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Increasingly, undergraduate institutions are incorporating original research into the curriculum as a matter of best practice. However, while the practice of science has grown more collaborative, undergraduate research has remained largely confined to single-institution studies. Incorporating long-term, distributed research projects into the undergraduate research experience can better prepare students to interpret and engage in science of the future. The Decomposition in Aquatic and Terrestrial Invaded Systems (DATIS) project within the Ecological Research as Education Network (EREN) offers a good model for examining how to minimize challenges and maximize opportunities associated with classroom use of long-term, collaborative research projects. Eleven key challenges are identified, and practical solutions are provided for each. By modeling this scientific approach in primarily undergraduate institutions, we are preparing graduates who will have the tools and knowledge to work collaboratively and create their own distributed research networks. Our goal is that the decomposition project we describe here can inform and inspire others seeking to engage in research at the undergraduate level, either as potential research coordinators or as collaborators in an existing network.

China is one of the world’s most rapidly growing countries and the largest consumer of energy in the world. As a result, China’s pollution emissions almost doubled from 2002 to 2007, and in 2006 it surpassed the United States to become the world’s top carbon dioxide emitter. Understanding the sources of emissions is essential towards designing policies aimed at curbing carbon emissions in China. The surge in China’s exports has been partially blamed for this increase in emissions. To understand the sources of emissions, this study uses a vector autoregression model to examine the relationship among exports, CO2 emissions, coal consumption and trade openness in China for the years 1970–2010. The study uses a modified version of Granger Causality developed by Toda and Yamamoto [56]. The main findings within the study indicate: (1) Granger Causality running from exports to emissions; (2) Granger Causality running from coal consumption to exports; and (3) GDP determines future variability in exports and CO2 emissions. Results suggest that governmental policies aimed at controlling coal consumption could affect CO2 emissions and exports. Results from this study should assist in formulating policies to mitigate both CO2 emissions and coal consumption.

West Valley Demonstration Project (WVDP) Annual Site Environmental Report (ASER) for Calendar Year 2014. The report, prepared for the U.S. Department of Energy West Valley Demonstration Project office (DOE-WVDP), summarizes the environmental protection program at the WVDP for calendar year (CY) 2014. Monitoring and surveillance of the facilities used by the DOE are conducted to verify protection of public health and safety and the environment. The report is a key component of DOE’s effort to keep the public informed of environmental conditions at the WVDP. The quality assurance protocols applied to the environmental monitoring program ensure the validity and accuracy of the monitoring data. In addition to demonstrating compliance with environmental laws, regulations, and directives, evaluation of data collected in 2014 continued to indicate that WVDP activities pose no threat to public health or safety, or to the environment.

We discuss the benefits that a collaborative research network, a group of faculty from different institutions who jointly conduct a research project, can have on undergraduate research (UR) by enhancing the diversity and significance of projects and by improving student motivation and breadth of learning. The main example used is the Ecological Research as Education Network (EREN), founded in 2010 to enhance undergraduate research in ecology at primarily undergraduate institutions (PUIs) by (1) providing networking and collaborative research opportunities for both faculty and students and (2) developing free educational resources. EREN comprises about 280 ecology faculty and staff nationally and has facilitated development of nine continental-scale, collaborative research projects. Project leaders design a research project that can be conducted by faculty and students at just about any college. Faculty and their students carry out the data collection at their home institution and submit it to the publicly available project database. Then participants (and even non-participants) can avail themselves of the large, multi-year, continent-wide data set. Substantial benefits have been reported for programs, faculty, and students. Undergraduate research programs are broadened and faculty benefit because they gain insights and laboratory techniques from colleagues in other institutions and fields, thereby expanding the diversity of potential undergraduate research projects and resulting in more broadly trained undergraduates. The research projects themselves have become educational resources incorporated into courses at all levels, as well as independent research projects. Because data collection happens nationwide, college faculty and students at small colleges are now able to investigate large-scale ecological questions. Preliminary assessments have shown significant improvements for some student-learning outcomes, including thinking across scales, use of best practices in data management, and describing scientific collaboration techniques. Students demonstrate increased motivation and retention through participation in a nationwide, authentic research project with publication-quality data, becoming part of a community of scholars and gaining a sense of belonging and responsibility. Despite challenges with coordination and communication, students are exposed to a wider range of techniques and subfields of ecology than they would be without this network.

The watershed characterization and modeling system (WCMS) was developed to support decision making and the management of water resources at a statewide level in West Virginia. Specific hydrological analysis functions were combined within a customized GIS interface to provide decision support capabilities to both technical and non-technical users. Components of the current system include: an overland flow path model that indicates optimum water quality sampling locations, flow estimation for all streams in an identified area, an instream water quality and loading model for pollutant levels, and a ranking model to prioritize treatment alternatives based on user defined criteria and preferences. The primary goals of this system are to provide consistent technical information related to natural watershed processes and to predict the impacts of alternative management scenarios for decision makers. WCMS is currently used by the West Virginia Department of Environmental Protection (WVDEP) to guide policy development and management decisions that address watershed and water quality issues throughout the state.

The growth in demand for cosmetic, graft and organ transplant surgical procedures, the increased use of antineoplastic and immunosuppressive agents, as well as multidrug resistance are some of the factors responsible for the marked rise in fungal infection rates in recent years. Consequently, there have been renewed calls from both the public and private sectors for new and improved drug targets to replace existing antifungal therapies, many of which have been in clinical circulation for several decades. Plants select themselves in such endeavors owing to their superior numbers and vast chemical diversities. With this as a backdrop, this survey examines the antifungal activities of Amaryllidaceae plant extracts against various fungal pathogens. Good growth inhibitory activities (MICs

PurposeThe purpose of the study is to evaluate the impact of China's current coal‐to‐liquids (CTL) activities on its coal and oil markets from 2005 to 2025.Design/methodology/approachA partial equilibrium multi‐equation model of China's oil and coal markets is developed based on data obtained from the existing literature. The impact of CTL technologies on China's oil and coal markets is evaluated using computer simulations by solving the model under scenarios with and without CTL production.FindingsThe simulation results show that on average, the planned CTL activities will decrease crude oil prices by 5.73 percent and China's oil imports by 6.09 percent and increase China's domestic oil supply by 9.26 percent over the 20 year period. Also, China's demand for oil will increase by 0.35 percent on average, suggesting that CTL production will slightly stimulate China's demand for oil because of the drop in oil prices. China's demand for coal will also increase by 1.02 percent because of the additional demand for coal created by CTL production. Surprisingly, both coal prices and China's coal supply will decline by 0.51 percent while the demand for coal and coal supply of the rest of the world will be reduced by 1.63 percent and 0.28 percent, respectively.Originality/valueThe paper is the first study on the implication of CTL conversion from an economist's point of view. It applies an economic model to quantify the impacts of such technology on overall energy prices and supplies.

The oil and gas industry has adopted several methods to obtain insight as to how a fluid may affect reservoir material. The Capillary Suction Time (CST) test has become a de facto standard test method, largely due to its simplicity and speed. The most obvious shortcoming of the CST test is that it introduces a medium (paper) that is far different from anything found in an actual reservoir; in fact, one may argue that the CST test is essentially a measure of the interaction of the test fluid with the paper. The lack of theoretical foundation of the CST test precludes reproduceable results or proper estimation of errors in measurement. We present a new test method that observes only intrinsic properties of the formation in contact with a test fluid, bolstered by a strong theoretical basis, in stark contrast to the CST test. Our method preserves the desirable attributes of the CST test, but replaces imbibition into paper with imbibition into reservoir material. The method uses a comminuted sample, and the results from the imbibition step are used to determine formation wettability in the form of the advancing contact angle. The results from a subsequent drainage test are used to determine the receding contact angle, and the capillary pressure versus saturation curve. Prior to performing the drainage test, test fluid is placed on top of the saturated pack and the permeability of the pack to the test fluid is determined. The permeability of the pack to liquid is then compared to the pretest permeability of the pack determined using nitrogen. Use of this pack as a testing environment allows the technique to be applied to formation samples of virtually any permeability and porosity. We have found that there is no correlation between CST test data and the permeability data obtained using the new method presented here. We present several cases in which a positive result from a CST test is inconsistent with the results obtained from the new test method. We maintain that the discrepancies cast serious doubts on the general applicability of the CST test as a tool for studying rock/fluid interactions. In summary, there is a great need to standardize testing that investigates rock/fluid interactions. The widely used CST method introduces a foreign material and it does not offer sufficient resolution, reproducibility, or estimation of error. Even if the CST method were adequate, the lack of standardization in testing and analysis methodologies makes comparisons of published results difficult. Our method provides superior results. The strong theoretical foundation of the new method allows rigorous analysis making comparisons between treating fluid options far more trustworthy.

As the cost of production is a key determinant of long-term viability, developing methods that reduce the cost of direct coal liquefaction has posed a challenge to scientists and industrial organizations worldwide. This paper summarizes recent developments in technology and processes and explores the overall economic competitiveness of direct coal liquefaction using the China Shenhua Group Corp. (Shenhua) project as a case study. A comparative analysis of the costs and economic competitiveness of the Shenhua approach and a variety of conceptual designs outlined in U.S. studies is presented. The comparison shows that the economic competitiveness of direct coal liquefaction is dependent on production costs that consist primarily of raw material, operation and management, and capital costs. Capital cost is shown to be a primary determinant of the cost of production. The relative competitiveness of the plant and supporting facilities depends heavily on the economic alternatives relevant to a particular plant ...

The remediation of infectious diseases is an ongoing concern in healthcare structures due to the continued loss of efficacies of existing schedules and, in particular, the poignant threat of multidrug resistance. In the search for new therapies plants have emerged as an attractive option owing to their vast chemical resources. Allied to this feature is the widespread use of plants in traditional approaches towards infectious diseases. As far as the family Amaryllidaceae is concerned, around fifty of its members are identifiable with such distinctive functions in traditional medicine. This review examines the in vitro antibacterial activities of its plant extracts and sheds light on instances where these are corroborative of the traditional usage.

Globalization and multidrug resistance are amongst the factors implicated in the resurgence of infectious diseases in recent years. This has fostered a compelling need in drug discovery to replace (or supplement) existing schedules. The floral biodiversity has been identified as a viable resource platform due to its inimitable chemical characteristics as well as the presence of numerous of its members in traditional medicinal approaches towards these diseases. Whilst the plant family Amaryllidaceae is conventionally associated with cancer and motor-neuron disease therapies, this survey shows that it has a significant presence in the remediation of infections and infection-related ailments. This verifiable indigenous knowledge could amplify efforts towards the identification of the active chemical constituents.

We determined whether the angiogenesis and growth of murine colon carcinomas growing in the wall of the cecum is dependent on infiltrating leukocytes. Syngeneic BALB/c or SCID mice were treated with a myelosuppressive, maximally tolerated dose of doxorubicin. Parental or multidrug resistant CT-26 colon carcinoma cells were implanted into the cecal wall 3 days after the second intravenous injection of doxorubicin. Control mice developed large, well-vascularized tumors, whereas doxorubicin-pretreated mice did not. Intravenous injection of spleen cells from normal BALB/c or SCID mice one day prior to tumor cell implantation reversed the decreased vascularity and tumorigenicity. The production of proangiogenic molecules and microvessel density in tumors directly correlated with the number of infiltrating leukocytes, suggesting that tumor-infiltrating leukocytes are essential to angiogenesis of murine colon carcinomas.

The challenge of disease and death caused by infectious diseases is strikingly apparent in both developed and developing nations around the world, with developing countries being the most affected. As infectious diseases evolve and pathogens develop resistance to existing pharmaceuticals, the search for new novel leads, possibly with different modes of action, against fungal, bacterial, and viral diseases has intensified in recent years. To most of the African population, the use of medicinal plants to combat these challenges forms an integral component of their culture and hence a prominent characteristic. To this extent, several species have been subjected to different pharmacological screening techniques using different pathological strains. As a result, varied ranges of bioactivities have been reported for a number of species, different plant parts, and even geographical location and season. We present here the best reported antimicrobial activities of “Africa’s top 50 medicinal plants.”

Purpose: These studies were designed to develop an orthotopic model for human bladder cancer and to isolate variant metastatic cell lines.Materials and Methods: The human bladder cancer cell line 253J was implanted into the muscular wall of the bladder of athymic nude mice. By in vivo recycling, we selected for 2 variant cell lines: 253J B-V, a bladder line isolated after 5 serial passages in the bladder, and 253J lung-IV, established from a lung tumor nodule that was recycled through the bladder.Results: These 2 cell lines showed enhanced tumorigenicity, as measured by a decreased latent period, and rapid growth as compared with the parental cell line. Moreover, orthotopic implantation of these cell lines resulted in metastasis to the lungs. These in vivo-selected, metastatic cell lines exhibited unique karyotypic alterations, increased anchorage-independent growth, overexpression of basic fibroblast growth factor, altered expression of adhesion molecules and the ability to migrate through Matrig...

I. INTRODUCTION Public awareness about the health and environmental consequences of agricultural chemical use has continued to grow following publication of Rachael Carson's Silent Spring in 1962. That concern led policymakers to form the Environmental Protection Agency (EPA) in 1972 and to enact legislation such as the Clean Water Act and the Federal Insecticide, Fungicide, and Rodenticide Act. However, agricultural nonpoint-source pollution--that is, water pollution from runoff of fertilizers, pesticides, and agricultural land sediment--remains largely unregulated.(1) Solving a number of important remaining water pollution problems requires reducing agricultural nonpoint pollution. However, the best way to achieve that reduction is unclear. Agricultural nonpoint pollution policy traditionally has relied on voluntary programs such as those administered by the USDA Soil Conservation Service. These programs often couple technical assistance with a subsidy covering a portion of the recommended practice's cost. Voluntary programs are popular with farmers. However, conventional wisdom suggests that farmers would be unlikely to adopt voluntarily pollution-reducing practices without a subsidy covering full costs of the practice plus any revenue loss. Abbreviations EPA: Environmental Protection Agency PMB: Private Marginal Benefit PMC: Private Marginal Cost WTA: Willingness-to-accept Alternatives to voluntary programs include regulation, increased farmer liability for water quality damages, and taxes on pesticide and fertilizer purchases. Policymakers commonly regulate pesticides but rarely regulate fertilizers. (Nebraska, for example, does restrict fertilizer use in areas that are susceptible to nitrate contamination of groundwater.) EPA, through its pesticide registration process, may limit pesticide use to particular crops or particular regions. EPA also may restrict farm laborers from entering fields just after spraying. The Food and Drug Administration sets maximum allowable tolerances for pesticide residues on foods. EPA may ban use of a pesticide that constitutes an undue health or environmental threat by cancelling its registration. Regulation is a reasonably effective way of dealing with toxic substances such as pesticides. However, regulation can be a cumbersome and expensive alternative for non-toxic substances that cause environmental damages when present in excessive amounts. With some exceptions, sediment pollution and fertilizer pollution fall into this category. Liability is another important alternative policy. Although certain states, such as Connecticut, use limited farmer liability for groundwater pollution, liability also is problematic. Lawsuits can produce "highly unsystematic levels of compensation, distorted incentives, and high transactions costs" (Menell, 1991). Economists often recommend taxes on fertilizer and pesticide purchases since such taxes would reduce the use of polluting inputs. However, studies show that to have a noticeable impact on nitrogen fertilizer usage, nitrogen taxes would have to be over 100 percent (Johnson et al., 1991). Voluntary programs coupled with subsidies are not free of shortcomings, but in certain cases voluntary programs may be more effective than one might expect because the farming business possesses a unique structure. In farming, the owner/operator and the owner/operator's family generally reside on the farm site. Industrial or "corporate" farms owned by nonresident shareholders are uncommon. In 1987, 99.2 percent of all farms were sole proprietorships, partnerships, or family held corporations (U.S. Department of Commerce, 1989). Therefore, the owners and decision makers on a farm may bear a portion of the pollution costs of their production decisions and thus have an incentive to reduce that pollution.(2) For example, pesticides and fertilizers can leach into the farmer's own well water and endanger family health in addition to polluting water off the farm, such as the community water supply. …

The general focus of this paper is the regional estimation of marginal benefits of targeted water pollution abatement to instream uses. Benefit estimates are derived from actual consumer choices of recreational fishing activities and the implied expenditures for various levels of water quality. The methodology is applied to measuring the benefits accruing to recreational anglers in Indiana from the abatement of pollutants that are by-products of agricultural crop production.

The assessment of environmental quality problems and the design and economic evaluation of alternative federal, state, and local policy strategies to address environmental issues require complex analyses which must address the underlying physical, biological, social, and economic processes. The study of environmental problems is thus inherently multidisciplinary and should involve the physical, biological, and social sciences. Unfortunately, the multidisciplinary nature of environmental issues has caused problems with the quality and general availability of the data necessary for appropriate analyses. While data have been collected in many areas to address discipline-specific problems, there has been little regard for the eventual need to coordinate analyses across disciplinary lines. As Portney points out, this lack of coordination in data collection is reflected in the often Bal

Current therapy of human superficial bladder cancer includes the intravesical administration of antitumor drugs and immunomodulators. The purpose of these studies was to determine whether phospholipid liposomes that bind to human bladder cancer cells can improve the delivery of interferon alpha (IFN-alpha) to neoplastic urothelium. The antiproliferative activity of free IFN-alpha and IFN-alpha encapsulated in liposomes was assessed in vitro against the human transitional cell carcinoma line 253J. The cells were exposed to free and liposome-encapsulated IFN-alpha for short periods ranging from 30 minutes to four hours, and inhibition of cell growth was determined three days later. The production of greater than 25 percent cytostasis of 253J cells by free IFN-alpha required four hours of continuous exposure. In contrast, IFN-alpha encapsulated in liposomes produced 35 percent and 60 percent cytostasis after a 30-minute and four-hour exposure, respectively. Liposome-encapsulated IFN-alpha was also effective (50 percent cytostasis) against a subline of 253J cells selected for resistance against free IFN-alpha. Liposomes containing IFN-alpha were stable in the presence of human urine. In vivo studies in mice showed that intravesical administration of radiolabeled IFN-alpha or radiolabeled liposomes did not yield significant systemic absorption and deposition in distant organs. Collectively, these results suggest that the encapsulation of IFN-alpha within multilamellar liposomes may augment its antiproliferative activity, overcome some forms of tumor cell resistance to IFN-alpha, and prove useful for intravesical therapy of superficial bladder cancer.

Once prostate cancer metastasizes to bone, conventional chemotherapy is largely ineffective. We hypothesized that inhibition of phosphorylation of the epidermal growth factor receptor (EGF-R) and platelet-derived growth factor receptor (PDGF-R) expressed on tumor cells and tumor-associated endothelial cells, which is associated with tumor progression, in combination with paclitaxel would inhibit experimental prostate cancer bone metastasis and preserve bone structure. We tested this hypothesis in nude mice, using human PC-3MM2 prostate cancer cells. PC-3MM2 cells growing adjacent to bone tissue and endothelial cells within these lesions expressed phosphorylated EGF-R and PDGF-Rα and -β on their surfaces. The percentage of positive endothelial cells and the intensity of receptor expression directly correlated with proximity to bone tissue. Oral administration of PKI166 inhibited the phosphorylation of EGF-R but not PDGF-R, whereas oral administration of STI571 inhibited the phosphorylation of PDGF-R but not EGF-R. Combination therapy using oral PKI166 and STI571 with i.p. injections of paclitaxel induced a high level of apoptosis in tumor vascular endothelial cells and tumor cells in parallel with inhibition of tumor growth in the bone, preservation of bone structure, and reduction of lymph node metastasis. Collectively, these data demonstrate that blockade of phosphorylation of EGF-R and PDGF-R coupled with administration of paclitaxel significantly suppresses experimental human prostate cancer bone metastasis.

BACKGROUND Expression of platelet-derived growth factor (PDGF) and activation (by autophosphorylation) of its receptor (PDGF-R), a tyrosine kinase, are associated with the growth of metastatic prostate tumor cells in the bone parenchyma. The tyrosine kinase inhibitor STI571 blocks the PDGF signaling pathway by inhibiting PDGF-R autophosphorylation. We examined the effects of STI571, given alone or with paclitaxel (Taxol), on tumor growth in a mouse model of prostate cancer metastasis. METHODS Human prostate cancer PC-3MM2 cells were injected into the tibias of male nude mice. Three days later the mice (20 per group) were randomly assigned to 5 weeks of treatment with oral and injected water (control), daily oral STI571, weekly injected paclitaxel, or STI571 plus paclitaxel. Lesions in bone and the surrounding muscles were then harvested and analyzed by histology, western blotting (for PDGF-R phosphorylation), immunohistochemistry (for expression of proangiogenic molecules), and double immunofluorescence (to identify endothelial cells and apoptotic tumor cells). Growth of bone lesions was monitored by digital radiography. Bone lesions from control mice were used to establish short-term cell cultures for analysis of PDGF-R phosphorylation. All statistical tests were two-sided. RESULTS PC-3MM2 cells cultured from bone lesions and treated in vitro with STI571 had less phosphorylated PDGF-R than untreated cells. In control mice, bone lesions expressed high levels of PDGF and activated (i.e., phosphorylated) PDGF-R, whereas lesions in the adjacent musculature did not. Activated PDGF-R was present on the surface of endothelial cells within the bone lesions but not in endothelial cells of uninjected bone. Mice treated with STI571 or STI571 plus paclitaxel had a lower tumor incidence, smaller tumors, and less bone lysis and lymph node metastasis than mice treated with water or paclitaxel alone (P

Since vascular endothelial growth factor (VEGF) plays a major role in tumor angiogenesis, we determined whether blockage of VEGF receptor signaling using a novel tyrosine kinase inhibitor (PTK 787) decreases the growth and metastasis of human pancreatic carcinoma growing orthotopically in nude mice. Human pancreatic L3.6pl cells were injected into the pancreas of nude mice. Seven days later, groups of mice were given daily oral administrations of PTK 787 alone, twice weekly i.p. injections of gemcitabine, or combination therapy. The mice were necropsied when control mice became moribund (day 35). Therapy with PTK 787 alone, gemcitabine alone, or the combination of both agents produced respectively 60%, 70%, and 81% inhibition in the volume of pancreatic cancers. The combination therapy significantly decreased the incidence of lymph node and liver metastasis, leading to a significant increase in survival. Microvessel density (MVD) was significantly decreased in tumors treated with either PTK 787 alone or PTK 787 plus gemcitabine. MVD directly correlated with tumor cell proliferation and inversely correlated with apoptosis of tumor cells and associated endothelial cells. Collectively, our results demonstrate that blockade of VEGF-R signaling may provide an additional approach to the therapy of pancreatic cancer.

Once a diagnosis of cancer is established, the urgent question is whether it is localized or has already spread to regional lymph nodes and visceral organs. Despite improvements in early diagnosis, surgical techniques, general patient care and local and systemic adjuvant therapies, most deaths of cancer patients result from the relentless growth of metastatic disease that is resistant to conventional therapies. Surgical excision of primary neoplasms is not curative in many patients because by the time of diagnosis, metastasis may well have occurred. The major challenge for treatment of metastasis is the biological heterogeneity of cancer cells within primary lesions and especially within metastases. A wide range of genetic, biochemical, immunological and biological characteristics that differ from subpopulation to subpopulation include the display of cell-surface receptors, enzymes, karyotypes, cell morphologies, growth properties, sensitivities to various therapeutic agents and the ability to invade and produce metastasis [1,2]. This heterogeneity is due to differences in etiology, origin and selection pressures. The outcome of the metastatic process depends on the interaction of metastatic cells with host homeostatic factors, which include various elements of the host immune system. The establishment and progressive growth of metastatic cells requires that they exploit, subvert and suppress, when necessary, natural host defense systems. This chapter will focus on the host-tumor interactions that result in immune modulation of tumor cell populations.

The authors recently reported that tumoricidal activation of macrophages by a new synthetic bacterial lipopeptide, JBT 3002, can augment chemotherapy-mediated tumor-cell killing. The aim of this study was to identify the mechanism responsible for the destruction of metastatic cells. Three daily oral doses of JBT 3002 before once-weekly intraperitoneal injections of 100 mg/kg irinotecan for 3 weeks significantly increased the eradication of established CT-26 murine colon cancer liver metastases compared with treatment with irinotecan alone. Immunohistochemical analyses revealed that the hepatic metastases in mice given combination therapy contained infiltrating CD8+ lymphocytes and a dense infiltrate of macrophages expressing both inducible nitric oxide synthase (iNOS) and interleukin-15. In vitro treatment of peritoneal macrophages with JBT 3002 plus interferon-gamma induced the expression of iNOS and the production of nitric oxide. In the presence of a low (subtoxic) dose of irinotecan, these activated macrophages produced significant lysis of CT-26 cells. The high level of cytotoxicity was inhibited by the specific inducible nitric oxide synthase inhibitor, NG-methyl-L-arginine. In contrast, irinotecan-mediated lysis of normal intestinal epithelial IEC-6 cells was not increased by activated macrophages. Scanning electron microscopy revealed that activated macrophages bound to CT-26 tumor cells but not to normal IEC-6 cells, confirming that nitric oxide-mediated cytotoxicity is specific for tumor cells. Collectively, the results suggest that augmentation of the therapeutic efficacy of irinotecan against colon cancer liver metastases by immunomodulation with JBT 3002 may be associated with elevated inducible nitric oxide synthase and endogenous interleukin-15 in tumor-infiltrating macrophages.

Astrocytic tumours of the central nervous system express cell adhesion receptors of the integrin superfamily, CD44 and adhesion receptors of the immunoglobulin superfamily. Glioma cells utilize these receptors to adhere to and migrate along components of the extracellular matrix (ECM), which is uniquely distributed and regulated within the brain and the spinal cord. For penetration into healthy brain tissue a number of proteases are expressed, which degrade proteins of the extracellular matrix. Thus, glioma cell invasion into the adjacent brain tissue is dependent on the interaction of glioma cells with the extracellular matrix and the subsequent destruction of matrix barriers. There is a critical balance between expression of various adhesion receptors and proteases. The tight regulation of critical levels of proteases and receptors expressed by glioma cells or other cells is necessary for the "physiological" behaviour of glioma cells. Shifts in the balance of protein expression determine glioma cell behaviour in their micro-environment and can initiate or influence the complex process of glioma cell invasion. The complex receptor-ECM interaction in glioma cell invasion is discussed focussing upon the role of integrin receptors and matrix-metalloproteinases. Influencing these molecules or their regulation may lead to novel therapeutic approaches in the treatment of malignant glioma.

Comments on an article by Bushman and Anderson. We are concerned that Bushman and Anderson's article on media violence contains data that are incorrect or irreproducible. This is a serious issue; the article has already been referenced by numerous other formal papers according to a Google scholarly article search as well as in a statement to the U.S. Senate, in legal proceedings, and in California State law (Assembly Bill 1179 in 2005). Language: en

Background Understanding the mechanism of prostate cancer metastasis is essential to the design of a more effective therapy. An effective therapy for this disease will depend on the development of a clinically relevant in vivo model. Purpose We describe the development of such a model by using orthotopic implantation of human prostate cells in BALB/c nude mice. Method We compared the tumorigenicity of and the incidence of metastasis of human prostate cancer PC-3M and LNCaP-FGC (LNCaP) cell lines subsequent to prostatic (orthotopic) or subcutaneous (ectopic) implantations in male nude mice. Results LNCaP cells produced tumors only in the prostate. Enhanced tumorigenicity at the orthotopic site was found for PC-3M cells. Lymph node metastases were observed in practically all mice given an injection of PC-3M cells in the prostate, but they were uncommon with subcutaneous injection of these cells. Bilateral orchiectomy did not alter the tumorigenicity of either PC-3M or LNCaP cells or the incidence of lymph node metastasis by PC-3M cells. LNCaP tumors in the mouse prostate (but not PC-3M tumors) elaborated detectable levels of human prostate-specific antigen (PSA) in the serum, even when tumors were small (1.5 mm in diameter). Immunohistochemistry analysis revealed the presence of the PSA marker in tissue sections of LNCaP but not of PC-3M tumors. Conclusions The implantation of human prostate cancer cells in an ectopic environment does not permit expression of metastatic potential. In contrast, intraprostatic implantation does. Implications These data suggest that the orthotopic injection of human prostate cancer cells into the nude mouse may provide a valuable model to study the biology and therapy of human prostate cancer.

We established variants resistant to human interferon (IFN) from an IFN-sensitive human colon carcinoma cell line and delineated some of the mechanisms for resistance to IFN-mediated cytotoxicity. The parent KM12C cells were incubated for 2 months in medium containing recombinant human IFN-alpha hybrid BBDD (r-IFN-alpha) or recombinant human IFN-gamma (r-IFN-gamma). Surviving variants were designated KM12 alpha R and KM12 gamma R, respectively. KM12 alpha R cells were cross-resistant to the cytostatic and cytolytic effects of r-IFN-alpha, r-IFN-beta, and r-IFN-gamma, whereas KM12 gamma R cells were resistant only to the effects of r-IFN-gamma. The parent and variant cell lines had similar in vitro growth rates and similar tumorigenicity in male BALB/c nude mice, but the mechanisms for resistance to IFNs differed in the two variant lines. The resistance of the cross-resistant KM12 alpha R cell line was not attributable to the loss of specific receptors, because our analyses demonstrated the presence of receptors for IFN-gamma, whereas the KM12 gamma R line lacked specific receptors for IFN-gamma. Northern blot analyses revealed that messenger RNA (mRNA) from the proto-oncogene c-myc was equally expressed in the IFN-sensitive and IFN-resistant cell lines and that treatment with r-IFN-gamma did not alter its expression. Treatment with r-IFN-gamma induced the expression of manganous superoxide dismutase mRNA in KM12C and KM12 alpha R cells, but not in KM12 gamma R cells, confirming that both KM12C and KM12 alpha R cells, but not KM12 gamma R cells, have functional receptors for IFN-gamma.

To the Editor .— I am concerned that one of the conclusions of the study “Association Between Television, Movie, and Video Game Exposure and School Performance”1 might easily be misinterpreted or overlooked. The authors examined middle school students' self-report of their school performance and correlated the resulting scores to several …

Background: Overexpression of epidermal growth factor receptor (EGF-R) is associated with increased malignant potential and correlates with poor clinical outcome in head and neck cancer. Therefore, inhibition of the EGF-R pathway provides an ideal target for molecular therapy. We examined in vitro and in vivo effects of PK1166, an orally administered EGF-R inhibitor, on 2 human squamous cell carcinoma of the oral cavity cell lines, Tu159 and MDA1986. Study Design: Basic science, laboratory investigation. Results: For Western blotting, Tu159 and MDA1986 cells were pretreated for 1 hour and then stimulated with EGF. The EGF-R-specific tyrosine kinase autophosphorylation was inhibited completely by PKI166 at all doses tested (1-10 μg/mL). By means of a tetrazolium-based viable cell assay, PK1166 was shown to arrest the growth of Tu159 and MDA1986 cells. The inhibitory concentration (50%), calculated from regression lines on the linear portion of the growth inhibition graphs, was 0.18μM (R=0.98) for Tu159 cells and 0.23μM (R=0.97) for MDA1986 cells. Nude mice were inoculated subcutaneously with 1 x 10 6 Tu159 tumor cells and observed for 7 days. Next, daily doses of PKI166 (0, 10, or 50 mg/kg) were delivered by orogastric lavage for 28 days and the animals were observed for tumor growth. PKI166 significantly reduced tumor growth in mice treated for 1 month with oral PKI166 in a dose-dependent fashion. Conclusions: Targeted molecular therapy with EGF-R blockade arrests the growth of oral cancer in vitro and reduces its proliferation in an experimental xenograft animal model.

Scanning electron microscopic studies revealed that the cell bodies of cultured C6 cells were densely covered with villi and that membrane blebs were rare. Exposure to a hydroxyl radical generating system resulted in rapid ultrastructural changes. Within 2.5 minutes, 98% of the cells lost their villi. The number of blebbed cells increased during the first 7.5 minutes of exposure, until virtually all cells were blebbed. After 20 and 30 minutes of exposure, the plasma membrane of the blebs ruptured, resulting in the escape of cell contents and cell necrosis. Trypan blue exclusion, a measure of cell viability, decreased between 1 and 7.5 minutes of exposure. No further significant decline in viability was observed for the remainder of the experiment. The hydroxyl radical generating system also initiated a rapid onset of membrane lipid peroxidation, as measured by accumulation of thiobarbiturate reactive material. After a short lag period, thiobarbiturate reactive material increased rapidly, with maximum lipid peroxidation occurring by 20 minutes. Increasing the concentration of the radical generating system components shortened the time course but not the level of maximal thiobarbiturate reactive material production. These data suggest that plasmalemmal lipid peroxidation plays a role in rapid morphological changes and necrosis that occur after free radical insult.

Qualitative behavioral deficits after bilateral lesion of the rat dorsal funiculus at T12–13 were studied during prelesion, postoperative (14 to 21 days postlesion), and terminal (the last 4 days before killing at 30, 45, 60, 90, or 120 days postlesion) periods. Utilizing each animal (36 with lesion, 5 sham stress) as its own preoperative control, hind limb performance was rated for five behavioral components (slips, recovery, manner of traverse, movement, tail position) on four apparatuses (wide platform, narrow platform, ladder, parallel bars). Significant postoperative deficits ( N = 36) occurred on slips, recovery, and manner; Spearman coefficients between apparatus pairs suggested that either of the platforms and/or parallel bars could have demonstrated most component deficits. Sham-stress controls ( N = 5) showed no significant deficits in postoperative performance. Postoperatively, lesion size correlated with some performance deficits. Also, significant postoperative deficits were obtained with 25 to 87% damage of the dorsal column, though solely in the manner of traverse as an individual component; additional destruction (90 to 100%) of the dorsal column added several other deficits. Larger dorsal funicular lesions which included at least 50% of the corticospinal tract significantly affected performance still further, particularly on the parallel bars. Terminal performance ( N = 24), in general, was significantly poorer than that at prelesion periods on 23 (of 29 possible) comparisons. Terminal performance degraded considerably at 90 and 120 days compared with post-operative behavior. Because, in related deafferentation studies, changes in bouton renewal and neuronal excitability can occur at these late postlesion periods, eroded behavioral deficits may reflect a loss of synaptic elements critical in mediating stable behavior.

Fetal spinal cord grafts survive for long periods in host spinal cord. We explored the ability of such grafts into a lesion in C3 fasciculus gracilis to influence the expected deterioration of hind limb performance following this lesion. Ten adult Sprague-Dawley rats were placed on a schedule of 23 h off and 1 h on water. These subjects were then trained to traverse a narrow platform for a water reward. Criterion was established as 10 trials/day completed in 15 s a trial for 2 consecutive days. Animals were ranked for hind limb and forelimb performance utilizing slips, recovery, and manner of traversing the platform. In a triple-blind experimental design, the animals' identification was coded and laminectomy performed at C3. The fasciculus gracilis was bilaterally transected at the rostral and caudal borders of the segment and aspirated. Five subjects were chosen at random immediately after the lesion was made for the implantation of two 1-mm segments of E14 spinal cord from fetuses of timed pregnant Sprague-Dawley dams at the time of the lesion. Coded lesion and lesion-transplant animals were then tested after 21, 30, 45, 60, and 90 days until criterion or for 4 days. Hind limb performance of the lesion-only (ANOVA chi 2 = 13.04, df 5; P less than 0.05) and lesion-transplant groups (ANOVA chi 2 = 11.82, df 5; P less than 0.05) showed that the C3 fetal transplants significantly decreased (P less than 0.05) the severity of hind limb deficit at 21 days postlesion and significantly (P less than 0.05) decreased the expected foot slips and limb recovery to the platform that was expected and did develop in lesion-only animals at 90 days. There were no significant differences in forelimb performance (ANOVAs P greater than 0.05). There were few small-caliber nerve fibers in the fasciculus gracilis at the level of C1 indicating that reinnervation was not a major factor in the reduction of the deficit.

Proper closure of most wounds will negate the need for later scar revision. The goals of wound closure in the primary care setting are to stop bleeding, prevent infection, speed healing, and preserve the appearance and function of the injured area. The physician must evaluate each wound separately and use those techniques of wound closure that will provide the best results. In this article, the goals, principles, and some of the techniques of wound closure, including types of debridement, undermining, and closure in layers, are discussed. Different types of stitches and closure of difficult lacerations are also discussed.

Successful transplantation of the fetal brain into adult host brain has been accomplished. These studies explore the growth, differentiation, and viability of E11, E12, and E15 rat fetal cortex and fetal spinal cord implantation into the spinal cord of adult rats (donor and host, Sprague-Dawley). Under deep Chloropent anesthesia, 70 rats had 1-mm cubes of fetal cortex inserted with pressure or by stylus injection subpially between the dorsal horn and dorsal column (left side), or implantation of whole segments of fetal spinal cord. Animals were prepared for light microscopy 14 and 21 days and 1, 2, and 3 months later. Implants by both fetal tissues had a 69% survival rate. The younger the fetal implant the higher the success of the implant (E11 greater than E15). The diameter of fetal spinal cord implants reached the diameter of control postnatal animals after 30 days. The implants not only increased in mass (up to 7-fold in some cases) but differentiated and matured (apolar, unipolar, bipolar, and multipolar) neurons were observed one to three months postimplantation. By 30 days postimplantation, fetal neurons had large, often crenated nuclei, with a large single prominent nucleolus. The most successful implants were the young E11 fetal spinal cord into the adult host spinal cord. These implants represent an initial successful transplantation of fetal spinal cord into adult spinal cord.