cssi/SciSciGPT-SciSciNet huggingface dataset:
Kv1.3 Deletion Biases T Cells toward an Immunoregulatory Phenotype and Renders Mice Resistant to Autoimmune Encephalomyelitis

Increasing evidence suggests ion channels have critical functions in the differentiation and plasticity of T cells. Kv1.3, a voltage-gated K(+) channel, is a functional marker and a pharmacological target for activated effector memory T cells. Selective Kv1.3 blockers have been shown to inhibit proliferation and cytokine production by human and rat effector memory T cells. We used Kv1.3 knockout (KO) mice to investigate the mechanism by which Kv1.3 blockade affects CD4(+) T cell differentiation during an inflammatory immune-mediated disease. Kv1.3 KO animals displayed significantly lower incidence and severity of myelin oligodendrocyte glycoprotein (MOG) peptide-induced experimental autoimmune encephalomyelitis. Kv1.3 was the only K(V) channel expressed in MOG 35-55-specific CD4(+) T cell blasts, and no K(V) current was present in MOG-specific CD4(+) T cell-blasts from Kv1.3 KO mice. Fewer CD4(+) T cells migrated to the CNS in Kv1.3 KO mice following disease induction, and Ag-specific proliferation of CD4(+) T cells from these mice was impaired with a corresponding cell-cycle delay. Kv1.3 was required for optimal expression of IFN-γ and IL-17, whereas its absence led to increased IL-10 production. Dendritic cells from Kv1.3 KO mice fully activated wild-type CD4(+) T cells, indicating a T cell-intrinsic defect in Kv1.3 KO mice. The loss of Kv1.3 led to a suppressive phenotype, which may contribute to the mechanism by which deletion of Kv1.3 produces an immunotherapeutic effect. Skewing of CD4(+) T cell differentiation toward Ag-specific regulatory T cells by pharmacological blockade or genetic suppression of Kv1.3 might be beneficial for therapy of immune-mediated diseases such as multiple sclerosis.
Blood lead levels in a continuity clinic population.

AbstractIntroduction: Lead toxicity is well recognized as a significant cause of morbidity in children, especially those under the age of six years. While lead toxicity has not been recognized as a public health problem in Houston, it is possible that children in the area suffer from low-level lead effect on the central nervous system. Objectives: To detect asymptomatic cases of lead toxicity in one population of Houston children and to assess the effectiveness of the lead risk questionnaire. Design: Venous blood samples for quantitative lead were analyzed utilizing the Anodic Stripping Voltameter. The Centers for Disease Control's lead risk assessment questionnaire was administered to each patient. Setting: Baylor College of Medicine Continuity Clinic at Texas Children's Hospital. Subjects: All patients, age 9–72 months, seen for routine care between December 1992 and June 1994 were screened once. Results: Blood lead levels were obtained on 801 children; all but 47 completed lead risk questionnaires. The...
Variability is the norm in performance, but not in beliefs.

Do children have coexisting but contradictory beliefs about things like magic? Some patterns of behavior that seem to reflect contradictory beliefs may stem from children's recognition that their knowledge about events is incomplete and therefore things may occur without them understanding how. In addition, children may hold certain beliefs that are inconsistent with the rest of their knowledge in a way that is very much like the premises of a game of make-believe. These beliefs are recognized to be “not really true” but children act as if they were true under specific circumstances. It is concluded that children do not hold contradictory beliefs except in this special sense.
Lawyers' Poker: 52 Lessons that Lawyers Can Learn from Card Players

Contents Preface 1. Introduction 000 2. A Critical Short History of the Electoral College, Part I: From the Constitutional Convention Through the Twelfth Amendment 000 3. A Critical Short History of the Electoral College, Part II: Operating Under the Twelfth Amendment 000 4. Evaluating the Electoral College: The Nationwide Popular Vote Alternative 000 5. The Contingent Procedure For Selection of the President By The House of Representatives 000 6. The Case of Two Candidates Ending Up In An Electoral College Tie 000 7. The Problem of Faithless Electors 8. Electoral Votes for Third Party (Or Independent) Candidates 000 9. Miscellaneous Pitfalls In The Electoral College Process 000 10. Popular Election of the President Without A Constitutional Amendment 000 11. Conclusion 000 Notes 000 Index 000
Metamorphic textures and deformation: A new mechanism for the development of syntectonic porphyroblasts and its implications for interpreting timing relationships in metamorphic rocks

The formation and growth of porphyroblasts is treated in detail, with particular reference to garnet. Previous explanations for included fabrics in porphyroblasts, and mechanisms of syntectonic growth leading to sigmoidal inclusion patterns, are shown to be based on invalid assumptions and are unacceptable. The following new mechanism for garnet porphyroblast growth is proposed. During deformation, fluid filled veins open, particularly where micaceous foliae open in folds associated with crenulation cleavages and kink bands. Garnet nucleates in these veins as they develop. The geometry of the veins depends on variability of strain rates, fluid diffusivity and the sequence of progressive deformation. In areas of low strain rate and high diffusivity, long and widely spaced macroscopic garnet veins form. These may be buckled during the continuous deformation process. Conversely, where strain rates are high, and diffusivity is low, short and closely spaced microscopic garnet veins form. Buckling and shear may alter the vein shapes during their formation and sigmoidal veins can result. Veins join and coalesce to form single porphyroblasts, leaving a selvage of quartz and other minerals as an included fabric. The finite geometry of the included fabric ranges from helicitic to sigmoidal, which is interpreted to reflect the local deformation history during vein propagation. The fabric geometry is finalized when the veins fail to respond individually to the deformation due to their coalescence and formation into a single porphyroblast. Continuous vein propagation without significant deformation of the veins could lead to augen textures, whilst a process of continuous vein formation and rotation is shown to explain apparent syntectonic rotations of more than 180°. This new hypothesis has the merit of being very simple, but it does require a new approach. This approach necessarily questions a number of previously well established “facts”, such as pre-, syn-, and post-tectonic textures. It is argued that extreme care must be taken, when relating deformation episodes and metamorphic growth periods.
Construction of Ontology-Based Software Repositories by Text Mining

Software document repositories store artifacts produced in the course of developing software products. But most repositories are simply archives of documents. It is not unusual to find projects where different software artifacts are scattered in unrelated repositories with varying levels of granularity and without a centralized management system. This makes the information available in existing repositories difficult to reuse. In this paper, a methodology for constructing an ontology-based repository of reusable knowledge is presented. The information in the repository is extracted from specification documents using text mining. Ontologies are used to guide the extraction process and organize the extracted information. The methodology is being used to develop a repository of recurring and crosscutting aspects in software specification documents.
Identification and tracking of structural parameters with unknown excitations

System identification and damage detection for structural health monitoring of civil infrastructures have received considerable attention recently. The traditional least square estimation (LSE) method requires that the external excitation data (input data) be available, which may not be the case for many structures. A recursive least square estimation with unknown inputs (RLSE-UI) approach is proposed to identify the structural parameters, such as the stiffness, damping and other nonlinear parameters. Analytical recursive solutions for the proposed RLSE-UI are derived and presented. An adaptive tracking technique recently developed is also implemented in the RLSE-UI approach to track the variations of structural parameters due to damages. Simulation results using an ASCE benchmark building for structural health monitoring demonstrate that the proposed RLSE-UI approach is capable of identifying the structural parameters and their variations due to damages.
A qualitative assessment of the efficacy of UML diagrams as a form of graphical documentation in aiding program understanding

Graphical documentation is often characterized as an effective aid in program understanding. However, it is an open question exactly which types of graphical documentation are most suitable for which types of program understanding tasks (and in which specific usage contexts). The Unified Modeling Language (UML) is the de facto standard for modeling modern software applications. This paper describes an experiment to assess the qualitative efficacy of UML diagrams in aiding program understanding. The experiment had participants analyze a series of UML diagrams and answer a detailed questionnaire concerning a hypothetical software system. Results from the experiment suggest that the UML's efficacy in support of program understanding is limited by factors such as ill-defined syntax and semantics, spatial layout, and domain knowledge.
A Model of the Lower Limb for Analysis of Human Movement

Computer models that estimate the force generation capacity of lower limb muscles have become widely used to simulate the effects of musculoskeletal surgeries and create dynamic simulations of movement. Previous lower limb models are based on severely limited data describing limb muscle architecture (i.e., muscle fiber lengths, pennation angles, and physiological cross-sectional areas). Here, we describe a new model of the lower limb based on data that quantifies the muscle architecture of 21 cadavers. The model includes geometric representations of the bones, kinematic descriptions of the joints, and Hill-type models of 44 muscle–tendon compartments. The model allows calculation of muscle–tendon lengths and moment arms over a wide range of body positions. The model also allows detailed examination of the force and moment generation capacities of muscles about the ankle, knee, and hip and is freely available at www.simtk.org.
Tests of platelet function.

Purpose of review Platelets play a vital role in the normal hemostasis, and derangements of their function can lead to hemorrhage or thrombosis. While we have made progress in elucidating the molecular mechanisms leading to platelet adhesion, aggregation, shape change, and secretion, clinically useful tests of platelet function have lagged behind. The following is a review of some of the currently available tests of platelet function, their advantages and drawbacks, as well as the clinical scenarios in which they are likely to be useful. Recent findings Attention is now being paid to standardization and optimization of older tests such as platelet aggregometry, in addition to better defining the role of newer tests such as the platelet function analyzer and thromboelastography in diagnosing and managing disorders of primary hemostasis and platelet function. Summary Platelet function is complex and may be disrupted at any of a number of steps, including adhesion, aggregation, shape change and secretion. We are better defining the role of the currently available tests, while identifying gaps in our ability to diagnose disorders of platelet function.
Transcript copy number estimation using a mouse whole-genome oligonucleotide microarray

The ability to quantitatively measure the expression of all genes in a given tissue or cell with a single assay is an exciting promise of gene-expression profiling technology. An in situ-synthesized 60-mer oligonucleotide microarray designed to detect transcripts from all mouse genes was validated, as well as a set of exogenous RNA controls derived from the yeast genome (made freely available without restriction), which allow quantitative estimation of absolute endogenous transcript abundance.
Tax Evasion as Crime

From the perspective of the criminal law, tax evasion is a baffling and anomalous offense. It deviates from the traditional paradigm of crime in that the harms it causes are highly diffuse, significant only in the aggregate, and hard to identify with any certainty. Tax evasion also differs from other offenses in terms of its incidence, which is probably higher than that of any other serious white collar crime. The laws concerning tax evasion are also enforced in a highly irregular and selective manner. Despite, or perhaps because of, such anomalies, tax evasion is a crime that has tended to fall between the cracks of normative analysis. Criminal law theorists have largely avoided the subject of tax evasion altogether, while tax law theorists, though not avoiding the subject as such, have only rarely applied to it the basic tools of criminal law theory. In this chapter, I will seek to do just that, by arguing, first, that an understanding of how taxes differ from fees, fines, penalties, forfeitures, and other types of government assessments is crucial to an understanding of why tax evasion is morally wrong. Second, I will offer an account of the moral content of tax evasion, explaining the role that the concepts of cheating, disobedience to the law, and what I call “deceptive covering up” play in defining its moral content; and why, further, the concept of stealing is largely inapposite. Finally, I will consider the extent to which my analysis of tax evasion might be helpful in assessing the moral content of tax avoidance.
Injuries and Falls in an Aging Cohort with Spinal Cord Injury: SCI Aging Study

Background: Limited research suggests that additional “subsequent” injuries occur frequently among persons with an existing spinal cord injury (SCI), which may result in further significant complications and added disability. Objective: The purpose of this study was to (a) report the 12-month incidence of injuries by age in an aging SCI cohort, (b) report the 12-month incidence of falls, (c) assess the impact of injuries on participation by age, and (d) assess the relationship of age with injuries and falls while controlling for potential confounding factors. Methods: Participants (N = 759) responded to questions about injuries and falls resulting in injury in the past year. Demographic and SCI characteristics, binge drinking, and prescription medication use were measured. Results: A total of 19.2% reported 1 or more injuries in the past year, and 10.4% reported a fall resulting in an injury in the past year. Among those who sustained 1 or more injuries, 22.8% had at least 1 hospitalization for an injury ...
Rainfall Studies Using Rain-Gage Networks and Radar

The results of three years’ work on concentrated rain-gage networks and, on measurements of rainfall extent and intensity by means of radar are described. Thunderstorm rainfall is shown to be multi...
Proportional degradation services in wireless/mobile adaptive multimedia networks: Research Articles

Adaptive multimedia services are very attractive since resources in wireless/mobile networks are relatively scarce and widely variable, and more importantly the resource fluctuation caused by mobility and channel fading can be mitigated using adaptive services. Therefore, there are extensive research activities on Quality of Service (QoS), call admission control, as well as bandwidth degradation and adaptation for adaptive multimedia services in wireless/mobile networks in recent years. However, fairness of bandwidth degradation has largely been ignored in previous work and remains an important issue in adaptive multimedia service provisioning. In this paper, we propose and study proportional degradation service provisioning in wireless/mobile networks that offer multiple classes of adaptive multimedia services. The proposed proportional degradation fairness model guarantees the proportional bandwidth degradation among different classes of services. Two proportional degradation scenarios are studied in this paper. In the first scenario, we study the proportional degradation provisioning with two QoS parameters for adaptive multimedia: the degradation ratio (DR) and the degradation degree (DD). In the second scenario, we study the proportional degradation provisioning with a new QoS parameter for adaptive multimedia: the degradation area (DA). For each scenario, based on the QoS parameters, proportional degradation adaptation algorithms are proposed to approximate the proportional degradation model, to fairly adapt calls' degradations, to utilize the system resource efficiently, as well as to optimize QoS parameters. Performance studies show that in the first scenario, proportional DR has been achieved very well, whereas proportional DD has not been well achieved. In other words, DR outperforms DD in terms of proportional degradation. In the second scenario, proportional DA has been well achieved. Furthermore, bandwidth resources have been efficiently utilized and DA has been minimized. Copyright © 2004 John Wiley & Sons, Ltd.
Beyond arctic and alpine: the influence of winter climate on temperate ecosystems

Winter climate is expected to change under future climate scenarios, yet the majority of winter ecology research is focused in cold-climate ecosystems. In many temperate systems, it is unclear how winter climate relates to biotic responses during the growing season. The objective of this study was to examine how winter weather relates to plant and animal communities in a variety of terrestrial ecosystems ranging from warm deserts to alpine tundra. Specifically, we examined the association between winter weather and plant phenology, plant species richness, consumer abundance, and consumer richness in 11 terrestrial ecosystems associated with the U.S. Long-Term Ecological Research (LTER) Network. To varying degrees, winter precipitation and temperature were correlated with all biotic response variables. Bud break was tightly aligned with end of winter temperatures. For half the sites, winter weather was a better predictor of plant species richness than growing season weather. Warmer winters were correlated with lower consumer abundances in both temperate and alpine systems. Our findings suggest winter weather may have a strong influence on biotic activity during the growing season and should be considered in future studies investigating the effects of climate change on both alpine and temperate systems.
MRI in the diagnosis of heterotopic gray matter. Report of three cases first discovered in adulthood.

This report illustrates the MR appearance of three cases of heterotopic gray matter first discovered in adulthood.
A Comparative Electrophoretic Study of Cicadellidae and Membracidae

A taxonomic study was conducted by acrylamide gel electrophoresis of Draeculacephala partola Ball. D. balli Van Duzee, Carneocephala flaviceps Riley, Chlorotettix viridius Van Duzee, Exitianus exitiosus Uhler, Cuerna costalis (F.), Graminella nigrifrons Forbes (Homoptera: Cicadellidae) and Stictocephala bubalus (F.) (Homoptera : Membracidae). Twenty-five anodically migrating protein bands were observed in whole-body homogenates of both Cicadellidae and Membracidae. Test specimens were easily classified to family, subfamily, tribe, genus, and species within different genera based on qualitative and quantitative analysis of the protein bands. Species within the same genus ( D. portola and D. balli ) could not be separated electrophoretically. Qualitative and quantitative differences of protein bands were sufficient to differentiate the sexes.
Popular Science Readers: An Aid for Achieving Scientific Literacy in the PRC: Perspective

The words of this revolutionary poem declare that the Chinese people are masters of their own fate. While conveying a spirit of self-reliance, this poem also serves a s a proclamation that the bonds of superstition that have constrained the Chinese peasants for ages are now broken. As one Peking commune official related to a foreign visitor, "Fifteen years ago, the people in this commune believed i t was the Dragon King who controlled the rain - now we understand the scientific reasons."l Indeed, well into modern times, the Chinese peasant has r e - garded any natural phenomenon, whether a calamity or an auspicious event, a s an expression of supernatural powers - thus a diseased crop was interpreted a s a visitation of the gods and stoically accepted. Now, a s a result of a vigorous, ongoing campaign to promote scientific literacy, every production team within an agricultural commune has members knowledgeable in plant blights to initiate remedial action when needed. Furthermore, i t i s reported that sci...
Comparative Theoretical Study on the Positional Preference for Functionalization of Two OH and SH Groups with (5,5) Armchair SWCNT

Covalent sidewall functionalization of (5,5) armchair single-walled carbon nanotube by OH and SH groups has been investigated using density functional theory. Two possibilities for each of 1,2- (adjacent), 1,3- (alternate), and 1,4-additions were considered. Strong intramolecular O–H···O hydrogen bond plays an important role in determining the positions for attachment of two OH groups with SWCNTs and reaction feasibility. The reactions of OH addition(s) are considerably more exothermic than the reactions of SH addition(s). The addition of two OH or SH functional groups prefers to attach at adjacent (1–2 and 1–1′) and 1,4-positions (1–4 and 3–6) rather than at alternate carbon sites (1–3 and 2–6). Owing to the strong intramolecular hydrogen bond, 1,2-addition (1-2-OH) is slightly more favored (by 2.4 kcal/mol) than 1,4-addition (1-4-OH), while 1,4-addition of two SH groups (1-4-SH) is more feasible (by 10 kcal/mol) than 1,2-addition (1-2-SH). Interestingly, the addition reactions of two SH groups at altern...
Regularized spectral learning

Spectral clustering is a technique for finding groups in data consisting of similarities Sij between pairs of points. We approach the problem of learning the similarity as a function of other observed features, in order to optimize spectral clustering results on future data. This paper formulates a new objective for learning in spectral clustering, that balances a clustering accuracy term, the gap, and a stability term, the eigengap with the later in the role of a regularizer. We derive an algorithm to optimize this objective, and semiautomatic methods to chose the optimal regularization. Preliminary experiments confirm the validity of the approach. We start by introducing notation and some basic facts in section 2, we define the learning problem in section 3 and introduce the new objective in 4. Sections 5, 6 present respectively a gradient algorithm for optimizing the criterion and a method for selecting the anlount of regularization. Experimental results are in section 7 and 8 concludes the paper. 2 Spectral clustering notation and background In spectral clustering, the data is a set of similarities Sij, satisfying Sij = Sji '2.: 0, between pairs of points i, j in a set V, IVI = n, The matrix S [Sij]i,jEV is called the similarity matrix. We denote by D i ;;:::: Vol {i} (1)
The Threat of Bioterrorism and the Public Health Response: Summary of the Johns Hopkins National Symposium on Medical and Public Health Response to Bioterrorism

As the world has grown smaller and more sophisticated, the tenets of biosafety and public health have become increasingly important. In this new age, terrorists have begun to use biologicals as a weapon, i.e., biological terrorism or the use of infectious microorganisms to dominate or coerce by intimidation, or to cause fear. The increasing importance of bioterrorism was recently noted by Darcy Bender of the Council on Foreign Relations, Washington, DC, who described that 47 anthrax hoaxes and threats have occurred in the United States between 1992 and mid­ February 1999. The majority of these incidents were not noted by either the electronic or print media. The Centers for Disease Control and Prevention (CDC) has responded to these incidents by publishing response guidelines to these threats (CDC, 1999) in a report in the Morbidity and Mortality Weekly Report (MMWR) entitled Bioterrorism Alleging Use of Anthrax and Interim Guidelines for Management - United States, 7998. This article supplemented an earlier paper by Kaufmann and co-workers (Kaufmann, et aI., 1997) who provided economic justification for developing preparedness programs to bioterrorist incidents and discussed the impact of three biological warfare agents. This rise in interest in bioterrorism was reflected by the one thousand people who registered to attend the Johns Hopkins National Symposium on Medical and Public Health Response to Bioterrorism in February, 1999. Attendees came from many walks of life; biological safety professionals, emergency response experts, health care providers, hospital administrators, government officials, hospital epidemiologists, intelligence experts, law enforcement officials, microbiologists, military experts, nurses, physicians, public health officials, public policy analysts, and of course the media. The Johns Hopkins University Center for Civilian Biodefense Studies sponsored
THE ROLE OF CALPAIN IN STIMULUS-RESPONSE COUPLING : EVIDENCE THAT CALPAIN MEDIATES AGONIST-INDUCED EXPRESSION OF PROCOAGULANT ACTIVITY IN PLATELETS

Although calpain (the Ca2(+)-dependent protease) is widely distributed, its function is poorly understood. One cell in which it becomes activated as a consequence of activation of the cell is the blood platelet. The aim of the present study was to determine whether activation of calpain was responsible for any of the responses of platelets to stimulation. Platelets were incubated with calpeptin, a membrane-penetrating inhibitor of calpain, before being exposed to an agonist. Concentrations of calpeptin that totally inhibited the agonist- induced hydrolysis of actin-binding protein (ABP) by calpain had no effect on many other responses associated with platelet activation: phosphorylation of myosin light chain, phosphorylation of P47, platelet shape change, aggregation of platelets, secretion of granule contents, or retraction of fibrin clots. However, these concentrations of inhibitor decreased the agonist-induced generation of procoagulant activity (assayed as the ability of platelets to catalyze the conversion of prothrombin to thrombin in the presence of factor Va and factor Xa). When thrombin was the agonist, the amount of ABP that was hydrolyzed was small; only a small component of the total agonist- induced procoagulant activity was inhibited by calpeptin. When collagen was the agonist, more ABP was hydrolyzed and the amount of procoagulant activity generated was greater; calpeptin decreased the collagen- induced procoagulant activity to levels comparable with those induced by thrombin in the presence of the inhibitor. We suggest that there are at least two mechanisms by which procoagulant activity is generated on activated platelets and that the agonist-induced activation of calpain mediates one of these mechanisms. These results show that activation of calpain is a component of the stimulus-response pathway in platelets.
RDFKB: a semantic web knowledge base

There are many significant research projects focused on providing semantic web repositories that are scalable and efficient. However, the true value of the semantic web architecture is its ability to represent meaningful knowledge and not just data. Therefore, a semantic web knowledge base should do more than retrieve collections of triples. We propose RDFKB (Resource Description Knowledge Base), a complete semantic web knowledge case. RDFKB is a solution for managing, persisting and querying semantic web knowledge. Our experiments with real world and synthetic datasets demonstrate that RDFKB achieves superior query performance to other state-of-the-art solutions. The key features of RDFKB that differentiate it from other solutions are: 1) a simple and efficient process for data additions, deletions and updates that does not involve reprocessing the dataset; 2) materialization of inferred triples at addition time without performance degradation; 3) materialization of uncertain information and support for queries involving probabilities; 4) distributed inference across datasets; 5) ability to apply alignments to the dataset and perform queries against multiple sources using alignment. RDFKB allows more knowledge to be stored and retrieved; it is a repository not just for RDF datasets, but also for inferred triples, probability information, and lineage information. RDFKB provides a complete and efficient RDF data repository and knowledge base.
The New Map of the Universe of Faiths

Let me begin this chapter by proposing a working definition of religion as an understanding of the universe, together with an appropriate way of living within it, which involves reference beyond the natural world to God or gods or to the Absolute or to a transcendent order or process. Such a definition includes such theistic faiths as Judaism, Christianity, Islam, Sikhism; the theistic Hinduism of the Bhagavad Gitā; the semi-theistic faith of Mahayana Buddhism and the non-theistic faiths of Theravada Buddhism and non-theistic Hinduism. It does not however include purely naturalistic systems of belief, such as communism and humanism, immensely important though these are today as alternatives to religious faith.
Collaborations Between Multicultural Educators and Archivists: Engaging Students with Multicultural History Through Archival Research Projects

ABSTRACTWhen multicultural educators and archivists collaborate to design projects that engage students with multicultural history through archival research, students can learn in-depth research skills with primary source documents, creatively share their knowledge, and, on a broader level, engage with their local community history. The projects shared in this article serve as examples of how partnerships between multicultural educators and archivists can occur, the types of projects that can be developed and how they are implemented, and students' responses to their work. The three student projects, including a display, a history guidebook, and an oral history project, are intended to offer a variety of ideas to inspire multicultural educators to reach out to their local archivists to develop archival research projects of their own. And, to promote effective and fruitful partnerships, also included are lessons learned as well as tips for successful collaborations between multicultural educators and archi...
Radiochemical purity assessment of radiolabeled monoclonal antibodies: A comparison of miniaturized chromatography and size-exclusion high performance liquid chromatography

2138 Objectives : Miniaturized chromatography may not be effective in evaluating radiochemical purity in proteins such as monoclonal antibodies. Our lab compared miniaturized chromatography to size-exclusion High Performance Liquid Chromatography (HPLC) in evaluating radiochemical purity of radiolabeled monoclonal antibodies. Methods : Three commercially available monoclonal antibody kits were evaluated: Tc-99m Fanolesomab (NeutroSpec, Mallinckrodt, St.Louis, MO), an IgM monoclonal antibody; In-111 Ibritumomab Tiuxetan (Zevalin, Biogen Idec, Cambridge,MA) and In-111 Capromab Pendetide (ProstaScint, Cytogen, Princeton,NJ), both IgG monoclonal antibodies. Following the manufacturer’s radiolabeling procedure, radiochemical purity was assessed in triplicate utilizing miniaturized instant thin-layer chromatography – silica gel (ITLC-SG) strips with normal saline, 2-butanone, and acetone. Size-exclusion HPLC of radiolabeled monoclonal antibodies was accomplished with a Rainin Isocratic HPLC system and a NaI(Tl) gamma scintillation detector interfaced to a multichannel analyzer. Chromatographic separation was achieved using a Phenomenex BioSep-SEC-S 2000. After injection of 50 ul, samples were eluted in phosphate buffered saline at a flow rate of 1.0 ml/minute. Results : Similar radiochemical purity results were obtained for In-111 Zevalin using miniaturized chromatography and size-exclusion HPLC. Significant differences in radiochemical purity were measured for In-111 ProstaScint due to radiolabeled antibody breakdown products which were not detected with miniaturized chromatography. Significant differences in radiochemical purity were also measured for Tc-99m NeutroSpec. Size-exclusion HPLC detected various radiolabeled breakdown products including an IgG component. In addition, differences in radiochemical purity were measured using a chromatography system consisting of ITLC-SG with 2-butanone compared to a more conventional miniaturized chromatography system for monoclonal antibodies consisting of ITLC-SG and normal saline. Conclusions : Miniaturized chromatography provides an accurate measure of unbound or “free” radionuclide in monoclonal antibodies. Size-exclusion High Performance Liquid Chromatography (HPLC) further reveals other radiochemical impurities such as radiolabeled aggregates and radiolabeled antibody breakdown products.
Why Does Nonsuicidal Self-Injury Improve Mood? A Preliminary Test of Three Hypotheses:

People who engage in nonsuicidal self-injury (NSSI) often state that it helps them feel better. We tested three hypotheses through which this mood modification might occur. Following a negative mood induction, adults reporting past year NSSI were randomized into a control (i.e., sitting alone quietly), mild distraction, or pain condition. All participants completed mood ratings at regular intervals. No mood repair occurred in the control condition. However, distraction improved mood both during and after the activity. Participants who self-administered pain reported no overall mood change, suggesting that contrary to popular NSSI theories, pain likely does not improve mood via distraction. However, as predicted, level of self-criticism moderated mood change during pain. Participants high on self-criticism felt significantly better during pain and participants low on self-criticism felt significantly worse during pain. Findings shed light on how NSSI improves mood by clarifying the circumstances under whic...
Abstract 494: MYC, dominant negative p53 and AKT transform human neural stem cells into primitive neuro-ectodermal tumors sensitive to glutaminase inhibitors

Primitive neuroectodermal tumors (PNET) are highly aggressive tumors that can arise in different regions of the brain. A subset of PNET have genomic amplification of MYC, and the MYC-regulator LIN28A is known to define a group of PNET. Both MYC and LIN28 regulate metabolism in normal and malignant cells. We hypothesized that a combination of dominant negative R248Wp53, MYC, AKT and hTERT would transform human neural stem cells into PNET-like tumors. We used lentiviral vectors to infect human neural stem cells derived from hindbrain and cortex with the same packages of oncogenic elements. Hindbrain neural stem cells transduced with MYC/R248Wp53/AKT/hTERT proliferated at an increased rate compared to control cells as measured by BrdU incorporation (Hindbrain pBABE vs. Hindbrain MYC/R248Wp53/AKT/hTERT: 4% vs. 50% BrdU positive, t-test p = 0.001). Similar results were observed in cortex derived human neural stem cells transduced with MYC/R248Wp53/AKT/hTERT (Cortex pBABE vs Cortex MYC/R248Wp53/AKT/hTERT: 5% vs. 24% BrdU positive, t-test p = 0.027). Both hindbrain and cortex derived human neural stem cells transformed with MYC /R248Wp53/hTERT, and MYC/R248Wp53/hTERT/AKT formed aggressive orthotopic xenograft tumors with histologic characteristics of PNET. The latency of tumor formation decreased with increasing addition of oncogenes. We detected increased glutaminase (GLS) in our MYC-driven human neural stem cell models compared to SV40 immortalized neural stem cells, and hypothesized that GLS inhibitors would inhibit the growth of MYC-driven and LIN28 driven brain tumors. The glutaminase inhibitors DON (6-Diazo-5-oxo-L-norleucine) and acivicin suppressed the growth of our MYC-driven neural stem cell models of PNET as well as the PNET cell line PFSK (p = 0.003) as measured by BrdU and MTT growth assay. Cell cycle analysis of MYC-transduced human neural stem cell models showed increased cell death as measured by sub G1 population after treatment with DON and acivicin. This data shows that glutaminase inhibition may be a useful therapeutic modality in PNET. Citation Format: Isabella Taylor, Sama Ahsan, Antoinette Price, Charles Eberhart, Eric H. Raabe. MYC, dominant negative p53 and AKT transform human neural stem cells into primitive neuro-ectodermal tumors sensitive to glutaminase inhibitors. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 494. doi:10.1158/1538-7445.AM2015-494
Exploring Non-ownership Apparel Consumption through Online Fashion Product Rental Services: An Application of Institutional Theory

The purpose of this study was to examine consumers’ use of online fashion product rental services as communicated through social media and interpreted through the framework of Institutional Theory.
Stochastic differential equations

Abstract When a system is acted upon by exterior disturbances, its time-development can often be described by a system of ordinary differential equations, provided that the disturbances are smooth functions. But for sound reasons physicists and engineers usually want the theory to apply when the noises belong to a larger class, including for example “white noise.” If the integrals in the system derived for smooth noises are reinterpreted as Ito integrals, the equations make sense; but in nonlinear cases they often fail to describe the time-development of the system. In this paper (extending previous work of the author) a calculus is set up for stochastic systems that extends to a theory of differential equations. When the equations are known that describe the development of the system when noises are smooth, an extension to the larger class of noises is proposed that in many cases gives results consistent with the smooth-noise case and also has “robust” solutions, that change by small amounts when the noises undergo small changes. This is called the “canonical” extension. Nevertheless, there are certain systems in which the canonical equations are inappropriate. A criterion is suggested that may allow us to distinguish when the canonical equations are the right choice and when they are not.
Health/Sexuality/Geography

As this publication suggests, there has been an emergence of critical theory related to the geographies of sexualities since Mapping Desire (Bell and Valentine 1995) was published over ten years ago. In similar ways, medical and health geographies have undergone rapid and dynamic change over the last fifteen or so years. In the 1990s, medical geographers and so-called post-medical or health geographers debated the efficacy of a purely biomedical-centric geography of health and health care, illness and disease. As they did, theorisations of health, the body, illness, experience and performativity became more nuanced, paralleling to a certain degree the important debates taking place in social and cultural geography. The inclusion, for example, of a chapter by Pamela Moss and Isabel Dyck (2002) – two feminist health geographers – in The Handbook of Cultural Geography implies that questions of healthy and ill bodies need to be the concern of geographers more broadly.
Time-encoded multiplexed imaging (Conference Presentation)

We describe a technique for multiplexed imaging that is based on the concept of mapping scene features to unique temporal codes, and using smart digital pixels to efficiently decode at the focal-plane. We use this technique to demonstrate multiplexed multispectral imaging using actively encoded LEDs, and multiplexed hyperspectral imaging using a digital micromiror spatial light modulator. Both experiments utilize a computational imaging array comprised of a 32x32 array of digital pixels with the capability of acquiring eight concurrent measurements that can be modulated with a time-varying duo-binary signal (+1,-1,0) at MHz rates. This results in eight decoded images per frame at a maximum frame rate of 1600 frames per second. The total frame rate of the imaging system depends on the number of encoded features and the number of decoding channels within the digital pixel. We explore these trades as well as discuss limitations and areas for future improvement.
Evaluation of bleeding in patients receiving direct oral anticoagulants

Direct oral anticoagulants (DOACs) are recognized by evidence-based treatment guidelines as the first-line option for the treatment of venous thromboembolism and prevention of stroke and systemic embolism in nonvalvular atrial fibrillation. As use of these anticoagulants has become favored over the past several years, reported bleeding-related adverse drug events with these agents has increased. In randomized clinical trials, all DOACs have a reduced risk for intracranial hemorrhage, while major and other bleeding results have varied among the agents compared to vitamin K antagonists. We have reviewed the bleeding incidence and severity from randomized and real-world data in patients receiving DOACs in an effort to provide the clinician with a critical review of bleeding and offer practical considerations for avoiding adverse events with these anticoagulants.
Children’s Geographic Proximity and Older Parents’ Depressive Symptoms in China

Objective: This study examined the association between children's proximity and older parents' depressive symptoms, and whether living with grandchildren modified this association. Method: Study sample was from the 2011 China Health and Retirement Longitudinal Study (N = 5,261). Elders' depressive symptoms were measured using the 10-item Center for Epidemiologic Studies Depression Scale. Children's proximity was measured by the geographic distance from an adult child to elders' residence. Linear and logit regressions were performed. Results: Elders who had their nearest child living 100 km away were 9% more likely to experience severe depressive symptoms (95% CI: [1%, 16%]) than those living together with children. Among those living far away from adult children, living with a grandchild in the same household increased the likelihood of having severe depressive symptoms by 23% (95% CI: [12%, 34%]). Discussion: Relationships between children's proximity and parents' health were identified and modified by whether living with grandchildren.
Application of frequency response methods in separate and integral effects tests for molten salt cooled and fueled reactors

Abstract Molten salt cooled and fueled reactors can be distinguished from other reactor types by their low volatility liquid coolant, which remains single-phase under most operating and accident conditions, and by the substantial heat capacity of both the coolant and solid structures. Forced and natural circulation of the molten salt coolant provide the primary heat transport mechanisms under power and shutdown operation, but thermal coupling to solid heat structures has important effects on dynamic system response during transients. These characteristics make frequency response methods particularly suitable to characterizing and predicting system response to transients. Predicting the temperature of coolant boundary structures during transients, including accidents, is also important for assessing whether damage may occur due to thermal stresses or accelerated thermal creep. This paper discusses how frequency response methods may be used in separate effect and integral effect tests, particularly with simulant fluids to measure the thermal inertia and coupling properties of heat structures and to validate transient response models. The methodology is discussed, followed by examples for application. The scaling parameters developed in this paper can be expected to play a major role in the design of integral effect test facilities for FHRs and MSRs.
Reduction in Aflatoxin Content of Maize by Atoxigenic Strains of Aspergillus flavus

In field plot experiments, an atoxigenic strain of Aspergillus flavus interfered with preharvest aflatoxin contamination of corn when applied either simultaneously with or one day prior to a toxigenic strain. The atoxigenic strain reduced preharvest aflatoxin contamination 80 to 95%. The atoxigenic strain was also effective in reducing postharvest aflatoxin contamination caused by both an introduced toxigenic strain and by strains resident on the kernels. The results suggest that atoxigenic strains of A. flavus may have potential use as biological control agents directed at reducing both preharvest and postharvest aflatoxin contamination of corn.
Low-Temperature Micropatterning of Thick-Film BaFe 12 O 19 Composites on Semiconductor Substrates for Integrated Millimeter Wave Devices

This paper reports the fabrication and characterization of thick, self-biased hexaferrite magnetic structures patterned on planar substrates for integrated millimeter-wave (mm-wave) device applications. Using all lowtemperature processes, BaFe 12 O 19 micro/nanoparticles (from three different vendors) and polymeric binder (PDMS) are screenprinted into removable molds to form 600-μm-diameter, 144-μm-thick test structures. The crystallography, morphology, and DC magnetic hysteresis curves are evaluated. Methods are shown for imposing magnetic anisotropy in the films. A direct measurement of the RF properties using a coplanar waveguide test structure is performed, showing a ferromagnetic resonance (FMR) frequency of 45.9 GHz with tunability via an external magnetic field.
"Look, Your Muscles Are Firing!": A Qualitative Study of Clinician Perspectives on the Use of Surface Electromyography in Neurorehabilitation.

Abstract Objective To examine the perceived value, benefits, drawbacks, and ideas for technology development and implementation of surface electromyography recordings in neurologic rehabilitation practice from clinical stakeholder perspectives. Design A qualitative, phenomenological study was conducted. In-depth, semistructured interviews and focus groups were completed. Sessions included questions about clinician perspectives and demonstrations of surface electromyography systems to garner perceptions of specific system features. Setting The study was conducted at hospital systems in a large metropolitan area. Participants Adult and pediatric physical therapists, occupational therapists, and physiatrists from inpatient, outpatient, and research settings (N=22) took part in the study. Interventions Not applicable. Main Outcome Measures Interviews and focus groups were audio-recorded, transcribed verbatim, then coded for analysis into themes. Results Four major themes emerged: (1) low-tech clinical practice and future directions for rehabilitation; (2) barriers to surface electromyography uptake and potential solutions; (3) benefits of surface electromyography for targeted populations; and (4) essential features of surface electromyography systems. Conclusions Surface electromyography systems were not routinely utilized for assessment or intervention following neurologic injury. Despite recognition of potential clinical benefits of surface electromyography use, clinicians identified limited time and resources as key barriers to implementation. Perspectives on design and surface electromyography system features indicated the need for streamlined, intuitive, and clinically effective applications. Further research is needed to determine feasibility and clinical relevance of surface electromyography in rehabilitation intervention.