cssi/SciSciGPT-SciSciNet huggingface dataset:
Identification of Human Idiotype-Specific T Cells in Lymphoma and Myeloma

Idiotype protein, among the first identified tumor-specific antigens, has been found to stimulate both humoral and cellular responses in lymphoma and myeloma patients. With the increasing use of B cell depletion treatments such as rituximab in clinic, the cellular response mediated by idiotype-specific T cells has become increasingly important as an adjunct therapy for lymphoma and myeloma. Here, we review the idiotype protein as a tumor antigen and the characteristics of the T cell response elicited idiotype vaccination. We also analyze the T cell epitopes that have been identified in idiotype protein and introduce our new findings of additional T cell epitopes derived from the Ig light chain. Finally, we propose new directions in the generation of idiotype-specific T cells for tumor therapy.
Magnetically Actuated Colloidal Chains in Microchannels

We report the use of chemically linked paramagnetic particles to manipulate microscopic flow in microchannels. In experiments with a rotating magnetic field linked chains show effective micromixing.
Media Representations of Immigration in the Chilean Press: To a Different Narrative of Immigration?:

This article examines representations of immigration in Chilean newspapers. From January to December 2016, a total of 507 articles from three mainstream newspapers were analyzed. The findings show ...
Tracing Effects of Parental Discipline on Child Psychopathology: The Devil's in the Detail.

Parenting practices are a key target for researchers, clinicians, and policymakers concerned with decreasing child psychopathology. Parents' approaches to disciplining their children are of particular interest, because the form and amount of parental discipline are believed to play a critical role in the development of children's problem behavior. However, the relative merits of different discipline strategies for modifying children's mental health are not all that clear. In the current issue of the Journal, Rajyaguru et al.1 address this question by investigating associations between different parental discipline approaches and child psychopathology in more than 4,000 mother and child study members of the UK Millennium Cohort Study.
Improving extrauterine growth: evaluation of an optimized, standardized neonatal parenteral nutrition protocol

Poor extrauterine growth in very low birth weight (VLBW) neonates is common and associated with worsened long-term outcomes. We aimed to decrease growth restriction, measured by the change in weight z-score from birth to 36 weeks post menstrual age, from − 1.13 (baseline) to < −1 within 12 months. The Model for Improvement was used in the design and implementation of an optimized, standardized parenteral nutrition protocol. Three Plan-Do-Study-Act cycles were completed and a $$\bar X$$ and S control chart was created for the primary outcome. Mean weight z-score change from birth to 36 weeks post menstrual age improved by 23% to − 0.87. Improvements in early weight gain and linear growth were seen as well. Use of the Model for Improvement to implement an optimized, standardized parenteral nutrition protocol can help improve extrauterine growth among VLBW infants.
Is Multifocal Regression a Risk Factor for Ipsilateral Breast Tumor Recurrence in the Modern Era After Neoadjuvant Chemotherapy and Breast Conservation Therapy

Purpose Multifocal pattern of regression after neoadjuvant chemotherapy has been identified as a risk factor for ipsilateral breast tumor recurrence (IBTR). We aimed to determine the significance of multifocal regression as a predictor of IBTR after neoadjuvant chemotherapy and breast conservation therapy in the modern era. Methods and Materials We retrospectively reviewed 346 patients treated between November 2009 and June 2017. Pattern of regression was categorized as pathologic complete response (pCR), unifocal (tumor present as a cohesive mass), limited multifocal (single cells or clusters of cells concentrated in 1 portion of the fibrotic area), or diffuse multifocal (cells spread over entire fibrotic area). IBTR was defined as new ipsilateral invasive or noninvasive breast tumor after breast conservation therapy. Predictive factors were analyzed using Cox regression. Results Incidence of multifocal regression was 25.7% for the overall cohort and 12.2% for estrogen receptor (ER) negative/progesterone receptor (PR) negative/human epidermal growth factor receptor 2 (HER2) positive, 17.5% for triple-negative, 36.9% for ER+ or PR+/HER2-, and 38.5% for triple-positive (P Conclusions Multifocal regression, hormone receptor–negative phenotype, and lack of nodal pCR predict for increased risk of IBTR after neoadjuvant chemotherapy. Although more common in hormone receptor–positive disease, multifocal regression was associated with worse outcome only in hormone receptor–negative patients.
How Should the United States Respond to the Opioid Addiction and Overdose Epidemic

The national epidemic of addiction to and overdose from opioids is the worst public health crisis the United States has faced in decades. The health care system is critical to the public policy response, both because of the services it can provide people with opioid use disorder and the changes in clinical practice it must make to prevent new cases of addiction. For historical and cultural reasons, health services for people with opioid use disorder are often of uneven quality and poorly integrated with the rest of health care. However, effective services are available that can make a major contribution to pushing back against the epidemic. These include opioid agonist therapies (e.g., buprenorphine maintenance), antagonist therapies (e.g., extended-release naltrexone), and psychosocial treatments. Interventions that reduce the mortality and morbidity risks of opioids, such as syringe exchange and naloxone provision, are also critical to an effective public health response. Supply-side policies within the US health care system are also essential because overprescribing is at an extraordinarily high level both historically and currently in comparison to other nations. A range of monitoring, educational, and incentive-based interventions show promise of returning the United States to a more rational prescribing pattern.
Text-Mining of Online Discourse to Characterize the Nature of Pain in Low Back Pain

PURPOSE: Text-mining has been shown to be useful for understanding the clinical characteristics and patients’ concerns regarding a specific disease. Low back pain (LBP) is the most common disease in modern society and has a wide variety of causes and symptoms. On the other hand, it is difficult to understand the clinical characteristics and the needs as well as demands of patients with LBP because of the various clinical characteristics. This study examined online texts on LBP to determine of text-mining can help better understand general characteristics of LBP and its specific elements. METHODS: Online data from www.spine-health.com were used for text-mining. Keyword frequency analysis was performed first on the complete text of postings (full-text analysis). Only the sentences containing the highest frequency word, pain, were selected. Next, texts including the sentences were used to re-analyze the keyword frequency (pain-text analysis). RESULTS: Keyword frequency analysis showed that pain is of utmost concern. Full-text analysis was dominated by structural, pathological, and therapeutic words, whereas pain-text analysis was related mainly to the location and quality of the pain. CONCLUSION: The present study indicated that text-mining for a specific element (keyword) of a particular disease could enhance the understanding of the specific aspect of the disease. This suggests that a consideration of the text source is required when interpreting the results. Clinically, the present results suggest that clinicians pay more attention to the pain a patient is experiencing, and provide information based on medical knowledge.
Anomalous diffusion of acoustic waves in 2D periodic media: Radiative transport and renormalization analysis

This work investigates the occurrence of anomalous transport of acoustic waves propagating in two-dimensional (2D) perfectly periodic media and presents dedicated analysis tools to explore and understand the properties of the medium controlling the transitions between different transport regimes. By leveraging a two-fold approach that combines both radiative transport and renormalization theory, the propagation properties of the inhomogeneous medium can be characterized both near and at the transition from normal to anomalous diffusion. The proposed approach builds upon the classical radiative transfer theory of bulk materials, and it is specifically designed to study 2D systems. The ability to simulate and interpret the field quantities that describe such transport mechanisms can play a significant role in the development of wave-based imaging technology for highly inhomogeneous and scattering media.
Practical Split Manufacturing Optimization

Trojans and backdoors inserted by untrusted foundries have become serious threats to hardware security. Split manufacturing is proposed to hide important circuit structures and prevent Trojan insertion by fabricating partial interconnections in trusted foundries. Existing split manufacturing frameworks, however, usually lack security guarantee and suffer from poor scalability. It is observed that inserting dummy cells and wires can have a high potential for overcoming the security and scalability problems of existing methods, but it is not compatible with current security definition. In this chapter, two major questions are answered: when the insertion of dummy cells and wires is considered, (1) how to define the notion of security and (2) how to realize the required security level effectively and efficiently. With extensive experiments, the proposed framework demonstrates significantly better efficiency, overhead reduction, and security guarantee compared with the previous state of the art.
Photovoice with Individuals with Intellectual and/or Developmental Disabilities: Lessons Learned from Inclusive Research Efforts

Inclusive research is an approach in which individuals with intellectual and/or developmental disabilities (IDD) are included as co-researchers throughout the research processes, and has demonstrated benefits for people with IDD. Because inclusive research is still not common within disability research, it is important for research teams to provide reflections and lessons learned to encourage future inclusive approaches. This paper provides case studies of two research projects completed in collaboration with adults with IDD using Photovoice as an approach that can increase access to the research process for co-researchers with IDD. Drawing upon previously defined inclusive research criteria, we reflect on lessons learned and challenges. Inclusive research requires time, flexibility, shared power, clear communication, and cultural humility. Across both studies, we discuss the importance of clear communication with Institutional Review Boards and collaboration with the extended support networks of individuals with IDD. We reflect on how the accessible nature of Photovoice supports inclusive research teams to combine the strengths of co-researchers with IDD and academically trained researchers, such that the knowledge production process is shifted to co-researchers with IDD.
Direct activation of tRNA methyltransferase-like 1 (Mettl1) gene by thyroid hormone receptor implicates a role in adult intestinal stem cell development and proliferation during Xenopus tropicalis metamorphosis

Thyroid hormone (T3) plays an important role in vertebrate development. Compared to the postembryonic development of uterus-enclosed mammalian embryos, T3-dependent amphibian metamorphosis is advantageous for studying the function of T3 and T3 receptors (TRs) during vertebrate development. The effects of T3 on the metamorphosis of anurans such as Xenopus tropicalis is known to be mediated by TRs. Many putative TR target genes have been identified previously. Among them is the tRNA methyltransferase Mettl1. We studied the regulation of Mettl1 gene by T3 during intestinal metamorphosis, a process involves near complete degeneration of the larval epithelial cells via apoptosis and de novo formation of adult epithelial stem cells and their subsequent proliferation and differentiation. We observed that Mettl1 was activated by T3 in the intestine during both natural and T3-induced metamorphosis and that its mRNA level peaks at the climax of intestinal remodeling. We further showed that Mettl1 promoter could be activated by liganded TR via a T3 response element upstream of the transcription start site in vivo. More importantly, we found that TR binding to the TRE region correlated with the increase in the level of H3K79 methylation, a transcription activation histone mark, and the recruitment of RNA polymerase II by T3 during metamorphosis. Our findings suggest that Mettl1 is activated by liganded TR directly at the transcriptional level via the TRE in the promoter region in the intestine during metamorphosis. Mettl1 in turn regulate target tRNAs to affect translation, thus facilitating stem cell formation and/or proliferation during intestinal remodeling.
Introduction: Will You Please Be Quiet, Please? Lawyers Listening to the Call of Stories

There is a saying: “You never know what you find when you scratch the surface of an idea,” The articles in this symposium scratch the surface of a simple idea: our legal culture is a storytelling culture. Practitioners and appellate judges are storytellers, and legal academics are increasingly sensitive to storytelling forms and aesthetics. Some scholars are becoming storytellers themselves.
An Introduction to Critical Developmental Psychology

Developmental psychology is a manifold of diverse human activities. It is not just a scientific discipline combining theory with practice and research. It is also wholly a part of society, a social institution with a professional structure and a public presence. Not only does it influence social behavior, but it also represents a special form of continuous participation in the political process. It not only reflects ongoing social activities but joins concertedly in their formation, regulation, and reformation.
MERCHMENOT: APPLYING MERCHANDISING CONCEPTS WITH ACTIVE LEARNING

Active learning engages students where they enjoy the learning process and gain a better understanding of course content. Active learning, such as an in-class game, can mitigate inattentive listeni...
Empathy plasticity: Decolonizing and reorganizing Wikipedia and other online spaces to address racial equity

The spring of 2020 represented a watershed-moment-in-the-making, as broad, inclusive discussions on how to best cultivate discursive and policy mechanisms towards racial equity presaged a reckoning...
The Future of the Implantable Cardioverter-Defibrillator

Since it was introduced 40 years ago, the implantable cardioverter-defibrillator (ICD) has become a mainstay of therapy for patients at risk for life-threatening ventricular tachycardia (VT) and fibrillation (VF). This chapter explores challenges and opportunities for future ICD therapy. Historically, transvenous leads have been the weak link in ICD systems. We review improved engineering standards for transvenous leads and methods to prevent proarrhythmia from ICD lead dislodgements, as well advantages and limitations of subcutaneous and substernal lead systems and their potential integration with leadless pacemakers. We consider better ways to ensure that necessary therapy is delivered for VT/VF while delivering fewer unnecessary and inappropriate shocks. Remote monitoring of ICD patients has become the standard of practice. We approach potential improvements in remote patient management related both to alerts generated in the ICD and potentially more computationally intensive analysis performed after device data is transmitted to servers. Perhaps the greatest unmet need is prediction and prevention of VT/VF. We review avenues for improvement both in long-term risk stratification to optimize utilization of ICDs and in short-term prediction of VT/VF to permit development of device-based preventive therapies.
Comparing the performance of first-order conditional estimation (FOCE) and different expectation–maximization (EM) methods in NONMEM: real data experience with complex nonlinear parent-metabolite pharmacokinetic model

First-order conditional estimation (FOCE) has been the most frequently used estimation method in NONMEM, a leading program for population pharmacokinetic/pharmacodynamic modeling. However, with growing data complexity, the performance of FOCE is challenged by long run time, convergence problem and model instability. In NONMEM 7, expectation-maximization (EM) estimation methods and FOCE with FAST option (FOCE FAST) were introduced. In this study, we compared the performance of FOCE, FOCE FAST, and two EM methods, namely importance sampling (IMP) and stochastic approximation expectation-maximization (SAEM), utilizing the rich pharmacokinetic data of oxfendazole and its two metabolites obtained from the first-in-human single ascending dose study in healthy adults. All methods yielded similar parameter estimates, but great differences were observed in parameter precision and modeling time. For simpler models (i.e., models of oxfendazole and/or oxfendazole sulfone), FOCE and FOCE FAST were more efficient than EM methods with shorter run time and comparable parameter precision. FOCE FAST was about two times faster than FOCE but it was prone to premature termination. For the most complex model (i.e., model of all three analytes, one of which having high level of data below quantification limit), FOCE failed to reliably assess parameter precision, while parameter precision obtained by IMP and SAEM was similar with SAEM being the faster method. IMP was more sensitive to model misspecification; without pre-systemic metabolism, IMP analysis failed to converge. With parallel computing introduced in NONMEM 7.2, modeling speed increased less than proportionally with the increase in the number of CPUs from 1 to 16.
Islamic Legal Authority in a Non-Muslim Society: Designing The Islamic Credit Union of Bellevue, Washington

This Article examines the current state of Islamic law within a community of Muslims in the United States as it relates to Shari’a-compliant financial products. After briefly reviewing the history of Islamic finance and Islamic authority structures within the United States, I rely on interviews with multiple parties involved in the establishment of one of the first Islamic credit unions in the United States to explore the development of Islamic law within American regulation and cultural mores. I examine the authority structure present among Muslims in the Puget Sound area, and I examine the qualities that define a credible religious scholar. Fundamentally, this Article contributes to the analysis of legal authority among Muslims in the United States.
A POLICY ENGINEERING FRAMEWORK FOR FEDERATED ACCESS MANAGEMENT

Federated systems are an emerging paradigm for information sharing and integration. Such systems require access management policies that not only protect user privacy and resource security but also allow scalable and seamless interoperation. Current solutions to distributed access control generally fail to simultaneously address both dimensions of the problem. This work describes the design of a policy-engineering framework, called X-FEDERATE, for specification and enforcement of access management policies in federated systems. It has been designed from the perspectives of both security management and software engineering to not only allow specification of requirements for federated access management but also allow development of standardized policy definitions and constructs that facilitate policy deployment and enforcement in a federated system. The framework comprises of an access control language specification that is an extension of the well-accepted Role Based Access Control (RBAC) standard. The language extends RBAC to incorporate various essential features for federated access management. The framework also includes the design of an administrative model targeted at access control policy administration in a decentralized environment. The framework has been implemented as a research prototype that illustrates the use of X-FEDERATE as an enabling technology for secure Web-based federation with applications in federated digital libraries and federated electronic healthcare management.
Environmental Quality and Social Equality

Abstract. The problems and contradictions which arise when an economically “poor” region is mandated to remain environmentally “pure“ are examined. The Adirondack region of New York State is such an area, being now protected by the 1972 Adirondack Park Land Use Plan. This limitation on development for environmental reasons has serious consequences for the 120,000 permanent residents within the park boundaries who, through their legislators, vigorously opposed the controls. A number of examples of the conflicts which have arisen are cited and a framework for “comprehensive” rather than “fragmented”planning is suggested.
Collaboration in BitTorrent Systems

Recent research efforts have shown that the popular BitTorrent protocol does not strictly enforce fairness and allows free-riding, mainly via optimistic unchokes. This paper proposes a BitTorrent-like protocol, that encourages peers of similar upload bandwidth to be buddies -- peers collaborating for mutual benefit. Buddy peers mostly satisfy their download needs through their buddies and perform optimistic unchokes only when absolutely necessary. As a result, the buddy protocol improves fairness via explicit cooperation between buddies, and limits bandwidth spent on random optimistic unchokes, leading to a system more robust against free-riders. We implemented the buddy protocol on top of an existing BitTorrent implementation and ran experiments on a controlled PlanetLab testbed to evaluate its impact. Our results show that the buddy protocol promotes fairness, discourages free-riding, and improves the robustness of the system as compared to regular BitTorrent. It also provides incentives to be adopted by all the peers in the system.
Relationship between patient age and duration of physician visit in ambulatory setting: Does one size fit all?

Objectives: To determine whether patient age, the presence of comorbid illness, and the number of prescribed medications influence the duration of a physician visit in an ambulatory care setting. Design: A cross-sectional study of ambulatory care visits made by adults aged 45 and older to primary care physicians. Setting: A probability sample of outpatient follow-up visits in the United States using the National Ambulatory Medical Care Survey (NAMCS) 2002 database. Participants: Of 28,738 physician visits in the 2002 NAMCS data set, there were 3,819 visits by adults aged 45 and older included in this study for analysis. Measurements: The primary endpoint was the time that a physician spent with a patient at each visit. Covariates included for analyses were patient characteristics, physician characteristics, visit characteristics, and source of payment. Visit characteristics, including the number of diagnoses and the number of prescribed medications, the major diagnoses, and the therapeutic class of prescribed medications, were compared for different age groups (45–64, 65–74, and ≥75) to determine the complexity of the patient's medical conditions. Endpoint estimates were computed by age group and were also estimated based on study covariates using univariate and multivariate linear regression. Results: The mean time±standard deviation spent with a physician was 17.9±8.5 minutes. There were no differences in the duration of visits between the age groups before or after adjustment for patient covariates. Patients aged 75 and older had more comorbid illness and were prescribed more medications than patients aged 45 to 64 and 65 to 74 (P<.001). Patients aged 75 and older were also prescribed more medications that require specific monitoring and counseling (warfarin, digoxin, angiotensin-converting enzyme inhibitors, diuretics, and levothyroxine) than were patients in other age groups (P<.001). Hypertension, coronary artery disease, atrial fibrillation, congestive heart failure, cerebrovascular disease, and transient ischemic attack were more common in patients aged 75 and older than in other age groups (P<.001). Despite these differences, there were no differences in unadjusted or adjusted duration of physician visit between the age groups. Conclusion: Although patients aged 75 and older had more medical conditions and were at higher risk for drug-related problems than younger patients, the duration of physician visits was similar across the age groups. These findings suggest that elderly patients may require a multidisciplinary approach to optimize patient care in the ambulatory setting.
Purification and Characterization of the β-Galactosidase of Aeromonas formicans

Rohlfing, S. R. (Western Reserve University, Cleveland, Ohio), and I. P. Crawford. Purification and characterization of the beta-galactosidase of Aeromonas formicans. J. Bacteriol. 91:1085-1097. 1966.-The beta-galactosidase of Aeromonas formicans was purified by diethylaminoethyl cellulose chromatography and gel filtration on Sephadex G-200. The properties of the enzyme molecule were compared with purified beta-galactosidase from Escherichia coli. The sedimentation coefficients and electrophoretic mobilities of the two enzymes were not significantly different; the electrophoretic mobility of urea-produced subunits of the two enzymes was also similar. The stabilities of the two enzymes to denaturing agents provided measurable differences; E. coli beta-galactosidase is relatively more heat-stable and more resistant to the action of urea. The amino acid compositions of the two proteins revealed significant differences in several amino acids, particularly alanine, arginine, glycine, and leucine. The comparisons cited suggest that A. formicans and E. coli are not completely unrelated, for their beta-galactosidases show considerable structural similarity.
Murine Models for Antiretroviral Therapy

Rauscher murine leukemia virus (RLV) infection of adult mice results in splenomegaly that is proportional to the virus titer. We have used this model to study the therapy of chronic viremia as well as chemoprophylaxis after viral exposure, both with single agents and with combination therapy. We showed that prompt initiation of effective antiviral therapy after viral exposure can prevent de novo infection. We have also developed a murine neurotropic retrovirus model which allows analysis of candidate antiviral agents for activity across the blood-brain barrier. This model can also be used to study therapeutic approaches to retroviral infections acquired at midgestation or during the neonatal period.
The Teratogenicity of Cyclophosphamide in Mice

Summary Cyclophosphamide, administered intraperitoneally to time-dated pregnant Swiss Webster mice on gestational Days 9 through 14 in a dosage of 20 mg/kg, resulted in increased numbers of resorptions and a variety of teratogenic effects. Gross examination of fetuses revealed cleft palate, exencephaly, digital defects, and kinky tail. Skeletal anomalies included polydactyly, syndactyly, ectrodactyly, adactyly, fusion of the long bones, curvature of the long bones, and missing ribs. Soft tissue malformations included open eyes, aphakia, microphakia, hydronephrosis, and hydrocephalus. Dosages of 5 and 10 mg/kg resulted in increased resorption and decreased growth rates in a dose-related manner but produced no discernible anomalies. Fetal mortality curves were biphasic, with the highest peak occurring on administration Days 9 and 10 and a second peak on Days 13 and 14.
ENHANCING GMM SCORES USING SVM "HINTS"

This paper proposes a classification scheme that combines statistical models and support vector machines. It exploits the fact (observed in [1]) that GMM and SVM classifiers with roughly the same level of performance produce uncorrelated errors. We describe a novel scheme which employs an SVM classifier as an “advisor” to the GMM classifier in uncertain cases. The utility of the combined generative/discriminative approach is demonstrated on standard text-independent speaker verification and speaker identification tasks in matched and mismatched training and test conditions. Results indicate significant improvements in performance without much computational overhead.
Nabumetone: A “Nonacidic” Nonsteroidal Antiinflammatory Drug

OBJECTIVE:To review the pharmacology, pharmacokinetic disposition, dosage recommendations, adverse effects, drug interactions, and efficacy of nabumetone in patients with selected rheumatic disorders and soft-tissue injuries.DATA SOURCES:Data from scientific literature were extracted, evaluated, and summarized for presentation. A MEDLINE search was conducted using the following indexing terms: antiinflammatory agents, nonsteroidal, nabumetone, rheumatoid arthritis (RA), and osteoarthritis (OA). Studies evaluating nabumetone reported in articles, abstracts, or proceedings involving human subjects were considered for inclusion.STUDY SELECTION:Special consideration was given to clinical studies using double-blind, randomized, parallel, controlled designs. Studies comparing the effectiveness and safety of nabumetone with placebo and other nonsteroidal antiinflammatory drugs (NSAIDs) were included.DATA EXTRACTION:Data from human studies published in the English language were evaluated. Trials were assessed acc...
PC Design, Use, and Purchase Relations

For 25 years, industry standard benchmarks have proliferated, attempting to approximate user activities. This has helped drive the success of PCs to commodity levels by characterizing apps for designers and offering performance information for users. However, the many new configurations of each PC release cycle often leave users unsure about how to choose one. This paper takes a different approach, with tools based on new metrics to analyze real usage by millions of people. Our goal is to develop a methodology for deeper understanding of usage that can help designers satisfy users. These metrics demonstrate that usages are uniformly different between high- and low-end CPU-based systems, regardless of why a user bought a given system. We outline how this data can be used to partition markets and make more effective hardware (hw) and software (sw) design decisions tailoring systems for prospective markets.
Characterization of a Neurotrophin Signaling Mechanism that Mediates Neuron Survival in a Temporally Specific Pattern

The temporally specific nature of neurotrophic factor-induced responses is a general feature of mammalian nervous system development, the mechanisms of which remain to be elucidated. We characterized a mechanism underlying the temporal specificity by which BDNF selectively promotes the survival of newly generated, but not mature, granule neurons of the mammalian cerebellum. We found that BDNF specifically induces the extracellular signal-regulated kinase 5 (ERK5)-myocyte enhancer factor (MEF2) signaling pathway in newly generated granule neurons and thereby induces transcription of neurotrophin-3 (NT-3), a novel gene target of MEF2. Inhibition of endogenous ERK5, MEF2, or NT-3 in neurons by several approaches including disruption of the NT-3 gene in mice revealed a requirement for the ERK5-MEF2-NT-3 signaling pathway in BDNF-induced survival of newly generated granule neurons. These findings define a novel mechanism that underlies the antiapoptotic effect of neurotrophins in a temporally defined pattern in the developing mammalian brain.
Metabolic conversion of 14C-indole-3-acetic acid to 14C-oxindole-3-acetic acid.

Abstract We have identified [1- 14 C]-oxindole-3-acetic acid as a catabolic product of [1- 14 C]-indole-3-acetic acid metabolism in Zea mays seedlings. The isolation, and chemical and mass spectral characterization of oxindole-3-acetic acid from corn kernel tissue is described together with data suggesting oxindole-3-acetic acid to be a major catabolic product of indole-3-acetic acid.
Pancreatitis Associated With Strongyloides Stercoralis Infection in a Patient Chronically Treated With Corticosteroids

Strongyloides stercoralis is a nematode that is a ubiquitous parasite in man. Life-threatening infections can occur in immunocompromised patients. We report a case of a 64-year-old Puerto Rican gentleman treated chronically with corticosteroids for reactive airway disease, who presented to our institution with pancreatitis complicated by sepsis and acute lung injury requiring mechanical ventilation. The initial working diagnosis was gallstone pancreatitis; however, several days into his hospital course, he was found to have a history of strongyloidiasis. Subsequent examination of his stool revealed the parasite, and the patient was treated with ivermectin. This case highlights the occasional association between pancreatitis and strongyloidiasis and the importance of proper treatment and consideration of infection in patients from endemic regions, which include Central America, Africa, and Asia.
Where to restore ecological connectivity? Detecting barriers and quantifying restoration benefits.

Landscape connectivity is crucial for many ecological processes, including dispersal, gene flow, demographic rescue, and movement in response to climate change. As a result, governmental and non-governmental organizations are focusing efforts to map and conserve areas that facilitate movement to maintain population connectivity and promote climate adaptation. In contrast, little focus has been placed on identifying barriers—landscape features which impede movement between ecologically important areas—where restoration could most improve connectivity. Yet knowing where barriers most strongly reduce connectivity can complement traditional analyses aimed at mapping best movement routes. We introduce a novel method to detect important barriers and provide example applications. Our method uses GIS neighborhood analyses in conjunction with effective distance analyses to detect barriers that, if removed, would significantly improve connectivity. Applicable in least-cost, circuit-theoretic, and simulation modeling frameworks, the method detects both complete (impermeable) barriers and those that impede but do not completely block movement. Barrier mapping complements corridor mapping by broadening the range of connectivity conservation alternatives available to practitioners. The method can help practitioners move beyond maintaining currently important areas to restoring and enhancing connectivity through active barrier removal. It can inform decisions on trade-offs between restoration and protection; for example, purchasing an intact corridor may be substantially more costly than restoring a barrier that blocks an alternative corridor. And it extends the concept of centrality to barriers, highlighting areas that most diminish connectivity across broad networks. Identifying which modeled barriers have the greatest impact can also help prioritize error checking of land cover data and collection of field data to improve connectivity maps. Barrier detection provides a different way to view the landscape, broadening thinking about connectivity and fragmentation while increasing conservation options.
WE‐E‐214‐03: Biology and Physiology of Targeted Radionuclide Therapy (TRT)

Radiolabeled agents are being developed for TRT (Targeted Radionuclide Therapy). Included in the 50 to 200 nm scale of this project are liposomes, short segments of DNA or RNA,nanoparticles and proteins. Because of possibly multiple lesion sites, these radiopharmaceuticals (RPs) are usually given by IV injection. Targeting, which requires a number of hours to days to accomplish, is effected by various means. The simplest method is to have the agent pass out of the blood and into the tumor space using the fenestrations in tumor capillaries. Liposomes are one such example whose membranes are dissolved in the lesion so as to release vesicle contents. Among the most specific localization processes is protein binding to a molecular marker on ‐ or near ‐ the tumor cell. Among such markers are Carcinoembryonic Antigen (CEA) and human epidermal growth factor receptor 2 (HER2). CEA is associated with colon, lung and some breast cancers, while HER2 is a breast cancer marker in approximately 25% of patients. These antigens are found in normal colon lumen and heart muscle respectively. A protein used in finding a molecular target may be something as simple as a mouse‐derived antibody or an engineered protein construct. One constraint is that proteins from alien species eventually generate their own human antibodies when repeatedly used in a given patient. This effect can be moderated by DNA manipulation of the alien antibody to change its structure to a more human‐like amino‐acid sequence. Use of a blood‐injection for the RP may result in sequestration by a normal tissue such as the liver or kidneys. In the renal case, small proteins (<25 kDa) would be very rapidly taken out of circulation so as to prevent significant tumor targeting. Various strategies have been developed to minimize sequestration; e.g., blocking or use of polyethylene glycol covering molecules (“stealth”) to prolong protein circulation. Because of the large numbers of possible RPs, it is necessary that preselection be done on any putative clinical RP. A figure of merit (FOM) may be used to choose one of a series of agents dedicated to the same tumor type; e.g., cognate antibodies to CEA. Both imaging and therapeutic FOMs have been developed. These indicators are used to differentiate RPs using animal data. This preferential ordering process is needed since the number of agents is large while volunteers for research studies are only a small fraction (2 to 5%) of the total patient population. One is still left with the question of the relationship between animal and clinical biodistribution data. Learning Objectives: 1. Know the types of agents presently being studied for TRT. 2. Understand the reasons for tumor targeting by engineered pharmaceuticals (RPs). 3. Realize the importance of the RP blood curve for the targeting process. 4. Use of Figures of Merit to select an optimal imaging or therapy agent.
Earth-space propagation above 10 GHz

Commercial satellite communications began in 1965 with the launch of Intelsat I (Early Bird), which was a geostationary satellite operating at 4 and 6 GHz. C-band satellite communications (satcom) continues today. As higher frequency bands were explored to expand capacity, problems were encountered with weather effects on the earth-space links, mainly rain attenuation. Many years of research was required to understand the influence of weather on signals above 10 GHz and to develop techniques to mitigate the effects. X-band, Ku-band, and Ka-band satcom links are in wide use today.
Chlorobiphenyls (PCBs) in the Milwaukee River

Abstract The analyses of water from the Milwaukee River indicated that isomers of chlorinated biphenyl similar to those used in industry were present in the river from West Bend to Lake Michigan. Analyses of municipal sewage treatment plant effluents, industrial discharges, and the Milwaukee River water near combined sewer outfalls presented evidence that chlorobiphenyls (PCBs) were discharged to natural waters through municipal and industrial wastes. PCBs concentration at the μg 1 -1 level suggested that PCBs in large ecosystems such as Lake Michigan have resulted, in part, through water transport from metropolitan areas.
Apatite Fission-Track Analysis

Apatite fission-track (AFT) analysis has been widely used during the past 30+ years to constrain the low-temperature thermal histories of many igneous, metamorphic and sedimentary rocks in a wide range of geological settings. Applicable geological settings include orogenic belts, rifted margins, faults, sedimentary basins, cratons, and mineral deposits. The types of geologic problems that can be addressed include the timing and rates of tectonic events, sedimentary basin evolution, the timing of hydrocarbon generation and ore mineralization, the absolute age of volcanic deposits, the effects of major climatic changes on the near-surface geothermal gradient, and long-term landscape evolution. Early work by Naeser (1967) and Wagner (1968, 1969) first established the basic procedures that enabled the fission-track dating method to be applied routinely to these geologic problems. Fleischer et al. (1975) summarized the early studies of the broader discipline of nuclear-track detection in different solid-state materials. More recent comprehensive overviews of fission-track applications have been provided by Naeser and McCulloh (1989), Wagner and Van den haute (1992), Gallagher et al. (1998), Van den haute and De Corte (1998), Dumitru (2000), and Gleadow et al. (2002). Etched, natural fission tracks in several apatite grains are shown in Figure 1⇓. Successful AFT analysis is limited by the following: 1) the availability of apatite from which useful AFT data can be obtained, often due to a lack of apatite of sufficient grain size and quality within available rock types, or, alternatively, the lack of available rock samples due to minimal outcrop exposure or other reasons, 2) economic considerations in terms of the time and money required to obtain sufficient AFT data, 3) the inherent limitations of AFT data to resolve geological thermal history information, often related to limited numbers of accumulated spontaneous fission tracks due to …
An analysis of clustering flows in a CFB riser

Abstract It has long been observed that drag correlations need to be modified such that the pressure drop in riser flow simulations more accurately predicts experimental findings. Simple early fixes were to increase the particle size until the correct pressure profile was obtained. Researchers have also added other closure algorithms such as energy minimization multiscale (EMMS) and more recently a cluster structure dependant (CSD) drag coefficient. This paper analyzes granular theory and proposes a reason based upon thermodynamics why the above mentioned “fixes” are required and why the EMMS and CSD fixes are more fundamentally sound than an arbitrary increase in the particle size. Granular theory is the analogous theory for discrete particles as the kinetic theory of gases is for gas molecules. In other words, the theory treats particles as though they were monatomic gas particles surrounded by vacuum. Eulerian–Eulerian simulation codes treat both gas and solids as two continuous fully miscible phases. In a circulating fluidized bed (CFB), granular behavior in the solids phase (stresses, pressure, and viscosity as well as transport and thermodynamic properties) depends on the granular temperature. Tests were conducted in a cold flow model of a circulating fluidized bed facility to gather particle velocity data which is used in calculating granular temperature. Cork particles approximately 800 μm in diameter. The particle velocity measurements under various operating conditions were obtained with an LDV system. This work extends granular theory to include a thermodynamic analysis of clustering flow in a CFB riser with the result being the development of an expression for the Gibbs free energy. Data from LDV measurements in the riser of a CFB indicated the existence of a minimum for the Gibbs free energy. The change in the Gibbs free energy was related to cluster size through the aerodynamic drag force. The result was that clusters on the order of 0.015 m in diameter and about 0.24 m in length ( 1 / 2 in. by 9 in.) were the most likely which was consistent with visual observation in the clear riser. These clusters were then related to the statistical definition of a cluster presented in earlier work by Breault et al. and indicated that the observable clusters consist of statistically similar microclusters.
Compensatory wayfinding behavior in topographic disorientation from brain injury

Recent studies of topographic disorientation from brain injury have focused on describing impairments, detailing neuroanatomical correlates of topographic disorientation, and classifying types of topographic disorientation. Normative models of environmental cognition have been applied in some studies of topographic disorientation, but more work is needed in this area. Few studies have produced data on everyday functioning with topographic disorientation. This paper presents data on compensatory wayfinding behavior in familiar environments, collected through case studies of three individuals with topographic disorientation from brain injury. Structured tests were used to evaluate visuo-spatial impairment, and normative models of wayfinding guided semi-structured and open-ended questioning about wayfinding inside and outside the home. All three-study informants were able to wayfind successfully within the home, though they varied in their ability to travel independently outside the home. Landmarks and scanning were important for orienting for all three subjects. The two subjects who were most able to travel independently also used sequencing of landmarks, directional heading and body position as elements of their wayfinding strategies. The information presented in this paper may prove useful to rehabilitation specialists who are treating brain-injured patients by providing new ideas about methods of compensation, and may contribute to emerging theory regarding impairments of orientation, and normative models of wayfinding.
Structural basis of cellular dNTP regulation by SAMHD1.

The sterile alpha motif and HD domain-containing protein 1 (SAMHD1), a dNTPase, prevents the infection of nondividing cells by retroviruses, including HIV, by depleting the cellular dNTP pool available for viral reverse transcription. SAMHD1 is a major regulator of cellular dNTP levels in mammalian cells. Mutations in SAMHD1 are associated with chronic lymphocytic leukemia (CLL) and the autoimmune condition Aicardi Goutieres syndrome (AGS). The dNTPase activity of SAMHD1 can be regulated by dGTP, with which SAMHD1 assembles into catalytically active tetramers. Here we present extensive biochemical and structural data that reveal an exquisite activation mechanism of SAMHD1 via combined action of both GTP and dNTPs. We obtained 26 crystal structures of SAMHD1 in complex with different combinations of GTP and dNTP mixtures, which depict the full spectrum of GTP/dNTP binding at the eight allosteric and four catalytic sites of the SAMHD1 tetramer. Our data demonstrate how SAMHD1 is activated by binding of GTP or dGTP at allosteric site 1 and a dNTP of any type at allosteric site 2. Our enzymatic assays further reveal a robust regulatory mechanism of SAMHD1 activity, which bares resemblance to that of the ribonuclease reductase responsible for cellular dNTP production. These results establish a complete framework for a mechanistic understanding of the important functions of SAMHD1 in the regulation of cellular dNTP levels, as well as in HIV restriction and the pathogenesis of CLL and AGS.
Side effects from amiodarone

Abstract Amiodarone causes many side effects involving all organ systems (Table VI). Although most of the side effects are mild and do not limit the use of the drug, there are several that are serious. Since many of these toxic reactions develop only after a prolonged period of therapy, careful foloww-up on a regular basis is essential (Table V).