cssi/SciSciGPT-SciSciNet huggingface dataset:
Identification of four classes of cell surface antigens appearing at gastrulation in sea urchin embryos

Abstract An antiserum to isolated membranes of gastrula-stage embryos of the sea urchin Lytechinus variegatus was characterized by absorption and cell agglutination specificities. The antiserum was found to recognize four distinct classes of antigens on the embryonic cell surface: (1) an early embryonic class or “maternal” class present from the earliest stages of development, (2) an embryonic class of antigens which appeared on all cells beginning at gastrulation, (3) a class of antigens present on ectoderm cells, and (4) a class of antigens present on endoderm cells. All four classes of antigens were shown indirectly to be synthesized on embryonic mRNA since a hybrid embryo of the cross Tripneustes ♀ × Lytechinus ♂ expressed all four classes of Lytechinus -specific antigens beginning at gastrulation. Each class was Lytechinus specific in that hybrid cells were agglutinated if beyond the beginning of gastrulation, while normal Tripneustes ♀ × Tripneustes ♂ cells were not agglutinated.
A new model to simulate the elastic properties of mineralized collagen fibril

Bone, because of its hierarchical composite structure, exhibits an excellent combination of stiffness and toughness, which is due substantially to the structural order and deformation at the smaller length scales. Here, we focus on the mineralized collagen fibril, consisting of hydroxyapatite plates with nanometric dimensions aligned within a protein matrix, and emphasize the relationship between the structure and elastic properties of a mineralized collagen fibril. We create two- and three-dimensional representative volume elements to represent the structure of the fibril and evaluate the importance of the parameters defining its structure and properties of the constituent mineral and collagen phase. Elastic stiffnesses are calculated by the finite element method and compared with experimental data obtained by synchrotron X-ray diffraction. The computational results match the experimental data well, and provide insight into the role of the phases and morphology on the elastic deformation characteristics. Also, the effects of water, imperfections in the mineral phase and mineral content outside the mineralized collagen fibril upon its elastic properties are discussed.
Manganese induces neurite outgrowth in PC12 cells via upregulation of αv integrins

Abstract Previous studies have demonstrated that the divalent cation manganese (Mn) causes PC12 cells to form neurites in the absence of NGF. Since divalent cations modulate the binding affinity and specificity of integrins, and integrin function affects neurite outgrowth, we tested the hypothesis that Mn induces neurite outgrowth through an integrin-dependent signaling pathway. Our studies support this hypothesis. Function-blocking antisera specific for β1 integrins block the neurite-promoting activity of Mn by 90–95%. Bioassays and biochemical studies with antisera specific for the αv, α5, or α8 integrin subunit suggest that the αvβ1 heterodimer is one of the principal β1 integrins mediating the response of PC12 cells to Mn. This is corroborated by studies in which Mn failed to induce neurite outgrowth in a clone of PC12 cells that does not express αv at levels detectable by immunoprecipitation or immunocytochemistry. SDS–PAGE analysis of biotinylated surface proteins immunoprecipitated from Mn-responsive PC12 cells, as well as confocal laser microscopy of PC12 immunostained for surface αv indicate that Mn increases the surface expression of αv integrins. This increase appears to be due in part to synthesis of αv since specific inhibitors of RNA and protein synthesis block the neurite-promoting activity of Mn. These data indicate that Mn induces neurite outgrowth in PC12 cells by upregulating αv integrins, suggesting that Mn potentially represents an additional mechanism for regulating the rate and direction of neurite outgrowth during development and regeneration.
Madhouse: A Tragic Tale of Megalomania and Modern Medicine

Surgery may not be the most obvious treatment for mental illness. Surgeons are people who find it extremely rewarding to act and see the impact of their actions on their patients. However, operating on the body may not have very specific effects on a disordered mind. This fact has not hindered enthusiasts intervening surgically believing their outcomes to be positive. Such excesses have been tragic, as is well known in the history of lobotomy (see review of The Lobotomist in this week's BMJ ). Less well known is the phase …
A Radio and X-Ray Study of Historical Supernovae in M83

We report the results of 15 years of radio observations of the six historical supernovae (SNe) in M83 using the Very Large Array. We note the near-linear decline in radio emission from SN 1957D, a Type II SN, which remains a nonthermal radio emitter. The measured flux densities from SNe 1923A and 1950B have flattened as they begin to fade below detectable limits; they are also Type II SNe. The luminosities for these three SNe are comparable with the radio luminosities of other decades-old SNe at similar epochs. SNe 1945B, 1968L, and 1983N were not detected in the most recent observations, and these nondetections are consistent with previous studies. We report the X-ray nondetections of all six historical SNe using the Chandra X-Ray Observatory, consistent with previous X-ray searches of other decades-old SNe and low inferred mass-loss rates of the progenitors [ ≈ ].
Different Gene Families in Arabidopsis thaliana Transposed in Different Epochs and at Different Frequencies throughout the Rosids

Certain types of gene families, such as those encoding most families of transcription factors, maintain their chromosomal syntenic positions throughout angiosperm evolutionary time. Other nonsyntenic gene families are prone to deletion, tandem duplication, and transposition. Here, we describe the chromosomal positional history of all genes in Arabidopsis thaliana throughout the rosid superorder. We introduce a public database where researchers can look up the positional history of their favorite A. thaliana gene or gene family. Finally, we show that specific gene families transposed at specific points in evolutionary time, particularly after whole-genome duplication events in the Brassicales, and suggest that genes in mobile gene families are under different selection pressure than syntenic genes.
Massive dissemination from spinal cord gangliogliomas negative for BRAF V600E: report of two rare adult cases.

Objectives: Metastatic leptomeningeal spread from spinal cord gangliogliomas (GGs) is exceedingly rare. Methods: Two adult women, aged 27 and 51 years, died of massive disseminations of cervicothoracic GGs 4 and 6 years, respectively, after initial diagnoses; full autopsies were performed. BRAF status was assessed by VE1 immunohistochemistry (IHC), Sanger sequencing, and a single-nucleotide base extension assay (SNaPshot, Applied Biosystems, Princeton, NJ). Results: The 27-year-old underwent two biopsies, chemotherapy, radiation, and ventriculoperitoneal shunt placement; she developed craniospinal and peritoneal dissemination. Autopsy confirmed shunt-mediated peritoneal metastases, microscopic bone marrow involvement, and profuse spinal and supratentorial leptomeningeal and parenchymal spread. The 51-year-old underwent two resections, radiation, and chemotherapy and developed pancytopenia with biopsy-proven bony metastases 15 months before death. Autopsy demonstrated leptomeningeal, subpial, and subependymal metastases. The tumors in both primary and metastatic sites were BRAF negative by VE1 IHC and two different mutational analyses. This compared with negative BRAF results for an additional four nonmetastatic adult nonsupratentorial GGs and in our study. Conclusions: We document two rare cases of massively metastatic spinal cord GGs in adult patients who were negative for BRAF V600E mutations via multiple methods.
Cardiac Embryology: Its Relevance to Congenital Heart Disease

The vast majority of congenital cardiac defects are due to disordered cardiac development, yet there is surprisingly little known about the fundamental processes that form the heart. To most physicians, cardiac embryology recalls memories of confusing diagrams, serially sectioned embryos, and opaque terminology. However, in the past 15 years there has been a renewed interest in cardiac development as the tools of the developmental biologist have been used to better understand how the heart forms. The purpose of this article is to review some of the recent developments in the field of cardiac embryology and correlate this new information with the clinical experience of the cardiologists, geneticists, and epidemiologists. These developments are changing the way we are thinking about congenital cardiac disease. This is particularly important since more and more children now are surviving with congenital cardiac defects to become young adults in the reproductive age group. Traditionally, cardiac embryology
Levels of Expression of CYR61 and CTGF Are Prognostic for Tumor Progression and Survival of Individuals with Gliomas

The biological properties of CCN proteins include stimulation of cell proliferation, migration, and adhesion, as well as angiogenesis and tumorigenesis. We quantified CYR61, CTGF, WISP-1, and NOV mRNA expression levels in samples from sixty-six primary gliomas and five normal brain samples using quantitative real-time PCR assay. Statistical analysis was performed to explore the links between expression of the CCN genes and clinical and pathological parameters. Overexpression of CYR61, CTGF, WISP-1, and NOV occurred in 48% (32 of 66), 58% (38 of 66), 36% (24 of 66), and 15% (10 of 66) of primary gliomas, respectively. Interestingly, significant associations were found between CYR61 expression versus tumor grade, pathology, gender, and age at diagnosis. Also, a significant correlation existed between CTGF mRNA levels versus tumor grade, gender, and pathology. In contrast to CYR61 and CTGF, no significant association was found between expression of either WISP-1 or NOV versus any of the pathological features. Furthermore, Cox regression analysis showed that CYR61 and CTGF expression had a significant correlation with patient survival. These results suggest that CYR61 and CTGF may play a role in the progression of gliomas; their levels at diagnosis may have prognostic significance; and these proteins might serve as valuable targets for therapeutic intervention.
The Lessons of Asilomar and the H5N1 “Affair”

ABSTRACT In mid-1974, soon after the first recombinant DNA molecules were replicated in Escherichia coli, scientists called for, and observed, a voluntary moratorium on certain experiments. One goal of the moratorium was to hold a conference (Asilomar) to evaluate the risks, if any, of this new technology. The Asilomar conference concluded that recombinant DNA research should proceed but under strict guidelines. The furor surrounding the recent genetic manipulation of the transmissibility of avian influenza virus H5N1 led to a short-term moratorium that has been extended indefinitely. The question is how long should the moratorium remain in place, or should it be permanent? Voltaire observed, “History never repeats itself; man always does.” I believe the parallels of Asilomar can be applied to the problem facing biomedical science today. We should move forward to establish standardized guidelines, using common sense and scientific creativity. The onus of responsibility falls on the individual scientist and involves the education of a new generation of scientists into the social and ethical implications of genetic engineering in a new age of genomics and synthetic biology. In addition, scientists who work with infectious agents must deal not only with biosafety but also, alas, with bioterrorism. The H5N1 “affair” is not a question of freedom of inquiry or the dissemination of scientific research; it is a question of the social responsibility of science and scientists to ensure that the public understands why this work is beneficial and worthwhile.
System support for many task computing

The popularity of large scale systems such as Blue Gene has extended their reach beyond HPC into the realm of commercial computing. There is a desire in both communities to broaden the scope of these machines from tightly-coupled scientific applications running on MPI frameworks to more general-purpose workloads. Our approach deals with issues of scale by leveraging the huge number of nodes to distribute operating systems services and components across the machine, tightly coupling the operating system and the interconnects to take maximum advantage of the unique capabilities of the HPC system. We plan on provisioning nodes to provide workload execution, aggregation, and system services, and dynamically re-provisioning nodes as necessary to accommodate changes, failure, and redundancy. By incorporating aggregation as a first-class system construct, we will provide dynamic hierarchical organization and management of all system resources. In this paper, we will go into the design principles of our approach using file systems, workload distribution and system monitoring as illustrative examples. Our end goal is to provide a cohesive distributed system which can broaden the class of applications for large scale systems and also make them more approachable for a larger class of developers and end users.
Flow cytometric analysis of DNA in cells obtained from deparaffinized formalin-fixed lymphoid tissues.

Abstract Flow cytometric analysis of DNA content was performed on nuclear suspensions prepared from fresh and from paraffin-embedded, formalin-fixed lymphoid tissues. We confirmed previous reports that it is possible to obtain nuclear suspensions from deparaffinized, formalin-fixed tissues, suitable for DNA analysis by flow cytometry. We observed a tendency for a larger coefficient of variation (CV) of the DNA measurements in the fixed tissues than in the unfixed material causing abnormalities in 2 of 19 lymphomas to become undetectable. Furthermore, samples from different paraffin blocks of a single tumor with an extra G1 (hyperdiploid) peak showed marked differences in the CV of the hyperdiploid peak while the CV of the diploid peak was similar in all samples. In both benign and malignant lymphoid tissues, the S-phase fraction was higher in paraffin-embedded tissues than in unfixed cells. This difference could be attributed to 4', 6'-diamidino-2-phenylindole dihydrochloride (DAPI), a DNA-binding dye commonly used in this technique. Nevertheless, intermediate and high grade lymphomas from paraffin-embedded tissues generally showed a greater S-fraction than low grade lymphomas, a similar observation as with unfixed tissues. Therefore, DNA content analysis of nuclei extracted from paraffin sections may be inadequate to resolve slight aneuploidy, but the measurement of S-fraction size may remain diagnostically or prognostically valuable. Large retrospective studies will be necessary to determine the clinical impact of this technique in the analysis of lymphomas.
Cooling and collisions of large gas phase molecules

Cold and dense samples of naphthalene (C10H8) are produced using buffer gas cooling in combination with rapid, high flow molecule injection. The observed naphthalene density is n ≈ 1011 cm−3 over a volume of a few cm3 at a temperature of 6 K. We observe naphthalene–naphthalene collisions through two-body loss of naphthalene with a loss cross section of σ– = 1.4 × 10−14 cm2. Analysis is presented that indicates that this combination of techniques will be applicable to many comparably sized molecules. This technique can also be combined with cryogenic beam methods1 to produce cold, high flux, continuous molecular beams.
Thermal Field Distributions of Girder Bridges with GFRP Panel Deck versus Concrete Deck

Temperature effects have always been considered to be one of the critical issues that affect the performance of traditional concrete and steel bridges. Currently, glass fiber-reinforced polymer (GFRP) composite panels, with the advantages of high strength, light weight, good corrosion resistance, long-term durability, etc., have been applied to slab replacements in bridge engineering. The thermal behaviors of these GFRP bridges, however, have not been fully understood. More specifically, the current temperature design specifications in the AASHTO LRFD may no longer be valid for GFRP bridges. Therefore, this paper presents the thermal field distribution behaviors through studying an as-built bridge with GFRP sandwich panels. First, a transient-state numerical modeling method is proposed. This method is capable of predicting the temperature field of a GFRP bridge based on local environmental conditions. Then, a parametric study is conducted to analyze the thermal responses of bridges with different structure combinations (i.e., GFRP panels, concrete slabs, concrete beams, and steel girders). The mechanical and physical properties of GFRP panels are predicted using the micro-macro mechanics theory and validated by a field measurement and an experimental study. Based on the results from the present study, the temperature distribution patterns for GFRP panel bridges are proposed, referring to the available AASHTO LRFD sign code. The thermal strains and stresses caused by temperature gradients along the depth of bridge superstructures are examined.
Sucrose, High-Fructose Corn Syrup, and Fructose, Their Metabolism and Potential Health Effects: What Do We Really Know?

Both controversy and confusion exist concerning fructose, sucrose, and high-fructose corn syrup (HFCS) with respect to their metabolism and health effects. These concerns have often been fueled by speculation based on limited data or animal studies. In retrospect, recent controversies arose when a scientific commentary was published suggesting a possible unique link between HFCS consumption and obesity. Since then, a broad scientific consensus has emerged that there are no metabolic or endocrine response differences between HFCS and sucrose related to obesity or any other adverse health outcome. This equivalence is not surprising given that both of these sugars contain approximately equal amounts of fructose and glucose, contain the same number of calories, possess the same level of sweetness, and are absorbed identically through the gastrointestinal tract. Research comparing pure fructose with pure glucose, although interesting from a scientific point of view, has limited application to human nutrition given that neither is consumed to an appreciable degree in isolation in the human diet. Whether there is a link between fructose, HFCS, or sucrose and increased risk of heart disease, metabolic syndrome, or fatty infiltration of the liver or muscle remains in dispute with different studies using different methodologies arriving at different conclusions. Further randomized clinical trials are needed to resolve many of these issues. The purpose of this review is to summarize current knowledge about the metabolism, endocrine responses, and potential health effects of sucrose, HFCS, and fructose.
Ulcerative keratitis in bullous keratopathy.

Abstract Purpose: The authors review a large series of patients with bullous keratopathy (BK) to analyze the frequency of ulcerative keratitis, and determine the contributory roles of bullae, bandage soft contact lenses, steroids, and prophylactic antibiotics. Methods: A retrospective review of all cases of pseudophakic or aphakic bullous keratopathy presenting to the cornea service between January 1, 1986 and September 1, 1995 was performed. The influence of time, bullae, bandage contact lenses, steroids, and prophylactic antibiotics was evaluated by actuarial methods and multivariate analysis. Results: Nine hundred eighteen patients were included in this study, 44 (4.7%) of whom had infectious or inflammatory complications; 813 cases were available for statistical analysis. Steroids ( P P = 0.004), and bullae ( P = 0.01) had statistically significant independent effects on the risk of developing ulcerative keratitis, and the combination of steroids and bandage lenses yielded the highest risk ( P P = 0.01). Increasing BK time was also associated with ulcer development, and the risk remained relatively constant over the 60 months of the study. Streptococcus was the most frequent organism cultured. Conclusions: Ulcerative keratitis developed in 4.7% of patients with bullous keratopathy. Prolonged BK time alone was a risk factor for infection. The strongest single additional risk factor for ulcer development was steroid use, followed by bandage soft contact lens use, and their simultaneous use had the greatest effect. The presence of bullae was also a risk factor for infection, and prophylactic antibiotic use did not prevent ulcer development.
Personal and social resources and adaptation to chronic vision impairment over time.

Objectives: To examine the effect of personal (coping strategies and locus of control) and social resources (family and friendship support) on adjustment to chronic vision impairment in older adults at baseline (rehabilitation service application), 6 months, and 18 months later. Method: 313 community dwelling, English speaking older adult applicants to a vision rehabilitation agency in the northeast were interviewed in their homes following informed consent. Results: A larger portion of variability was accounted for in positive compared to negative outcomes. Greater use of acceptance coping, less use of wishfulness coping, lower endorsement of chance locus of control, and higher family support were associated with better baseline adaptation, yet these predictors had little effect on short- or long-term change in adaptation. Higher friendship support predicted increased adaptation to vision loss at both follow-up points. Friendship support was also associated with decreased depression at Time 3, and lower ...
Proposed BioRepository platform solution for the ALS research community

AbstractALS is a rare disorder whose cause and pathogenesis is largely unknown (). There is a recognized need to develop biomarkers for ALS to better understand the disease, expedite diagnosis and to facilitate therapy development. Collaboration is essential to obtain a sufficient number of samples to allow statistically meaningful studies. The availability of high quality biological specimens for research purposes requires the development of standardized methods for collection, long-term storage, retrieval and distribution of specimens. The value of biological samples to scientists and clinicians correlates with the completeness and relevance of phenotypical and clinical information associated with the samples (). While developing a secure Web-based system to manage an inventory of multi-site BioRepositories, algorithms were implemented to facilitate ad hoc parametric searches across heterogeneous data sources that contain data from clinical trials and research studies. A flexible schema for a barcode la...
Electoral Reform and Public Policy Outcomes in Thailand: The Politics of the 30-Baht Health Scheme

How do changes in electoral rules affect the nature of public policy outcomes? The current evidence supporting institutional theories that answer this question stems almost entirely from quantitative cross-country studies, the data of which contain very little within-unit variation. Indeed, while there are many country-level accounts of how changes in electoral rules affect such phenomena as the number of parties or voter turnout, there are few studies of how electoral reform affects public policy outcomes. This article contributes to this latter endeavor by providing a detailed analysis of electoral reform and the public policy process in Thailand through an examination of the 1997 electoral reforms. Specifically, the author examines four aspects of policy-making: policy formulation, policy platforms, policy content, and policy outcomes. The article finds that candidates in the pre-1997 era campaigned on broad, generic platforms; parties had no independent means of technical policy expertise; the government targeted health resources to narrow geographic areas; and health was underprovided in Thai society. Conversely, candidates in the post-1997 era relied more on a strong, detailed national health policy; parties created mechanisms to formulate health policy independently; the government allocated health resources broadly to the entire nation through the introduction of a universal health care system, and health outcomes improved. The author attributes these changes in the policy process to the 1997 electoral reform, which increased both constituency breadth (the proportion of the population to which politicians were accountable) and majoritarianism.
Modeling mechanisms with nonholonomic joints using the Boltzmann-Hamel equations

This article describes a new technique for deriving dynamic equations of motion for serial chain and tree topology mech anisms with common nonholonomic constraints. For each type of nonholonomic constraint, the Boltzmann-Hamel equations produce a concise set of dynamic equations. These equations are similar to Lagrange's equations and can be applied to mechanisms that incorporate that type of constraint. A small library of these equations can be used to efficiently analyze many different types of mechanisms.Nonholonomic constraints are usually included in a La grangian setting by adding Lagrange multipliers and then eliminating them from the final set of equations. The ap proach described in this article automatically produces a minimum set of equations of motion that do not include La grange multipliers.
Staphylococcus aureus agr and sarA Functions Are Required for Invasive Infection but Not Inflammatory Responses in the Lung

Staphylococcus aureus strains lacking agr- and sarA-dependent gene products or specific MSCRAMM (microbial surface components recognizing adhesive matrix molecules) adhesins were compared for the ability to activate inflammatory responses in the lung. The mutants were evaluated for virulence in a mouse model of pneumonia and by quantifying their ability to stimulate interleukin-8 (IL-8) and granulocyte-macrophage colony-stimulating factor (GM-CSF) expression in respiratory epithelial cells. In a neonatal mouse, only strains with intact agr and sarA loci were consistently associated with invasive, fatal pulmonary infection (P < 0.001) and sarA was specifically required to cause bacteremia (P < 0.001). The agr and/or sarA mutants were, nonetheless, fully capable of producing pneumonia and were as proficient as the wild-type strain in stimulating epithelial IL-8 expression, a polymorphonuclear leukocyte chemokine, in airway cells. In contrast, agr and especially sarA mutants induced less epithelial GM-CSF expression, and MSCRAMM mutants lacking fibronectin binding proteins or clumping factor A, a ligand for fibrinogen, were unable to stimulate epithelial GM-CSF production. The ability to induce IL-8 expression was independent of the adherence properties of intact bacteria, indicating that shed and/or secreted bacterial components activate epithelial responses. While conserved staphylococcal components such as peptidoglycan are sufficient to evoke inflammation and cause pneumonia, the agr and sarA loci of S. aureus are critical for the coordination of invasive infection of the lungs.
Biology of the Pine Webworm in Florida Slash Pine Plantations

Tetralopha robustella Zeller (Lepidoptera: Pyralidae) has 3 generations/year in young slash pine plantations in northeast Florida. First, 2nd, and 3rd instars mine needles and usually stay in the area of the mined needles. Fourth, 5th, and 6th instars share a common frass nest, sometimes with 2nd and 3rd instars, on a branch or the main bole and collect needles to take back to the frass nest where they feed. Sixth instars move to the soil, construct cocoons, and pupate. Adult moths emerge between Apr. and Oct. and lay eggs on the flat surface of the needles. Eleven parasitic species were reared from field-collected colonies during a 2-year period. Syzeuctus elegans (Cresson) was the most common hymenopteran parasite found and a Eufrontina sp. the most common dipteran parasite. Of the pine webworm colonies collected in 1972 and 1973, one or more parasites were found in 9, 17, 50, and 47% of the field colonies from 1-, 2-, 3-, and 4-year-old pines, respectively.
Identification of Large Conductance Calcium Activated Potassium Channel Accessory β4 Subunit in Rat and Mouse Bladder Smooth Muscle

Purpose: The BK (large conductance voltage and Ca2+ activated K+) channel is a key regulator of bladder smooth muscle contractility. To our knowledge in bladder smooth muscle the BK channel pore forming α subunit BKα associates in homotetramers with 4 regulatory smooth muscle specific β1 subunits. We challenged this concept in identify whether other regulatory BKβ subunits exist in mouse and rat bladder smooth muscle.Materials and Methods: We used a novel approach with single cell reverse transcriptase-polymerase chain reaction combined with immunocytochemical studies in freshly isolated mouse and rat bladder smooth muscle cells. Western blot was also performed.Results: Reverse transcriptase-polymerase chain reaction identified the mRNA expression of various BK channel subunits in freshly isolated bladder smooth muscle cells. Our data indicate that, in addition to BKα and BKβ1, neuronal specific BKβ4 is expressed in mouse and rat bladder smooth muscle cells. BKβ4 expression was also revealed by Western bl...
Smoking cessation with adolescents: a comparison of recruitment strategies.

Abstract This study compared two methods for recruiting high school students into a voluntary smoking cessation program. A person-to-person approach was compared to an approach that resembled normal school publicity procedures. Active personal recruitment produced 31 volunteers, while the normal procedures produced only one. Subsequent application of the active approach at sites where only static procedures had been used produced an additional 21 volunteers. Results suggest that active person-to-person recruitment may be an important component of a smoking cessation effort with high school students.
Some achievements and limitations of educational television

Educational television in almost all of its forms is used successfully at Purdue University. Two particular courses are described, one involving taped lectures to small classes of electrical engineering sophomores, and the other enabling two professors and two graduate classes to meet simultaneously at locations 100 miles apart. Although the use of television has improved many aspects of these courses, limitations in the receivers prevent optimum performance. The video and audio quality of the receivers is discussed, and suggestions are made for an improved unit. Disadvantages in the external design of the receivers are in-d icated, and the current status of talk-back systems is described.
PHOTOFRIN-mediated photodynamic therapy for treatment of early stage oral cavity and laryngeal malignancies.

Background and Objective: To determine the efficacy of PHOTOFRIN-mediated photodynamic therapy (PDT) for treatment of diffuse field cancerization of the oral cavity and Cis-T2N0M0 squamous cell carcinoma (SqCCa) of the larynx in patients not amenable or that have failed conventional head and neck treatment. Study Design/Materials and Methods: Over the past 15 years 10 patients with early stage Tis-T2N0M0 SqCCa of the oral cavity and oropharynx and 10 patients with Tis-T2N0M0 SqCCa of the larynx were treated. Intravenous PHOTOFRIN (porfimer sodium) (dose 2.0 mg/kg) was administered outpatient, followed 48-60 hours later by intraoperative light photoactivation at 630 nm via fiber-optic microlens (ML) delivery (surgical light dose, 50-100 J/cm 2 ) and/or cylindrical diffuser (CD) delivery (80-100 J/cm). Results: Complete responses (CRs) (follow up 6 months-9 years) were achieved in eight of 10 patients with diffuse field cancerization of the oral cavity. CRs (follow up 6 months-8 years) were achieved in eight of 10 patients with superficial laryngeal cancer obviating the need for total laryngectomy in previously treated radiation therapy patients. Conclusion: PHOTOFRIN-mediated PDT provides a surgical oncologic modality for potentially curative treatment of early stage oral cavity and laryngeal malignancies with minimal side effects, absence of systemic toxicity, preservation of oral function and voice quality, with multiple drug administration, and laser light retreatment capability.
Arterial and Venous Vessel Patterns in Rat Septal Structures

Previous studies of the rat cerebral vasculature were directed in large part towards investigation of the circle of Willis and regional distributions of the major cerebral vessels. Green (8) identified the three major cerebral arteries and illustrated the superficial veins. The developing arteries were investigated by Moffat (10,11,12) and patterns of variation in the circle of Willis were studied by Brown (1). Accounts of some smaller arterial branches including the choroidal arteries were given in Craigie’s Neuroanatomy of the Rat (17) and by Moffat (12). Capillary densities for different strata in the hippocampus and fascia dentata were reported by Craigie (3,4,5). The rat subfornical artery, a branch of the anterior cerebral artery, was described by Spoerri (14). Accounts of vessel patterns in rat septal structures were not found in the English literature. No information was located on distributions of septal venous vessels for this commonly utilized laboratory animal. The current study was undertaken to identify and chart the course of vessels supplying and draining septal structures. Hopefully, the data can be applied to improve experimental approaches in investigating septal structures and provide background material for interpretation of findings following procedures which could lead to vascular insults.
The Legitimization of Paltry Contributions as a Compliance-Gaining Technique: A Meta-Analysis Testing Three Explanations:

The legitimization of paltry contributions (LPC) has been shown to be an effective compliance-gaining technique across a variety of empirical investigations. However, the theoretical explanations regarding the effectiveness of the tactic and the effects of LPC messages on donation amounts warrant further consideration. A meta-analytic review of LPC research was conducted to examine these issues. Consistent with a prior meta-analysis, LPC messages increased compliance rates (r = .22, k = 34, n = 3,181) relative to control conditions. Three moderators were also tested. The results indicated that impression management concerns and perceptions of requestor need explained the effects of LPC messages on compliance rates. A second analysis (r = −.23, k = 11, n = 1,531) offered evidence that LPC messages led to smaller mean donation amounts. A third analysis showed that LPC messages produced similar donation totals relative to control messages.
Time-Encoded Imagers.

This report provides a short overview of the DNN R&D funded project, Time-Encoded Imagers. The project began in FY11 and concluded in FY14. The Project Description below provides the overall motivation and objectives for the project as well as a summary of programmatic direction. It is followed by a short description of each task and the resulting deliverables.
Winter Survival in Arizona of Thurberia Weevils Released from Thurberia Bolls

Anthonomus grandis thurbelriae Pierce, released from hibernation cells in bolls of wild cotton, Gossypium thurberi Todaro, in December and February survived until late June and July. Longevity of released weevils increased when moisture was made available. However, a large percentage of weevils remaining in hibernation cells were still alive when all released weevils had died. In laboratory tests, released weevils readily moved to moist niches.
An ethnohistorical consideration of the role of Antilocapra americana in the lives of indiginous peoples and American pioneers.

American pronghorn, Antilocapra americana, have been known to Euro-Americans for over 450 years. The species importance as a food source has varied over time and from region to region over western North America. Both Native Americans and Euro-American pioneers relied upon pronghorn for food to varying degrees, but only Euro-Americans hunted pronghorn for sport. Sport hunting together with changed environmental conditions and land-use practices nearly resulted in the extinction of pronghorn. Finally, the developing conservation ethos and subsequent game management regulations stemmed the slaughter of pronghorn in the early twentieth century.
Factors associated with placement of rural primary care physicians in North Carolina.

Objectives The objective of this study was to determine what factors influence primary care physicians to choose rural practice locations to better develop the rural workforce in North Carolina. To better recruit and retain physicians, residents, and medical students for rural practice, we must understand what factors positively influence their choice of practice location. Methods A survey was sent to all primary care physicians licensed in the state of North Carolina (N = 2829), with 975 usable (return rate 34.5%). Results were analyzed using basic descriptive statistics and χ(2) automatic interaction detection analysis. Results Findings indicated that solo practice, critical access hospital, community health center, or federally qualified health center sites were strongly associated with rural practice. Pay as a factor in choosing a work site, financial support from a hospital, and medical school loan repayment also was correlated with rural practice. Seventy-two percent of rural physicians reported being raised in a town of ≤11,000, which was found to be highly associated with working in a rural area. This single point is highly indicative of rural practice and by defining this new level it roughly doubles the predictive value previously defined by other researchers. Conclusions Incentives such as loan repayment, salary guarantees, and practice assistance for rural physicians currently provided under several federal and state programs should continue to assist in attracting primary care physicians to rural areas. Having been raised in an area of ≤11,000 was highly predictive of future rural medical practice and could be used in the recruitment of physicians and residents to increase the ultimate yield for rural areas. With these new data, North Carolina medical schools and practices serving rural areas may be able to better recruit and retain physicians with a predilection to rural practice.
Monogenic Autoinflammatory Diseases

Defects in the immune system that result in spontaneous inflammation are termed autoinflammatory disorders. In contrast to autoimmune diseases, they are not mediated by autoantibodies or autoreactive lymphocytes. Prominent features include fevers and rash, although other symptoms are observed. Flares are typically episodic and vary in severity, but do not worsen over time as in autoimmune disorders. Recent improvements in genetic technologies have led to the characterisation of multiple autoinflammatory syndromes. Prior to understanding the underlying mechanisms, these were treated with systemic anti-inflammatory medications such as NSAIDs or glucocorticoids, which have adverse side effects. Advances in understanding the underlying etiologies have led to the discovery of novel options for targeted treatments. Key Concepts Autoinflammatory syndromes are characterised by fevers, rash, arthritis, myalgias and various other symptoms, although each syndrome may not present with all of these. Autoinflammatory syndromes are related to the innate arm rather than the adaptive arm of the immune system. The autoinflammatory syndromes typically first present in childhood. The inflammasome and interleukin 1 (IL-1) are key mediators in many autoinflammatory syndromes. Genetic testing provides a definitive diagnosis of the underlying etiology of autoinflammatory syndromes. Understanding the various pathways of autoinflammatory syndromes provides multiple targets of novel treatment modalities. Keywords: autoinflammatory; periodic fever; fever syndrome; interleukin-1; tumour necrosis factor; inflammasome
An Anti-Phosphatidylserine (PS) Antibody, Tarvacin™ That Targets Tumor Blood Vessels Does Not Affect Platelet Function In Vitro.

Abstract Tarvacin™ is a chimeric anti-PS antibody that is currently in Phase I clinical trials in cancer patients. It acts by targeting PS that becomes exposed on vascular endothelium in tumors in response to oxidative stress in the tumor microenvironment. Tarvacin™ recognizes a complex of PS and the PS-binding protein, β2 glycoprotein I. Host leukocytes are induced to bind to the complex in tumor vessels and destroy tumor vessels by antibody-dependent cellular cytotoxity. However, antibodies directed against PS-associated proteins are also known to elicit anti-phospholipid syndromes (APS). Anti-PS antibodies possibly cause APS by displacing anticoagulant proteins from PS on activated cell or by enhancing the binding of prothrombin; another explanation might be a direct activation of endothelial cells and platelets. The aim of the study was to determine whether Tarvacin ™ induces or interferes with platelet activation caused by ADP, collagen type I or calcimycin in vitro. Blood was drawn from 3 healthy volunteers, aged 31–54, who have not taken any antiplatelet medication for 14 days prior to the study. Dual channel whole blood aggregometer (Chronolog, Havertown, PA, USA) was employed for platelet aggregation studies in whole blood (WB/impedance method) and platelet rich plasma (PRP/optical method). Platelet count in PRP was adjusted to 200 K/μL. Platelet agonists (PS exposure triggers) used in the experiments were as follows: collagen (0.5, 1, 2 μg/mL), ADP (1.25, 2.5, 5, 10 μM), Calcimycin (10, 20, 30 μM) and Calcium ions (1, 2 mmol/L). Tarvacin™ was provided by Peregrine Pharmaceuticals Inc, Tustin, CA. The Anti-CD 20 antibody, Rituxan ™ and physiologic saline were used as controls. Specimens (WB diluted with saline in 1:1 ratio or PRP) with the addition of Tarvacin™ (100 μg/mL) or Rituxan ™ (100 μg/mL) or saline were first incubated on a gentle mixer for 10 minutes; incubation was then continued at 37 ° in the aggregometer well for another 5 minutes. Agonist-induced platelet aggregation was subsequently examined. Platelet aggregation studies in both WB and PRP showed that Tarvacin™ neither induced platelet activation, nor inhibited platelet activation in response to ADP, collagen or calcimycin in vitro. In conclusion, Tarvacin™ does not affect platelet function in the present in vitro assays. Possibly, the epitope on the PS -β2 glycoprotein I complex does not orientate the antibody in a manner that interferes with platelet activation. Alternatively, activated endothelial cells or other factors may be critical to support platelet activation.
How do kidney cells adapt to survive in hypertonic inner medulla

The hypertonic inner medulla poses challenges to the cells that inhabit this area of the nephron. We employed discovery tools including proteomics and genomics to identify proteins that subserve the adaptive response. The γ subunit of the Na/K-ATPase is critical to the survival of cells in hypertonic conditions, as silencing it increases osmosensitvity, and overexpression increases osmotolerance. The inner medullary collecting duct (IMCD) has high transepithelial resistance (TER). Proteins responsible for tight junction integrity are upregulated in hypertonic states. Multi PDZ protein 1 (MUPP1), a PDZ scaffolding protein, targets Claudin 4 to the tight junction. The silencing of either of these proteins decreases TER and renders the epithelium leaky. The accumulation of inert osmolytes is integral to the adaptive response. The genes involved are regulated by the transcription factor Tonicity Enhancer Binding Protein. An osmoregulated nuclear protein Nup88 is critical to the retention of this transcription factor in the nucleus and to the generation of the osmolytes. In summary, IMCD cells bring forth a coordinated response to hypertoncity that is necessary for cell survival and function of these cells in anisotonic conditions.
Optimisation of Intestinal Fibrosis and Survival in the Mouse S. Typhimurium Model for Anti-fibrotic Drug Discovery and Preclinical Applications.

Background and aims Intestinal fibrosis is a frequent complication in Crohn's disease [CD]. The mouse Salmonella typhimurium model, due to its simplicity, reproducibility, manipulability, and penetrance, is an established fibrosis model for drug discovery and preclinical trials. However, the severity of fibrosis and mortality are host- and bacterial strain-dependent, thus limiting the original model. We re-evaluated the S. typhimurium model to optimise fibrosis and survival, using commercially available mouse strains. Methods Fibrotic and inflammatory markers were evaluated across S. typhimurium ΔaroA:C57bl/6 studies performed in our laboratory. A model optimisation study was performed using three commercially available mouse strains [CBA/J, DBA/J, and 129S1/SvImJ] infected with either SL1344 or ΔaroA S. typhimurium. Fibrotic penetrance was determined by histopathology, gene expression, and αSMA protein expression. Fibrosis severity, penetrance, and survival were analysed across subsequent CBA studies. Results Fibrosis severity and survival are both host- and bacterial strain-dependent. Marked tissue fibrosis and 100% survival occurred in the CBA/J strain infected with SL1344. Subsequent experiments demonstrated that CBA/J mice develop extensive intestinal fibrosis, characterised by transmural tissue fibrosis, a Th1/Th17 cytokine response, and induction of pro-fibrotic genes and extracellular matrix proteins. A meta-analysis of subsequent SL1344:CBA/J studies demonstrated that intestinal fibrosis is consistent and highly penetrant across histological, protein, and gene expression markers. As proof-of-concept, we tested the utility of the SL1344:CBA/J fibrosis model to evaluate efficacy of CCG-203971, a novel anti-fibrotic drug. Conclusion The S. typhimurium SL1344:CBA/J model is an optimised model for the study of intestinal fibrosis.
Enthymematic Elasticity in the Biomedical Backstage

To investigate the rhetorical underpinnings of medical evidence’s argumentative authority, this chapter examines the persuasive power of topological structures in case studies of cancer care. Findings suggest that the practice of mobilizing evidence in the biomedical backstage consistently involves enthymematic elasticity: that is, oncologists perform medical expertise by “tacking back-and-forth” between statistically standardized medical evidence and individual patients’ unique embodied experiences. Enthymematic elasticity is a productive topological tactic for mitigating uncertainty, making decisions, and maintaining medical expertise. Two insights for rhetorical theory and medical practice may be gleaned from this study: namely, rhetoricians may evaluate medical practice by assessing the degree to which it remains committed to enthymematic elasticity; and, future research might gainfully explore methods for marshaling evidence that resists quantification (e.g., patient-reported outcomes).