cssi/SciSciGPT-SciSciNet huggingface dataset:
Chronic Migraine: Epidemiology, Mechanisms, and Treatment

Chronic migraine is a debilitating primary headache disorder associated with high personal, familial, and social impact. The diagnosis is made when there are at least 15 headache days monthly including 8 migraine days per month for at least 3 months. The prevalence is 1.4–2.2% in the population. Among individuals diagnosed with chronic migraine, there may be significant variability in headache days with a potential to remit, remain unchanged, or progress to even greater disability. Most chronic migraine progresses from episodic migraine, with several identified risk factors for chronic migraine and migraine progression. The exact mechanism of chronic migraine is unknown but is associated with an increased cortical excitability, central sensitization, alternations in nociceptive signaling, as well as physiological, structural, and functional brain changes. There is evidence for both nonpharmacological and pharmacological treatment options to restore function. The best currently established pharmacologic evidence for the treatment of chronic migraine is onabotulinumtoxinA and topiramate. Behavioral treatments may improve headache symptoms and comorbidities. Emerging data shows potential benefit for neurostimulation, and large well-designed studies are needed. Multicenter randomized placebo-controlled studies of monoclonal antibodies to the calcitonin gene-related peptide, or its receptor, have demonstrated efficacy, tolerability, and safety. Biomarkers are needed to guide prognosis, treatment response, and clinical trials. The concept and management of refractory chronic migraine is discussed, and clinically meaningful endpoints are reviewed.
Coryphopteris simulata (Thelypteridaceae), A New Combination For The Massachusetts Fern

Previous hypotheses on the evolutionary affinities of the eastern North American fern species most recently recognized as Parathelypteris simulata have included hybrid origin from North American progenitors and disjunctions with east Asian species. Recent phylogenetic evidence indicates that Parathelypteris sensu Ching is not monophyletic and that its species belong to two distinct clades, each of which includes members of other widely recognized genera: one of these clades includes the type of Parathelypteris, and the second includes southeast Asian and Pacific species of the more recently recognized genus Coryphopteris along with some temperate Asian species of Parathelypteris. Newly generated rbcL data representing the North American taxon Parathelypteris simulata places it in the Coryphopteris clade, as well. In consideration of ecological and phylogenetic evidence, the new combination Coryphopteris simulata is proposed.
Nondestructive Targeted Microbubble Detection Using a Dual-Frequency Beamforming Deep Neural Network

Targeted microbubbles (MBs)enable ultrasound molecular imaging (USMI)by binding to specific biomarkers and producing strong reflections to ultrasound. However, current USMI techniques are not easily translatable for clinical use. In particular, preclinical studies often utilize destruction-subtraction imaging, wherein a strong destructive pulse is used to destroy MBs to confirm their locations. This approach is potentially unsafe, and is intrinsically not real-time. In this work, a novel neural-network-based beamformer is proposed for the purpose of achieving safe and real-time USMI. The network was designed to utilize nondestructive channel data acquired at two distinct frequencies and to produce a pixel-wise estimate of MB probability. The network was trained using a total of 20 USMI datasets acquired in a mouse model of hepatocellular carcinoma and in microvessel flow phantoms. The network was then evaluated on 5 distinct datasets: a positive control, a negative control, and three previously unseen mouse tumors. Across the 5 datasets, the neural network achieved a mean AUC of 0.91 and DC of 0.56 compared to the destruction-subtraction images. These results demonstrate that a neural network can nondestructively distinguish MBs from background tissue and noise by exploiting characteristic differences in their fundamental and harmonic responses. The nondestructive dual-frequency DNN beamformer enables safe and real-time USMI and can aid in the translation to clinical applications.
Advance care planning and terminal intensive care unit admissions for cancer patients: We can do better.

e23000Background: Terminal oncology intensive care unit (ICU) admissions are associated with high healthcare costs and decreased quality of life. Chemotherapy can be given in non-curative settings ...
Dynamic Bridge Foundation Identification

The reuse of existing bridge foundations during superstructure replacement is increasing in popularity due to the potential for time and cost savings. In many cases, an existing foundation will need to be reanalyzed for new loading or design codes for it to be suitable for another 75-year design life. While these foundations have a demonstrated history of performance, there is often limited data available from their original construction, and important details like depth or type may not be available. There is interest in the bridge engineering community for solutions to determining the details of unknown foundations, and to verify the performance of existing foundations. A method is presented that uses dynamic strain and acceleration measurements taken from substructure elements during operational loading to characterize the behavior of the underlying foundations. These measurements are used to assemble frequency response functions (FRFs) that describe the load-response behavior of the tested foundation element as a function of frequency. This method only requires that a limited number of measurements be performed on exposed portion of the bridge substructure (piers, columns piles, etc.), and can be performed during daily operational conditions. The direct result of this analysis is an updated boundary condition that be used during modeling of the superstructure in place of the fixed conditions typically used. Furthermore, this method can be used to identify foundation depth and type, verify design parameters, and update models of pile and drilled shaft behavior. A case study is presented where dynamic measurements were taken from an in-service drilled shaft foundation during operational loading.
ECG-Derived Evaluation of Cardiac Repolarization

The resting 12-lead electrocardiogram (ECG) is the oldest tool and the most widely adopted clinical test for detection of heart disease. Today, it is still one of the most useful methods for risk stratification for sudden cardiac death. A number of ECG repolarization measures have been assessed in large population studies, as well as in research focused on high-risk cohorts, for the purpose of estimating arrhythmic risk, and will be discussed in this chapter. They include static parameters, such as QT interval duration, as well as dynamic markers, such as QT variability, and computationally derived variables, such as T-wave alternans. It has become increasingly apparent that repolarization heterogeneity is present in a variety of cardiovascular diseases and syndromes and may also be predictive of sudden cardiac death in the general population. However, at the present time, there is no consensus on how to best measure repolarization heterogeneity in human subjects. A wider adoption of repolarization indices in clinical practice would require an improved diagnostic accuracy, as well as the implementation of standardized computational signal processing techniques.
'Is the Time Right Now?': Reconciling Sociotemporal Disorder in Distributed Team Work

Temporal coordination endures as a central topic in computer-supported cooperative work (CSCW) because information systems still struggle to adequately support varying representations of time in the context of collaborations that areboth temporally and geographically dispersed. Moreover, the adaptive practices of these broadly dispersed groups are still not well understood. We ask:How do globally distributed teams temporally coordinate to accomplish their work? We examine an extreme case of online temporal coordination: high-tempo information curation about the urgent humanitarian crisis following the 2017 Hurricane Maria landfall in Puerto Rico. Our analysis of synchronous chat transcripts and data artifacts produced by The Standby Task Force reveals how this digital humanitarian group establishes temporal coordination through different shared understandings of time relative to the crisis, the globally distributed work, and the collaborative information technologies. We make four contributions from our analysis: First, we developed a pluritemporal analytical framework that describes different forms of socially constructed time and disambiguates their meaning in talk. Next, we present empirical evidence of how this distributed team establishes shared temporal orders to collectively orient their work in time. Then, we describe how they reconcile multiple and conflicting instances of sociotemporal "disorder'' to enable productive work. Last, we reflect on the design implications for collaborative information systems informed by this work.
Asteroid Diversion Considerations and Comparisons of Diversion Techniques

The threat of asteroid impacts on Earth poses a low-probability but high consequence risk, with possible outcomes ranging from regional to global catastrophe. However, unique amongst such global threats we have the capability of averting such disasters. Diversion approaches by either kinetic impactor or nuclear energy deposition are the two most practical technologies for mitigating hazardous near Earth asteroids. One of the greatest challenges in understanding our options is the uncertain response of asteroids to such impulsive techniques, due both to our lack of knowledge of the composition and structure of these objects as well as their highly varied nature. Predicting whether we will simply divert or break up a given object is a crucial: the weak self-gravity and inferred weak structure of typical asteroids present the strong possibility the body will fragment for modest impulses. Predictive modeling of failure and fragmentation is one important tool for such studies. In this paper we apply advances in modeling failure and fracture using Adaptive Smoothed Particle Hydrodynamics (ASPH) to understand mega-cratering on asteroids as a validation exercise, and show examples of diverting the near Earth asteroid Bennu using both a kinetic impactor and ablative blow-off due to nuclear energy deposition.
Molecular Regulation of the RhoGAP GRAF3 and Its Capacity to Limit Blood Pressure In Vivo

Anti-hypertensive therapies are usually prescribed empirically and are often ineffective. Given the prevalence and deleterious outcomes of hypertension (HTN), improved strategies are needed. We reported that the Rho-GAP GRAF3 is selectively expressed in smooth muscle cells (SMC) and controls blood pressure (BP) by limiting the RhoA-dependent contractility of resistance arterioles. Importantly, genetic variants at the GRAF3 locus controls BP in patients. The goal of this study was to validate GRAF3 as a druggable candidate for future anti-HTN therapies. Importantly, using a novel mouse model, we found that modest induction of GRAF3 in SMC significantly decreased basal and vasoconstrictor-induced BP. Moreover, we found that GRAF3 protein toggles between inactive and active states by processes controlled by the mechano-sensing kinase, focal adhesion kinase (FAK). Using resonance energy transfer methods, we showed that agonist-induced FAK-dependent phosphorylation at Y376GRAF3 reverses an auto-inhibitory interaction between the GAP and BAR-PH domains. Y376 is located in a linker between the PH and GAP domains and is invariant in GRAF3 homologues and a phosphomimetic E376GRAF3 variant exhibited elevated GAP activity. Collectively, these data provide strong support for the future identification of allosteric activators of GRAF3 for targeted anti-hypertensive therapies.
Feasibility of improving patient's safety with in vivo dose tracking in intracavitary and interstitial HDR brachytherapy.

Abstract Purpose The in vivo dosimetric monitoring in HDR brachytherapy is important for improving patient safety. However, there are very limited options available for clinical application. In this study, we present a new in vivo dose measurement system with a plastic scintillating detector (PSD) for GYN HDR brachytherapy. Methods An FDA approved PSD system, called OARtrac (AngioDynamics, Latham, NY), was used with various applicators for in vivo dose measurements for GYN patients. An institutional workflow was established for the clinical implementation of the dosimetric system. Action levels were proposed based on the measurement and system uncertainty for measurement deviations. From October 2018 to September 2019, a total of 75 measurements (48 fractions) were acquired from 14 patients who underwent HDR brachytherapy using either a multichannel cylinder, Venezia applicator, or Syed-Neblett template. The PSDs were placed in predetermined catheters/channels. A planning CT was acquired for treatment planning in Oncentra (Elekta, Version-4.5.2) TPS. The PSDs were contoured on the CT images, and the PSD D90% values were used as the expected doses for comparison with the measured doses. Results The mean difference from patient measurements was −0.22% ± 5.98%, with 26% being the largest deviation from the expected value (Syed case). Large deviations were observed when detectors were placed in the area where dose rates were less than 1 cGy/s. Conclusions The establishment of clinical workflow for the in vivo dosimetry for both the intracavitary and interstitial GYN HDR brachytherapy will potentially improve the safety of the patient treatment.
Metagenome-Assembled Genome Sequence of Aphanizomenon flos-aquae Strain Clear-A1, Assembled from an Enrichment Culture.

ABSTRACT Aphanizomenon flos-aquae is a significant harmful algal bloom-forming cyanobacterial species. Here, we report the draft genome for a strain of A. flos-aquae (Clear-A1) from a harmful algal bloom enrichment culture. This metagenome-assembled genome (MAG) sequence comprises 4,452,466 bp in 60 contigs with a GC content of 37.1%.
The Brent-WTI spread revisited: A novel approach

Abstract This paper takes a novel approach to analyze movements of the Brent-WTI spread over the years 2005 through early 2020. It adds to the existing literature by providing new insights that allow us to better understand to what extent the world crude oil market is truly ‘one great pool’. Our research is based on the premise that the place of physical competition between Brent and WTI is an important factor in determining traders’ actions and therefore the Brent-WTI spread. Changing crude oil flows in the U.S. due to the tight oil revolution together with changes in worldwide demand and supply have changed trade patterns and the location of physical competition between these two crudes. We develop three scenarios using ARIMAX-GARCH and Markov-Switching models. Scenarios 1–3 provide estimates of the impact that variables driving crude oil traders’ decisions have on the Brent-WTI spread. Additionally, we find that the change in the relationship between Brent and WTI that has been observed in the past decade appears to be fundamental, suggesting that the historical premium of WTI to Brent in the futures market is unlikely to return in the near future.
Statistical Challenges in Agent-Based Modeling

Agent-based models (ABMs) are popular in many research communities, but few statisticians have contributed to their theoretical development. They are models like any other models we study, but in g...
Teaching Effective Informed Consent Communication Skills in the Virtual Surgical Clerkship.

Background The disruption by the COVID-19 pandemic on undergraduate medical education allowed for assessment of virtual curricular innovations. One of the difficulties encountered in the virtual curriculum is the teaching of clinical competencies that would traditionally require students to undergo in-person simulations and patient encounters. We implemented a novel informed consent activity module, with standardized patients, to improve self-efficacy in communication within our core surgery clerkship. Study Design All medical students who participated in the virtual surgery clerkship were recruited to participate in a retrospective survey study regarding the novel informed consent module. These questions evaluated their perceived competence in 4 domains relating to informed consent: identifying the key elements, describing common challenges, applying the New Mexico Clinical Communication Scale (NMCCS), and documenting. Results Thirty-four of 90 students participated in the study (38% of the cohort). Respondents to the survey reported that their self-efficacy in communication skills related to informed consent improved as a result of their participation in the activity in each of the 4 domains surveyed (p Conclusions A virtual module of communication skills training, using standardized patients and faculty, improved students’ belief in their self-efficacy in obtaining informed consent. This communication module can be useful in a virtual or mixed curricular structure for both current and future medical students.
Arap1 Loss Causes RPE Phagocytic Dysfunction and Subsequent Photoreceptor Death

ABSTRACT Purpose Arap1 is an Arf-directed GTPase-activating protein (GAP) shown to modulate actin cytoskeletal dynamics by regulating Arf and Rho family members. We have previously shown that Arap1-/- mice develop photoreceptor degeneration similar to the human condition retinitis pigmentosa (RP), corroborated by fundus examination, histopathology, and ERG analysis. However, Arap1 expression was not detected in photoreceptors, but in Muller Glia and retinal pigment epithelium (RPE), suggesting a non-cell-autonomous mechanism for degeneration. The aim of this study was to elucidate the role of retinal Arap1 in photoreceptor maintenance. Methods Albino Arap1-/- mice were generated via breeding pigmented Arap1-/- mice onto a Tyr-/- C57BL/6J background. Conditional knockout (cKO) mice were generated for Muller Glia/RPE, Muller Glia, and RPE via targeting Cralbp, Glast, and Vmd2 promoters, respectively, to drive Cre recombinase expression to knock out Arap1. Mice were analyzed by fundus photography, optical coherence tomography (OCT), histology, and immunohistochemistry. Arap1 binding partners were assayed by affinity purification mass spectrometry. Results Vmd2-Cre Arap1tm1c/tm1c and Cralbp-Cre Arap1tm1c/tm1c mice, but not Glast-Cre Arap1tm1c/tm1c mice, recapitulated the photoreceptor degeneration phenotype originally observed in germline Arap1−/− mice. These findings were corroborated by fundus exam, OCT, and histological analysis. Mass spectrometry analysis of ARAP1 co-immunoprecipitation identified putative binding partners of ARAP1, revealing numerous interactants involved in phagocytosis, cytoskeletal composition, intracellular trafficking, and endocytosis. Quantification of rod outer segment (OS) phagocytosis in vivo demonstrated a clear phagocytic defect in Arap1−/− mice compared to Arap1+/+ littermate controls while cone phagocytosis was preserved. Conclusions Arap1 expression, specifically in RPE, is necessary for photoreceptor survival due to its indispensable function in RPE phagocytosis. We propose a model in which Arap1 regulates G-protein function for nonmuscle myosin II targeting during phagocytosis. This novel role of Arap1 is important for further understanding of both the diversity of its functions and the complex molecular regulation of RPE phagocytosis.
E-Cigarettes and Adult Smoking

Over the past few years, adult use of e-cigs has been increasing while adult smoking has been declining. Although there is a negative time correlation, it is important to determine if there is a causal effect of e-cig use on smoking. This is important because of the known health hazards associated with smoking. A key concern with most prior studies of e-cigs and smoking is that causality between e-cig use and cigarette use is ignored. One contribution of this paper is to estimate structural and reduced form equations that replace e-cig use with e-cig price in order to avoid this endogeneity problem. The data employed to estimate the empirical models come from the Tobacco Use Supplements (TUS). These data are from the combined July 2014, January 2015 and May 2015 waves of the TUS. The results show that e-cig use increases the probability of a quit attempt, the probability of a quit failure, the number of quit failures and the probability of a quit success. It is also estimated that a 10% federal excise tax on e-cigs would reduce the number of quitters in the US by more than 250,000 per year.
Teens, Screens, and Violence: Promoting Healthy Media Use Among Adolescents

The role of violence in the media often enters the debate over how to address and mitigate the national gun violence epidemic. Since the early days of television, there have been concerns about the corrupting influence of violent media on the minds of young people. As teens consume more hours of media per day and the types of available media have evolved, these concerns have become more complex. Current research is unclear as to whether a causal relationship between violent media and violent actions exists but there is evidence that exposure to guns in video games increases interest in real guns. The internet poses unique threats to the mental health and safety of young people in the form of cyberbullying and pro-suicide websites. Child health professionals should screen children and teens for unhealthy media use and should ask research questions to clarify any causal relationship between media violence and violent acts.
The Mayo Clinic Hemodynamic Cath Lab: A 70-Year Journey

Given the universal presence of cardiac catheterization laboratories across the United States, it is difficult to imagine that for many years only a few institutions were able to perform invasive hemodynamic procedures. Since its inception more than seven decades ago, the Mayo Clinic Cardiac Catheterization Laboratory has played a pivotal role in advancing the field as well supporting the clinical practice. We provide an overview of Mayo’s invasive hemodynamic laboratory from its early work in congenital heart disease under the direction of Drs. Earl Wood and Jeremy Swan and the seminal studies in ischemic heart disease performed by Dr. Robert Frye, to classic simultaneous echocardiography-catheterization studies that became the hallmark of the clinic’s research endeavors from the 1980s to 2000s and provided the foundation for the widespread use of Doppler echocardiography in the noninvasive assessment of hemodynamics and valvular disease.
A call auction's impact on price formation and order routing: Evidence from the NASDAQ stock market

Electronic call auctions are used globally to open and close equity market trading; as such, they are a critically important facility that needs to be better understood. The paper focuses on the impact NASDAQ's calls (introduced in 2004) have had on bid-ask spreads, price volatility, and order routing in the continuous market that follows daily openings and which precedes daily closings. NASDAQ's closing call has significantly reduced both spreads and volatility for all market capitalization groups. Its opening call similarly reduced spreads, while a generally similar, though somewhat weaker, pattern of volatility reduction was realized. Although the pattern of trading volume has, for the most part, not been significantly affected, our findings, comprehensively viewed, suggest that the calls have had a positive spillover effect on the dynamic behavior of price formation in NASDAQ's continuous market.
Educating BSW and MSW Social Workers to Practice in Child Welfare Services

Child welfare generally refers to a broad range of services provided by agencies charged with maintaining the safety and well-being of children according to legally mandated or socially sanctioned standards of conduct. For the purpose of this chapter, child welfare specifically denotes services provided to at-risk children and their families who have been referred to Child Protective Services (CPS) agencies because of confirmed maltreatment, neglect, or the likelihood of this occurrence.
Polyphenylalanine Synthesis and Binding of Phenylalanyl Transfer Ribonucleic Acid by Ribosomes from Muscle of Normal and Diabetic Rats

Abstract Ribosomes from muscle of diabetic rats synthesized less polyphenylalanine than normal ribosomes at low magnesium concentrations (5 to 10 mm), but they were more active than normal ribosomes at high magnesium concentrations (12.5 to 20 mm). The magnesium dependence of binding of phenylalanyl transfer RNA to normal and diabetic ribosomes closely paralleled the synthesis of polyphenylalanine. A portion of the radioactivity associated with ribosomes when binding of 14C-Phe-tRNA was assayed cochromatographed, after hydrolysis, with phenylalanine; the remainder did not migrate from the origin. At 7.5 mm magnesium, the greater amount of 14C-Phe-tRNA bound to normal ribosomes was accounted for by the formation of origin material. The origin material was identified as a peptide with carboxyl-terminal 14C-phenylalanine. Removal of peptidyltRNA by incubation with puromycin abolished the difference in the ability of normal and diabetic ribosomes to synthesize polyphenylalanine and to bind Phe-tRNA. We suggest that only ribosomes that have peptidyl-tRNA can bind Phe-tRNA at low magnesium concentrations. Since normal ribosomes contain more peptidyl-tRNA than diabetic ribosomes, they would bind more Phe-tRNA and synthesize more polyphenylalanine at low magnesium concentration.
The Community Dynamics of Entrepreneurship: the Birth of the American Film Industry, 1895–1929

The study of entrepreneurship has traditionally focused on the founders of new organizations, especially those that emerge as leaders in the creation of new industries. Much of this work follows what Gartner (1989) called the ‘traits’ approach. Studies of this type posit a causal link between the founding and success of new organizations and the personal attributes of the entrepreneurs. However, more recent research has documented the many ways in which successful entrepreneurship requires more than just the ‘right’ person; a multitude of factors, operating at both the organizational and evironmental levels of analysis, also affect the success of entrepreneurial efforts. Examples include technological change (Shane, 1996), changes in sources of firm capital (Cable and Shane, 1997), changes in strategic alliances (Eisenhardt and Schoonhoven, 1996), personal networks (Ostgaard and Birley, 1996), national environments (Shane and Kolvereid, 1995), location choice (Stearns, Carter, Reynolds, and Williams, 1995), and national culture (Shane, 1992).
News from the Edge of Interstellar Space

Auroral activity and magnetic storms that occasionally disrupt electric power grids are caused by the supersonic solar wind that sweeps past Earth as it blows radially away from the Sun. This wind creates the heliosphere, a bubble of magnetized plasma that surrounds the Sun and includes the orbits of all known planets. Two spacecraft, Voyager 1 and 2, are approaching the edge of the heliosphere the heliopause where the radially decreasing pressure of the expanding solar wind balances the inward pressure of the local interstellar medium. En route, the spacecraft are sending back important information about the far reaches of the solar system.
A review of the scientific rationale and methods used in the search for other planetary systems

Planetary systems appear to be one of the crucial links in the chain leading from simple molecules to living systems, particularly complex (intelligent?) living systems. Although there is currently no observational proof of the existence of any planetary system other than our own, techniques are now being developed which will permit a comprehensive search for other planetary systems. The scientific rationale for and methods used in such a search effort are reviewed here.
A Comparative Study of Youth Gangs in China and the United States: Definition, Offending, and Victimization

While the research on youth gangs in the United States has been around for generations, relatively little research on Chinese youth gangs has been published in Western journals. The purpose of this study is to examine the prevalence of the gang involvement of school-age youth in China and to explore whether or not some of the correlates associated with gang participation in the West, such as patterns of offending and victimization, are found in China. The data were collected from 7th, 8th, and 9th graders in both China and the United States using the same survey instrument, namely, the second International Self-Report Delinquency (ISRD-2). The results suggest that the U.S. sample has higher prevalence of self-nominated gang membership than the Chinese sample. In addition, the lifetime and last year participation rates in various criminal acts among the gang members in the Chinese sample were much lower than those in the U.S. sample. Last year prevalence of victimization was also examined between the gang members and nongang members in both samples. Finally, the definition of gang member identification was further explored to probe how culture, language, and social context can affect the understanding of a gang among the survey respondents.
Electrophoresis in density gradients of metrizamide

Abstract Linear density gradients of metrizamide have been used to prevent convection during electrophoresis in an apparatus originally designed for use with cylindrical gels. The procedures used are comparatively easy to perform. Two capsids of bacteriophage T7 previously shown to differ in average electrical surface charge density (σ) have been separated from each other by electrophoresis in gradients of metrizamide. These capsids were cleanly separated from both T7 DNA and a complex of a T7 capsid with T7 DNA. Thus, electrophoresis in density gradients of metrizamide is a technique for separating capsid-DNA complexes from DNA-free capsids and should be capable of separating other supramolecular complexes and organelles which differ in σ, some of which may be too large to be separated by electrophoresis in gels.
Marked radiosensitization of cells in culture to X ray by 5-chlorodeoxycytidine coadministered with tetrahydrouridine, and inhibitors of pyrimidine biosynthesis

Abstract Our approach to overcome the problem of rapid catabolism and general toxicity encountered with 5-halogenated analogues of deoxyuridine (5-bromo, chloro or iododeoxyuridine~ which has limited their use as tumor radiosensitizers, is to utilize 5-chlorodeoxycytidine (CldC with tetrahydrouridine (H 4 U) We propose that CIdC, co-administered with H 4 is metabolized in the following manner: CldC → CIdCMP → CIdUMP → CIdUTP → DNA. All the enzymes of this pathway are elevated in many human malignant tumors and in HEp-2 cells. In X irradiation studies with HEp-2 cells, limited to 1 or 2 radiation doses, we have obtained 3.0 to 3.8 apparent dose enhancement ratios (these represent upper limits) when cells are preincubated with inhibitors of pyrimidine biosynthesis: N-(Phosphonacetyl)-L-aspartate (PALA) and 5-fluorodeoxyuridine (FdU) or 5-fluorodeoxycytidine (FdC) + H 4 U Optimum conditions for radiosensitization are: PALA (0.1 mg/ml) 18–20 hr prior to FdU (0.1 μM or FdC (0.02 μM + H 4 U (0.1 mM) followed 6 hr later by CIdC (0.1-0.2 mM) + H 4 U (0.1 mM) for 56–68 hr. Viabilities of 10 ± 4% to 15 ±t 1% (±S.E.) were obtained for drug-treated unirradiated cells. Enzymatic studies indicate that this toxicity may be tumor selective. CIdC + H 4 alone (at these concentrations) results in 20% substitution of CIdU for thymidine in DNA (determined by HPLC analysis). Preliminary toxicity studies indicate that mice will tolerate treatment protocols involving a single dose of PALA (200 mg/kg) followed by a dose of FdU (50 mg/kg) and 3 cycles of CldC (500 mg/kg) + H 4 U (100 mg/kg) at 10 hour intervals, with marginal weight loss (496). In this approach we seek to obtain preferential conversion of CIdC to CIdUTP at the tumor site by taking advantage of quantitative differences in enzyme levels between tumors and normal tissues.
The hidden costs of infant vaccination.

Abstract Combination vaccines to minimize injections required for infant vaccination, and new vaccines with improved safety profiles, will pose increasingly complex choices for vaccine purchasers in the future. How much of a premium to pay for such vaccines might be determined by taking into account (1) the psychological burden of multiple injections during a single clinic visit, and the costs of any additional visits to minimize these, and (2) the medical, work-loss, and incidental costs of common vaccine-associated symptoms. This cross-sectional survey included randomly-selected parents of 1–8-month-old infants who received vaccines in a Northern California health maintenance organization (HMO) in 1997. Interviewers called parents 14 days after the infant’s vaccination to administer a 10-minute closed-ended interview in English or Spanish. Parents were asked about infant symptoms after vaccination, their preferences regarding multiple injections and their (theoretical) willingness to pay to reduce the number of injections their infant would receive, or to avoid the adverse symptoms experienced. Among 1769 eligible infants, interviews were completed with parents of 1657 (93%). The psychological cost of multiple injections was estimated by the willingness of parents to pay a median of $25 to reduce injections from 4 to 3, $25 from 3 to 2, and $50 from 2 to 1. Vaccine-associated symptoms caused mean costs of $42 in medical utilization and $192 in work-loss among the families who experienced those events ( N s=62 and 35, respectively). When averaged among all 1657 study infants, vaccine-associated symptoms after the index vaccination visit resulted in $2.91 in medical utilization, $4.05 in work-loss, and $0.74 in direct nonmedical costs, yielding total financial costs of $7.70. Parents of infants who had vaccine-associated symptoms said they would have paid a median of $50 to avoid these symptoms. Fever and fussiness were associated in logistic regression analysis with a two-fold increase in the odds of medical utilization, and fever with more than a three-fold increase in work loss. We conclude that multiple injections during a single clinic visit entail psychological costs. The psychological costs of vaccine-associated symptoms, as measured by willingness-to-pay methods, are higher than those resulting from multiple injections. The financial costs of medical utilization and work-loss resulting from common vaccine-associated symptoms are non-negligible and should be incorporated in economic analyses.
Writing in the Health Professions. Barbara A. Heifferon. New York: Longman, 2005. 315 pp.: Health and the Rhetoric of Medicine. Judy Z. Segal. Carbondale, IL: Southern Illinois University Press, 2005. 217 pp

Writing in the Health Professions is one of the latest books in the very popular Allyn and Bacon Series in Technical Communication published by Pearson/Longman and is the first one in the series to...
L-type Ca2+ channels contribute to current-evoked spike firing and associated Ca2+ signals in cerebellar Purkinje neurons.

The physiological properties of Purkinje neurons play a central role in their ability to regulate information transfer through the cerebellum. A number of ion channels contribute to Purkinje neuron physiology including an abundance of P-type Ca2+ channels, particularly in the dendritic region. Purkinje neurons also express L-type Ca2+ channels both during development and in the mature state. However, a role for L-type channels in Purkinje neuron physiology has yet to be fully defined. In the current study we used physiological recordings from cultured Purkinje neurons and the L-type Ca2+ channel agonist S-(2)-Bay K to assess a potential role for L-type Ca2+ channels in spike firing. Results show that Bay K alters current-evoked spike firing in young, immature Purkinje neurons without dendritic structure and in older, more mature Purkinje neurons with dendritic structure. Bay K also enhanced Ca2+ signals associated with the current-evoked spike firing. The effect of Bay K was more prominent in the young Purkinje neurons than in the older Purkinje neurons, suggesting that L-type Ca2+ channels may be more important in the Purkinje neuron physiology during the early stages of development rather than at mature stages. In the older Purkinje neurons, immunohistochemical studies using antibodies to L-type Ca2+ channels showed more intense immunolabeling in the somatic region than in the dendritic region. This result suggests that L-type Ca2+ channels may play a more important role in somatic physiology than dendritic physiology, whereas P-type channels may play a more important role in dendritic physiology.
Spectroelectrochemical kinetic studies of cytochrome-c and cytochrome c oxidase

Abstract The spectroelectrochemical method using optically transparent electrodes has been applied to the evaluation of the kinetic rates of electron transfer from electrogenerated methyl-viologen radical cation to the oxidized forms of the two heme proteins, cytochrome c and cytochrome c oxidase. Rates have also been determined for transfer from the reduced forms of these two heme proteins to the electrogenerated oxidant, bis-(hydroxymethyl) ferricinium ion. The rates have been compared to those calculated using the MARCUS theory. The experimental problems associated with the spectroelectrochemical method when applied to fast rates involving slowly-diffusing macromolecules are discussed.
Performance of a modified downstream-cathode MPD thruster.

Discussion of the improvements incorporated since 1969 in a low-power MPD thruster design which is considered a potential candidate for satellite station keeping and attitude control. The improvements include a new cathode design, and changes in thruster geometry, with xenon used as the propellant. A better thermal design is found to be necessary for further improvement of the thruster.
Studies of culture conditions and environmental stability of human metapneumovirus

Human metapneumovirus (HMPV) is a paramyxovirus that is a leading cause of acute respiratory disease. HMPV is difficult to cultivate and limited published data describe the in vitro growth characteristics of the virus and its ability to replicate in different cell lines. Stability of HMPV to different temperatures or environmental conditions has not been described. Nosocomial infections due to HMPV have been reported, and thus the survival of infectious particles on environmental surfaces is important. We tested multiple cell lines for the ability to support HMPV replication both in the presence and absence of exogenous trypsin. The most permissive monkey kidney epithelial cells were LLC-MK2 and Vero, while the most permissive human airway epithelial cell line was BEAS-2B. LLC-MK2 cells were tolerant of trypsin and thus remain an ideal cell line for HMPV cultivation. Spinoculation significantly increased the infectivity of HMPV for cells in monolayer culture. Infectious virus was very stable to repeat freeze-thaw cycles, ambient room temperature, or 4 degrees C, while incubation at 37 degrees C led to degradation of virus titer. Finally, nonporous materials such as metal or plastic retained infectious virus for prolonged periods, while virus deposited on tissue and fabric rapidly lost infectivity. These findings provide guidance for laboratories attempting to culture HMPV and relevant information for infection control policies.
Identity among first and second generation African immigrants in the United States

This article explores the increasing waves of Africans migrating to the United States and the ways in which complex and multi‐layered notions of identity have surfaced. Issues of identity include self‐identification as well identities imposed on African immigrants. Factors such as location, accent, and socialization are especially important in determining how Africans in America self‐identify and which identities are placed upon them. Special attention is paid to identity formation among second generation African immigrants, specifically those who represent the offspring of the increased immigration flows from Africa beginning in the 1980s.
Humoral antigenic targets of the ribosomal P0 lupus autoantigen are not limited to the carboxyl region.

: Autoantibodies binding the ribosomal P phosphoproteins are highly specific for systemic lupus erythematosus (SLE) and can be found in precipitating levels in approximately 15% of these patients. Anti-ribosomal P antibodies are directed against three proteins, and the primary autoimmune target of this response has been described as a common 22-amino acid sequence. Sera from 31 anti-ribosomal P immunodiffusion-positive SLE patients were tested for C-terminal P-peptide reactivity by ELISA. Sera from three patients (9.7%) were negative for the peptide ELISA, despite having anti-ribosomal P by immunodiffusion and Western blot. In addition, inhibition experiments showed that the common P-peptide response accounts for a variable amount of anti-ribosomal P0 reactivity (52-89% of the response dependent upon the patient serum). Based upon these findings, fine-specificity sequential humoral epitope mapping of ribosomal P0 was performed. Several common sequential antigenic targets were defined dispersed throughout the molecule. The most commonly targeted epitopes included RDMLLANKVPAAARA (amino acids 99-113, 11 of 12 patients reactive) and QALGITTKISRGT (amino acids 139-151, 9 of 12 patients reactive). This study confirms that the P22 ribosomal peptide is commonly targeted in SLE and accounts for a variable percentage of the anti-ribosomal P response. Additional anti-ribosomal P humoral epitopes are described.
Translatability of schemas over restricted interpretations

We study a notion of translatability between classes of schemas when restrictions are placed on interpretations. Unlike the usual notion of translatability, our translatability lets the translation depend on the interpretation. We consider five classes of schemas. Three of these have been extensively studied in the literature: flow-chart, flow-chart with counters, and recursive. The two others are defined herein; the first of which is a class of ''maximal power'' and is equivalent to similarly motivated classes of other investigators; while the second is, in some sense, a nontrivial class of ''minimal power''. Our main results specify restrictions on interpretations that will allow the translatability of a class into a class , not being translatable into over all (or unrestricted) interpretations. Additional results specify restrictions on interpretations under which is not translatable into ; the proofs of these clarify the mechanisms in the main results. Last, we consider the notion of effective computability in algebraic structures in the light of the main results.
Shear strength measurements of lubricants at high pressure

Measurements of lubricant shear rheological behavior in the amorphous solid region and near the liquid-solid transition are reported on three lubricants under pressure. Elastic, plastic and viscous behavior was observed. The maximum yield shear stress (limiting shear stress) is a function of temperature and pressure and is believed to be the property which determines the maximum traction in elastohydrodynamic contacts such as traction drives.
A Single Intravenous Injection of Adeno-associated Virus Serotype-9 Leads to Whole Body Skeletal Muscle Transduction in Dogs

The success of many gene therapy applications hinges on efficient whole body transduction. In the case of muscular dystrophies, a therapeutic vector has to reach every muscle in the body. Recent studies suggest that vectors based on adeno-associated virus (AAV) are capable of body-wide transduction in rodents. However, translating this finding to large animals remains a challenge. Here we explored systemic gene delivery with AAV serotype-9 (AAV-9) in neonatal dogs. Previous attempts to directly deliver AAV to adult canine muscle have yielded minimal transduction due to a strong cellular immune response. However, in neonatal dogs we observed robust skeletal muscle transduction throughout the body after a single intravenous injection. Importantly, systemic transduction was achieved in the absence of pharmacological intervention or immune suppression and it lasted for at least 6 months (the duration of study). We also observed several unique features not predicted by murine studies. In particular, cardiac muscle was barely transduced in dogs. Many muscular dystrophy patients can be identified by neonatal screening. The technology described here may lead to an effective early intervention in these patients.
Sliding wear behavior of Cu50Hf41.5Al8.5 bulk metallic glass

Abstract Sliding wear behavior of a copper-based bulk metallic glass (Cu 50 Hf 41.5 Al 8.5 ) was investigated for both as-cast and annealed samples. The wear resistance increased during isothermal annealing near the glass transition temperature. Nanocrystals developed during the annealing for annealing times up to 300 min. A linear relation between hardness and wear resistance was observed during the early stages of devitrification, but at longer annealing times the wear resistance increased less than the hardness. For the as-cast sample and a sample that was structurally relaxed, nanocrystallites developed during sliding and the wear resistance improved for longer sliding distances when the nanocrystals developed. The transmission electron microscopy analysis of the annealed samples suggests that the deviation from the linear hardness vs. wear resistance relation occurs at a critical volume fraction of the nanocrystals. The improvement in wear resistance with sliding appears to result from an increased surface temperature rather than directly from the sliding-induced nanocrystal formation.
Self-contained control for turn-on transition of an optically driven IGBT

This paper presents a novel photonic control mechanism to control the turn-on transition of insulated gate power semi-conductor devices (PSDs), used in the hard switched power electronics applications. Turn-on transition control decreases the overshoot of the turn-on current caused by reverse-recovery current (IRR) of the free-wheeling diode (FWD) due to high slope of current during turn-on. It also adjusts the turn-on dv/dt to control the switching loss and electro-magnetic interference (EMI) while keeps the PSD in the safe-operating area. In contrast to other works, the proposed control method independently adjusts the turn-on di/dt and dv/dt in different operating conditions using a single circuit. The onset of transition between di/dt and dv/dt control regions is determined using a self-contained control circuit. The error between the desired and actual onset of transition is compensated using a partially activated PI compensator. Another feature of the presented work is using a single optical link for both pulse-width modulation (PWM) and switching transition control of an Optically-triggered (OT) hybrid device comprising an IGBT as the main PSD and a pair of GaAs-based optically-triggered power transistors (OTPTs) serving as the driver for the IGBT. The proposed control circuit operation and advantages are presented and verified by experimental results.