cssi/SciSciGPT-SciSciNet huggingface dataset:
An agonist murine monoclonal antibody to the human c-Mpl receptor stimulates megakaryocytopoiesis.

Thrombopoietin (TPO) is a hematopoietic growth factor that stimulates megakaryocytopoiesis and platelet production in vivo and promotes the development of identifiable megakaryocytes in vitro. We have developed a murine monoclonal antibody, BAH-1, raised against human megakaryocytic cells, which specifically recognizes the c-Mpl receptor and shows agonist activity by stimulating megakaryocytopoiesis in vitro. BAH-1 antibody specifically binds to platelets and to recombinant c-Mpl with high affinity. Similar to TPO, BAH-1 alone supported the formation of colony-forming unit-megakaryocyte (CFU-MK) colonies. The combination of BAH-1 plus interleukin-3 or of BAH-1 plus human TPO significantly increased the number of human CFU-MK colonies. In addition, BAH-1 monoclonal antibody stimulated the proliferation and maturation of primary bone marrow megakaryocytes in a dynamic heterogeneous liquid culture system. Individual large megakaryocytes as well as small megakaryocytic cells were observed in cultures of CD34+ CD41+cells in the presence of BAH-1 antibodies. Similar to TPO, BAH-1 antibody induced a significant response of murine immature megakaryocytes as observed by an increase in the detectable numbers of acetylcholinesterase-positive megakaryocytes. No effects of BAH-1 antibody were observed on colony-forming unit–granulocyte-macrophage, burst-forming unit-erythroid, or colony-forming unit-erythroid colonies. In vivo studies showed that BAH-1, alone or in combination with TPO, expands the numbers of megakaryocytic progenitor cells in myelosuppressed mice. This antibody should prove useful in understanding the structure-function aspects of the c-Mpl receptor as well as in evaluating the effects of the sustained activation of this receptor in preclinical models of severe thrombocytopenia. © 1998 by The American Society of Hematology.
411. Predicting Tumor Response to Oncolytic Virotherapy Using Dual Isotope SPECT/CT Imaging with NIS Reporter Gene and Duramycin

Oncolytic virotherapy is a promising modality for cancer therapy and diverse viruses from various families have been genetically engineered to be tumor selective anticancer agents. To obtain an early readout on tumor susceptibility to the oncolytic virus, and potential toxicity from off target viral infection, we have engineered our oncolytic viruses to encode the thyroidal sodium iodide symporter gene (NIS) to enable noninvasive longitudinal imaging of the pharmacokinetics and sites of virus spread. The high resolution images obtained from the new generation of small animal SPECT/CT or PET/CT machines enable us to visualize increasing numbers of infectious foci daily within the subcutaneous tumors and to establish a mathematical model to develop strategies that will improve the outcome of virotherapy. In this study, we used the oncolytic Vesicular Stomatitis Virus (VSV) encoding NIS to evaluate the kinetics of intratumoral viral spread, and the subsequent aftermath of tumor cell death by apoptosis. Through I-125 SPECT/CT and NIS imaging, we showed rapid VSV spread within the susceptible MPC-11 murine plasmacytoma tumors, and the infectious foci grew larger and increased in numbers over 5 days. Since SPECT imaging enables concurrent dual isotope imaging, we also gave the same animal Tc-99m duramycin that detects apoptotic cells. In this MPC-11 model, we found rapid onset of apoptosis within the tumor. The infectious foci of viral infection (NIS imaging) and cell death (duramycin imaging) were coincident, overlapping at the acute phase of infection. In contrast, the CT-26 tumor was significantly less responsive to VSV-mIFN-NIS therapy, and there was minimal positive NIS signals or apoptosis. We are keen to further evaluate the potential of using dual isotope SPECT imaging using NIS reporter gene and the duramycin apoptosis tracer, with the goal of using this twin set of imaging methods to give us an early prediction of tumor response to oncolytic virotherapy.
Toxicogenomic module associations with pathogenesis: a network-based approach to understanding drug toxicity

Despite investment in toxicogenomics, nonclinical safety studies are still used to predict clinical liabilities for new drug candidates. Network-based approaches for genomic analysis help overcome challenges with whole-genome transcriptional profiling using limited numbers of treatments for phenotypes of interest. Herein, we apply co-expression network analysis to safety assessment using rat liver gene expression data to define 415 modules, exhibiting unique transcriptional control, organized in a visual representation of the transcriptome (the 'TXG-MAP'). Accounting for the overall transcriptional activity resulting from treatment, we explain mechanisms of toxicity and predict distinct toxicity phenotypes using module associations. We demonstrate that early network responses complement traditional histology-based assessment in predicting outcomes for longer studies and identify a novel mechanism of hepatotoxicity involving endoplasmic reticulum stress and Nrf2 activation. Module-based molecular subtypes of cholestatic injury derived using rat translate to human. Moreover, compared to gene-level analysis alone, combining module and gene-level analysis performed in sequence identifies significantly more phenotype-gene associations, including established and novel biomarkers of liver injury.
Arthroscopic Treatment of FAI: Supine Position, My First Option

The concept of femoroacetabular impingement has been popularized by Ganz et al. as mechanical cause of hip pain and the development of osteoarthritis in the hip [1]. Contact resulting from the loss of anterior offset at the femoral head–neck junction has been termed “cam impingement,” and contact due to increased coverage of the anterior aspect of the acetabulum has been termed “pincer impingement.”
BRAIN AND NERVOUS SYSTEM | Functional Morphology of the Nervous System: An Introduction

As in the other vertebrate groups, the brain in fishes comprises three major divisions – the hindbrain, midbrain, and forebrain – and contains multiple ascending sensory system pathways, association areas in the forebrain for integrating the sensory information, and descending motor system pathways. Marked differences in brain structure and organization result from variation in the numbers of neurons that are generated by the germinal zone, which lies along the ventricular surface; variation in the degree to which the neuron cell bodies migrate away from that zone; and variation in the neuronal phenotypes in terms of features such as dendritic tree morphology and neurotransmitter and neuromodulator profiles. In the adult, neurons are arranged into either cortices, which have multiple defining features including the presence of several different layers, or nuclei, which are more homogeneous in their composition. Many structures in brains of fishes are similar across this taxon and also to those in the other major groups of vertebrates, including many of the cranial nerve nuclei and the various sensory and motor system pathways, but many instances of specializations also occur across this widely diverse taxon.
Surgical Management of Chylous Reflux and Effusions

Chylous disorders are uncommon but serious and frequently life-threatening conditions. Chylous reflux through incompetent abdominal and pelvic lymphatics causes lymphatic congestion and lymphedema; chylous effusion results when dilated lymph vessels rupture and chyle accumulates in body cavities or in joints. Rupture of skin lymphatics results in chylous leak. Conservative therapy is usually the first line of treatment using dietary manipulation and aspiration of the effusion. In patients with primary chylous disorders who fail conservative management, the selective use of ligation of lymphatic fistulas, excision of dilated lymphatics, sclerotherapy, lympho-venous reconstruction (LVR), and placement of a peritoneovenous shunt (PVS) are additional treatment options suggested. Specifically, for chylothorax, ligation of the leaking lymphatics or the thoracic duct (TD) along with pleurodesis via thoracotomy or VATS is frequently effective; LVR may be considered as a surgical option in selected patients. Ligation of the incompetent retroperitoneal lymphatics and oversewing ruptured lymphatics can produce long-term improvement in lymphangiectasia and lymphatic reflux. Chylous ascites can be treated with ligation of the mesenteric or retroperitoneal lymphatic fistula, or LVR or bypass grafting in cases with large lymph vessel and patent venous system, or PVS, although the role of PVSs in the treatment of chylous ascites remains controversial. Endovascular treatment such as percutaneous embolization is increasingly used, but surgical treatment still plays an essential role especially in patients who fail to or not eligible for endovascular therapy. Individualized treatment based on the etiology, the site of lymph leaks, the amount of drainage volume, and the extent of chylous disease is required to achieve treatment success. In this chapter we review principles, indications, results, and problems of these surgical techniques.
Increased Calcific Aortic Valve Disease in response to a diabetogenic, procalcific diet in the LDLr-/-ApoB100/100 mouse model

Abstract Objective Calcific aortic valve disease (CAVD) is a major cause of aortic stenosis (AS) and cardiac insufficiency. Patients with type II diabetes mellitus (T2DM) are at heightened risk for CAVD, and their valves have greater calcification than nondiabetic valves. No drugs to prevent or treat CAVD exist, and animal models that might help identify therapeutic targets are sorely lacking. To develop an animal model mimicking the structural and functional features of CAVD in people with T2DM, we tested a diabetogenic, procalcific diet and its effect on the incidence and severity of CAVD and AS in the, LDLr -/- ApoB 100/100 mouse model. Results LDLr -/- ApoB 100/100 mice fed a customized diabetogenic, procalcific diet (DB diet) developed hyperglycemia, hyperlipidemia, increased atherosclerosis, and obesity when compared with normal chow fed LDLr -/- ApoB 100/100 mice, indicating the development of T2DM and metabolic syndrome. Transthoracic echocardiography revealed that LDLr -/- ApoB 100/100 mice fed the DB diet had 77% incidence of hemodynamically significant AS, and developed thickened aortic valve leaflets and calcification in both valve leaflets and hinge regions. In comparison, normal chow (NC) fed LDLr -/- ApoB 100/100 mice had 38% incidence of AS, thinner valve leaflets and very little valve and hinge calcification. Further, the DB diet fed mice with AS showed significantly impaired cardiac function as determined by reduced ejection fraction and fractional shortening. In vitro mineralization experiments demonstrated that elevated glucose in culture medium enhanced valve interstitial cell (VIC) matrix calcium deposition. Conclusions By manipulating the diet we developed a new model of CAVD in T2DM, hyperlipidemic LDLr -/- ApoB 100/100 that shows several important functional, and structural features similar to CAVD found in people with T2DM and atherosclerosis including AS, cardiac dysfunction, and inflamed and calcified thickened valve cusps. Importantly, the high AS incidence of this diabetic model may be useful for mechanistic and translational studies aimed at development of novel treatments for CAVD.
Inferior vena cava filter placement in a left IVC and drainage into duplicated SVC via hemiazygous continuation.

Abstract Left-sided inferior vena cava (IVC) is the second most common anatomical anomaly of the IVC. We report a drainage pattern of the left IVC into a left duplicated superior vena cava (SVC) diagnosed during IVC filter placement consultation. The patient was a 66-year-old man with symptomatic hematuria caused by bladder cancer diagnosed with IVC thrombus and a left IVC found on a staging computed tomography urogram. The patient underwent computed tomography pulmonary angiogram, which ruled out pulmonary embolism, but demonstrated hemiazygous continuation of the left IVC above the diaphragm to meet a persistent left SVC (prevalence approximately 0.3%-0.5%) (Kim et al. 1995) [1] emptying into the right atrium via the coronary sinus. We report a novel drainage pattern of the left IVC into a duplicated left SVC via hemiazygous continuation.
Histopathological and molecular predictors of growth patterns and recurrence in craniopharyngiomas: a systematic review.

Craniopharyngiomas (CPs) are rare, benign tumors derived from Rathke’s pouch, known for their high recurrence rates and associated morbidity and mortality. Despite significant investigation on risk factors for recurrence, a lack of consensus persists. Recent research suggests that specific histopathological and molecular characteristics are prognostic for disease progression. In this systematic review, we analyzed and consolidated key features of CPs that contribute to increased recurrence rates. This systematic review was performed in accordance with PRISMA guidelines. A search string was created with the keywords “craniopharyngioma,” “histology,” “histopathology,” “molecular,” and “recurrence.” Literature was collected from 2006 to 2016 on the PubMed/Medline and Web of Science databases. The initial search resulted in 242 papers, examined with inclusion and exclusion criteria. The final review included a total of 37 studies, 36 primary studies covering a total of 1461 patients and 1 previous meta-analysis. Cystic lesions and whorl-like arrays were found to be associated with increased recurrence, while previously considered reactive gliosis and finger-shaped protrusions were not. The genetic elements found to be associated with increased risk of recurrence were Ki-67, Ep-CAM, PTTG-1, survivin, and certain RAR isotypes, as well as the glycoproteins osteonectin and chemokines CXCL12/CXCR4. The effects of VEGF, HIF-1α, and p53, despite extensive study, yielded conflicting results. Certain histopathological and molecular characteristics of CPs provide insight into their pathogenesis, likelihood of recurrence, and potential novel targets for therapy.
Framing and visual type: Effect on future Zika vaccine uptake intent.

Introduction: The Zika virus is associated with the birth defect microcephaly, and while a vaccine was not available in early- 2017, several were under development. This study’s purpose was to identify effective communication strategies to promote uptake of a new vaccine, particularly among women of reproductive age.Design and methods: In order to study the effects of Zika message framing (gain vs. loss) and visual type (photo vs. infographic) on future Zika vaccine uptake intent, a 2×2 between-subjects experiment was performed via an online survey in 2017 among 339 U.S. women of reproductive age (18-49 years). Participants were exposed to one of four messages, all resembling Instagram posts: gain-framed vs. loss-framed infographic, and gain-framed vs. loss-framed photo. These messages were followed by questions about Zika vaccine uptake intent as well as intermediate psychosocial variables that could lead to intent. Results: There was no interaction between framing and visual type (P=0.116), and there was no effect for framing (P=0.185) or visual type (P=0.724) on future Zika vaccine uptake intent, which is likely indicative of insufficient dosage of the intervention. However, when focusing on intermediate psychosocial constructs that are known to influence behavior and intent, gain-framed messages were more effective in increasing subjective norms (P=0.005) as related to a future Zika vaccine, as well as perceived benefits (P=0.016) and self-efficacy (P=0.032). Conclusions: Gain-framed messages seem to be more effective than loss-framed messages to increase several constructs that could, in turn, affect future Zika vaccine uptake intent. This is a novel finding since, traditionally, loss-framed messages are considered more beneficial in promoting vaccine-related health behaviors.
Engaging Children in Play Therapy: The Coupling of Virtual Reality Games with Social Robotics

Individuals who have impairments in their motor skills typically engage in rehabilitation protocols to improve the recovery of their motor functions. In general, engaging in physical therapy can be tedious and difficult, which can result in demotivating the individual. This is especially true for children who are more susceptible to frustration. Thus, different virtual reality environments and play therapy systems have been developed with the goal of increasing the motivation of individuals engaged in physical therapy. However, although previously developed systems have proven to be effective for the general population, the majority of these systems are not focused on engaging children. Given this motivation, we discuss two technologies that have been shown to positively engage children who are undergoing physical therapy. The first is called the Super Pop VR™ game; a virtual reality environment that not only increases the child’s motivation to continue with his/her therapy exercises, but also provides feedback and tracking of patient performance during game play. The second technology integrates robotics into the virtual gaming scenario through social engagement in order to further maintain the child’s attention when engaged with the system. Results from preliminary studies with typically-developing children have shown their effectiveness. In this chapter, we discuss the functions and advantages of these technologies, and their potential for being integrated into the child’s intervention protocol.
Electrical Propulsion System Design of Chevrolet Bolt Battery Electric Vehicle

The propulsion system design of General Motors’ Chevrolet Bolt battery electric vehicle (BEV) incorporates the use of a permanent magnet synchronous motor. Magnets are buried inside the rotor in double layer “V” arrangement and the rotor design optimizes the magnet placement between the adjacent poles asymmetrically to lower torque ripple and radial force. Rotor design also optimizes the placement of a pair of small slots stamped near the rotor outer surface at different locations in adjacent poles to provide further reduction in torque ripple and radial force. As a result of all these design features, the Chevrolet Bolt BEV electric motor is able to meet the GM stringent noise and vibration requirements without implementing rotor skew, which is known to lower the motor performance and add complexity to the rotor manufacturing. Similar to Chevrolet Spark BEV, a bar-wound stator construction known to provide high slot fill, shorter end-turn length, and other benefits is implemented in Chevrolet Bolt BEV. To lower the winding ac effect at higher speeds, the Chevrolet Bolt BEV motor implements six conductors per slot design while four conductors per slot design was used in the Chevrolet Spark motor design. As a result, individual conductor size is smaller in new design resulting in reduced winding ac effects and improved joule loss at high-speed operations. Chevrolet Bolt BEV stator design also adopts a special feature, introduced in Gen2 (2nd generation) Chevrolet Volt; the size and placement of stator slot openings under each pole are optimized to lower torque ripple and radial force. This feature acts as a supplement to the torque ripple and radial force reduction features introduced in the rotor design as described above.
In-hospital outcomes of tumor lysis syndrome: A population-based study using the National Inpatient Sample (NIS).

6582Background: The epidemiology and outcomes of tumor lysis syndrome (TLS) are understudied. We use the NIS to study outcomes and predictors of mortality in hospitalized patients with TLS. Methods...
Bisphenol A alteration of type 1 diabetes in non-obese diabetic (NOD) female mice is dependent on window of exposure.

Type 1 diabetes (T1D) is an autoimmune disease in which pancreatic β-cell destruction can be mediated by dysbiosis, infiltration of pro-inflammatory immune cells, and cytokines/chemokines. Exposure to bisphenol A (BPA), an endocrine disruptor (ED), can lead to aberrant immunity and gut microbiota. We determined whether BPA had age-dependent effects on T1D by modulating immune homeostasis following various windows of exposure in non-obese diabetic (NOD) mice. Juvenile NOD females were orally exposed to 0 or 30 µg BPA/kg BW from postnatal day (PND) 28 to PND56. Adult NOD females were exposed to 0 or 300 µg BPA/kg BW. Female and male NOD offspring were exposed to 0 or 300 µg BPA/kg BW perinatally from gestation day 5 to PND28 by dosing the dams. It was found that BPA increased T1D risk in juvenile females with gut microbiota shifted towards pro-inflammation (e.g. increased Jeotgalicoccus). In agreement with our previous study, adult females had a trend of increased T1D and a general increase in immune responses. However, female offspring had a reduced T1D development. Consistently, female offspring had a shift towards anti-inflammation (e.g. decreased pro-inflammatory F4/80+Gr1+ cells). In contrast, BPA had minimal effects on immunity and T1D in male offspring. Thus, it was concluded that BPA had age- and sex-dependent effects on T1D with the alteration of gut microbiota and inflammation being the primary mechanisms for T1D exacerbation in juvenile exposure and decreases of inflammation being responsible for attenuated T1D in perinatally exposed females.
Adherence to guideline recommendations for human rabies immune globulin patient selection, dosing, timing, and anatomical site of administration in rabies postexposure prophylaxis

Rabies is a fatal disease that mandates proper prophylaxis after a rabies virus exposure to prevent death. This study evaluated adherence to Centers of Disease Control and Prevention (CDC) recommen...
The frugal entrepreneur: A self-regulatory perspective of resourceful entrepreneurial behavior

Abstract The present research complements extant perspectives of resourcefulness, which assert that resourceful behaviors arise out of responses to environmental constraints, by developing a model illustrating that entrepreneurs self-impose constraints on resource acquisition and deployment for differing reasons. Specifically, we introduce a novel conceptualization of frugality and differentiate it from self-control to develop a set of hypotheses that frugality predicts resource use behaviors based on long-held preferences (e.g., effectuation and bricolage) and self-control predicts resource use behaviors based on known end states or goals (e.g., causation and pre-commitments). After accumulating evidence of reliability and validity for a new measure of frugality contextualized for entrepreneurship research, the results support our self-regulatory theoretical framework. Our study contributes to research on resourcefulness by making multiple theoretical insights, and we outline numerous future research opportunities for applying the construct of frugality to explain entrepreneurial behavior.
La pace è femmina: lo sguardo neocon sulle questioni di genere

My essay provides a few elements to analyse how the neoconservative perspective on gender issues has evolved from its early phases to the last years. The aim is to highlight how neoconservative authors shifted from an openly patriarchal view of gender roles to more or less successful attempts at appropriating “feminist” themes and issues, in view of the affirmation of America’s moral superiority as a justification of hard power.
CRISPR-Based Synthetic Transcription Factors In Vivo: The Future of Therapeutic Cellular Programming.

Pinpoint control over endogenous gene expression in vivo has long been a fevered dream for clinicians and researchers alike. With the recent repurposing of programmable, RNA-guided DNA endonucleases from the CRISPR bacterial immune system, this dream is becoming a powerful reality. Engineered CRISPR/Cas9-based transcriptional regulators and epigenome editors have enabled researchers to perturb endogenous gene expression in vivo, allowing for the therapeutic reprogramming of cell and tissue behavior. For this technology to be of maximal use, a variety of technological hurdles still need to be addressed. Better understanding of the design principle controlling gene expression together with technologies that enable spatiotemporal control of transcriptional engineering are fundamental for rational design, improved efficacy, and ultimately safe translation to humans. In this review, we will discuss recent advances and integrative strategies that can help pave the path toward a new class of transcriptional therapeutics.
Is the Taylor rule optimal? Evaluation using a wavelet-based control model

This paper extends the wavelet-based control (WBC) model of Crowley and Hudgins (2015) to compare the simulated performance of jointly optimal fiscal and monetary policy, where the policymakers pla...
Differential and experimental approaches to studying intelligence in humans and non-human animals

Abstract Why do some individuals learn more quickly than others, or perform better in complex cognitive tasks? In this article, we describe how differential and experimental research methods can be used to study intelligence in humans and non-human animals. More than one hundred years ago, Spearman (1904) discovered a general factor underpinning performance across cognitive domains in humans. Shortly thereafter, Thorndike (1935) discovered positive correlations between cognitive performance measures in the albino rat. Today, research continues to shed light on the underpinnings of the positive manifold observed among ability measures. In this review, we focus on the relationship between cognitive performance and attention control: the domain-general ability to maintain focus on task-relevant information while preventing attentional capture by task-irrelevant thoughts and events. Recent work from our laboratory has revealed that individual differences in attention control can largely explain the positive associations between broad cognitive abilities such as working memory capacity and fluid intelligence. In research on mice, attention control has been closely linked to a general ability factor reflecting route learning and problem solving. Taken together, both lines of research suggest that individual differences in attention control underpin performance in a variety of complex cognitive tasks, helping to explain why measures of cognitive ability correlate positively. Efforts to find confirmatory and disconfirmatory evidence across species stands to improve not only our understanding of attention control, but cognition in general.
Abstract TP22: Longer Procedure Time in General Anesthesia versus Conscious Sedation During Mechanical Thrombectomy for Large Vessel Occlusion Ischemic Stroke

Introduction: There is no definitive evidence currently to guide the choice between general anesthesia (GA) over conscious sedation (CS) for patients undergoing mechanical thrombectomy (MT). As MT ...
High Pressure Reinjection CO[sub]2[/sub] Oscillator

The design and performance of a uv preionized CO2 oscillator capable of 10 atm operation is described. When used as a reinjection oscillator this device is capable of subnanosecond pulses of CO2 radiation with powers in excess of 1 GW.
Parties and Factions in the Russian Orthodox Church, 1480–1580: some Observations

The existence of parties in the Russian Orthodox Church 1480–1580 does not imply parties in the sense of coherent ideological groupings, as Don Ostrowski, David Goldfrank and Charles Halperin correctly argue. Iosif Volotskii and Nil Sorskii had complementary, not rival views. The issue of monastic lands was about regulation, not confiscation, and the parties were actually “old boy networks”. The Russian story needs a Byzantine context for the treatment of heresies, monastic lands, and other issues. Byzantium had different practices than the West, and so did the Russians. Western practice and terminology is not relevant.
By the assemblage: physical education teachers’ encounters of a state teacher accountability system

With a focus on the American context, the study investigates a teacher accountability reform as an expanding assemblage of neoliberal governance by providing an account of physical education teache...
Fractional Laser Treatment Boosts Systemic Anti-Tumor Immunity in Combination with OX40 Agonist and PD-1 Blockade

While ablative fractional photothermolysis (aFP) with a 10,600 nm CO2 laser is employed for a wide variety of dermatologic conditions, its applications in oncology are relatively unexplored. Building off our previous work, we investigated the effect of unilateral aFP treatment in combination with anti-PD-1 blocking antibody and OX40 agonist on bilateral tumor growth and remission. A CT26 wild type (CT26WT) colon carcinoma cell line was established bilaterally on the hind flanks of a standardized mouse model and tumor characteristics were investigated on aFP treated and untreated sides. Remarkably, triple therapy with fractional CO2 laser in combination with anti-PD-1 antibodies and OX40 agonists resulted in significantly slower tumor growth and complete remissions on bilateral tumors. Flow cytometric analysis showed the triple treatments elicited an increase of granzyme B+ CD8+T cells due to synergistic effect of aFP treatment and the checkpoint molecules, including the induction of CD103+ CCR7+ dendritic cells (DCs) in aFP-treated tumor by aFP treatment, XCR1+ DCs in drainage lymph node by anti-PD-1 inhibitor and OX40+ Ki67+ CD8+ T cells in the lymph node by OX40 agonist. Triple therapy-mediated tumor regression and survival was abrogated upon CD8+ T cell depletion. Importantly, when two mismatched cancer cells were implanted into mice, the effect of the triple therapy on distant tumor was abrogated, showing antigen specificity of the T cell immunity induced by triple therapy. This study highlights the efficacy of aFP a novel adjuvant for current cancer immunotherapeutics.
Effects of surface treatments and coatings on tribological performance of Ti–6Al–4V in the mixed fretting and gross slip regimes

Abstract Although titanium alloys are chemically resistant and have desirable mechanical properties, these materials are known to experience high wear rates and friction when they are in contact and in relative motion with themselves or most other materials. In this study, titanium-containing MoS 2 and Ti containing amorphous carbon coatings have been applied to Ti–6Al–4V discs and were examined in mixed fretting and gross slip regimes against uncoated, NiPO 4 , and MnPO 4 coated AISI 52100 counterfaces. Experiments were carried out at two different temperatures and wear coefficients were obtained for the various material pairs. Whereas the smallest friction and wear coefficients were obtained for MnPO 4 /Ti–MoS 2 pairs at both high and low temperatures, the NiPO 4 /Ti–MoS 2 coupling is incompatible. On the other hand, NiPO 4 /Ti–aC appears to be a very compatible material pair.
Abstract 11587: Acidosis/GPR4 Signaling Regulates Inflammatory and Endoplasmic Reticulum Stress Responses in Vascular Endothelial Cells

An acidotic tissue microenvironment is commonly found in ischemic organs, inflammatory sites, solid tumors, and in many other pathophysiological conditions. Due to hypoxia, glycolytic cell metabolism, and poor blood perfusion, production and accumulation of protons derived from lactic acid and other metabolic products acidify the microenvironment. Acidosis is an important stress factor that aggravates ischemic tissue injury and modulates the function of blood vessels and immune cells. Recent studies show that acidotic activation of the pH-sensing G protein-coupled receptor 4 (GPR4) increases endothelial cell inflammation and leukocyte adhesion. Numerous inflammatory genes such as adhesion molecules, chemokines, cytokines, NF-κB factors, and cyclooxygenase 2 are up-regulated by acidosis and GPR4 in endothelial cells. However, the signaling pathways by which acidosis/GPR4 regulates the inflammatory responses of endothelial cells are largely unknown. Using genetic and biochemical approaches we demonstrate that Gs, Gq and G13 G protein pathways are imperative for acidosis/GPR4-induced inflammatory gene expression in endothelial cells. Each of these G protein pathways controls the expression of a subset of the inflammatory target genes. Moreover, interaction between these G protein pathways has been observed; e.g., induction of VCAM-1 by acidosis/GPR4 is positively regulated by the Gs pathway but negatively regulated by the G13 pathway. We also demonstrate that acidosis/GPR4 induces the endoplasmic reticulum (ER) stress response, a process closely associated with inflammation, in endothelial cells. Interestingly, treatment with a novel GPR4 small molecule inhibitor diminishes the acidosis-induced endothelial cell ER stress response. Together, these results suggest that acidosis/GPR4 signaling is a novel regulatory mechanism of endothelial cell inflammation and ER stress response. Inhibition of the GPR4 receptor may be exploited as potential new means to suppress inflammation associated with cardiovascular disorders.
How students come to be, know, and do : a case for a broad view of learning

Introduction 1. The context lens 2. How ways of knowing, doing, and being emerged in the classroom: interpersonal interactions and the creation of community, part I 3. How ways of knowing, doing, and being emerged in the classroom: interpersonal interactions and the creation of community, part II 4. Personal lens of analysis: individual learning trajectories Conclusion.
Designing the capital‐labour accord

Examines the origins and ideology of the Beyer Plan, a co‐operative productivity venture designed in 1918 for railway labour by Taylor Society member, Otto Beyer, but not implemented until after the 1922 strike. Argues that the traditional depictions of the plan as a sign of labour′s ebbing strength in the 1920s neglect the extent to which the plan marks the emergence of a constellation of interests that influenced industrial relations in the following decades. The plan promoted a reformulation of the wage relation, involving a break with piece‐work and a focus on aggregate productivity levels. Reveals the significant role played by a labourist cadre within the Taylor Society (including Beyer and Morris L. Cooke) in the development of the politics of productivity that characterized labour relations in America′s core industries by the 1940s.
Clinical comparison of ICD detection algorithms that include rapid-VT zones.

Introduction: The safe use of antitachycardia pacing (ATP) to terminate rapid ventricular tachycardias (VTs) (cycle length 240–320 ms) is predicated on the ability of implantable cardioverter defibrillators (ICDs) to distinguish rapid VT from ventricular fibrillation (VF). We set out to compare the time to device charging following the induction of VF of various ICD multizone detection algorithms for rapid VT/VF discrimination. Methods and Results: Data on the time to device charging following the induction of VF at the time to device implantation were collected on 62 consecutive patients in a nonrandomized prospective cohort fashion. Multizone programming for the Boston Scientific, Medtronic, and St. Jude Medical devices was based on prior clinically validated data. Sixty-two subjects were studied (Boston Scientific = 16, Medtronic = 27, St. Jude Medical = 19) and 124 tests for VF detection were performed (Boston Scientific = 32, Medtronic = 54, St. Jude Medical = 38). Mean time to charging was significantly prolonged in the Boston Scientific group as was the percentage of tests where charge initiation occurred >5 seconds from VF-induction: 4.24, 3.99, and 3.00 seconds and 19%, 4%, and 0% for the Boston Scientific, Medtronic, and St. Jude Medical groups, respectively, P < 0.05. ATP was the first therapy administered in 9.4% of tests in the Boston Scientific group. Conclusion: The Boston Scientific multizone VT/VF discrimination algorithm results in a prolonged time to VF detection, and consequently, prolonged time to appropriate initiation of device charging. Further studies are needed to determine whether prolonged detection times lead to clinically significant events. (PACE 2012; 35:1222–1231)
Concordance among Holdouts

Holdout problems prevent decentralized aggregation of complementary goods, but the coercion required to overcome holdout may encourage abuse and violate fairness standards. We propose second-best efficiency, abuse-prevention, and fairness criteria for procedures intended to reduce holdout. Our criteria are jointly satisfied by a class of “Concordance” procedures. In these procedures, the prospective buyer makes a take-it-or-leave-it offer to the group of sellers, and the sellers use an efficient collective choice mechanism to decide as a group whether to accept the buyer’s offer. In the case of sale, the buyer’s offer is divided among the sellers in a fashion independent of individual sellers’ actions. Each seller retains the option to receive, in the event of sale, her share of the offer (without making any additional payments) in exchange for not influencing the collective decision. Our approach is applicable in a range of contexts including land assembly, spectrum aggregation, corporate acquisitions, and patent pool formation.
Some applications of small accelerators

With the frontiers of nuclear physics pushed toward higher and higher energies, an increasing number of small accelerators are being freed for other uses. A description of some of the areas of small accelerator applications will therefore serve a useful purpose. Since the topics are both rich and varied, a reasonably detailed description must be confined to a selected few. These topics are compositional studies of layered materials, channeling of heavy charged particles., and characteristic radiation of channeled relativistic electrons. All interface closely with nuclear physics and are aspects of particle-solid interactions which is a field receiving increasing attention.
Determining land use policy via the ballot box: The growth initiative blitz in California

Abstract Californians are afforded the opportunity to participate in the planning process and to voice their opinions to their elected officials in a variety of ways. However, for various reasons citizens have taken the opportunity to develop local legislation designed to manage or control growth. Once passed by the electorate, this legislation becomes law and must be enforced by the municipality. The use of direct democracy and ballot box planning in California is increasing and is expected to increase in the future. This paper examines how and why Californians have turned to the ballot box to decide land use matters. Examples of recent ballot measures and implications of ballot box planning are provided.
The cost of feeding bred dairy heifers on native warm-season grasses and harvested feedstuffs

Heifer rearing is one of the largest production expenses for dairy cattle operations, which is one reason milking operations outsource heifer rearing to custom developers. The cost of harvested feedstuffs is a major expense in heifer rearing. A possible way to lower feed costs is to graze dairy heifers, but little research exists on this topic in the mid-south United States. The objectives of this research were to determine the cost of feeding bred dairy heifers grazing native warm-season grasses (NWSG), with and without legumes, and compare the cost of grazing with the cost of rearing heifers using 3 traditional rations. The 3 rations were corn silage with soybean meal, corn silage with dry distillers grain, and a wet distillers grain-based ration. Bred Holstein heifers between 15- and 20-mo-old continuously grazed switchgrass (SG), SG with red clover (SG+RC), a big bluestem and Indiangrass mixture (BBIG), and BBIG with red clover (BBIG+RC) in Tennessee during the summer months. Total grazing days were calculated for each NWSG to determine the average cost/animal per grazing day. The average daily gain (ADG) was calculated for each NWSG to develop 3 harvested feed rations that would result in the same ADG over the same number of grazing day as each NWSG treatment. The average cost/animal per grazing day was lowest for SG ($0.48/animal/grazing d) and highest for BBIG+RC ($1.10/animal/grazing d). For both BBIG and SG, legumes increased the average cost/animal per grazing day because grazing days did not increase enough to account for the additional cost of the legumes. No difference was observed in ADG for heifers grazing BBIG (0.85 kg/d) and BBIG+RC (0.94 kg/d), and no difference was observed in ADG for heifers grazing SG (0.71 kg/d) and SG+RC (0.70 kg/d). However, the ADG for heifers grazing SG and SG+RC was lower than the ADG for heifers grazing either BBIG or BBIG+RC. The average cost/animal per grazing day was lower for all NWSG treatments than the average cost/animal per day for all comparable feed rations at a low, average, and high yardage fee. Results of this study suggest that SG was the most cost-effective NWSG alternative to harvested feeds for bred dairy heifer rearing.
Synthesis and some immunologic properties of an O-acetyl pectin [poly(1-->4)-alpha-D-GalpA]-protein conjugate as a vaccine for typhoid fever

Pectin, a plant polysaccharide, is mostly a linear homopolymer of poly(1-->4)-alpha-D-GalpA with < 5% neutral sugars: its molecular size has a broad distribution around 400 kDa, and the degree of esterification is < 5%. The structure of the capsular polysaccharide of Salmonella typhi (Vi) differs from pectin in that it is N acetylated at C-2 and O acetylated at C-3, and has a molecular size of approximately 2 x 10(3) kDa. There is no serological cross-reaction between pectin and Vi. Pectin, when O acetylated at C-2 and C-3, is antigenically identical to Vi in double immunodiffusion. Unlike Vi, O-acetylated pectin (OAcPec) is not immunogenic in mice, probably because of its comparatively low molecular weight. After storage at 3 to 8 degrees C for 3 months, there was no change in the O-acetyl content or the M(r) of OAcPec. At 60 degrees C, the M(r) of OAcPec declined more rapidly than that of Vi. OAcPec conjugated to tetanus toxoid elicited Vi antibodies in mice, and reinjection elicited a booster response. The levels of Vi antibodies elicited by OAcPec-tetanus toxoid conjugates were lower than those elicited by Vi conjugates, but these differences were not statistically significant. OAcPec has some advantages because it can be measured by standardized colorimetric assays and because it forms more soluble conjugates with proteins than does Vi. One disadvantage is that its glycosidic bond is not as stable as that of Vi. The use of a plant polysaccharide, pectin, as an immunogen for prevention of a systemic infection caused by a capsulated pathogen (S. typhi) provides a novel approach to improve the preparation and immunogenicity of polysaccharide-based vaccines.
Relationship Between Urinary Estrone Conjugates as Measured by Enzyme Immunoassay and Serum Estradiol in Women Receiving Gonadotropins for in Vitro Fertilization

Our purpose was to determine whether urinary estrone conjugates (E1C) as measured by enzyme immunoassay correlate with serum estradiol (E2) in women undergoing controlled ovarian hyperstimulation with human menopausal gonadotropins. This was a prospective, clinical study. The study took place in an outpatient, university-affiliated in vitro fertilization (IVF) unit. First morning urine samples were analyzed for E1C using a competitive solid-phase microtiter enzyme immunoassay and the value was corrected for urinary creatinine (E1C/Cr). The value was compared to morning serum E2 as determined by radioimmunoassay. Mean E2 and E1C/Cr levels demonstrated a similar pattern on the days before hCG administration. The correlation between E1C and E2 was 0.85 (P<0.0001). Furthermore, the correlation between the number of follicles greater than 12 mm was as high for E1C/Cr (ρ =0.71, P<0.001) as it was for E2 (ρ = 0.74, P<0.0001). Urinary E1C/Cr levels in women receiving hMG correlate with serum E2. Further studies are necessary to determine whether E1C is clinically useful to predict ovarian hyperstimulation syndrome.
Behavioral tolerance to the force differentiation effects of diazepam and midazolam in rats.

Rationale: Several benzodiazepines (BZs) have been shown to increase the peak force of operant responses at doses that increased, decreased, or had no effect on response rate, suggesting that operant response force may be a sensitive index of BZs’ effects rather than solely a correlate of rate-dependent effects. In addition, contingent tolerance to the rate-dependent effects of BZs has been reported, but the degree of contingent tolerance that develops when the critical variable of the task is force of the response has not been explored. Objectives: These experiments examined the effects of acute and repeated oral administration of diazepam (DZ) and midazolam (MZ) on a force-differentiation task to explore the importance of task requirements on the development of contingent tolerance. Methods: Two groups of rats were trained to press a force-sensing operandum, and responses having peak forces falling within fixed lower and upper limits [low force (8–10 g) or high force (40–50 g)] were reinforced with water. Acute effects of the oral administration of DZ (0.3, 1.0, 3.0, 10.0, 30.0 mg/kg) and MZ (same doses) were determined for the discriminated-force task before and after a repeated-administration procedure. Results: When administered acutely, both drugs increased the peak force of responses in a dose-related manner and concomitantly reduced the proportion of reinforced responses, with MZ exhibiting greater potency. For the next 36 days, one group received drug before experimental sessions and the other group received drug after the experimental session. A second dose–effect determination demonstrated that rats chronically dosed with DZ or MZ pre-session displayed more contingent tolerance to alterations in peak force than rats that had received 36 drug injections post- session, where there was no opportunity to practice the force-discrimination response while under the drug state. Conclusions: These results suggest that perceptual motor difficulty of the task rather than effort may be an important variable in predicting the degree of contingent tolerance that develops. Additionally, these results suggest that both behavioral and pharmacological mechanisms are involved in the development of drug tolerance to the BZs.
Fretting maps and fretting behavior of some F.C.C. metal alloys

Abstract The aim of the research was to achieve a systematic knowledge of fretting contact and damage over a wide range of testing conditions, with emphasis on the relations between different testing parameters. In particular, the effect of material parameters on the fretting characteristics was to be studied with the aid of fretting maps. The work has concentrated on metal specimens. Three alloys were chosen to represent different hardness levels for essentially the same crystallographic structure: pure copper, a solution-hardened Cu-Si alloy and an austenitic stainless steel. Fretting testing was performed in a controlled atmosphere of dry air at a pressure of 500 Torr. Critical amplitudes of the tangential force and displacement for transitions between different fretting regimes were found and used to produce fretting maps. In addition, microstructural studies were performed with the aid of light and scanning electron microscopies to clarify the fretting mechanisms occurring. It was found that, in the present materials, there is a gradual transition from regime I (low damage) into regime II (mixed stick-slip and fretting fatigue), rather than a well-defined boundary. The boundary between regimes II and III, however, was established and plotted in fretting maps. Fretting maps are compared and discussed together with the influence of the hardness for the three materials. Characteristic fretting scar structures are shown and are related to mechanisms of fretting damage for each regime in all three materials.