SC) over the frequency range of 1–50 kHz and temperature range of 23–300 C under sinusoidal voltage excitation. The effects of maximum magnetic flux density, frequency, and temperature on the specific core loss and on the size and shape of the B‐H loops are examined. The Supermalloy and Metglas 2605S‐3A and 2605SC data are used to compare the core loss of transformers with identical kVA and voltage ratings.
The interface crack in a tension field : an eigenvalue problem for the gap

The problem of the interface crack in a tension field is reexamined with the objective of obtaining simple and explicit expressions for all quantities of physical interest. The known exact solution to this problem is complicated and difficult to analyze. Here the gap is shown to satisfy an eigenvalue problem. The condition that the gap is nonnegative implies that the smallest eigenvalue is the correct one. A simple uniform approximation for the gap is obtained by using the method of matched asymptotic expansions to take advantage of the smallness of the contact zones. As the tangential shift satisfies the same differential equation as the gap, a uniform approximation for this quantity is obtained by the same method. The tractions are also shown to satisfy a second order ordinary differential equation, and uniform approximations are given for the quantities.
Specification of energetic magnetospheric electrons

In order to make prompt and accurate assessments of whether enhancements in near-Earth energetic particles are related to space system operational problems, it is necessary to know well the present (and recent past) space radiation environment. Ideally, this means that one should be able to specify the temporal behavior of electrons and ions at all relevant altitudes, latitudes, and local times over the entire energy range of interest to space system operators. Through the use of data from a variety of scientific and operational spacecraft, it has been possible in recent times to develop dynamic radiation belt models. Our present work in this regard uses a type of data assimilation technique. With such modeling, we are generally able to achieve high accuracies (> 75%) of energetic electron flux specification throughout the outer electron radiation belt (2 ≤ 7). Future work employing these methods should allow accurate, reliable specification for magnetospheric ion populations as well.
Error and Generalization in Discrete Choice Under Risk

I compare the generalization ability, or out-of-sample predictive success, of four probabilistic models of binary discrete choice under risk. One model is the conventional homoscedastic latent index modelthe simple logitthat is common in applied econometrics: This model is context-free in the sense that its error part is homoscedastic with respect to decision sets. The other three models are also latent index models but their error part is heteroscedastic with respect to decision sets: In that sense they are context-dependent models. Context-dependent models of choice under risk arise from several different theoretical perspectives. Here I consider my own contextual utility model (Wilcox 2011), the decision field theory model of Busemeyer and Townsend (1993) and the Blavatskyy-Fishburn model (Fishburn 1978; Blavatskyy 2014). In a new experiment, all three context-dependent models outperform the context-free model in prediction, and significantly outperform a linear probability model (suggested by contemporary applied practice a la Angrist and Pischke 2009) when the latent preference structure is rank-dependent utility (Quiggin 1982). All of this holds true for function-free estimations of outcome utilities and probability weights as well as parametric estimations. Preoccupation with theories of the deterministic structure of choice under risk, to the exclusion of theories of error, is a mistake.
Autologous c-Kit+ Mesenchymal Stem Cell Injections Provide Superior Therapeutic Benefit as Compared to c-Kit+ Cardiac-Derived Stem Cells in a Feline Model of Isoproterenol-Induced Cardiomyopathy.

Background Cardiac- (CSC) and mesenchymal-derived (MSC) CD117+ isolated stem cells improve cardiac function after injury. However, no study has compared the therapeutic benefit of these cells when used autologously. Methods MSCs and CSCs were isolated on day 0. Cardiomyopathy was induced (day 28) by infusion of L-isoproterenol (1,100 ug/kg/hour) from Alzet minipumps for 10 days. Bromodeoxyuridine (BrdU) was infused via minipumps (50 mg/mL) to identify proliferative cells during the injury phase. Following injury (day 38), autologous CSC (n = 7) and MSC (n = 4) were delivered by intracoronary injection. These animals were compared to those receiving sham injections by echocardiography, invasive hemodynamics, and immunohistochemistry. Results Fractional shortening improved with CSC (26.9 ± 1.1% vs. 16.1 ± 0.2%, p = 0.01) and MSC (25.1 ± 0.2% vs. 12.1 ± 0.5%, p = 0.01) as compared to shams. MSC were superior to CSC in improving left ventricle end-diastolic (LVED) volume (37.7 ± 3.1% vs. 19.9 ± 9.4%, p = 0.03) and ejection fraction (27.7 ± 0.1% vs. 19.9 ± 0.4%, p = 0.02). LVED pressure was less in MSC (6.3 ± 1.3 mmHg) as compared to CSC (9.3 ± 0.7 mmHg) and sham (13.3 ± 0.7); p = 0.01. LV BrdU+ myocytes were higher in MSC (0.17 ± 0.03%) than CSC (0.09 ± 0.01%) and sham (0.06 ± 01%); p < 0.001. Conclusions Both CD117+ isolated CSC and MSC therapy improve cardiac function and attenuate pathological remodeling. However, MSC appear to confer additional benefit.
Harmonic and loss reduction in three-phase thyristor-controlled AC/DC converters for reactive power compensation

In this paper a new control method for the conventional, 12-pulse, thyristor-controlled, AC/DC converter for reactive power compensation is presented. A relatively small inductance is used with its rated current reached in the discontinuous mode to have a discontinuous rated inductor current. This results in lower inductor size, cost and loss, and greatly reduces the converter switching losses. With a proper choice of the control range and inductor size, a great reduction in the AC harmonics has been achieved. Experimental results are shown to demonstrate the validity of the proposed method. >
Experimental analysis of pulsing techniques in a proton exchange fuel cell

The purpose of this study is to investigate the impact of pulsing reactant flows on the performance of a PEMFC at low current density. This study considers a full range of pulsing flows and their effect in voltage over time. The factors evaluated were voltage, pressure, and flow rates of each reactant flow over time. A specific current density was set for the experiments. The experiments were performed at lower flow rates and temperatures of reactants than in standard operating conditions. The experiments used constant temperature of reactants as well as constant relative humidity. Comparison made between continuous flow and several sets of pulsing flows for hydrogen and air were developed. Pulsing of reactants opens an opportunity as a practical water management procedure. In addition, this technique helps extending performance range on PEMFC when a limited amount of reactants is supplied. The data collected was presented in graphical form.
State stem cell policy and the geographic preferences of scientists in a contentious emerging field

In the USA, stem cell research policy has been addressed at both federal and state levels. This paper focuses on the heterogeneous state policy environment and compares data from surveys of stem cell scientists and other biomedical researchers to evaluate the impact of supportive state policies on stem cell scientists' geographic preferences. At least early in the development of the field, permissive state policies were a strong predictor of scientists' geographic preferences. Combined with an analysis of scientists' policy awareness and explanations of their preferences, these findings suggest that supportive state science policies have influenced scientists' geographic preferences and, at least in the case of stem cell research where federal funding restrictions are prevalent, may help states to successfully recruit scientists. Copyright The Author 2012. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com, Oxford University Press.
INSTRUMENTAL TEXTURE ASSESSMENT AND CONSUMER ACCEPTABILITY OF COOKED BROILER BREASTS EVALUATED USING A GEOMETRICALLY UNIFORM‐SHAPED SAMPLE

The objective of this study was to determine the relationship of Warner-Bratzler shear values obtained from sample chicken strips cut to a standard geometric configuration with consumer tenderness acceptability. A relationship with deboning time was also evaluated. One breast from each bird, alternating right and left, were sous vide cooked (78C internal) and an average WBS value (kg) was determined. The remaining companion breasts were sorted into one of five ranges (1.1–2.0, 2.1–3.1, 3.2–4.0, 4.2–5.0, 5.2–6.7 kg) based on shear value. Consumer sensory evaluation was affected (P 0.05). Logistic regression was incorporated to predict the probability that a chicken breast in a specific shear value category would receive each consumer acceptability score.
Time-dependent effects of haloperidol on glutamine and GABA homeostasis and astrocyte activity in the rat brain

Rationale Schizophrenia is a severe, persistent, and fairly common mental illness. Haloperidol is widely used and is effective against the symptoms of psychosis seen in schizophrenia. Chronic oral haloperidol administration decreased the number of astrocytes in the parietal cortex of macaque monkeys (Konopaske et al., Biol Psych 63:759–765, 2008). Since astrocytes play a key role in glutamate metabolism, chronic haloperidol administration was hypothesized to modulate astrocyte metabolic function and glutamate homeostasis.
Components and Controls of Water Flux in an Old-growth Douglas-fir–Western Hemlock Ecosystem

We report measurements of rates of sap flow in dominant trees, changes in soil moisture, and evaporation from coarse woody debris in an old-growth Douglas-fir–western hemlock ecosystem at Wind River, Washington, USA, during dry periods in summer. The measurements are compared with eddy-covariance measurements of water-vapor fluxes above the forest (Ee) and at the forest floor (Eu) to examine the components of ecosystem water loss and the factors controlling them. Daily values of Eu were about 10% of Ee. Evaporation from coarse woody debris was only about 2% of Ee. Transpiration (Et), estimated by scaling sap-flow measurements accounted for about 70% of (Ee− Eu); transpiration from subdominant trees may account for the remainder. The daily total change in soil moisture (Es) in the top 30 cm was larger than the net change, probably because of hydraulic redistribution of soil water by roots. Observed differences between Es and Ee were probably because roots also extract water from greater depth, and/or because the measuring systems sample at different spatial scales. The ratio of Et to Es decreased with decreasing soil water content, suggesting that partitioning in water use between understory and overstory changed during the season. The rate of soil drying exceeded Ee early in the day, probably because water vapor was being stored in canopy air space and condensed or adsorbed on tree stems, lichens, and mosses. The daily variation of Ee with vapor-pressure deficit showed strong hysteresis, most likely associated with transpiration of water stored in tree stems and branches.
Enterprise program management: A Sprint case study

In the midst of a major corporate reorganization and an ever‐changing industry landscape, how does a corporate real estateorganization successfully build enterprise alliances and create integrated approaches to problem solving in order to 1) realign the real estate portfolio and 2) achieve optimal real estate portfolio efficiencies? The answer lies in the use of enterprise program management approaches to identify stakeholders and to invest in lifecycle management. This case study will examine how Sprint Enterprise Property Services successfully adopted the use of enterprise program management principles in order to achieve significant gains in process improvements, to transform a traditional work environment, and to institute a dynamic long‐term vacancy reduction plan for the corporate real estate portfolio.
N.m.r., d.s.c., t.m.a. and high-pressure electrical-conductivity studies in solid, crosslinked dimethylsiloxane-ethylene-oxide copolymer networks containing sodium

Abstract Audio frequency electrical conductivity and 23 Na n.m.r. studies have been made on solid, crosslinked dimethylsiloxane-ethylene-oxide copolymer networks containing sodium. Electrical measurements were made in vacuum over the temperature range 5 K to 380 K at pressures up to 0.65 GPa over the temperature range 230 K to 380 K. The electrical conductivity for the complexed material and the electrical relaxation time associated with the α-relaxation in the uncomplexed material exhibit Vogel-Tamman-Fulcher (V.T.F.) or Williams-Landel-Ferry (W.L.F.) behaviour. From a V.T.F. analysis of the electrical conductivity, the activation energy, E a , is found to be about 0.11 eV and T 0 is found to be about 45°C below the ‘central’ glass transition temperature as determined by both d.s.c. and t.m.a. Also, T 0 is found to increase by about 50 K GPa −1 and E a to increase significantly with pressure. In addition, the high-pressure studies show that the activation volume associated with electrical conductivity decreases from 44 to 23 cm 3 mol −1 over the temperature range 262 K to 323 K. The 23 Na n.m.r. measurements reveal the presence of both bound and mobile sodium species, the relative concentrations of which change by about a factor of 10 over the temperature range −100°C to +100°C. Broadening of the bound 23 Na line above room temperature suggests the possible presence of ion pairs or higher aggregates in the complex.
Patterns of Causal Analysis in Tocqueville's Democracy in America

Alexis de Tocqueville's Democracy in America was written to persuade his French compatriots that their fears of American-style democracy were ungrounded. In pursuing this end, Tocqueville used a nu...
Genotypic and haplotypic associations of the DBH gene with plasma dopamine β -hydroxylase activity in African Americans

Several variants at DBH are significantly associated with plasma DβH activity (pDβH). However, the overwhelming majority of data on this genotype–phenotype relationship has been gathered in samples from Europeans and European Americans (EAs). In this study, we examined the relationship between DBH polymorphisms and pDβH in samples from African-American (AA) subjects. Genotypes were determined at a 19-bp insertion/deletion polymorphism (ins/del) and four single-nucleotide polymorphisms (SNPs) at DBH in 109 samples. Analyses were performed using analyses of variance (ANOVAs) (for individual SNPs) and regression procedures (to assess the joint effects and the specific SNP-based haplotypes). We found: (1) single-variant analysis of all polymorphisms revealed apparent associations to pDβH, with rs1611115 accounting for the largest proportion of the variance in pDβH (28.7%) and ins/del the smallest (6.5%); (2) modest but significant linkage disequilibrium (LD) existed between ins/del and rs1611115; (3) LD between all other pairs of variants was not observed; (3) stepwise regression showed that a model containing rs1611115, rs2519152 and rs6271 accounted for 37.6% of the variance in pDβH, with rs6271 showing additional 7.6% above the effect of rs1611115, and rs2519152 showing additional 2% above rs1611115 and rs6271; (4) two common haplotypes, C-T-C and T-C-C at rs1611115-rs2519152-rs6271 were significantly associated with pDβH (P=0.0025 and 0.0036, respectively). The data support the validity of prior reported associations and underscore the importance of analyzing multiple SNPs across DBH in future association studies examining disease and biochemical phenotypes.
The surprising role of magnetism on the phase stability of Fe (Ferro)

Abstract We discuss the phase stability of the important element Fe in terms of the contributions to stability from the various forms of magnetism that exist in Fe. We point out that the ferromagnetic Fe is not cubic and that it is reasonable to return the beta phase of Fe to the phase diagrams based on Fe to designate paramagnetic BCC form of iron. We give a working definition of a phase, which includes the term “order parameter” following the insights of Landau.
The interactions between inflammation and coagulation

Inflammation initiates clotting, decreases the activity of natural anticoagulant mechanisms and impairs the fibrinolytic system. Inflammatory cytokines are the major mediators involved in coagulation activation. The natural anticoagulants function to dampen elevation of cytokine levels. Furthermore, components of the natural anticoagulant cascades, like thrombomodulin, minimise endothelial cell dysfunction by rendering the cells less responsive to inflammatory mediators, facilitate the neutralisation of some inflammatory mediators and decrease loss of endothelial barrier function. Hence, downregulation of anticoagulant pathways not only promotes thrombosis but also amplifies the inflammatory process. When the inflammation-coagulation interactions overwhelm the natural defence systems, catastrophic events occur, such as manifested in severe sepsis or inflammatory bowel disease.
Viennese Positivism in the United States

THE affirmative pursuit of truth is more profitable than the negative elimination of error, for there is more of the former than we could ever reach and more of the latter than we should hope to avoid. Known truth is scarce, while accepted error is plentiful; and to spend all available time in rejecting one set of falsehoods would merely mean to hand on the tradition to the promulgator of new ones. Hence refutation is a form of self-indulgence even though the blows be struck in the interest of truth and blocks on the road to inquiry have to be removed by someone. Nietzsche’s maxim, “where you cannot love, there should youâ€”pass by,” is good, yet need not preclude all criticism if it be performed in the spirit of condemning the sin rather than the sinner. Logical positivism has a value and has made a contribution; but it is rather the excess and the claim of absoluteness that is to be questioned here.
Photon energy spectrum emitted by a novel polymer-encapsulated 103Pd source and its effect on the dose rate constant.

Two independent groups have published intrinsic dosimetry parameters for the recently introduced OptiSeed103 interstitial brachytherapy source which contains 103Pd encapsulated by a novel polymer shell. The dose rate constant (Λ) reported by the two groups, however, differed by more than 6% and there is currently no AAPM recommended consensus value for this source in clinical dosimetry. The aim of this work was to perform an independent determination of Λ for the OptiSeed103 source using a recently developed photon spectrometry technique. Three OptiSeed103 sources (model 1032P) with known air-kerma strength were used in this study. The photon energy spectrum emitted along the radial direction on the source’s bisector was measured in air using a high-resolution intrinsic germanium spectrometer designed and established for low-energy brachytherapy source spectrometry. The dose rate constant of each source was determined from its emitted energy spectrum and the spatial distribution of radioactivity in the source. Unlike other sources made with traditional titanium encapsulation, the photons emitted by the OptiSeed103 sources exhibited only slight spectral hardening, yielding a relative energy spectrum closer to that emitted by bare 103Pd. The dose rate constant determined by the photon spectrometry technique for water was 0.664±0.025 cGy h−1 U−1. This value agreed, within experimental uncertainties, with the Monte Carlo-calculated value (MCΛ) of 0.665±0.014 cGy h−1 U−1 and the TLD-measured value (with a Monte Carlo-calculated solid-phantom-to-water conversion factor) of 0.675±0.051 cGy h−1 U−1 reported by Wang and Hertel [Appl. Radiat. Isot. 63, 311–321 (2005)]. However, it differed by −6.7% from the MCΛ of 0.712±0.043 cGy h−1 U−1 reported by Bernard and Vynckier [Phys. Med. Biol. 50, 1493–1504 (2005)]. The results obtained in this work provide additional information needed for establishing a consensus value for the dose rate constant for the OptiSeed103 source. It suggests that an eventual consensus value of Λ for the OptiSeed103 source is likely to be closer to a value of 0.668 cGy h−1 U−1 rather than 0.693 cGy h−1U−1 as initially recommended by the source manufacturer based on the two previously published results.
Changes in FSH Activity of Anterior Pituitary Glands and of Blood Plasma During the Laying Cycle of the Hen

Anterior pituitary and blood plasma were collected from 285 laying hens with regular clutch sequences at 8 sampling times within the period from ovulation of the second to the ovulation of the third egg of the clutch. Plasma concentrates used for assay material were obtained by a procedure based on the cold acetone fractionation method. A modification of the Steelman-Pohley assay was found adequate to estimate FSH potency of pituitary homogenates or the plasma concentrates obtained from laying hens. Using NIH-FSH-S4 as standard, a 2×2 design was employed in all assays to measure pituitary and plasma FSH levels during the laying cycle. Two peaks in plasma and 3 peaks in pituitary FSH were found when FSH concentrations or contents in pituitary and plasma of hens of 8 groups were arranged according to the time after Ci oviposition and 11 hr before Cs ovulation. The first peak in FSH release occurred immediately after C2 ovulation. Perhaps this peak is essential for rapid growth of the C3 follicle which occur...
Instruments and new technologies for the in vivo diagnosis of melanoma

Abstract The principal objective of screening individuals at risk for melanoma is detection of cutaneous melanoma during the curable stages of its early evolution. Unaided visual inspection of the skin is often suboptimal at diagnosing melanoma. Improving the diagnostic accuracy for melanoma remains an area of active research. These research efforts have focused on both the detection of early melanoma and the in-depth evaluation of suspicious pigmented lesions for the presence or absence of melanoma. Numerous instruments are under investigation to determine their usefulness in imaging and ascertaining a correct in vivo diagnosis of melanoma. It is anticipated that some of these tools, alone or in combination, will improve our ability to differentiate, in vivo, melanoma from its simulators. Ultimately, these advances may prevent unnecessary biopsies (increased specificity) while increasing the sensitivity for diagnosing melanoma. This article reviews the current instruments and new technologies for the in vivo diagnosis of melanoma. Learning objective At the conclusion of this learning activity, participants should be acquainted with the instruments designed to facilitate the early detection of melanoma. They should also be familiar with the basic technology behind these instruments and should recognize the potential benefits and limitations inherent in each.