Search

Autonomous underwater vehicles (AUVs) have gained more interest in recent years for military as well as civilian applications. One potential application of AUVs is for the purpose of undersea surveillance. As research into undersea surveillance using AUVs progresses, issues arise as to how an AUV acquires, acts on, and shares information about the undersea battle space. These issues naturally touch on aspects of vehicle autonomy and underwater communications, and need to be resolved through a spiral development process that includes at sea experimentation. This paper presents a recent AUV implementation for active anti-submarine warfare tested at sea in the summer of 2010. On-board signal processing capabilities and an adaptive behavior are discussed in both a simulation and experimental context. The implications for underwater surveillance using AUVs are discussed.

Diacylglycerol acyltransferase-1 (DGAT-1) is the enzyme that catalyzes the final and committed step of triglyceride formation, namely, the acylation of diacylglycerol with acyl coenzyme A. DGAT-1 deficient mice demonstrate resistance to weight gain on high fat diet, improved insulin sensitivity, and reduced liver triglyceride content. Inhibition of DGAT-1 thus represents a potential novel approach for the treatment of obesity, dyslipidemia, and metabolic syndrome. In this communication, we report the identification of the lead structure 6 and our lead optimization efforts culminating in the discovery of potent, selective, and orally efficacious carboxylic acid derivatives of 2-phenyl-5-trifluoromethyloxazole-4-carboxamides. In particular, compound 29 (DGAT-1 enzyme assay, IC(50) = 57 nM; CHO-K1 cell triglyceride formation assay, EC(50) = 0.5 μM) demonstrated dose dependent inhibition of weight gain in diet induced obese (DIO) rats (0.3, 1, and 3 mg/kg, p.o., qd) during a 21-day efficacy study. Furthermore, compound 29 demonstrated improved glucose tolerance determined by an oral glucose tolerance test (OGTT).

Surveillance in antisubmarine warfare (ASW) has traditionally been carried out by means of submarines or frigates with towed arrays. These techniques are manpower intensive. Alternative approaches have recently been suggested concerning distributed mobile and stationary sensors, such as sonobuoys and autonomous underwater vehicles (AUVs). To field a fully operational system, many technological hurdles need to be overcome. These include battery life, limited acoustic communications ranges, incorporating sonar signal processing on the AUV's embedded hardware, and increasing autonomy to ensure that the system as a whole acts in a sensible and appropriate fashion. The main thrust of this paper is how the latter two issues have been addressed for a real experimental system and how the proposed solutions have been demonstrated at sea. This paper describes ongoing development at the NATO Undersea Research Centre (NURC) to construct an autonomous distributed sensor system that uses AUVs for ASW applications. In a series of at-sea experiments, we have demonstrated real-time processing—incorporating traditional ASW processing as far as tracking—and adaptive autonomous behaviors, which concern AUV navigation to optimize target localization. This paper describes the hardware and software configurations that facilitated the rapid development of this system and details the recent at-sea successes that have been demonstrated with our AUV, towed arrays, and active acoustic sources. Results are given of our most recent at-sea trial, GLINT09, held in the summer of 2009, when an AUV with a towed array detected and maneuvered in response to an active source. © 2010 Wiley Periodicals, Inc.

We present a scalable end-to-end system for vision-based monitoring of natural environments, and illustrate its use for the analysis of avian nesting cycles. Our system enables automated analysis of thousands of images, where manual processing would be infeasible. We automate the analysis of raw imaging data using statistics that are tailored to the task of interest. These “features” are a representation to be fed to classifiers that exploit spatial and temporal consistencies. Our testbed can detect the presence or absence of a bird with an accuracy of 82%, count eggs with an accuracy of 84%, and detect the inception of the nesting stage within a day. Our results demonstrate the challenges and potential benefits of using imagers as biological sensors. An exploration of system performance under varying image resolution and frame rate suggest that an in situ adaptive vision system is technically feasible.

Sensor networks promise to transform and expand environmental science. However, many technological dif- ficulties must be overcome to achieve this potential. Partnerships of ecologists with computer scientists and engineers are critical in meeting these challenges. Technological issues include promoting innovation in new sensor design, incorporating power optimization schemes, integrating appropriate communication protocols, streamlining data management and access, using innovative graphic and statistical analyses, and enabling both scientists and the public to access the results. Multidisciplinary partnerships are making major contribu- tions to technological advances, and we showcase examples of this exciting new technology, as well as new approaches for training researchers to make effective use of emerging tools.

This review of the Twitter weekly discussion group, #sachat, discusses the benefits of using this social media for professional and personal development.

This article reviews ongoing work to increase awareness of, and raise standards in relation to, freedom of peaceful assembly across Europe, the South Caucasus, and Central Asia. The work is led by the Office of Democratic Institutions and Human Rights (ODIHR) at the Organisation of Security and Co-operation in Europe (OCSE). The article begins by highlighting the importance of freedom of peaceful assembly within democratic societies, and then describes the development of the ODIHR Guidelines on Peaceful Assembly. The article outlines some of the key issues of contention relating to the regulation of freedom of assembly, and discusses the process of reviewing the existing and draft legislation against the standards articulated in the Guidelines. In this context, the article also explores the potential for constructive engagement between government, civil society, and the OSCE to facilitate legislative amendments that respect key human rights norms and principles. Finally, the article reviews recent developments in training monitors of public assemblies with the aim of building local monitoring capacity and thus developing an evidence base of the practical implementation of laws relating to freedom of peaceful assembly.

Plant phenology relates strongly to primary productivity and the energy that enters into ecological food webs, and thus is vital in understanding ecosystem function and the effects of climate and climate change. The manual collection of phenological data is labor-intensive and not easily scalable, thus the ability to quantify leaf flush and other parameters at many locations requires innovative new methodologies such as the use of visible light digital cameras. Improved imaging performance was obtained by using a cabled, mobile camera system that allowed a repeated image census of branches of Rhododendron occidentale in the understory along a 30 m transect during leaf flush. Automatic division of acquired images into areas of interest (leaves) and background for calculating leaf area was accomplished by thresholding images in different color spaces. Transformation of the color space into the hue, saturation, and luminance (HSL) color space before thresholding resulted in a mean RMS error of 21.2 cm 2 compared to hand-counts of leaf area. Thresholding in the native red, green, and blue (RGB) color space to isolate leaves resulted in a larger error, as did using algebraic combinations of the color components or color ratios. Relating physiological function to images, as for sap flow for branches of R. occidentale , indicates that the greening and calculated leaf area of a species as detected by imagers requires additional meteorological sensor data for interpretation.

A phase I study of AVN944, an inosine monophosphate dehydrogenase (IMPDH) inhibitor, was carried out to assess its safety, tolerability, pharmacokinetics, and pharmacodynamics. Healthy male volunteers (N = 25) participated in this double-blind, randomized, placebo-controlled trial. Sixteen received oral doses ranging from 25 to 250 mg on 3 separate occasions at intervals of 3 or 6 days after overnight fasting. Six participants received two 100-mg doses, and 2 participants received 2 placebo doses, one with food and the other after fasting overnight. Clinical and laboratory parameters, including excretion of AVN944 and thiocyanate and IMPDH inhibition, were made at intervals for 48 hours postdosing. There were 13 mild and 2 moderate but no serious adverse events. One mild and 1 moderate event could be treatment related. AVN944 disappeared rapidly from plasma, but clearance decreased at doses > 50 mg. Food reduced absorption, with a geometric mean Cmax ratio of 33% and a geometric mean AUC0-infinity ratio of 44%. Urinary excretion was negligible. AVN944 doses > 100 mg showed definite IMPDH inhibition lasting at least 4 to 6 hours. AVN944, when administered orally to healthy volunteers, is well tolerated, absorbs better with fasting, and exhibits a pharmacodynamic profile that suggests potential for significant anticancer activity.

Discontinuous sills of felsic gneiss in the interior and western margin of the Berkshire massif and granite sills on the eastern margin of the massif were correlated by Ratcliffe (1984a, 1984b, 1985) and Ratcliffe and Hatch (1979), and interpreted by them as syntectonic anatectic melts that intruded Taconic thrusts. We dated three felsic gneiss sills and two granite sills in an attempt to constrain the age of Taconic thrusting, but discovered that the sills are not coeval. Rather, they were intruded during two widely separated episodes, one during the Mesoproterozoic at approximately 1000 Ma and the other during the Silurian at approximately 430 to 435 Ma. The 1000 Ma sills of felsic gneiss in the interior of the massif are located in Mesoproterozoic units and many of the mapped Taconic thrusts within the massif closely follow the distribution of this unit, here informally called the felsic gneiss of Harmon Brook. These 1000 Ma sills formed during the Ottawan or Rigolet orogeny and they have no connection to the Taconic orogeny. The 430 to 435 Ma granite sills along the eastern margin of the massif, informally called the granite of Becket Quarry, are found in both Mesoproterozoic basement and the Neoproterozoic Hoosac Formation. The sills are too young to have intruded during the Ordovician Taconic orogeny, but they may have formed during later faulting near the contact between Mesoproterozoic basement and Neoproterozoic cover rocks. The Tyringham Gneiss is one of the most common Mesoproterozoic units in the Berkshire massif. Zircons from the Tyringham Gneiss contain cores with oscillatory zoning and thin unzoned rims. The weighted average of eight 206 Pb/ 238 U analyses from the cores is 1179 /- 9 Ma, whereas nine spot analyses from the rims yield an age of 1004 /- 9 Ma. We interpret these two ages to represent the crystallization of the Tyringham Gneiss protolith and a subsequent high grade metamorphism, coeval with the intrusion of the felsic gneiss of Harmon Brook. The western contact between Mesoproterozoic rocks of the Berkshire massif and underlying Early Paleozoic rocks is clearly a thrust, but there is no independent evidence that movement occurred during the Taconic orogeny; displacement may also have occurred during the Silurian Salinic or the Devonian Acadian orogeny. Many contacts mapped as Taconic thrusts within the Berkshire massif follow the distribution of the 1000 Ma felsic gneiss of Harmon Brook. The age of the sills is clearly incompatible with this interpretation, and evidence for faulting along these mapped thrusts is lacking. Instead of being deformed into an imbricate stack, the massif behaved as a rigid block during Paleozoic uplift. Finally, the age of granite sills along the eastern margin of the massif does not constrain the basement-cover contact to be a Taconic thrust, as previously interpreted. The contact may be a Silurian fault, possibly related to extension and the opening of the Connecticut Valley trough as a back-arc basin. According to this model, the magma for the granite sills was generated above a west-dipping subduction zone under the Laurentian margin, which developed after the Taconic orogeny.

Soil organisms undertake every major ecosystem process, from primary production to decomposition to carbon sequestration, and those processes they catalyze have a bearing on the management of issues from agriculture to global climate change. Nonetheless, until recently, research to measure the dynamics of microscopic organisms living belowground has largely been limited to infrequent field sampling and laboratory extrapolation. Now, however, new sensor technologies can measure and monitor soil organisms and processes at rapid and continuous temporal scales. In this article, we describe these technologies and how they can be arrayed for an integrated view of soil dynamics.

A method for objective quantification of bleeding symptoms in immune thrombocytopenic purpura (ITP) has not been established. The ITP Bleeding Scale (IBLS) is a novel bleeding assessment system comprising 11 site-specific grades. Implementation of the IBLS on 100 patient visits revealed that although platelet count and large platelet count correlated well with bleeding symptoms overall, this relationship disappeared in marked thrombocytopenia. The IBLS is a useful clinical tool for monitoring bleeding and may be used to aid the development of laboratory parameters that correlate with underlying bleeding propensity in thrombocytopenia.

Baseball, which is one of the most popular sports in the world, has a uniquely discrete gameplay structure. This stop-and-go style of play creates a natural ability for fans and observers to record information about the game in progress, resulting in a wealth of data that is available for analysis. Major League Baseball MLB, the professional baseball league in the US and Canada, uses a system known as PITCHf/x to record information about every individual pitch that is thrown in league play. We extend the classification to pitch prediction fastball or nonfastball by restricting our analysis to pre-pitch features. By performing significant feature analysis and introducing a novel approach for feature selection, moderate improvement over published results is achieved.

Simple visible‐light digital cameras offer a potential for expanded forms of plant ecological research. The moss Tortula princeps undergoes changes in reflected visible light during cycles of drying and hydrating in the field, and the MossCam project has collected digital images of T. princeps at least daily since 2003. Laboratory studies can be used to calibrate these images to indicate field physiological conditions. Drying the moss 6 d in the laboratory resulted in a decrease of net CO2 uptake to near 0; recovery after rewetting occurred within 10 min. The difference in reflectance between hydrated and dry T. princeps was maximal ca. 550 nm, and maximal net CO2 uptake was linearly related to the green:red ratio of laboratory images when net CO2 uptake was positive. Using the green:red ratio of field images and otherwise assuming ideal conditions, the total carbon gain for a 6‐d period around a 1.3‐mm rain event was ca. 208 mmol CO2 m−2, equivalent to 69 d of respiration under dry conditions. Using a vi...

Animals with oral masses are a relatively common presentation in small animal practice, with the oral cavity reported as the fourth most common site of neoplasia in dogs1 and tumours in this site representing approximately 6% of all canine neoplasms2. Although a variety of benign conditions can present as a proliferative lesion or local swelling within the mouth, any oral mass should be seen as potentially malignant and investigated accordingly. Part 1 of this two article series discusses the diagnosis, classification and biological behaviour of oral neoplasms in the dog and cat and Part 2 will discuss prognosis and available treatment options.

The consequences of restricting or not restricting the right to freedom of assembly are potentially magnified in transitional societies. Yet determining whether such consequences are indeed ‘harmful’, and whether their cost should be borne despite the harms caused, requires the elaboration of criteria which define what are valid and relevant harms. While a human rights framework can perform this task, open-textured rights standards prescribe neither the threshold of legal intervention nor the goals of transition. By extension, the rule of law - underpinned by this rights discourse - is silent about whether liberal or communitarian ideals should inform the reconstruction of public space in conflicted or nascent democracies. Illustrated by analysis of legal interventions in parade disputes in Northern Ireland, this article argues that the rule of law is necessarily orientated by ethical consensus about its scope. Furthermore, this consensus operates as a restraint upon the degree of normative discontinuity permitted during transitional compromises. The article frames the ethical options in terms of three liberty-limiting principles - the argument from democracy, the argument for toleration, and the argument for recognition. Each suggests different parameters for the transitional project and for the role of law within it.

Sabastiya is located in the West Bank 15 km. north-west of the city of Nablus, on the eastern slope of the hill below the ancient site of Samaria-Sebaste. At the centre of the village the main mosque stands within the remains of a Crusader cathedral. Winding, dusty alleys and lanes radiate from the village square in front of the mosque. A few medieval and many Ottoman buildings survive, some in a good state of preservation. One of the buildings from the Ottoman period, the Bayt al-Hawwari, was the subject of the twelfth season of the Medieval and Ottoman Survey (MOS) carried out during four weeks from mid-August to mid-September 2000. It is a semi-private family compound (hawsh) with numerous rooms built at different times around a central courtyard reached by a formal entrance doorway from the street. Local tradition has it that the earliest part of the building was constructed in the late eighteenth century, with other parts added later.

Purpose To determine the clinical toxicities of 17-(allylamino)-17-demethoxygeldanamycin (17-AAG) given as a 1-hour infusion daily for 5 days every 3 weeks. Patients and Methods Nineteen patients received 17-AAG over six dose levels (10 to 56 mg/m2) using an accelerated titration scheme. Drug levels of 17-AAG were determined by high-performance liquid chromatography. Biologic effects of 17-AAG were monitored by changes in the content of target proteins by immunoblot analysis of lysates prepared from peripheral-blood mononuclear cells. Results Toxicity was acceptable at doses up to 28 mg/m2. The cohort was expanded to three patients at 40 mg/m2 because a second occurrence of grade 2 hepatic transaminitis occurred. Two of six assessable patients who received 56 mg/m2 had reversible, grade 3 hepatic transaminitis. Five additional patients were enrolled at 40 mg/m2; none had dose-limiting toxicity. The maximum plasma concentrations (Cmax) of 17-AAG at 40 and 56 mg/m2 were 1,724 and 2,046 ng/mL, respectively; the average plasma exposures (AUC) were 2,809 and 6,708 hours·ng/mL, respectively. Less than 3% of the daily dose was excreted into the urine. Clearance did not correlate with body-surface area. Possible biologic activity was suggested by apparent increased protein content of either glucose-related 78 kd protein or heat shock protein 70 with ≥ 14 mg/m2 and decreased protein content of either Lck or Raf1 with ≥ 28 mg/m2 of 17-AAG. Conclusion 17-AAG 40 mg/m2 (median dose, 70 mg) was well tolerated when given daily for 5 days every 3 weeks.

Since preclinical studies have shown more than additive cytotoxicity and DNA damage with the combination of gemcitabine and 5-fluoro-2'-deoxyuridine (FUDR), we studied this combination in a phase I trial.Gemcitabine alone was given in cycle 1 as a 24-h, 2-h or 1-h i.v. infusion weekly for 3 of 4 weeks; if tolerated, a 24-h i.v. infusion of FUDR was added with oral leucovorin. The cycle was aborted for grade 3 thrombocytopenia, grade 4 neutropenia, and grade 2 or worse nonhematologic toxicity.During cycle 1, six of eight patients who received 150 or 100 mg/m2 over 24 h had dose-limiting neutropenia, thrombocytopenia, fatigue or mucositis. Six of seven patients treated with 1000 mg/m2 over 2 h required a gemcitabine dose reduction for cycle 2 (thrombocytopenia, neutropenia, fatigue). Of 25 assessable patients who received gemcitabine 1000 mg/m2 over 1 h, 7 did not complete cycle 1 due to thrombocytopenia (n=6) or diarrhea (n=1). Of 42 patients entered, 27 received at least one course of gemcitabine/FUDR (5-19.5 mg/m2 over 24 h) without appreciable toxicity. Due to a shortage of FUDR, the protocol was closed early. Gemcitabine plasma concentrations averaged 0.061 micro M (24 h), 16.3 micro M (2 h), and 31.9 micro M (1 h). In 21 paired bone marrow mononuclear cell samples obtained before treatment and during FUDR infusion, thymidylate synthase ternary complex was only seen during FUDR infusion.Gemcitabine 100-150 mg/m2 over 24 h was poorly tolerated, whereas toxicity was acceptable with 800-1000 mg/m2 over 1 h. Inhibition of the target enzyme was demonstrated at all FUDR doses.

In this phase I/II clinical trial the antitumor activity of high-dose tamoxifen when administered in combination with vinblastine was assessed and the toxicity profile of this combination characterized. All 25 patients enrolled in this study were required to have androgen-independent prostate cancer and to maintain androgen ablation during treatment. Vinblastine was given by continuous infusion over 5 days. Doses were increased from 0.9 mg/m2/day to 1.5 mg/m2/day in successive cohorts of at least 3 patients, with no further escalation even in the absence of dose-limiting toxicity. Intra-patient dose escalation was permitted. Tamoxifen was administered at a dose of 200 mg/kg on day 1, then 120 mg/kg/day on day 2. Standard response criteria were utilized to assess antitumor activity and CTC toxicity criteria were used. Quality of life (QOL) pain assessments were evaluated at each visit to the clinic. Most patients tolerated the highest dose of vinblastine at 1.5 mg/m2/day by continuous infusion over 5 days with 200 mg/kg/day of tamoxifen on day 1 and day 2. One patient had a greater than 50% decline in prostate-specific antigen that lasted for 170 days. Two patients received dose reductions because of toxicity. The most common serious toxicities included neutropenia, and fatigue. Reversible neurosensory, neuromotor, neurocortical and neurocerebellar toxicities were reported. Six of the 25 patients enrolled in the study (24%) experienced reversible neurologic toxicity of at least grade III. No statistically significant differences between precycle assessment of QOL and subsequent cycles were observed. It is concluded that vinblastine at 1.5 mg/m2/day continuous i.v. infusion combined with tamoxifen 200 mg/kg/day on day 1 and day 2 is inactive, and not without toxicity in the treatment of advanced metastatic androgen-independent prostate cancer.

BACKGROUND A Phase I trial of recombinant vaccinia prostate specific antigen (rV-PSA) in patients with advanced metastatic prostate cancer was conducted. This report describes 42 patients who were treated with up to three monthly vaccinations. METHODS All patients were entered on a dose-escalation phase I study of recombinant vaccinia containing the gene for PSA (rV-PSA). The primary objective of this study was to determine the safety of this vaccine in metastatic androgen-independent prostate cancer patients. A secondary objective was to assess evidence of anti-tumor activity by PSA measurements, radiologic findings, and immunologic methods. RESULTS There was no significant treatment-related toxicity apart from erythema, tenderness, and vesicle formation that lasted several days at the site of injection in some patients. There were immunologic responses, in selected patients, as evidenced by an increase in the proportion of PSA-specific T cells after vaccination. Furthermore, we show that these patients' T cells can lyse PSA-expressing tumor cells in vitro. CONCLUSION Given the low toxicity profile and the evidence of immunologic activity, we believe future study is warranted with PSA-based vaccines in prostate cancer. New PSA-based vaccines and vaccine strategies are currently being evaluated. Prostate 53: 109–117, 2002. © 2002 Wiley-Liss, Inc.

The prevalence of overweight and obesity is increasing worldwide. During the last two decades, the prevalence of adults in the higher body mass index (BMI) categories in the US has increased the most, as much as 300% for those with a BMI above 40kg/m2. In children and adolescents, a doubling of the prevalence of severe overweight poses a serious health risk to future generations of young adults who may develop chronic diseases normally associated with aging. The simple definition of obesity, an imbalance between energy intake and energy expenditure, ignores the complexity of, and largely unknown interactions between, genes, food intake and physical activity, which together determine bodyweight and fat distribution. Although the etiology and manifestations of overweight and obesity are complex, the assessment of overweight and obesity requires only an accurate measurement of bodyweight, height and abdominal circumference, as well as a history and physical examination attuned to the morbidities that commonly accompany overweight and obesity such as diabetes mellitus, hypertension, dyslipidemia and sleep apnea. The treatment of patients with overweight and obesity continues to be based on changes to diet and physical activity. Simple behavior modification techniques are within the reach of busy clinicians. The additional use of available bodyweight reduction medications can reliably lead to a 5 to 10% reduction from initial bodyweight, a loss that has been shown to provide significant health benefit. The use of meal replacements has also been shown to be effective and is probably an under-appreciated treatment resource. Surgery is the most successful treatment for those with severe obesity and should be discussed as an option for those in the appropriate bodyweight categories. Because societal trends favor the greater intake of calorie-dense foods and less physical activity to accomplish the activities of daily life, the future of obesity treatment will require the development of bodyweight reduction medications that work by a variety of mechanisms to decrease food intake or increase energy expenditure. Such medications should not be viewed as a 'crutch' but rather as a 'helping hand' that enable people to better adhere to a healthier lifestyle.

Helicobacter pylori is a microaerophilic, gram-negative bacterium that is linked to adverse health effects including ulcers and gastrointestinal cancers. The goal of this analysis is to develop the necessary inputs for a quantitative microbial risk assessment (QMRA) needed to develop a potential guideline for drinking water at the point of ingestion (e.g., a maximum contaminant level, or MCL) that would be protective of human health to an acceptable level of risk while considering sources of uncertainty. Using infection and gastric cancer as two discrete endpoints, and calculating dose-response relationships from experimental data on humans and monkeys, we perform both a forward and reverse risk assessment to determine the risk from current reported surface water concentrations of H. pylori and an acceptable concentration of H. pylori at the point of ingestion. This approach represents a synthesis of available information on human exposure to H. pylori via drinking water. A lifetime risk of cancer model suggests that a MCL be set at1 organism/L given a 5-log removal treatment because we cannot exclude the possibility that current levels of H. pylori in environmental source waters pose a potential public health risk. Research gaps include pathogen occurrence in source and finished water, treatment removal rates, and determination of H. pylori risks from other water sources such as groundwater and recreational water.

Background Mutant Ras oncogenes produce proteins that are unique to cancer cells and represent attractive targets for vaccine therapy. We have shown previously that vaccinating cancer patients with mutant ras peptides is feasible and capable of inducing a specific immune response against the relevant mutant proteins. Here, we tested the mutant ras peptide vaccine administered in combination with low dose interleukin-2 (IL-2) or/and granulocyte-macrophage colony-stimulating factor (GM-CSF) in order to enhance the vaccine immune response. Methods 5000μg of the corresponding mutant ras peptide was given subcutaneously (SQ) along with IL-2 (Arm A), GM-CSF (Arm B) or both (Arm C). IL-2 was given SQ at 6.0 million IU/m2/day starting at day 5, 5 days/week for 2 weeks. GM-CSF was given SQ in a dose of 100μg/day one day prior to each ras peptide vaccination for 4 days. Vaccines were repeated every 5 weeks on arm A and C, and every 4 weeks on arm B, for a maximum of 15 cycles or until disease progression. Results We treated 53 advanced cancer patients (38 with colorectal, 11 with pancreatic, 1 with common bile duct and 3 with lung) on 3 different arms (16 on arm A, 18 on arm B, and 19 on arm C). The median progression free survival (PFS) and overall survival (OS) was 3.6 and 16.9 months, respectively, for all patients evaluable for clinical response (n = 48). There was no difference in PFS or OS between the three arms (P = 0.73 and 0.99, respectively). Most adverse events were grade 1-2 toxicities and resolved spontaneously. The vaccine induced an immune response to the relevant ras peptide in a total of 20 out of 37 evaluable patients (54%) by ELISPOT, proliferative assay, or both. While 92.3% of patients on arm B had a positive immune response, only 31% of patients on arm A and 36% of patients on arm C had positive immune responses (P = 0.003, Fisher’s exact test). Conclusions The reported data showed that IL-2 might have a negative effect on the specific immune response induced by the relevant mutant ras vaccine in patients with advanced cancer. This observation deserves further investigations. Trial registration NCI97C0141

Major League Baseball, a professional baseball league in the US and Canada, is one of the most popular sports leagues in the world. Partially because of its popularity and the wide availability of data from games, baseball has become the subject of significant statistical and mathematical analysis. Pitch analysis is especially useful for helping a team better understand the pitch behavior it may face during a game, allowing the team to develop a corresponding batting strategy to combat the predicted pitch behavior. We apply several common machine learning classification methods to PITCHf/x data to classify pitches by type. We then extend the classification task to prediction by utilizing features only known before a pitch is thrown. By performing significant feature analysis and introducing a novel approach for feature selection, moderate improvement over former results is achieved.

New therapeutic alternatives are needed to improve outcomes in patients with androgen-independent prostate cancer (AIPC). For several years, researchers at the National Cancer Institute have been interested in elucidating the importance of angiogenesis in the pathogenesis of prostate cancer and in identifying inhibitors of this process. Thalidomide has been shown to inhibit the ability of tumors to recruit new blood vessels. In a recent phase II trial of thalidomide in AIPC, 28% of patients achieved a prostate-specific antigen (PSA) decrease of >40%. The taxane docetaxel also produces PSA and measurable disease responses when used as monotherapy or as a component of combination chemotherapy for AIPC. Thus, based on the single-agent activity of thalidomide and docetaxel, we initiated a randomized phase II study of weekly docetaxel with or without thalidomide, 200 mg at bedtime, in patients with chemotherapy-naive metastatic AIPC. Docetaxel, 30 mg/m(2) intravenously, was administered every 7 days for 3 weeks, followed by a 1-week rest period. Both regimens have been well tolerated among the first 59 treated patients, with a near absence of grade (3/4) myelosuppression. Fatigue, hyperglycemia, and pulmonary toxicity were seen in both groups. Thrombotic events have been seen in the combination arm. Thirty-five percent (6 of 17) of the patients receiving docetaxel alone and 53% (19 of 36) of those receiving docetaxel and thalidomide have had a PSA decrease of at least 50%. Combining a cytotoxic agent with an angiogenesis inhibitor is a promising area of investigation for prostate cancer management.

As new fabrication and integration technologies reduce the cost and size of micro-sensors and wireless interfaces, it becomes feasible to deploy densely distributed wireless networks of sensors and actuators. These systems promise to revolutionize biological, earth, and environmental monitoring applications, providing data at granularities unrealizable by other means. In addition to the challenges of miniaturization, new system architectures and new network algorithms must be developed to transform the vast quantity of raw sensor data into a manageable stream of high-level data. To address this, we propose a tiered system architecture in which data collected at numerous, inexpensive sensor nodes is filtered by local processing on its way through to larger, more capable and more expensive nodes.We briefly describe Habitat monitoring as our motivating application and introduce initial system building blocks designed to support this application. The remainder of the paper presents details of our experimental platform.

In order to better define the facies architecture and processes controlling the evolution of wave-dominated deltas, a detailed sedimentary and geomorphologic study was undertaken on the Brazos Delta, Texas. The delta has formed since 1929, when the Brazos River was diverted by the U.S. Army Corps of Engineers. The Brazos Delta is composed primarily of fine-grained sediments. Prodelta clay constitutes more than half of the sediment volume. Thick sands are restricted to the narrow delta-front environment, whereas back-bar lagoonal clays are a significant component of the delta-plain sequence. The facies architecture is not representative of the classic strandplain model for wave-dominated deltas. This is due to the strong influence of floods on deltaic evolution. In early 1992, statewide flooding gave rise to a major constructional phase of the delta. Significant quantities of fine-grained sediments were deposited in the prodelta. One year after the onset of flooding, a channel mouth bar emerged offshore of the river mouth and enabled progradation of the delta. Similar flood events that occurred during 1941, 1957, and 1965 were recorded as ridge-trough pairs in the delta headland. The Brazos delta is therefore fluvially influenced during floods and wave influenced during intervening periods.

Varicella zoster (V-Z) infections are common among patients with hematological malignancies, particularly Hodgkin's disease (HD). The common denominator in both HD and V-Z infections is immunosuppression. Most of V-Z infections occur in patients with HD during the remission period, who have mixed cellularity sub-type, with stage III disease and who have received combined chemo-radiation therapy. Involvement of the central nervous system usually manifests as post-herpetic neuralgia or encephalitis. Angiitis has also been found in association with V-Z infections. The authors describe a case of HD who developed V-Z meningitis preceeded by superficial thrombophlebitis of upper extremities during the period of active chemotherapy.

A stochastic model wiuh exponential components is used to describe our data collected from a phase III cancer clinical trial. Criteria which guarantee that disease-free survival (DFS) can be used as a surrogate for overall survival are explored under this model. We examine several colorectal adjuvant clinical trials and find that these conditions are not satisfied. The relationship between the hazard ratio of DFS for an active treatment versus a control treatment and the cumulative hazard ratio of survival for the same two treatments is then explored. An almost linear relationship is found such that a hazard ratio for DFS of less than a threshold R corresponds to a non-null treatment effect on survival The threshold value R is determined for our colorectal adjuvant trial data. Based on this relationship, a one-sided test of equal hazard rate of survival is equivalent to a test of hazard ratio of DFS small than R This approach assumes that recurrence information is unbiasedly and accurately assessed; an as...

In the effort to design three-dimensional gestural interfaces for surface ship platforms, this study was conducted to evaluate the critical anthropometric factors that influence developing mutually exclusive static posture recognition algorithms. Using the Microsoft Kinect, 400 inter-joint distances determining critical key joint factors were collected to identify 15 static postures. By using a discriminant analysis, 9 out of 400 possible key inter-joint distances were identified for distinguishing the 15 postures. Comparing the discriminant function model predictions to the actual observed values for the 15 postures resulted in an overall prediction accuracy of 97 percent.

With touchscreen-enabled devices becoming more prevalent throughout military applications, it is important to create a standardized set of touchscreen gestures for military purposes. This standardized set must easily transfer among devices military personnel use for operations. The authors describe the identification of common gestures using mockups of large-screen and small-screen devices. Results show the majority of gestures were similar among participants, concluding that establishing military gesture standardization is very possible and could be put into practice throughout the military population, with training for less common gestures, and buttons or menu items used for very uncommon gestures. Through this research, the authors provide a beneficial first step in evaluating the set of gestures currently under development, and suggest further research with military personnel as a necessary next step for the development of a standardized gesture set for use in military purposes.

Background In eukaryotic organisms, gene expression is regulated at multiple levels during the processes of transcription and translation. The absence of a tight regulatory network for transcription in the human malaria parasite suggests that gene expression may largely be controlled at post-transcriptional and translational levels. Results In this study, we compare steady-state mRNA and polysome-associated mRNA levels of Plasmodium falciparum at different time points during its asexual cell cycle. For more than 30% of its genes, we observe a delay in peak transcript abundance in the polysomal fraction as compared to the steady-state mRNA fraction, suggestive of strong translational control. Our data show that key regulatory mechanisms could include inhibitory activity of upstream open reading frames and translational repression of the major virulence gene family by intronic transcripts. In addition, we observe polysomal mRNA-specific alternative splicing events and widespread transcription of non-coding transcripts. Conclusions These different layers of translational regulation are likely to contribute to a complex network that controls gene expression in this eukaryotic pathogen. Disrupting the mechanisms involved in such translational control could provide novel anti-malarial strategies.

The development of recombinant vaccines for specific immunotherapy of carcinoma represents a novel approach for the treatment of breast cancer and other tumor types. This article reviews the various parameters that should be considered in the development of recombinant vaccines. Several breast cancer associated antigens are also discussed which may provide potential target molecules. The human carcinoembryonic antigen (CEA), which is expressed on approximately 50% of breast cancers, represents one such target for immunotherapy. To enhance the immunogenicity of this antigen, a recombinant CEA-vaccinia vaccine, designated rV-CEA, was produced. To study the effects of this vaccine in an animal model, a murine colon carcinoma cell line was transduced with CEA and transplanted into immunocompetent mice for protection and therapy studies. Pre-clinical toxicity studies were also conducted in non-human primates. The results of these studies showed the rV-CEA vaccine to be immunogenic and safe in both rodents and primates, and to elicit good anti-tumor responses in the rodent model. In a Phase I clinical trial in metastatic breast, lung, and colorectal cancer patients involving three immunizations of rV-CEA, at three dose levels, enhancement of T-cell and antibody responses to vaccinia virus proteins were observed with no toxicity. Specific T-cell responses were studied via stimulation of peripheral blood lymphocytes with specific peptide epitopes from the CEA molecule. These studies demonstrated clear cut differences in establishment of T-cell lines pre- versus post-immunization. The T-cell lines were shown to be CD8+ and/or CD4+/CD8+, to lyse EBV transformed B-cells transduced with the CEA gene, and to lyse CEA positive carcinoma cells in a HLA restricted manner. Thus, in a Phase I clinical trial the rV-CEA vaccine has been shown to stimulate a CTL response specific for CEA defined epitopes in cancer patients.

To document outcome in 2 dogs and 2 cats after conversion of femoral head and neck excision (FHNE) to total hip replacement (THR).Case series.Dogs (n = 2) and 2 cats.For 1 dog and 2 cats, THR was performed using cemented acetabular and femoral components. Noncemented acetabular and cemented femoral components were used in 1 dog.All animals presented with severe hip pain and chronic lameness after unsuccessful FHNE. Potential causes of suboptimal outcome after FHNE were incomplete resection of the femoral neck (n = 3) and fibrous adhesions involving the sciatic nerve (n = 2). Post-FHNE remodeling of the proximal femur and acetabulum necessitated unconventional modifications of surgical technique. In all 4 cases, final clinical outcome and radiographic reassessment were satisfactory. Aseptic loosening of the acetabular bone-cement interface necessitating surgical revision was the only complication noted in 1 cat.Despite severe preoperative pain and chronic functional impairment in all cases, conversion of FHNE to THR produced marked clinical improvement including return to unrestricted exercise within 12 weeks of surgery.

This paper is a preliminary report on the development of a new instrument, the Impact of Weight on Quality of Life (IWQOL) questionnaire, that assesses the effects of weight on various areas of life. We conducted two studies utilizing subjects in treatment for obesity at Duke University Diet and Fitness Center. The first study describes item development, assesses reliability, and compares pre- and post-treatment scores on the IWQOL. In the second study we examined the effects of body mass index (BMI), gender, and age on subjects' perceptions of impact of weight on quality of life. Results indicate adequate psychometric properties with test-retest reliabilities averaging .75 for single items, and .89 for scales. Scale internal consistency averaged .87. Post-treatment scores differed significantly from pre-treatment scores on all scales, indicating that treatment produced positive changes in impact of weight on quality of life. The results of the second study indicate that the impact of weight generally worsened as the patients' size increased. However for women there was no association between BMI and impact of weight on Self-Esteem and Sexual Life. Even at the lowest BMI tertile studied, women reported that weight had a substantial impact in these areas. There were also significant gender differences, with women showing greater impact of weight on Self-Esteem and Sexual Life compared with men. The impact of age was a bit surprising, with some areas showing positive changes and others showing no change.

Extensive alternative splicing (AS) of precursor mRNAs (pre-mRNAs) in multicellular eukaryotes increases the protein-coding capacity of a genome and allows novel ways to regulate gene expression. In flowering plants, up to 48% of intron-containing genes exhibit AS. However, the full extent of AS in plants is not yet known, as only a few high-throughput RNA-Seq studies have been performed. As the cost of obtaining RNA-Seq reads continues to fall, it is anticipated that huge amounts of plant sequence data will accumulate and help in obtaining a more complete picture of AS in plants. Although it is not an onerous task to obtain hundreds of millions of reads using high-throughput sequencing technologies, computational tools to accurately predict and visualize AS are still being developed and refined. This review will discuss the tools to predict and visualize transcriptome-wide AS in plants using short-reads and highlight their limitations. Comparative studies of AS events between plants and animals have revealed that there are major differences in the most prevalent types of AS events, suggesting that plants and animals differ in the way they recognize exons and introns. Extensive studies have been performed in animals to identify cis-elements involved in regulating AS, especially in exon skipping. However, few such studies have been carried out in plants. Here, we review the current state of research on splicing regulatory elements (SREs) and briefly discuss emerging experimental and computational tools to identify cis-elements involved in regulation of AS in plants. The availability of curated alternative splice forms in plants makes it possible to use computational tools to predict SREs involved in AS regulation, which can then be verified experimentally. Such studies will permit identification of plant-specific features involved in AS regulation and contribute to deciphering the splicing code in plants.

Sulofenur (LY186641), a diarylsulfonylurea, was evaluated clinically utilizing either a daily x 21 schedule or a daily x 5 (with 2 days off) for 3 weeks schedule. Eighteen patients with refractory solid tumors received 47 evaluable courses of sulofenur given p.o. daily x 21 every 28 days at five dose levels while 14 received 29 courses of sulofenur given daily x 5 for 3 weeks every 28 days at three dose levels. Toxicities included anemia, methemoglobinemia and hemolysis. One patient experienced a fatal subendocardial infarction on the daily x 21 schedule. One partial response was observed in a patient with a sertoli cell tumor on the daily x 5 for 3 weeks schedule. Daily x 5 for 3 weeks is the schedule recommended for phase II trials.

To report use of, and outcome after, string-of-pearls (SOP™) plate and multiple cerclage wire fixation for treatment of periprosthetic femoral fractures (PFF) associated with total hip replacement (THR) in dogs.Case series.Dogs (n=6) with PFF after THR.Clinical records (2005-2010) and radiographic evaluations of dogs that had PFF associated with THR, treated with a SOP™ plate and cerclage wires were retrospectively reviewed. Clinical and radiographic postoperative assessments were performed 4, 12, and 24 weeks postoperatively. Telephone follow-up was performed12 months postoperatively.Three fractures occurred intraoperatively and 3 occurred postoperatively. One SOP™ failed at 2 weeks necessitating revision using 2 parallel SOP™ implants. One dog was euthanatized because of quadriceps muscle tie-down at 6 weeks. Other dogs were free of lameness with full range of motion of the stifle and hip joints at final clinical examination, and positive outcomes were maintained at12 month telephone questionnaire. There was no evidence of implant failure and positive evidence of fracture healing at final radiographic follow-up.Stabilization resulted in bone healing in 5 dogs; failure in 1 dog may be attributable to technical error. Optimal technical guidelines for use of the SOP™ in this circumstance are unknown, particularly where fracture configuration varies.

To describe a surgical technique for reinforced augmentation of the dorsal acetabular rim (DAR) using a string-of-pearls (SOP™) locking plate and polymethylmethacrylate (PMMA) bone cement, and to report clinical outcome in 7 dogs.Case series.Dogs (n=7).Medical records (November 2009-April 2010) of 7 dogs with large DAR deficits, that had total hip replacement (THR) with reinforced augmentation of the DAR using a SOP™ plate and PMMA were evaluated retrospectively. Reinforced augmentation of the DAR involved anchorage of a precontoured 2.0 or 2.7 mm SOP™ plate dorsal to the acetabulum followed by application of PMMA cement to cover the reamed acetabulum and plate. Cemented acetabular components were used. Implant associated complications were recorded and ≥6-month follow-up obtained.In all dogs, lameness improved at medium-term reassessment (median, 8 months; range, 6-11 months). Complications included transient sciatic neurapraxia in 2 dogs, which resolved by 3 months.Reinforced augmentation of the DAR using a SOP™ plate and PMMA cement may facilitate placement of acetabular THR component implantation in dogs with severe DAR insufficiency.

Forty years after the European Convention on Human Rights (ECHR) was drafted, the political climate of the region was transformed. Fledgling democracies in post-communist Eurasia faced many challenges, including the need to earn the political loyalty previously demanded by the so-called Peoples’ democracies. Ensuring this loyalty entailed the reconfiguration of the public sphere and, to varying degrees, the selective restriction of core political rights. In turn, this reconfiguration resulted in new dynamics of inclusion and exclusion – the inclusion of those previously excluded from the political domain, and the exclusion of those who would seek a return to the past or might otherwise undermine democratic consolidation. Restrictions upon political rights included the dissolution of successor communist parties and other political associations, lustration laws designed to ensure discontinuity with the prior regime, and the exclusion of certain categories of individuals from running for or holding political office.