cssi/SciSciGPT-SciSciNet huggingface dataset:
WIZARD and the design of trials for secondary prevention of atherosclerosis with antibiotics.

Abstract Clinical trials to assess the merit of antibiotic intervention in the treatment of ischemic cardiovascular disease are now underway, spurred on by an association between Chlamydia pneumoniae and atherogenesis noted in epidemiologic investigations, histopathologic studies, and results from various animal models. The design of such clinical trials must take into account a number of issues: the primary event as strictly defined by objective criteria, the event rate in the chosen population, the potential treatment effect, the availability of patients, the underlying cause of their atherosclerotic disease, the determination of the C pneumoniae– infected population to study, the dose and duration of the antibiotic, and the length of follow-up. In the design of the WIZARD study (Weekly Intervention with Zithromax for Atherosclerosis and its Related Disorders), an attempt was made to take these issues under consideration. Patients were randomly assigned either to 600 mg/d zithromax for 3 days then 600 mg/wk for 11 additional weeks or to placebo. Patients in the study had a myocardial infarction at least 6 weeks previously, had no recent coronary artery bypass graft or percutaneous transluminal coronary angioplasty, and did not required long-term administration of antibiotics. Patients were required to have an immunoglobulin G titer to C pneumoniae of ≥1:16. The primary end point was the time to a composite of all-cause death, myocardial infarction, a revascularization procedure, or hospitalization for angina. The study enrolled 3500 patients, sufficient to detect a 25% reduction in the presumed 8% placebo event rate with 90% power. Follow-up will continue through the prespecified number of end points. (Am Heart J 1999;138:S542-S544.)
Clinical experience with recombinant human thrombopoietin in chemotherapy-induced thrombocytopenia

Since the identification and cloning of c-Mpl ligand, two forms of recombinant human thrombopoietin have undergone clinical development. Both the full-length molecule, known as rhTPO, and the truncated version of the molecule, known as pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), have been evaluated in phase I/II clinical trials in cancer patients receiving myelosuppressive chemotherapy. Early clinical trials with PEG-rHuMGDF in cancer patients demonstrated its clinical safety and platelet-stimulating activity. However, the development of neutralizing antibodies and clinically significant thrombocytopenia in some patients and normal donors who received PEG-rHuMGDF have led to discontinuation of clinical trials with this molecule in the United States. Clinical experience with rhTPO so far indicates that this full-length glycosylated molecule is remarkably well tolerated and has a favorable safety profile. In these studies, rhTPO exhibited dose-dependent increases in circulating platelet counts and bone marrow megakaryocytes before chemotherapy. In addition, there was an increase in the frequency and proliferation of bone marrow progenitor cells and mobilization of progenitors into the peripheral blood. Early results also showed that rhTPO can attenuate chemotherapy-induced severe thrombocytopenia and reduce the need for platelet transfusions. However, in this setting, the optimal schedule of rhTPO administration may depend on the length of the regimen and anticipated timing of the platelet nadir. These initial results indicate that rhTPO is a safe and potentially useful agent in the prevention and management of chemotherapy-induced thrombocytopenia. Results of larger randomized clinical trials will determine the therapeutic potential of this novel growth factor in various clinical settings.
Restaurant Choice: The Role of Information

The purpose of this study was to examine how consumers' choice of restaurant differs depending on whether they have information about a restaurant or not. A convenience sample using a self-administered questionnaire was completed by adult restaurant patrons. There was a significant difference in the importance of food quality and location in choosing a restaurant based on availability or lack of information. Information sources from friends or relatives were the most important sources when influencing restaurant choice over media source. Information or lack of information coupled with demographic variables also had an impact on restaurant choice. The more frequently respondents dine out in restaurants; the more important it was to have information about value for money.
Workforce turnover at local health departments: nature, characteristics, and implications

Background Employee turnover, defined as total separations from employment, is expensive, can result in lost capacity, and can limit local health departments' (LHDs') ability to respond to public health needs. Despite the importance of workforce capacity in public health, little is known about workforce turnover in LHDs. Purpose To examine the extent to which LHDs experience turnover and identify LHD characteristics that are associated with turnover. Methods A cross-sectional data set of employee turnover and LHD characteristics from the 2013 National Profile of LHDs was analyzed. Descriptive statistics and bivariate analyses were conducted in 2014 on turnover rates. The effect of the following LHD characteristics on turnover rates were examined: population size, governance type, degree of urbanization, top executive experience level, expenditures per capita, and LHD budget cuts. Results In 2013, LHDs experienced a mean turnover rate of 9.88%; approximately one third of turnover was due to retirements. LHDs with shared state and local governance experienced a higher turnover rate than LHDs with exclusive state or local governance. LHDs that are units of state agencies had a significantly higher retirement rate than those governed by local authorities. Top executive experience level, per capita expenditures, and LHD budget cuts were also related to turnover rates. Conclusions LHDs experienced a lower overall turnover rate than state health departments in 2011 and lower than all local and state government agencies in 2012. Strengthening leadership skills of new top executives and ensuring adequate funding may reduce turnover in LHDs.
A multicomponent sectional model applied to flame synthesis of nanoparticles

Sodium/halide flame synthesis and encapsulation (SFE) is a promising technique for producing nonoxide materials. The reaction produces nanoparticles of the core product and a condensable by-product (e.g., NaF). In this research, the SFE process was studied numerically for a spherically symmetric non-premixed flame in a low-pressure atmosphere of sodium vapor. Experimentally, this flame can be established in microgravity. A transient flame code incorporating detailed chemistry and transport processes was developed to perform the investigation. In addition, a two-component sectional method was developed and integrated into the flame code to simulate aerosol dynamics, including coagulation and condensation. For the simulation, the reaction of CF 4 with Na was chosen such that solid carbon was the core product and NaF was the condensable by-product. the results show that near the reaction region, a large number of core particles form, yet condensation of the condensable species does not occur because of the high temperature. Slightly away from the reaction region toward the ambient, there is a narrow region within which rapid condensation of NaF occurs and a few large, heavily coated particles are formed. Most of the small core particles are not coated in this region, but instead are being scavenged by the large, heavily coated particles. Condensation is negligible further downstream because the concentration of the condensable species becomes too low. The simulation also shows that thermophoresis is important, especially at low pressure, to the distribution of particles and that the effect of sticking coefficient on NaF(1) is minimal. The effect of pressure also has been studied, and the results show that the mass fractions of carbon and NaF(1) are insensitive to pressure.
Diffusion of major and trace elements in compositionally complex Cl- and F-bearing silicate melts

Abstract Chemical diffusion experiments on halogenated, multicomponent silicate melts at 10 MPa, 200 MPa and 1.0 GPa have yielded diffusivities for both major (Al, Fe, Si) and trace elements (Mn, Zn, Y, Zr, Nb) over the temperature range 900 to 1400 ° C. At any given temperature and pressure, diffusivities of all elements are the same within an order of magnitude; they display no apparent dependence upon cation size, but do correlate crudely with cation field strength (Z/r). Comparison with diffusion data on unhalogenated melts revealed that addition of Cl and F tends to increase cation diffusivities and lower activation energies for diffusion. The effect of increasing pressure is also to enhance diffusion for all elements studied except the high field-strength network-modifiers Zr and Nb. As pressure increases, low Z/r elements experience a decrease in activation energy for diffusion, whereas high Z/r elements display increasing activation energies. It is proposed that the change in activation energy is related to the existence of two distinct network structures characterized by different TOT angles. The network structures with lower TOT angles apparently can provide charge-balanced sites for low Z/r cations but not for high Z/r cations. The effect of elevated pressure on the melt structure may be to increase the proportion of network structures having low TOT angles. The resulting increase in available sites for low Z/r cations is believed responsible for the observed reduction in activation energy for diffusion of the cations.
Detection of 677CT/1298AC "double variant" chromosomes: implications for interpretation of MTHFR genotyping results.

Purpose: Genotyping 37,026 individuals as part of a thrombophilia evaluation, we determined and analyzed the genotypic frequencies of the 677CT and 1298AC mutations in the methylenetetrahydrofolate reductase (MTHFR) gene. Methods: The 677CT and 1298AC mutations in the MTHFR gene were determined by either a laboratory-developed test involving PCR amplification and restriction digestion utilizing the ABI 3100 capillary electrophoresis apparatus (Applied Biosystems Inc) or by using an Analyte Specific Reagent (ASR) supplied by Third Wave Technologies. The genotype for three specimens with triple variant MTHFR mutations were confirmed by DNA sequencing on the ABI 3100 capillary electrophoresis apparatus. Results: The MTHFR frequencies of the 677CT/1298AA, 677CC/1298AC, 677CT/1298AC, 677CC/1298AA, 677TT/1298AA, 677CC/1298CC, 677TT/1298AC, and 677CT/ 1298CC genotypes were 0.228, 0.208, 0.198, 0.153, 0.122, 0.088, 0.0005, and 0.0003, respectively. Conclusions: Individuals containing double variant MTHFR mutations on one allele (cis) cannot be distinguished between compound heterozygotes (trans) for 677CT and 1298AC mutations in routine clinical testing, a genotype associated with thrombophilia. Such patients could be inappropriately counseled for being at high risk for thrombotic episodes. Until information regarding prevalence and the clinical consequences of this double variant (cis) allele becomes available, caution should be used in interpreting the genotyping results of compound heterozygosity for 677CT and 1298AC.
The visual status of the nursing home resident

Abstract Objective: To determine the visual status and eye care needs of long-term care nursing home residents. Study design: Eye examinations were performed on 39 nursing home residents (mean = 72.1 years, range 39–94, 36 males and three females) in the Department of Veterans Affair long-term care facility. The prevalence of low vision and legal blindness as well as ocular conditions in this population was recorded. Results: The results of 39 eye examinations indicate that a high prevalence of low vision and legal blindness as well as ocular conditions such as cataracts, macular degeneration, and glaucoma exist in these nursing home residents. There were also large percentages of people with reduced contrast sensitivity, reduced stereo acuities, and visual field defects. Conclusion: The findings indicate a large need for routine eye care in this population
Exploring alternative flexible OpenCL (FlexCL) core designs in FPGA-based MPSoC systems

Open Compute Language (OpenCL) has been proposed as a platform-independent parallel execution framework to target multicores, graphics processing units (GPUs), digital signal processors (DSPs), and other custom accelerators. Traditionally OpenCL is designed to scale across system generations by having each new model increase the available resources: processing cores, register file entries, and shared (localized) physical memory. However, when evaluating all potential models capable of running OpenCL the numerous performance trade-offs associated with these competing resources makes for a large exploration space. Specifically there are advantages to systematically analyzing the OpenCL parallel expressions to eliminate processor elements that constrain the overall design. We have designed an analysis tool for evaluating OpenCL kernels and the potential processor configurations in FPGA-based multiprocessor systems-on-chip (MPSoC) designs. The Flexible OpenCL (FlexCL) system determines integrated hardware-software customization opportunities related to processor design across sets of OpenCL applications. The paper provides an evaluation of various OpenCL components synthesized to FPGA-based multicore design alternatives.
Conclusion: women around the world reshaping leadership for education

Purpose – This short essay aims to reflect on the global experiences women in education have had in becoming leaders as noted in the articles in this special issue on women's leadership.Design/methodology/approach – The essay draws upon relevant historical and contemporary literature about women in the professions and in the workforce.Findings – The case is made for women educational leaders from kindergarten through higher education to reshape leadership rather than lead as men have done in the past.Originality/value – The essay highlights this moment in history is seen as particularly promising for women leaders who are no longer anomalies, but who have not yet redefined leadership.
On a proposed divide-and-conquer minimal spanning tree algorithm

In a recent paper published in this journal, R. Chang and R. Lee purport to devise anO(N logN) time minimal spanning tree algorithm forN points in the plane that is based on a divide-and-conquer strategy using Voronoi diagrams. In this brief note, we present families of problem instances to show that the Chang-Lee worst-case timing analysis is incorrect, resulting in a time bound ofO(N2 logN). Since it is known that alternate, trulyO(N logN) time algorithms are available anyway, the general utility of the Chang-Lee algorithm is questionable.
Compressive sensing and 3-D radar imaging

Nonstandard image formation methods can enable fully threedimensional fine resolution radar images of some objects of interest to be constructed from certain types of sparsely sampled three-dimensional apertures, which contain too little collected data to support traditional imaging methods. Such three-dimensional image products provide more target information than traditional SAR and ISAR imagery, and eliminate most of the difficulties associated with interpretation, mensuration, and recognition that result from overlay effects, self shadowing, scaling and viewing angle uncertainties.
Nonrandom karyotypic changes in immortal and tumorigenic Syrian hamster cells induced by diethylstilbestrol.

Abstract Treatment of Syrian hamster embryo cells with diethylstilbestrol (DES) resulted in the induction of immortal cell lines that progressed and formed tumors in nude mice. Four independently treated cell lines were analyzed cytogenetically at several passages during neoplastic progression. The immortal cell lines at the early passages had no structural abnormalities but did have numerical changes. For example, gain of chromosome 11 was found in all immortal cell lines, and gain of chromosome 19 was found in two of four cell lines. Tumorigenic cells showed not only a variety of numerical abnormalities but also structural abnormalities. Loss of a sex chromosome and gain of chromosome 19 were found in six of seven tumors. Gain of chromosome 11, which was found in all immortal cell lines, disappeared in five of seven tumors. Structural abnormalities involving chromosomes 2 and 3 were found in three of seven tumors. Many marker chromosomes were also found in the tumors. These results support our hypothesis that DES-induced nondisjunction is important in its ability to induce cell transformation and suggests that gain of chromosome 11 and/or 19 may play a role in DES-induced genicity, additional numerical or structural changes are needed, suggesting that multiple genetic events are required in the multistep process of carcinogenesis.
p-nitrophenyl phosphate hydrolysis and calcium ion transport in fragmented sarcoplasmic reticulum.

The calcium ion pump of fragmented sarcoplasmic reticulum can be coupled to hydrolysis of p-nitrophenyl phosphate, in the absence of added adenosine triphosphate. Comparison of the activities obtained with the two substrates suggests an analogous mechanism of transport. Independent of the substrate, a 2 : 1 ratio between calcium ion transport and substrate hydrolysis is displayed by the system, and an identical amount of work is required for ion transport against a given gradient. A phosphate ester appears necessary for substrate utilization in the pump mechanism, whereas the structure of the substrate determines the rates of activity and the affinity of the system for calcium ion.
Distinct roles for classical nuclear import receptors in the growth of multinucleated muscle cells

Proper muscle function is dependent on spatial and temporal control of gene expression in myofibers. Myofibers are multinucleated cells that are formed, repaired and maintained by the process of myogenesis in which progenitor myoblasts proliferate, differentiate and fuse. Gene expression is dependent upon proteins that require facilitated nuclear import, however little is known about the regulation of nucleocytoplasmic transport during the formation of myofibers. We analyzed the role of karyopherin alpha (KPNA), a key classical nuclear import receptor, during myogenesis. We established that five karyopherin alpha paralogs are expressed by primary mouse myoblasts in vitro and that their steady-state levels increase in multinucleated myotubes, suggesting a global increase in demand for classical nuclear import during myogenesis. We used siRNA-mediated knockdown to identify paralog-specific roles for KPNA1 and KPNA2 during myogenesis. KPNA1 knockdown increased myoblast proliferation, whereas KPNA2 knockdown decreased proliferation. In contrast, no proliferation defect was observed with KPNA4 knockdown. Only knockdown of KPNA2 decreased myotube growth. These results identify distinct pathways involved in myoblast proliferation and myotube growth that rely on specific nuclear import receptors suggesting that regulation of classical nuclear import pathways likely plays a critical role in controlling gene expression in skeletal muscle.
The IAB Iron-Meteorite Complex: A Group, Five Subgroups, Numerous Grouplets, Closely Related, Mainly Formed by Crystal Segregation in Rapidly Cooling Melts

We present new data or iron meteorites that are members of group IAB or are closely related to this large group, and we have also reevaluated some of our earlier data for these irons. In the past it was not possible to distinguish IAB and IIICD irons on the basis of their positions on element-Ni diagrams. We now find that plotting, the new and revised data yields six sets of compact fields on element-Au diagrams, each set corresponding to a compositional group. The largest set includes the majority (approximately equal to 70) of irons previously designated IA: We christened this set the IAB main group. The remaining five sets we designate subgroups within the IAB complex. Three of these subgroups have Au contents similar to the main group, and form parallel trends in most element-Ni diagrams. The groups originally designated IIIC and IIID are two of these subgroups: they are now well resolved from each other and from the main group. The other low-Au subgroup has Ni contents just above the main group. Two other IAB subgroups have appreciably higher Au contents than the main group and show weaker compositional links to it. We have named these five subgroups on the basis of their Au and Ni contents. The three subgroups having Au contents similar to the main group are the low-Au (L) subgroups the two others the high-Au (H) subgroups. The Ni contents are designated high (H), medium (M), or low (L). Thus the old group IIID is now the sLH subgroup. the old group IIIC is the sLM subgroup. In addition, eight irons assigned to two grouplets plot between sLL and sLM on most element-Au diagrams. A large number (27) of related irons plot outside these compact fields but nonetheless appear to be sufficiently related to also be included in the IAB complex.
Decidual GM-CSF is a critical common intermediate necessary for thrombin and TNF induced in-vitro fetal membrane weakening

Abstract Introduction Inflammation/infection and decidual bleeding/abruption are highly associated with pPROM. As no animal model for pPROM exists, we have developed an in-vitro model system for the study of human fetal membrane (FM) weakening/rupture. Using it we have demonstrated that both TNF/IL-1 (modeling inflammation) and thrombin (modeling bleeding) weaken full thickness FM in a dose dependent manner concomitant with inducing biochemical changes similar to those seen in the FM physiological weak zone. Methods As the physiological site of infection and bleeding is the choriodecidua (CD), we modified our model system with full thickness FM tissue mounted on modified Transwell culture inserts to permit directional TNF/thrombin exposure on the decidua only (rather than both sides of the FM). After incubation, medium was sampled separately from the CD facing (maternal side) or from the amnion facing (fetal side) compartments and probed for cytokine release and confirmed with western blots. The FM was strength tested within the insert. Results Full-thickness FM fragments exposed to TNF or thrombin on CD side only showed dose dependent weakening and biochemical changes consistent with previous reports. Concomitantly, GM-CSF increased markedly on the CD but not the amnion side. Numerous proteases including MMP1 and MMP3 also increased on the CD side. Pre-incubation with GM-CSF antibody blocked both thrombin and TNF induced weakening. Finally, GM-CSF weakened FM in a dose dependent manner. Discussion GM-CSF is a critical common intermediate in the thrombin and TNF FM weakening pathways.
Assessing Aggregate Structural Change

The aim of this paper is to investigate the evolution of Italian aggregate structural change over the years 1965–85. We use annual input–output (IO) tables in current and constant prices to derive an aggregate index of structural change. We adopt several techniques for such an explorative analysis. First, we borrow from qualitative matrix analysis and graph theory some basic concepts to assess direct and indirect links among sectors, and interrelatedness measures are derived in a straightforward way. However, qualitative analysis of indirect links may be flawed, since it can establish a path that is quantitatively negligible. Then, we turn our attention to a non-standard quantitative index derived from structural path analysis, expressed by a simple function of the input matrix determinant. Since empirical findings indicate a structural break in 1975, we derive another measure of technical change: the dominant eigenvalue. Such an index has several interesting properties but no clear relationship to the ci...
Diagnostic approach to ocular, retro-ocular and orbital pain

Headache is among the most common complaints, bringing patients to their physician's office. Patients with headaches are often referred to an ophthalmologist. The authors are going to deal with the patient who, in the classification of headache syndrome, localizes the pain to the eye, behind the eye or to the orbital area. They would like to suggest a diagnostic decision tree or algorithmic approach to the evaluation of those patients.This diagnostic approach is based on clinical symptoms such as proptosis, lid retraction, decreased visual acuity and pain, together with slit lamp examination, physical examination and the patient's history and complaints. Ocular, retro—ocular and orbital pain is an important topic for the ophthalmologist and are difficult to approach. Their importance is currently underestimated in the ophthalmologic literature.
Noise-injected neural networks show promise for use on small-sample expression data.

Background: Overfitting the data is a salient issue for classifier design in small-sample settings. This is why selecting a classifier from a constrained family of classifiers, ones that do not possess the potential to too finely partition the feature space, is typically preferable. But overfitting is not merely a consequence of the classifier family; it is highly dependent on the classification rule used to design a classifier from the sample data. Thus, it is possible to consider families that are rather complex but for which there are classification rules that perform well for small samples. Such classification rules can be advantageous because they facilitate satisfactory classification when the class-conditional distributions are not easily separated and the sample is not large. Here we consider neural networks, from the perspectives of classical design based solely on the sample data and from noise-injection-based design. Results: This paper provides an extensive simulation-based comparative study of noise-injected neural-network design. It considers a number of different feature-label models across various small sample sizes using varying amounts of noise injection. Besides comparing noise-injected neuralnetwork design to classical neural-network design, the paper compares it to a number of other classification rules. Our particular interest is with the use of microarray data for expression-based classification for diagnosis and prognosis. To that end, we consider noise-injected neural-network design as it relates to a study of survivability of breast cancer patients. Conclusion: The conclusion is that in many instances noise-injected neural network design is superior to the other tested methods, and in almost all cases it does not perform substantially worse than the best of the other methods. Since the amount of noise injected is consequential, the effect of differing amounts of injected noise must be considered.
New perspectives on neuronal development via microfluidic environments

Understanding the signals that guide neuronal development and direct formation of axons, dendrites, and synapses during wiring of the brain is a fundamental challenge in developmental neuroscience. Discovery of how local signals shape developing neurons has been impeded by the inability of conventional culture methods to interrogate microenvironments of complex neuronal cytoarchitectures, where different subdomains encounter distinct chemical, physical, and fluidic features. Microfabrication techniques are facilitating the creation of microenvironments tailored to neuronal structures and subdomains with unprecedented access and control. The design, fabrication, and properties of microfluidic devices offer significant advantages for addressing unresolved issues of neuronal development. These high-resolution approaches are poised to contribute new insights into mechanisms for restoring neuronal function and connectivity compromised by injury, stress, and neurodegeneration.
Patient perceptions of vulvar vibration therapy for refractory vulvar pain

The objective of this study was to describe acceptability of vulvar vibration therapy (VVT), a novel treatment approach to vulvodynia. We included women with vulvodynia who attended the Pelvic Pain Clinic and had used VVT for at least two weeks. Participants completed a three-page, 65-item, questionnaire assessing demographics, VVT usage and responses to Likert statements regarding accessibility, comfort and symptom response to VVT. Of 69 qualifying patients, results from 49 (72%) were eligible for analysis. Participants were primarily white, married and well-educated, with a median age of 30 (range 19-68 years). Median duration of vulvar pain and dyspareunia was two years (0-23) and three years (0-30), respectively. Median duration of VVT was five months (1-18) and three days per week (0.5-7). Fully, 83% said that, "vibrator treatment is an acceptable treatment", 83% said that they were "satisfied with vibrator treatment", 76% endorsed vibrator as comfortable to use, 73% indicated that sex is less painful since starting vibration treatment and 88% would recommend VVT to others. We conclude that the therapeutic rationale for VVT is based on the anti-nocioceptive properties of vibration and on the favorable response of vulvodynia to physical therapy. Vulvar vibration therapy is safe, inexpensive and, in this survey, acceptable to most patients, many of whom described improvement in symptoms.
The Effects of Industrialization–Its Opportunities and Consequences–Upon French-Canadian Society

Societies usually do not define explicitly the criteria of the legitimacy of the penetration of the price-system into different areas, and I suppose that, as social scientists, we should be grateful for this omission, since this is the kind of thing that forms the basis of our livelihood.
Mobilizing aluminum in crustal and mantle fluids

Aluminum is a major rock-forming element, but its low solubility in H2O at upper crustal conditions has led to the assumption that it is effectively immobile during fluid–rock interaction in the deep crust and upper mantle. However, new experimental results on Al solubility in H2O–SiO2–NaCl fluids at high pressure and temperature challenge this view. The combined effects of temperature, pressure, dissolved SiO2 and NaCl yield increases in corundum (Al2O3) solubility at 800°C, 1GPa of N10 3 or 10 4 relative to that at b0.3GPa in pure H2O. Enhancement of Al solubility is best explained by formation of polynuclear Na–Al–Si–O clusters and/or polymers. Aluminum should not be assumed to be immobile during fluid–rock interaction in deep environments. © 2006 Elsevier B.V. All rights reserved.
Vortex development and breakdown

Abstract : A line vortex is assumed to consist of a thin viscous core of laminar embedded in an inviscid flow of uniform circulation and with axial velocity that may depend upon the distance along the core. Self-similar solutions are obtained for the particular case of an external velocity inversely proportional to the core length. These solutions exhibit linear core growth. The primary mechanism of vortex breakdown is discussed involving a fundamental incompatibility of the axial and azimuthal flow modes within the confines of a thin layer. A quantitative method is developed to predict the breakdown point in terms of initial and external aerodynamic conditions. Breakdown diagrams pertaining to flow mode incompatibility are presented for a particular family of initial core velocity profiles. Numerical examples exhibit the effect of external pressure gradients.
Trust management for Web Services

Service-Oriented Architecture (SOA) is increasingly used in enterprise information systems, particularly in the form of Web Services. This paper describes a practical trust management system for Web Services that allows information in databases to be used seamlessly and efficiently in trust management policies.
FRI0097 Comparative effectiveness and time to response among adalimumab, abatacept, etanercept, infliximab and rituximab in a real world routine care registry

Background With the availability of multiple biologic agents, with different modes of action, and no head to head trials, it is of use to examine comparative effectiveness of these agents in real world registries to inform physicians how they might be used for the treatment of rheumatoid arthritis. Objectives To compare time to response and efficacy among biologic agents. Methods Usage of the biologic medications abatacept, adalimumab, etanercept,infliximab and rituximab along with self-reported disease activity and clinic measures were abstracted from ARMD registry at NYU. Time to first response defined as an improvement in RAPID3 of at least 3.6 was calculated; change from biologic medication initiation to first response for self-reported disease activity and clinic measures was estimated. Differences in time to first response between biologic medications were estimated using Cox proportional hazards model. Results 4299 encounteres were reviewed for this analysis. A total of 526 treatment courses were determined. 406 of 526 courses represent the first biologic medication used by an individual; 88 individuals used two biologic medications at different times, while 26 had used three biologics, and 6 had used 4. Abatacept had more patients achieve response (66%) characterized by a reduction in RAPID of 3.6 points or greater than adalimumab (63%), etanercept (61%), infliximab (43%), rituximab (41%) although this difference was not statistically siginficant. Increased age and increased duration of disease were associated with decreased likelihood of achieving a RAPID3 reponse. Time to reponse in the first 6 months after treatment was not significantly different among any of the biologics (Fig. 1). Conclusions No differences in efficacy and time to response among adalimumab, abatacept, etanercept, infliximab or rituximab in the first 6 months after RA treatment was initiated were noted. With no difference in clinical outcomes, most treatment decisions may be based on ease of use and safety data of respective biologics agents when they are being considered for RA treatment. Disclosure of Interest Y. Yazici Grant/Research support from: Abbott, BMS, Celgene, Genentech, Consultant for: Abbott, BMS, Centocor, Celgene, Pfizer, genentech, UCB, Takeda, A. Regens: None Declared, C. Swearingen: None Declared
The Alice M. Baldwin Scholars Program

(2009). The Alice M. Baldwin Scholars Program. NASPA Journal About Women in Higher Education: Vol. 2, No. 1, pp. 243-244.
Sodium selenite radiosensitizes hormone-refractory prostate cancer xenograft tumors but not intestinal crypt cells in vivo.

Purpose We have previously shown that sodium selenite (SSE) increases radiation-induced cell killing of human prostate carcinoma cells in vitro . In this study we further evaluated the in vivo radiosensitizing effect of SSE in prostate cancer xenograft tumors and normal radiosensitive intestinal crypt cells. Methods and Materials Immunodeficient (SCID) mice with hormone-independent LAPC-4 (HI–LAPC-4) and PC-3 xenograft tumors (approximately 200 mm 3 ) were divided into four groups: control (untreated), radiation therapy (XRT, local irradiation), SSE (2 mg/kg, intraperitoneally, 3 times/week), and XRT plus SSE. The XRT was given at the beginning of the regimen as a single dose of 5 Gy for HI–LAPC-4 tumors and a single dose of 7 Gy followed by a fractional dose of 3 Gy/d for 5 days for PC-3 tumors. The tumor volume was measured 3 times per week. The radiosensitizing effect of SSE on normal intestinal epithelial cells was assessed by use of a crypt cell microcolony assay. Results In the efficacy study, SSE alone significantly inhibited the tumor growth in HI–LAPC-4 tumors but not PC-3 tumors. Sodium selenite significantly enhanced the XRT-induced tumor growth inhibition in both HI–LAPC-4 and PC-3 tumors. In the toxicity study, SSE did not affect the intestinal crypt cell survival either alone or in combination with XRT. Conclusions Sodium selenite significantly enhances the effect of radiation on well-established hormone-independent prostate tumors and does not sensitize the intestinal epithelial cells to radiation. These results suggest that SSE may increase the therapeutic index of XRT for the treatment of prostate cancer.
Circadian Rhythm Sleep Disorders in Children and Adolescents

This article describes the circadian and homeostatic processes involved in the modulation of sleep and wakefulness. It defines the six currently identified primary circadian rhythm sleep disorders and the process for diagnosing each entity. It then focuses on the use of chronotherapy, phototherapy, and melatonin to treat delayed sleep phase syndrome, the circadian rhythm sleep disorder most commonly seen in children and adolescents.
RNA Processing and Clinical Variability in Neurofibromatosis Type I (NF1)

Neurofibromatosis type 1 (NF1) is a common genetic disorder which predisposes affected individuals to a variety of clinical features including tumors of the central and peripheral nervous systems. The product of the NF1 gene, neurofibromin, is a tumor suppressor which most likely acts through the interaction of its GTPase activating protein (GAP) related domain (GRD) with RAS to regulate cellular growth. Two intriguing features of NF1 are the wide range of potentially affected tissues and the great variation in expressivity of disease traits across those affected. To date, the underlying source of this variation remains somewhat unclear, but evidence suggests that aberrations in normal NF1 RNA processing may be involved. This evidence includes: (i) differences in the relative ratios of the type I and type II splice variants in NF1 tumors compared with nontumor tissues; (ii) unequal expression of mutant and normal NF1 alleles in cultured cells derived from NF1 patients; (iii) the existence of NF1 tumors which display NF1 mRNA editing levels that are greater than that seen in non-NF1 tumors; and (iv) tissue-specific and developmental stage-specific expression of particular alternative NF1 transcripts. These findings suggest that the classical 2-hit model for tumor suppressor inactivation used to explain NF1 tumorigenesis can be expanded to include the post-transcriptional mechanisms which regulate NF1 gene expression. Aberrations in these mechanisms may lead to the pathogenesis of NF1 and may play a role in the observed clinical variability.
Acyl-Coenzyme A:Cholesterol Acyltransferase Inhibition Ameliorates Proteinuria, Hyperlipidemia, Lecithin-Cholesterol Acyltransferase, SRB-1, and Low-Denisty Lipoprotein Receptor Deficiencies in Nephrotic Syndrome

Background— Nephrotic syndrome (NS) is associated with hyperlipidemia, altered lipid regulatory enzymes and receptors, and increased risk of progressive renal and cardiovascular diseases. Acyl-coenzyme A:cholesterol acyltransferase (ACAT) catalyzes intracellular esterification of cholesterol and plays an important role in production of apolipoprotein B-containing lipoproteins, regulation of cholesterol-responsive proteins, and formation of foam cells. Because hepatic ACAT-2 is markedly upregulated in NS, we tested the hypothesis that inhibition of ACAT may improve cholesterol metabolism in NS. Methods and Results— Rats with puromycin-induced NS were treated with either the ACAT inhibitor CI-976 or placebo for 2 weeks. Normal rats served as controls. Plasma lipids, renal function, and key lipid regulatory factors were measured. Untreated NS rats showed heavy proteinuria; hypoalbuminemia; elevated plasma cholesterol, triglyceride, LDL, VLDL, and total cholesterol-to-HDL cholesterol ratio; increased hepatic ...
High-throughput single-molecule studies of protein-DNA interactions.

Fluorescence and force-based single-molecule studies of protein–nucleic acid interactions continue to shed critical insights into many aspects of DNA and RNA processing. As single-molecule assays are inherently low-throughput, obtaining statistically relevant datasets remains a major challenge. Additionally, most fluorescence-based single-molecule particle-tracking assays are limited to observing fluorescent proteins that are in the low-nanomolar range, as spurious background signals predominate at higher fluorophore concentrations. These technical limitations have traditionally limited the types of questions that could be addressed via single-molecule methods. In this review, we describe new approaches for high-throughput and high-concentration single-molecule biochemical studies. We conclude with a discussion of outstanding challenges for the single-molecule biologist and how these challenges can be tackled to further approach the biochemical complexity of the cell.
Identical complementary deoxyribonucleic acids encode a human renal and bone parathyroid hormone (PTH)/PTH-related peptide receptor.

Identical complementary DNAs (cDNAs) that encode a 593-amino acid human PTH (PTH)/PTH-related peptide (PTHrP) receptor were isolated by hybridization techniques from two cDNA libraries which had been constructed from human kidney and human osteoblast-like osteosarcoma cells (SaOS-2). Northern blot analysis of total RNA from human bone- and kidney-derived tissue revealed one single major messenger RNA species of about 2.5 kilobases in both tissues. The human PTH/PTHrP receptor has 91% and 81% identity, respectively, with the previously cloned rat and opossum receptors, indicating a high degree of conservation among mammals. Despite this striking degree of amino-acid conservation, the human PTH/PTHrP receptor has several unique biological properties when transiently expressed in COS-7 cells. The apparent dissociation constants for [Nle8,18,Tyr34] bovine PTH(1-34) amide [bPTH(1-34)] are similar for the human and the rat receptor (approximately 8 vs. approximately 15 nM) whereas [Tyr36]PTHrP(1-36) amide has a...
Transsacral exenteration of fixed primary and recurrent anorectal cancer.

Abstract Background Posteriorly fixed anorectal cancer is often considered incurable, but may be resectable using transsacral approaches. Methods We reviewed 45 patients undergoing transsacral exenteration for this problem since 1983 to determine outcome of such surgery. Results The group consisted of 38 men and 7 women; 17 had primary tumors, 28 had recurrent cancer: local excision, 1; low anterior resection, 11; or abdominoperineal resection, 16. Thirty-nine had prior XRT. Operative mortality was 4%. Severe pain was relieved in 16 of 22 (72%) patients. Crude recurrence rates are local 22%, local plus distant 11%, distant 16%. Five-year disease-free survival is 31% for primary disease, 32% for recurrence. Median survival is abdominoperineal resection recurrence, 24 months; primary cancer, 30 months; low anterior resection recurrence, 37 months. Conclusions Transsacral exenteration relieved pain in 70% of patients with fixed anorectal cancer, and led to long-term survival in 31% to 32%. Prognosis trended toward benefit for recurrence after low anterior resection.
Digoxin Therapy Does Not Improve Outcomes in Patients with Advanced Heart Failure on Contemporary Medical Therapy

Background— The impact of digoxin on outcomes of patients with advanced heart failure (HF) receiving optimal contemporary therapy is not known. Methods and Results— We retrospectively reviewed data of 455 advanced HF patients referred for transplant evaluation (age, 52�12 years; ejection fraction, 18.3�8%); 227 (49.9%) were on digoxin at baseline. Primary outcome was death (n=101), urgent transplantation (n=14), or ventricular assist device implantation (n=4); secondary outcomes included HF and all-cause hospitalizations. Digoxin use was evaluated (1) in the original cohort; (2) in a propensity score–matched subset (n=322); (3) as a time-dependent covariate; and (4) after adjustment for Seattle Heart Failure Score. Patients were on optimal therapy: angiotensin-II modulation, 92.5%; β-blockers, 91.2%; aldosterone antagonists, 45.6%; and devices, 71.0%. After a median of 27 months, 83 of 277 (36.6%) patients treated with digoxin versus 36 of 228 (15.8%) patients without digoxin met primary outcome (hazard r...
Molecular and genetic analysis of REC103, an early meiotic recombination gene in yeast.

In the yeast Saccharomyces cerevisiae at least 10 genes are required to begin meiotic recombination. A new early recombination gene REC103 is described in this paper. It was initially defined by the rec103-1 mutation found in a selection for mutations overcoming the spore inviability of a rad52 spo13 haploid strain. Mutations in REC103 also rescue rad52 in spo13 diploids. rec103 spo13 strains produce viable spores; these spores show no evidence of meiotic recombination. rec103 SPO13 diploids produce no viable spores, consistent with the loss of recombination. Mutations in REC103 do not affect mitotic recombination, growth, or repair. These phenotypes are identical to those conferred by mutations in several other early meiotic recombination genes ( e.g., REC102, REC104, REC114, MEI4, MER-2, and SPO11 ). REC103 maps to chromosome VII between ADE5 and RAD54. Cloning and sequencing of REC103 reveals that REC103 is identical to SK18, a gene that depresses the expression of yeast double-stranded (“killer”) (ds)RNA viruses. REC103/SK18 is transcribed in mitotic cells and is induced ∼15-fold in meiosis. REC103 has 26% amino acid identity to the Schizosaccharomyces pombe rec14 + gene; mutations in both genes confer similar meiotic phenotypes, suggesting that they may play similar roles in meiotic recombination.
Comment on Measurements of the temperature dependent diffusion coefficient of nanoparticles in the range of 295-600 K at atmospheric pressure by V.Y. Rudyak, S.N. Dubtsov, A.M. Baklanov

In a recent paper in this journal, Rudyak, Dubtsov, and Baklanov (2009) presented results of measurements of the penetration of nanoparticles with diameters from 3.5 to 84 nm at temperatures from � 300 to 600 K through a set of wire screens, from which they inferred diffusion coefficients. They argued that the formulation typically used for C ,t he Cunningham correction that accounts for non-continuum effects on the diffusion of nanoparticles, is not valid for temperatures greater than � 300 K, and they proposed a modification of this formulation which depends on both temperature and particle size. It is shown here that this modification produces unphysical results in that it yields negative values of the momentum accommodation coefficient. A likely reason for their results is that they used a polydisperse size distribution, for which the main contribution to the measured penetration would be from particles at sizes far from those attributed to them.
Fine-Scale Genetic Population Structure of Southern Pine Beetle (Coleoptera: Curculionidae) in Mississippi Forests

The southern pine beetle, Dendroctonus frontalis Zimmerman, is the most destructive insect pest of pine forests in the southeastern United States, Mexico, and Central America. Southern pine beetle aggressively attacks pine trees, and when in epidemic stages, they are capable of killing even the most healthy pine trees in a short period of time. Despite the amount of destruction caused by the southern pine beetle and the amount of monetary loss faced by the timber industry and recreation, the population genetics of this species has been limited to comparisons among distant geographic locations. This study investigates the fine-scale genetic population structure of the southern pine beetle in Mississippi. Very little genetic differentiation was observed among samples. Bayesian assignment testing failed to detect multiple groups within all samples; estimates of genetic differentiation and genetic distance were very low in magnitude; and a Mantel test did not reveal a significant relationship between genetic distance and geographic distance. These results suggest that management of the southern pine beetle needs to consider the potential movements of individuals within and among national forests and should be focused on a large scale, at least as big as continuously forested areas and possibly even multiple forests. These results further suggest that removal of beetle-infested trees is important.