Search

Spray rolling combines spray forming with twin-roll casting to process metal flat products. It consists of atomizing molten metal with a high velocity inert gas, cooling the resultant droplets in flight and directing the spray between mill rolls. In-flight convection heat transfer from atomized droplets teams with conductive cooling at the rolls to rapidly remove the alloy’s latent heat. Hot deformation of the semi-solid material in the rolls results in fully consolidated, rapidly solidified product. While similar in some ways to twin-roll casting, spray rolling has the advantage of being able to process alloys with broad freezing ranges at high production rates. This paper describes the process and summarizes microstructure and tensile properties of spray-rolled 2124 and 7050 aluminum alloy strips. A Lagrangian/Eulerian poly-dispersed spray flight and deposition model is described that provides some insight into the development of the spray rolling process. This spray model follows droplets during flight toward the rolls, through impact and spreading, and includes oxide film formation and breakup when relevant.

GABAergic signaling in the CNS is terminated in part through uptake of GABA by GABA transporters. We used the yeast two-hybrid system to identify proteins that associate with the carboxy-terminus of the neuronal GABA transporter GAT1. We found an interaction between GAT1 and the MAGUK protein Pals1. When coexpressed in COS-7 cells, Pals1 co-immunoprecipitates with GAT1. We demonstrate cellular coexpression of GAT1 and Pals1 in the mouse hippocampus and striatum. Functionally, coexpression of GAT1 and Pals1 in COS-7 cells increases [3H]-GABA uptake by GAT1. The mechanism underlying increased uptake is increased levels of GAT1 protein. We hypothesize that Pals1 contributes to the stability of the GAT1, thus promoting the expression level of the transporter protein. In the CNS, Pals1 may stabilize GAT1 at appropriate levels in specific GABAergic neurons.

We wrote a program that runs as a Microsoft Excel spreadsheet to calculate the diffusion of Ca2+in a spherical cell in the presence of a fixed Ca2+buffer and two diffusible Ca2+buffers, one of which is considered to be a fluorescent Ca2+indicator. We modeled Ca2+diffusion during and after Ca2+influx across the plasma membrane with parameters chosen to approximate amphibian sympathetic neurons, mammalian adrenal chromaffin cells, and rat dorsal root ganglion neurons. In each of these cell types, the model predicts that spatially averaged intracellular Ca2+activity ([Ca2+]avg) rises to a high peak and starts to decline promptly on the termination of Ca2+influx. We compared [Ca2+]avgwith predictions of ratiometric Ca2+measurements analyzed in two ways. Method 1 sums the fluorescence at each of the two excitation or emission wavelengths over the N compartments of the model, calculates the ratio of the summed signals, and converts this ratio to Ca2+([Ca2+]avg,M1). Method 2 sums the measured number of moles of Ca2+in each of the N compartments and divides by the volume of the cell ([Ca2+]avg,M2). [Ca2+]avg,M1peaks well after the termination of Ca2+influx at a value substantially less than [Ca2+]avgbecause the summed signals do not reflect the averaged free Ca2+if the signals come from compartments containing gradients in free Ca2+spanning nonlinear regions of the relationship between free Ca2+and the fluorescence signals. In contrast, [Ca2+]avg,M2follows [Ca2+]avgclosely.

The first purpose of this article is to examine general signaling transduction processes that become deranged in diabetes and the means by which they damage cells. However, among the cells that can be damaged by diabetes, the primary sensory neurons, also known as dorsal root ganglion (DRG) neurons, are uniquely sensitive. Damage to these cells results in diabetic peripheral neuropathy (DPN), one of the costliest and most common diabetic complications. Therefore, the second purpose of this article is to focus attention on factors that make these cells particularly vulnerable to hyperglycemic damage. Some clinical inferences are drawn from these considerations. Finally, limitations in our knowledge about the effects of diabetes on signaling in DRG neurons are illustrated in an overview of the basic research literature.

OBJECTIVES: To compare 2 days of antibiotic therapy (AT) to 4 days of AT in neonates with pneumonia and to assess the usefulness of neutrophil values (NV), C-reactive protein (CRP), and procalcitonin (PCT) in this population. DESIGN:The study population consisted of consecutive, eligible term neonates begun on AT for suspected pneumonia. Of 51 neonates, 26 qualified for randomization (14, 2-day group; 12, 4-day group). NV were obtained with the initial evaluation and 12 and 24 hours later. CRP and PCT were obtained 12 and 48 hours after the initial evaluation. RESULTS: None of the 12 neonates in the 4-day group developed recurrent respiratory symptoms. Three of the 14 neonates randomized to the 2-day group had recurrence of symptoms, resulting in study termination. NV, CRP, and PCT were similar in the 2- and 4-day groups. In the three neonates who developed respiratory symptoms, all absolute total neutrophil values and five out of nine absolute total immature neutrophil values were abnormal. However, all immature:total neutrophil values were normal, and CRP was strikingly elevated in only one neonate; only one of six PCT values was abnormal. In a secondary analysis of all 51 study neonates, CRP and PCT did not provide additional benefit over NV in differentiating neonates with pneumonia. CONCLUSIONS:Four days of AT appears to be adequate for selected term neonates with pneumonia; however, 2 days of AT appears to be inadequate for this population. Relative to NV, CRP and PCT appear to have a limited role.

Groupware or collaborative systems allow a team to interact in a shared workspace despite geographical separation or diverse schedules. Current collaborative integrated manufacturing systems tend to focus on the design stage of the development process. However, design is only one stage of standard frameworks for problem-solving-based development, which typically include a more comprehensive set of stages from problem formulation, planning and design to testing and deployment. Problem solving methodologies and tools, originally developed for single-user environments, can be extended to multi-user collaborative problem solving models and systems. This paper considers the characteristics of existing collaborative systems in manufacturing and then proposes a methodology-based, object-oriented view of the structure of such systems, which also addresses such factors as the effect of distributed cognition and social protocols. We then show that existing research on both individual and collaborative problem solvi...

BACKGROUND: There is little research on overall cardiovascular (CV) health among couples. Our aim was to examine concordance levels for CV health among couples, using the American Heart Association ideal health metrics, and to investigate if the CV health of an individual is associated with that of his or her partner. HYPOTHESIS: There is a positive association between the overall cardiovascular health of an individual and that of his/her partner. METHODS: The Mitchelstown Study is a community‐based cohort study of middle‐aged Irish adults. Potential couples were identified as 2 study participants living at the same address. This list was cross‐referenced with self‐reported marital status and telephone number in the electronic patient record. Information on CV health metrics (smoking, body mass index, physical activity, diet, blood pressure, cholesterol, and glucose) was collected using standardized methods. Participants were categorized as ideal, intermediate, or poor for each of the metrics and for overall CV health. The 0‐ to 14‐point CV health metrics score was compared within couples using linear regression. RESULTS: Of 2047 participants, 191 potential couples were identified. We excluded 6 sibling pairs, 1 divorced couple, and 3 couples who self‐reported being single. The analysis includes 181 couples. There were significant associations between partners for smoking, diet, blood pressure, cholesterol, and glucose (P < 0.05). No couple had ideal CV health (ie, both partners with 7 ideal metrics). Most couples (n = 127, 69%) were concordant for poor CV health. There was a significant relationship between partners for the CV health metrics score (P < 0.05). CONCLUSIONS: Our results suggest an individual's CV health is associated with that of his or her partner. Therefore, prevention strategies targeting couples and families may be appropriate.

The brain-derived neurotropic factor (BDNF) Val66Met polymorphism has been associated with abnormalities of synaptic plasticity in animal models, and abnormalities in motor cortical plasticity have also been described in humans using transcranial direct current stimulation. No study has yet been done on plasticity in non-motor regions, and the effect of two Met alleles (i.e. ‘Met dose’) is not well understood. We studied the effect of the BDNF Val66Met polymorphism on the after-effects of transcranial direct current stimulation and tetanic auditory stimulation in 65 subjects (23; Val66Val, 22; Val66Met and 20; Met66Met genotypes). In the first session, motor evoked potentials (MEP) were recorded under stereotaxic guidance for 90 min after 9 min of anodal transcranial direct current stimulation (TDCS). In the second session, auditory-evoked potentials (AEP) were recorded before and after 2 min of auditory 13 Hz tetanic stimulation. There was a difference in MEP facilitation post-TDCS comparing Met carriers with non-Met carriers, with Met carriers having a modest late facilitation at 30–90 min. There was no difference in responses between Val66Met genotype and Met66Met genotype subjects. Tetanic auditory stimulation also produced late facilitation of N1-P2 AEP at 25 min, but there was no apparent effect of genetic status. This study indicates that Met66Met carriers behave like Val66Met carriers for TDCS-induced plasticity, and produce a late facilitation of MEPs. Auditory cortical plasticity was not affected by the BDNF Val66Met polymorphism. This study sheds light on the differences between auditory and motor cortical plasticity and the role of the BDNF Val66Met polymorphism.

The malignant potential of smooth muscle tumors correlates strongly with the disappearance of gamma-smooth muscle isoactin, a lineage-specific marker of smooth muscle development. In this paper, we identify a 36-base pair regulatory motif containing an AT-rich domain, CArG box, and a non-canonical NK-2 homeodomain-binding site that has the capacity to regulate smooth muscle-specific gene expression in cultured intestinal smooth muscle cells. Serum-response factor associates with an NK-2 transcription factor via protein-protein interactions and binds to the core CArG box element. Our studies suggest that the NK-2 transcription factor that associates with serum-response factor during smooth muscle differentiation is Nkx2-3. Myocyte-specific enhancer factor 2 binding to this regulatory complex was also observed but limited to uterine smooth muscle tissues. Smooth muscle neoplasms displayed altered transcription factor binding when compared with normal myometrium. Differential nuclear accessibility of serum-response factor protein during smooth muscle differentiation and neoplastic transformation was also observed. Thus, we have identified a unique regulatory complex whose differential binding properties and nuclear accessibility are associated with modulating gamma-smooth muscle isoactin-specific gene expression in both normal and neoplastic tissues.

This study examined the cellular response to DNA damage induced by antitumor enediynes C-1027 and neocarzinostatin. Treatment of cells with either agent induced hyperphosphorylation of RPA32, the middle subunit of replication protein A, and increased nuclear retention of RPA. Nearly all of the RPA32 that was not readily extractable from the nucleus was hyperphosphorylated, compared toor =50% of the soluble RPA. Enediyne concentrations that induced RPA32 hyperphosphorylation also decreased cell-free SV40 DNA replication competence in extracts of treated cells. This decrease did not result from damage to the DNA template, indicating trans-acting inhibition of DNA replication. Enediyne-induced RPA hyperphosphorylation was unaffected by the replication elongation inhibitor aphidicolin, suggesting that the cellular response to enediyne DNA damage was not dependent on elongation of replicating DNA. Neither recovery of replication competence nor reversal of RPA effects occurred when treated cells were further incubated in the absence of drug. C-1027 and neocarzinostatin doses that caused similar levels of DNA damage resulted in equivalent increases in RPA32 hyperphosphorylation and RPA nuclear retention and decreases in replication activity, suggesting a common response to enediyne-induced DNA damage. By contrast, DNA damage induced by C-1027 was at least 5-fold more cytotoxic than that induced by neocarzinostatin.

Pleural tuberculosis (TB) was employed as a model to study T cell apoptosis at sites of active Mycobacterium tuberculosis (MTB) infection in human immunodeficiency virus (HIV)-coinfected (HIV/TB) patients and patients infected with TB alone. Apoptosis in blood and in pleural fluid mononuclear cells and cytokine immunoreactivities in plasma and in pleural fluid were evaluated. T cells were expanded at the site of MTB infection, irrespective of HIV status. Apoptosis of CD4 and non-CD4 T cells in the pleural space occurred in both HIV/TB and TB. Interferon (IFN)-gamma levels were increased in pleural fluid, compared with plasma. Spontaneous apoptosis correlated with specific loss of MTB-reactive, IFN-gamma-producing pleural T cells. Immunoreactivities of molecules potentially involved in apoptosis, such as tumor necrosis factor-alpha, Fas-ligand, and Fas, were increased in pleural fluid, compared with plasma. These data suggest that continued exposure of immunoreactive cells to MTB at sites of infection may initiate a vicious cycle in which immune activation and loss of antigen-responsive T cells occur concomitantly, thus favoring persistence of MTB infection.

Stability of cladding materials under off-normal conditions is an important issue for the safe operation of light water nuclear reactors. Metals, ceramics, and metal/ceramic composites are being investigated as substitutes for traditional zirconium-based cladding. To support down-selection of these advanced materials and designs, a test apparatus was constructed to study the onset and evolution of cladding oxidation, and deformation behavior of cladding materials, under loss-of-coolant accident scenarios. Preliminary oxidation tests were conducted in dry oxygen and in saturated steam/air environments at 1000OC. Tube samples of Zr-702, Zr-702 reinforced with 1 ply of a s-SiC CMC overbraid, and sintered a-SiC were tested. Samples were induction heated by coupling to a molybdenum susceptor inside the tubes. The deformation behavior of He-pressurized tubes of Zr-702 and SiC CMC-reinforced Zr-702, heated to rupture, was also examined.

In 1929, Drury and Szent-Gyorgyi described the effects of a simple extract of heart muscle and other tissues on the mammalian heart. This extract was identified as adenylic acid and found to have profound effects on the cardiovascular system. The discovery and identification of adenyl purines and their effects on the cardiovascular system has now extended to other biological functions such as neurotransmission, neuromodulation, and endocrine/exocrine secretory functions and beyond. This review examines the history of the discovery and identification of the many roles played by adenyl purines in regulation of physiological homeostasis.

This paper discusses methodology and technology to aid students learning programming. We have identified and integrated the problem solving and program development skills and knowledge students need to apply when programming with the cognitive activities required to accomplish these tasks. We then developed a composite methodological/software environment that supports the overall process of programming in a manner that gives appropriate weight to both language issues and problem solving. The results of a classroom evaluation of the method and the tool are then presented.

The cyclopropylpyrroloindole anti-cancer drug, adozelesin, binds to and alkylates DNA. Treatment of human cells with low levels of adozelesin results in potent inhibition of both cellular and simian virus 40 (SV40) DNA replication. Extracts were prepared from adozelesin-treated cells and shown to be deficient in their ability to support SV40 DNA replication in vitro. This effect on in vitro DNA replication was dependent on both the concentration of adozelesin used and the time of treatment but was not due to the presence of adozelesin in the in vitro assay. Adozelesin treatment of cells was shown to result in the following: induction of p53 protein levels, hyperphosphorylation of replication protein A (RPA), and disruption of the p53-RPA complex (but not disruption of the RPA-cdc2 complex), indicating that adozelesin treatment triggers cellular DNA damage response pathways. Interestingly, in vitro DNA replication could be rescued in extracts from adozelesin-treated cells by the addition of exogenous RPA. Therefore, whereas adozelesin and other anti-cancer therapeutics trigger common DNA damage response markers, adozelesin causes DNA replication arrest through a unique mechanism. The S phase checkpoint response triggered by adozelesin acts by inactivating RPA in some function essential for SV40 DNA replication.

The purpose of this paper is to report the longitudinal experience with deaths in a United States' newborn intensive care unit. Retrospective analysis comparing infant deaths in two epochs: Epoch 1: 1985-1988 (n = 127) and Epoch 2: 1991-1994 (n = 75). Data included demographic factors, age at death, episodes of cardiopulmonary resuscitation, do not resuscitate status, and whether withdrawal of support occurred. Infants in Epoch 2 were significantly younger at birth (28.7 +/- 0.7 vs. 30.6 +/- 0.5 wks', p = 0.02) and death (31.5 +/- 0.9 vs. 34.0 +/- 0.7 wks', p = 0.02) than those in Epoch 1. There was no difference in length of stay (19.5 +/- 5.1 vs. 24.4 +/- 4.2 days, Epoch 2 vs. Epoch 1). Infants were more likely to receive cardiopulmonary resuscitation in Epoch 2 than Epoch 1 (60 vs. 41%, p = 0.008). However, more infants in Epoch 2 also had do not resuscitate status (80% vs. 59%, p = 0.002) or withdrawal of support (72% vs. 52%, p = 0.005). The majority of newborn intensive care deaths currently occur with do not resuscitate status and/or withdrawal of support.

We report an extraction-free assay in which the same slot blot membrane can be used to assess total genomic DNA damage (i.e., crosslinks or strand breaks) and DNA replication (i.e., bromodeoxyuridine incorporation) or protein levels (i.e., γ-H2AX). 14C-thymidine radiolabeling of HCT116 cells loaded directly on a Hybond N+ membrane slot blot enables the quantitation of DNA interstrand crosslinks and DNA breaks, while bromodeoxyuridine incorporation or levels of γ-H2AX can be assessed by incubating blots with primary monoclonal antibodies followed by detection with horseradish peroxidase (HRP) secondary antibodies. Uniform Ponceau staining of all samples on the membrane indicates that protein binding to the membrane is independent of DNA damage or elution. The use of a single membrane to assay levels of DNA damage and concomitant changes in damage response proteins or replication allows the direct quantitation of diverse parameters under identical conditions.

To investigate the rate of undiagnosed rheumatologic diseases and hepatitis C infection among patients with the clinical diagnosis of Mooren ulcer seen at Aravind Eye Hospital, Madurai, South India.Twenty-one patients with the clinical diagnosis of Mooren ulcer and 44 control patients underwent a complete ophthalmic history and examination, as well as serologic testing for antinuclear antibodies, rheumatoid factor, antineutrophil cytoplasmic antibodies, herpes simplex virus 1 antibodies, and hepatitis C virus antibodies.There were no statistically significant differences in the rates of seropositivity for antinuclear antibodies, rheumatoid factor, antineutrophil cytoplasmic antibodies, herpes simplex virus 1 antibodies, and hepatitis C virus antibodies between patients with Mooren ulcer and control patients. Two patients with Mooren ulcer and four control patients were found to have a rheumatoid factor titer of greater than 1:20. One of the control patients, but none of the patients with Mooren ulcer, was found to have serologic evidence of hepatitis C infection. A history of corneal trauma, surgery, or infection was reported by 68% of patients with Mooren ulcer, compared with 20% of control patients (P.001). Among patients with Mooren ulcer, bilateral disease occurred in 37% of patients, visual acuity was reduced to light perception in 15% of eyes, and perforation occurred in 19% of eyes.Nineteen (90%) of 21 patients with the clinical diagnosis of Mooren ulcer were found to have no evidence of an underlying rheumatologic disease by history, examination, or serologic testing, and none was seropositive for hepatitis C. However, patients with Mooren ulcer were more likely than control patients to report a history of corneal trauma, surgery, or infection.

Bizelesin, a bifunctional DNA minor groove alkylating agent, inhibits both cellular and viral (SV40) DNA replication in whole cells. Bizelesin inhibition of SV40 DNA replication was analyzed in SV40-infected cells, using two-dimensional (2D) neutral agarose gel electrophoresis, and in a cell-free SV40 DNA replication assay. Within 1 h of bizelesin addition to infected cells, a similar rapid decrease in both the level of SV40 replication intermediates and replication activity was observed, indicating inhibition of initiation of SV40 DNA replication. However, prolonged bizelesin treatment (>/=2 h) was associated with a reduced extent of elongation of SV40 replicons, as well as the appearance on 2D gels of intense spots, suggestive of replication pause sites. Inhibition of elongation and induction of replication pause sites may result from the formation of bizelesin covalent bonds on replicating SV40 molecules. The level of in vitro replication of SV40 DNA also was reduced when extracts from bizelesin-treated HeLa cells were used. This effect was not dependent upon the formation of bizelesin covalent bonds with the template DNA. Mixing experiments, using extracts from control and bizelesin-treated cells, indicated that reduced DNA replication competence was due to the presence of a trans-acting DNA replication inhibitor, rather than to decreased levels or inactivation of essential replication factor(s).

Objective : Using a clinical electromyographic (EMG) protocol, motor units were sampled from the quadriceps femoris during isometric contractions at fixed force levels to examine how average motor unit size and firing rate relate to force generation. Methods : Mean firing rates (mFRs) and sizes (mean surface-detected motor unit action potential (mS-MUAP) area) of samples of active motor units were assessed at various force levels in 79 subjects. Results : MS-MUAP size increased linearly with increased force generation, while mFR remained relatively constant up to 30% of a maximal force and increased appreciably only at higher force levels. A relationship was found between muscle force and mS-MUAP area ( r 2 =0.67), mFR ( r 2 =0.38), and the product of mS-MUAP area and mFR (mS-MUAP·mFR) ( r 2 =0.70). Conclusions : The results support the hypothesis that motor units are recruited in an orderly manner during forceful contractions, and that in large muscles only at higher levels of contraction (>30% MVC) do mFRs increase appreciably. MS-MUAP and mFR can be assessed using clinical EMG techniques and they may provide a physiological basis for analyzing the role of motor units during muscle force generation.

We present a domain-specific problem solving model to facilitate the study of programming. Specifically, we address how problem solving and programming can be closely integrated and taught to beginning students and what are the necessary knowledge and skills to enhance students' ability to become effective problem solvers and programmers. To accomplish this, we synthesized a common model for problem solving, based on a review of existing methodologies, that integrates the tasks of program development, and elaborates the required cognitive knowledge and skills. The common model explicitly encourages students to adhere to a well-specified six-stage process of formulating the problem, planning, designing, translating, testing, and delivering the solution.

Inflammation of the human intestine causesthickening of the smooth muscle layers, and studies inrats infected with Trichinella spiralis (Tsp) have shownhyperplasia of the intestinal smooth muscle cells (ISMC). We have shown that Tsp-inducedinflammation caused a fivefold increase in total proteinper ISMC over control, while ISMC from the noninflameddistal ileum also showed a threefold increase. The amount of α-smooth muscle (SM) actin perISMC increased nearly 500% over control by postinfection(PI) day 6. The proportion of α-SM actin in thetotal cellular protein increased 200% by day 6 PI, indicating a higher density of α-SM actinin the hypertrophied ISMC. γ-SM actin mRNAincreased sharply and was matched by an increasedfractional content of γ-SM actin protein. Theseincreases in the smooth muscle-specific actins may affectforce production and further demonstrate the plasticityof smooth muscle in the inflamed intestine.

Background & Aims: Cultured gastrointestinal smooth muscle cells have been shown to dedifferentiate and reinitiate their myogenic program in vitro. The aim of this study was to determine whether the cellular phenotypes observed in vitro were similar to those previously characterized in vivo. Methods: Differential isoactin expression was examined in primary cultures of intestinal smooth muscle cells (ISMCs) by Northern blot and immunohistochemical analysis. Cellular phenotype was determined for cultured ISMCs grown at high density, at low density, in the presence and absence of serum supplementation, and on several distinct substrates including collagen type IV, laminin, fibronectin, and plastic. Results: The unique patterns of isoactin protein and gene expression observed in cultured ISMCs indicate that distinct cellular phenotypes were present in vitro. The production and maintenance of these distinct smooth muscle cell phenotypes was dependent on cell density, serum supplementation, and substrate used. Conclusions: Cultured ISMCs appear to recapitulate a portion of their in vivo myogenic program in vitro, providing a unique opportunity for the molecular mechanisms controlling gastrointestinal smooth muscle myogenesis and pathogenesis to begin to be identified.

Systems and methodologies have been developed to improve the learning and practice of programming. We examine the kinds of support tools that have been developed to date, and we discuss their role ...

A teaching reform initiative, started in the spring semester of 1993 at the New Jersey Institute of Technology (NJIT), is described. The program seeks to increase student success in a freshman computer science course, and ultimately in the entire NJIT curriculum. The traditional teaching methods where the teacher presided over a lecture session supplying facts and figures, providing ideas, and presenting problems and their solutions, has been altered. The new learning environment described in this paper aims to create an all-inclusive setting inviting the students to make the transformation from passive learners to active participants. Rather than merely listening to lectures, students formulate problems and devise their own approaches to answering questions and finding solutions. Such a teaching/learning methodology requires instructional redesign and role redefinition. The presentation of class material is reordered as the teacher and students cross each other's confines becoming a more cohesive entity.

Over the last 12 months, the Trustees and senior management of the Royal Society of Tropical Medicine and Hygiene (RSTMH) have devoted significant thought, attention and time to the development of a strategic plan for the 5-year period ending December 2019. This follows the implementation of an initial 5-year plan of wide-reaching organisational change and modernisation; RSTMH is now financially stable and able to significantly scale-up its activities. It has a strong and engaged governance team and expert staff to work with the Trustees to achieve its strategic objectives. Our collective vision for RSTMH by the end of this next 5-year period is set out below. In 2019, RSTMH will be a more vibrant and higher-profile charity. We will engage regularly with our constituencies all over the world, making our services accessible through expert use of information technology and digital communications. Our profile within the arena of tropical medicine and global health will be significantly higher and we will have an authoritative voice on policy matters. We will have developed our services to a much higher and bolder level. Our peer-reviewed journals will attract leading research groups and authors, and will be known for their authoritative, highly citable content and excellent author experience. We will have a full calendar of meetings, many run in partnership with other organisations in the United Kingdom and overseas. We will be a thoughtful and responsible grant-maker, focusing on niche and under-funded disciplines. Financially, we will be operating with a small healthy surplus and a higher level of income. The overarching objective of this new 5-year plan will be to significantly extend the reach and impact of our work: geographically, politically, demographically and financially. Our specific objectives will be to support the wide-ranging and varied tropical medicine and global health constituencies we represent by facilitating discussion, debate and learning through the provision of high-quality journals and meetings, using the latest technology to extend the reach of our content across the globe, as well as resourcing learning and career development by investing at least £400 000 per annum in educational activity by 2019, and by promoting and positively influencing the work of people working in tropical medicine and global health by developing an authoritative voice on a wide range of policy issues. The strategies we will employ to achieve our objectives are interlinked and mutually supportive, the first of which is effective engagement with Fellows and potential Fellows. Effective engagement will enable us to better understand, serve and represent our constituencies, improve our recruitment and retention rates and increase our political influence. We will look to demonstrate innovation in our global engagement, primarily with the redevelopment of www.rstmh.org in late 2014, using the new site to reposition RSTMH as a community or network, where Fellows can upload professional profiles including career histories, recent blogs and speaking engagements in a networking directory. We will also introduce a ‘resources’ section with information on career pathways and job vacancies and we will offer a blog facility as a platform for Fellows to post entries and generate online dialogue. With a view to making meeting and journal content more accessible, we will include in the ‘resources’ section videos from keynote lectures at RSTMH meetings and short lectures from disease or discipline experts giving overviews of journal web collections and signposting to supplementary material. Our second strategy is an increased focus on the development of RSTMH meeting activity; this will include extending our reach digitally by ensuring wider access to meeting content through filming and streaming of keynote lectures and scientific sessions and introducing a Twitter option for question and answer sessions, as well as extending our reach geographically, with the development of at least one tropics-based meeting every year, and extending our reach politically with the introduction of a flagship biennial policy-focussed meeting (in alternate years to the established biennial meeting), the first of which is currently timetabled for September 2015. Moreover, we intend to extend our influence and networks through the development of additional United Kingdom meetings, either in partnership or solo, to support

Antibody to HCV core and NS3 was quantified by using a microsphere immunoassay and flow cytometry. Antibody to core and NS3 was elevated in the 85 seropositive blood donors tested. The amount of either antibody varied over two logs although greater variation was seen with the antibody to NS3 than was seen with antibody to core. In three documented acute HCV cases, the microsphere assay detected antibody prior to antibody detection using the reference methods. Twenty donor samples were indeterminate by the reference methods: 45% of these were indeterminate with the microsphere assay while 25% were negative and 30% were positive. As compared to enzyme immunoassay the microsphere assay showed a 5-fold increase in sensitivity. The microsphere assay demonstrated increased sensitivity for the quantification of specific antibody to HCV core and NS3 and was useful in resolving a significant proportion of indeterminate samples. Cytometry 29:106‐112, 1997. r 1997 Wiley-Liss, Inc.

Gastrointestinal smooth muscle development proceeds by the linear differentiation of distinct smooth muscle cell phenotypes. In an effort to identify specific gene products associated with distinct smooth muscle cell phenotypes, we performed differential display on smooth muscle myoblasts versus immature smooth muscle myocytes. This analysis identified a novel short-chain alcohol dehydrogenase-like isozyme which was preferentially expressed in smooth muscle myoblasts over immature and mature smooth muscle myocytes. We postulate that this novel short-chain alcohol dehydrogenase-like isozyme may play a role in potentiating the dedifferentiation of smooth muscle cells in vitro.

Several new vinyl and allyloxybenzoate steroidal-based mesogens were synthesized and attached to cyclic tetramethylhydrosiloxane rings using standard hydrosilation chemistry. The steroids examined, all derivatives of cholesterol, 3 β-hydroxy-24α-ethyl-cholest-5,22-diene, 3 α-hydroxyandrostan- 17-one, 3 β-hydroxyandrostan- 17-one, and 3 β-hydroxypreg-5-en-20-one were chosen because structural variations in the 17-β aliphatic chain of the tetracyclic core were present. The synthesis and phase behavior of these mesogenic compounds are discussed with respect to previous systematic investigations linking structural features to mesomorphic behavior. Macromolecular cyclic siloxanes derivatized with these steroidal mesogens were characterized for liquid crystallinity using differential scanning calorimetry (DSC), polarized optical microscopy (POM), and X-ray diffraction. Compounds with 17-β ketone substituents possessing vinylbenzoate spacer groups do not exhibit liquid crystallinity, whereas similar compounds with allyloxybenzoate spacer units exhibit broad smectic mesophases. The ability to form partially or fully interdigitated layered mesophases with respect to the 17-β substituent is examined using X-ray diffraction. The results indicate the length and flexibility of the 17-β group must be considered along with the nature of the spacer group in determining phase behavior.

Decomposition-enhanced spike-triggered averaging (DE-STA) was applied to the vastus medialis muscle to examine size distributions of surface-detected motor-unit action potentials (S-MUAPs) at various force levels. Using DE-STA, 15-20 S-MUAPs were identified during 5%, 10%, 20%, and 30% of maximum voluntary contraction. Average S-MUAPs showed increase in peak to peak (and negative peak) amplitude with force (In microV): 5% = 37.9 +/- 6.1 (16.6 +/- 2.5), 10% = 44.0 +/- 4.0 (20.4 +/- 1.8), 20% = 80.7 +/- 9.3 (41.3 +/- 4.5), and 30% = 102.5 +/- 10.3 (53.6 +/- 5.0). Test-retest variability of peak to peak (and negative peak amplitude) between repeated trials was 0.10 (0.14), 0.14 (0.14), 0.17 (0.15), and 0.21 (0.20) at 5%, 10%, 20%, and 30% respectively. A relationship was found between the S-MUAP amplitude and force (r2 = 0.78, df = 90, F = 160, P < 0.001). Increase in average S-MUAP amplitude with force suggests that STA performed only at low levels of contraction may result in a biased sampling and small average S-MUAP amplitudes.

BACKGROUND The determination of the malignant potential of smooth muscle neoplasms remains ambiguous, and yet has far reaching clinical, therapeutic, and social implications. METHODS In this pilot study, the authors examined smooth muscle isoactin gene expression by polymerase chain reaction in a variety of smooth muscle tumors. RESULTS A lack of γ-smooth muscle isoactin gene expression correlated 100% with a pathologic diagnosis of sarcoma. These results suggest that γ-smooth muscle isoactin gene expression represents a unique molecular marker of oncogenic transformation. CONCLUSIONS γ-Smooth muscle isoactin gene expression provides a valuable molecular adjunct to the diagnosis of smooth muscle neoplasms. Cancer 1997; 80:211-7. © 1997 American Cancer Society.

BACKGROUND & AIMS: The pathogenesis of Hirschsprung's disease is not well understood. The suitability of the animal model for the unknown pathogenesis of inhibitory neurotransmission in Hirschsprung's disease was investigated. METHODS: Circular smooth muscle strips from the internal anal sphincter (IAS) and distal colon (2, 6, 8, 16, and 24 mm from the anal verge) from normal and Ls/Ls mice (mice homozygous for the lethal spotting mutation that develop fetal megacolon after aganglionosis of the terminal colon) were prepared to record changes in isometric tensions in response to different agents and nonadrenergic, noncholinergic nerve stimulation by electrical field stimulation. RESULTS: Bethanechol was used to produce contraction of the smooth muscle strips of distal colon to record a decrease in the tension. Conversely, the IAS smooth muscle strips developed spontaneous tone. In the normal homozygous mice, electrical field stimulation caused a biphasic response, an initial decrease followed by an after- contraction, whereas in Ls/Ls mice, the predominant response was contraction. All smooth muscle strips from normal and Ls/Ls mice produced relaxation in response to sodium nitroprusside and vasoactive intestinal polypeptide. CONCLUSIONS: Ls/Ls mice may serve as an appropriate animal model to investigate the pathogenesis of the inhibitory neurotransmission in Hirschsprung's disease in the distal colon and IAS. (Gastroenterology 1997 May;112(5):1575-85)

To determine whether the differential expression of bladder smooth muscle isoactin can be used as a molecular marker for the development of interstitial cystitis (IC).Three groups of five female Sprague-Dawley rats each underwent urethral catheterization and intravesical instillation of 0.5 ml. of 0.4N HCl. One group was sacrificed one, two and four weeks after the application of HCl, and their bladders harvested for histologic examination and evaluation using Northern blot analysis of bladder smooth muscle isoactins. Five control animals were sacrificed and their bladders harvested to establish isoactin gene expression of bladder smooth muscle in the normal state. The bladders of the rats in each group were excised, immediately frozen in liquid nitrogen, pooled, then stored -70 degrees C until needed for RNA isolation. Isoactin cDNA probes have been developed, therefore isoactin specific cDNA insert fragments were isolated and insert DNA was purified by gel electrophoresis. Total cellular RNA was isolated from 1.0 gm. of bladder smooth muscle from each group. After spectrophotometric quantification, Northern Blot analysis was performed using 2% agarose-formaldehyde gels and Biotrans nylon membranes. Two complete Northern Blot series were run on a single gel and blotted to a single membrane to eliminate gel and blotting discrepancies.Microscopic histologic analysis revealed detrusor mastocystosis and eosinophilia as has been noted in humans with chronic interstitial cystitis. Two weeks after the intravesical application of hydrochloric acid, the relative expression of gamma-smooth muscle isoactin was noted to increase by 1.7-fold, while alpha-smooth muscle isoactin expression increased by a factor of 9. These effects were seen to stabilize four weeks after acid application.The intravesical application of dilute HCl in rats results in a histologic appearance which mimics that seen in humans with interstitial cystitis. The appearance of detrusor mastocytosis and eosinophilia was accompanied by a relative decrease in the expression of gamma- and a relative increase in alpha-smooth muscle isoactin gene expression. This pattern of smooth muscle isoactin expression is consistent with a more immature and possibly synthetic smooth muscle phenotype, which may be responsible for the clinical presentation of those with IC. Northern blot analysis of bladder smooth muscle cells may serve as an effective marker for the development of interstitial cystitis in humans.

Performances of anti-nuclear antibody testing by immunofluorescence assay (ANA-IFA) and enzyme immunoassay (ANA-EIA) were compared in relation to patient diagnosis. A total of 467 patient serum samples were tested by ANA-IFA (Kallestad; Sanofi) and ANA-EIA (RADIAS; Bio-Rad), and their age, sex, diagnosis, disease status, and medications were obtained through chart review. Reference ranges were established by testing 98 healthy blood donor samples. Eighty-six samples came from patients with diffuse connective tissue diseases, including systemic lupus erythematosus, discoid lupus erythematosus, or drug-induced lupus (n = 71); systemic sclerosis, CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal motility abnormalities, sclerodactyly, and telangiectasia), or Raynaud's syndrome (n = 8); Sjögren's syndrome (n = 5); mixed connective tissue disease (n = 5); and polymyositis or dermatomyositis (n = 3). The sensitivity, specificity, positive predictive value, and negative predictive value for ANA-IFA were 87.2, 48.0, 29.1, and 93.9%, respectively, for the reference range of < 1:160. For ANA-EIA, they were 90.7, 60.2, 35.8, and 96.4%, respectively, for the reference range of < 0.9. ANA-EIA offers equivalent sensitivity and higher specificity compared to ANA-IFA.

Monoclonal antibodies derived from the actin multigene family are routinely used as an adjunct to morphologic diagnoses of smooth muscle tumors. Northern blot analysis was performed on 60 surgical resections utilizing isoactin-specific cDNAs. A comparison of this analysis to immunohistochemical studies demonstrated that actin-specific monoclonal antibodies represent reliable markers of the smooth muscle lineage. Smooth muscle neoplasms showed a unique pattern of gamma-smooth muscle isoactin gene expression, providing a potentially valuable molecular adjunct to the morphologic diagnosis of uterine smooth muscle tumors.

Presidents have been required to give an inaugural address on commencing office at the Royal Society of Tropical Medicine and Hygiene (RSTMH) since its foundation in 1907. All presidential addresses were identified, sourced and assembled into an annotated bibliography. The majority of presidential addresses have been published in Transactions of the Royal Society of Tropical Medicine and Hygiene. Unpublished and in some cases ‘lost’ contributions have now been sourced where possible and archived at the RSTMH. This unique, rich and rewarding archive provides a vista into the development of the RSTMH and the discipline of tropical medicine. The archive is freely available to all.

Biomineralization of hydroxyapatite (Ca10(PO4)6(OH)2) is of significant importance in biomedical applications such as bone and dental repair, and biomimetic control of mineral formation may lead to more effective restorative procedures. Gold nanoparticles are functional scaffolds on which to assemble multi-component monolayers capable of mimicking protein activity in the templated synthesis of calcium phosphate. The goal of this research was to explore nanoparticle templates with mixed-monolayers of uncharged polar polyethylene glycol (PEG) molecules and highly charged polynucleotide and amino acid molecules in their ability to influence mineralization rates and mineral particle size and morphology. This research demonstrates through time-resolved optical density and dynamic light scattering measurements that the combination of tiopronin, PEG, and DNA presented on a nanoparticle surface decreases nanoparticle aggregation from 59 to 21 nm solvated radius, increases mineralization kinetics from 1.5 × 10−3 to 3.1 × 10−3 OD/min, and decreases mineral particle size from 685 to 442 nm average radius. FT-IR and TEM data demonstrate that mineralized material, while initially amorphous, transforms to a semi-crystalline material when guided by template interactions. This demonstrates that surface-tailored monolayer protected cluster scaffolds are successful and controllable mineralization templates with further potential for biomedical applications involving calcium phosphate and other biomaterials.

Beta defensins (BDs) are cationic peptides with antimicrobial activity that defend epithelial surfaces including the skin, gastrointestinal, and respiratory tracts. However, BD expression and function in the urinary tract are incompletely characterized. The purpose of this study was to describe Beta Defensin-1 (BD-1) expression in the lower urinary tract, regulation by cystitis, and antimicrobial activity toward uropathogenic Escherichia coli (UPEC) in vivo. Human DEFB1 and orthologous mouse Defb1 mRNA are detectable in bladder and ureter homogenates, and human BD-1 protein localizes to the urothelium. To determine the relevance of BD-1 to lower urinary tract defense in vivo, we evaluated clearance of UPEC by Defb1 knockout (Defb1(-/-)) mice. At 6, 18, and 48 hours following transurethral UPEC inoculation, no significant differences were observed in bacterial burden in bladders or kidneys of Defb1(-/-) and wild type C57BL/6 mice. In wild type mice, bladder Defb1 mRNA levels decreased as early as two hours post-infection and reached a nadir by six hours. RT-PCR profiling of BDs identified expression of Defb3 and Defb14 mRNA in murine bladder and ureter, which encode for mBD-3 and mBD-14 protein, respectively. MBD-14 protein expression was observed in bladder urothelium following UPEC infection, and both mBD-3 and mBD-14 displayed dose-dependent bactericidal activity toward UPEC in vitro. Thus, whereas mBD-1 deficiency does not alter bladder UPEC burden in vivo, we have identified mBD-3 and mBD-14 as potential mediators of mucosal immunity in the lower urinary tract.

Congenital obstructive nephropathy is a common cause of chronic kidney disease and a leading indication for renal transplant in children. The cellular and molecular responses of the kidney to congenital obstruction are incompletely characterized. In this study, we evaluated global transcription in kidneys with graded hydronephrosis in the megabladder (mgb (-/-)) mouse to better understand the pathophysiology of congenital obstructive nephropathy. Three primary pathways associated with kidney remodeling/repair were induced in mgb (-/-) kidneys independent of the degree of hydronephrosis. These pathways included retinoid signaling, steroid hormone metabolism, and renal response to injury. Urothelial proliferation and the expression of genes with roles in the integrity and maintenance of the renal urothelium were selectively increased in mgb (-/-) kidneys. Ngal/Lcn2, a marker of acute kidney injury, was elevated in 36% of kidneys with higher grades of hydronephrosis. Evaluation of Ngal(high) versus Ngal(low) kidneys identified the expression of several novel candidate markers of renal injury. This study indicates that the development of progressive hydronephrosis in mgb (-/-) mice results in renal adaptation that includes significant changes in the morphology and potential functionality of the renal urothelium. These observations will permit the development of novel biomarkers and therapeutic approaches to progressive renal injury in the context of congenital obstruction.

It has been suggested that the BDNF Val66Met polymorphism modulates episodic memory performance via effects on hippocampal neural circuitry. However, fMRI studies have yielded inconsistent results in this respect. Moreover, very few studies have examined the effect of met allele load on activation of memory circuitry. In the present study, we carried out a comprehensive analysis of the effects of the BDNF polymorphism on brain responses during episodic memory encoding and retrieval, including an investigation of the effect of met allele load on memory related activation in the medial temporal lobe. In contrast to previous studies, we found no evidence for an effect of BDNF genotype or met load during episodic memory encoding. Met allele carriers showed increased activation during successful retrieval in right hippocampus but this was contrast-specific and unaffected by met allele load. These results suggest that the BDNF Val66Met polymorphism does not, as previously claimed, exert an observable effect on neural systems underlying encoding of new information into episodic memory but may exert a subtle effect on the efficiency with which such information can be retrieved.

This paper presents a predicate-driven document filing system for organizing and automatically filing documents. A document model consists of two basic elements: frame templates representing document classes, and folders which are repositories of frame instances. The frame templates can be organized to form a document type hierarchy, which helps classify and file documents. Frame instances are grouped into a folder on the basis of user-defined criteria, specified as predicates which determine whether a frame instance belongs to a folder. Folders can naturally organized into a folder organization which represents the user's real world document filing system. The predicate consistency problem is discussed to eliminate two abnormalities from a folder organization: inapplicable edges (filing paths) and redundant folders. An evaluating net (including an association dictionary, an instantiation component and a production system) is then proposed for evaluating whether a frame instance satisfies the predicate of a folder during document filing. And the concept of consistency a rule base is also discussed.