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Nuclear waste management facilities at Chalk River Laboratories (CRL) use below-ground “tile-holes” to store solid waste from various activities such as medical isotope production. After long periods of isotopic decay, some of the waste has decayed down to low activities and can be transferred to low-level waste storage facilities. This paper presents a method to verify the radiation level of the waste inside tile-holes by performing gamma radiation scans along the depth of waste storage tile-holes. Such measurements allow for noninvasive verification of tile-hole contents and provide input to the assessment of radiological risk associated with removal of the waste. Using the radiation profile system, the radiation level of the radioactive waste may be identified based on the radiation profile. This information will support planning for possible transfer of this waste to a licensed waste storage facility designed for low-level waste, thus freeing storage space for possible tile-hole re-use for more highly radioactive waste. CRL-developed small diode-based gamma radiation sensors have been used in these radiation scans. The diode sensors were deployed into verification tubes adjacent to the tile-holes to measure the radiation profile. Over 10 tile-holes have been scanned using this technique since 2009.

Advances in radio astronomy are allowing for deeper and wider areas of the sky to be observed than ever before. Source counts of future radio surveys are expected to number in the tens of millions. Source finding techniques are used to identify sources in a radio image, however, these techniques identify single distinct sources and are challenged to identify multi-component sources, that is to say, where two or more distinct sources belong to the same underlying physical phenomenon, such as a radio galaxy. Identification of such phenomena is an important step in generating catalogues from surveys on which much of the radio astronomy science is based. Historically, identifying multi-component sources was conducted by visual inspection, however, the size of future surveys makes manual identification prohibitive. An algorithm to automate this process using statistical techniques is proposed. The algorithm is demonstrated on two radio images. The output of the algorithm is a catalogue where nearest neighbour source pairs are assigned a probability score of being a component of the same physical object. By applying several selection criteria, pairs of sources which are likely to be multi-component sources can be determined. Radio image cutouts are then generated from this selection and may be used as input into radio source classification techniques. Successful identification of multi-component sources using this method is demonstrated.

Background: Distal radius fractures represent a common fracture pattern frequently treated with volar locked plating for fixation. However, other methods may provide equivalent outcomes and minimize risks associated with the volar approach and hardware placement. One such method is the radial plate. Methods: After confirmation of institutional board review, we retrospectively reviewed data from 7 patients with our primary functional outcomes measured by Mayo wrist and Disabilities of the Arm, Shoulder and Hand (QuickDASH) scores. The most recent radiographic and motion parameters were recorded. Results: Mean age at time of injury was 49 years (range, 19-68 years) with clinical follow-up of 81.6 months (range, 43.5-95.5 months). Five patients had good to excellent outcomes with a mean QuickDASH score of 0.92 for those patients. The mean QuickDASH score for all patients was 18.5. Mean radial height, inclination, and volar tilt were within 5% of the contralateral side. Standard deviation values for radiographic measures and clinical range of motion indicate significant variability in our data set. Conclusions: Although the results are mixed, our small cohort indicates radial plate fixation could provide a viable alternative to volar plate fixation of distal radius fractures. Further prospective investigation is warranted to better describe long-term outcomes using this technique.

While considerable research has targeted gait, balance and preventing falls in individuals with Parkinson’s disease (PD), less in known about the ability to rise from the floor in this population. The aims of this study were to 1) Examine the relationship between locomotion and physical performance tests and the timed supine to stand performance measure and to 2) Identify both the time required and predominant motor patterns utilized by persons with PD to complete to floor rise transition. A cross-sectional design was utilized. Twenty community-dwelling older adults with PD (mean age 74.8+/-9.5 years; 13 men) performed a standardized floor rise test and locomotion tests in a structured task circuit. Subject demographic and anthropometric data were also collected. Statistical analyses included descriptive statistics and Pearson Product Moment correlations. Fifteen subjects (75%) demonstrated the crouch kneel pattern and fourteen (70%) used an all-4’s strategy to rise to stand. The mean time to rise from the floor was 14.9 (+/- 7.6) seconds and slower than published norms for persons without PD. Nine subjects required the use of a chair to perform floor recovery. Supine to stand performance time was significantly correlated with the: Dynamic Gait Index (r= - 0.66; p

In the setting a near or complete upper extremity amputations with significant soft tissue loss and neurovascular compromise, upper extremity surgeons are faced with the challenge of limb salvage. There are a multitude of treatment options for managing skeletal and soft tissue injuries including provisional fixation, staged reconstruction, and an acute shortening osteotomy with primary rigid internal fixation. However, many complications are associated with these techniques. Complications of provisional fixation include pin tract infection and loosening, tethering of musculotendinous units, nonunion, and additional surgeries. Staged reconstruction includes a variety of techniques: distraction osteogenesis, bone transport, or vascularized and non-vascularized structural autograft or allograft, but the risks often outweigh the benefits. Risks include nonunion, postoperative vascular complications necessitating reoperation, and the inability to return to the previous level of function at an average of 24 months. Acute shortening osteotomy with internal fixation offers the advantage of a single-stage procedure that provides for decreasing the soft tissue loss, provides a rigid platform to protect the delicate neurovascular repair, and alleviates unwanted tension at the repair sites. This review discusses the literature on the surgical treatment of severe upper extremity trauma with associated neurovascular injury over the past 75 years, and aims to evaluate the indications, surgical techniques, clinical and functional outcomes, and complications associated with acute shortening osteotomy with rigid internal fixation. Although this technique is not without risks, it is well-tolerated in the acute setting with a complication profile comparable to other techniques of fixation while remaining a single procedure.

The modeling of biological data can be carried out using structured sound and musical process in conjunction with integrated visualizations. With a future goal of improving the speed and accuracy of techniques currently in use for the production of synthetic high value chemicals through the greater understanding of data sets, the madBPM project couples real-time audio synthesis and visual rendering with a highly flexible data-ingestion engine. Each component of the madBPM system is modular, allowing for customization of audio, visual and data-based processing.

Plastic labware is used in all processes of modern pharmaceutical research, including compound storage and biological assays. The use of these plastics has created vast increases in productivity and cost savings as experiments moved from glass test tubes and capillary pipettes to plastic microplates and multichannel liquid handlers. One consequence of the use of plastic labware, however, is the potential release of contaminants and their resultant effects on biological assays. We report herein the identification of biologically active substances released from a commonly used plastic microplate. The active contaminants were identified by gas chromatography-mass spectroscopy as dodecan-1-ol, dodecyl 3-(3-dodecoxy-3-oxopropyl)sulfanylpropanoate, and dodecanoic acid, and they were found to be selective monoamine oxidase-B inhibitors.

This paper proposes methods for generation and implementation of uniform, large-scale data from auralized MIDI music files for use with deep learning networks for polyphonic pitch perception and impulse response recognition. This includes synthesis and sound source separation of large batches of multitrack MIDI files in non-real time, convolution with artificial binaural room impulse responses, and techniques for neural network training. Using ChucK, individual tracks for each MIDI file, containing the ground truth for pitch and other parameters, are processed concurrently with variable Synthesis ToolKit (STK) instruments, and the audio output is written to separate wave files in order to create multiple incoherent sound sources. Then, each track is convolved with a measured or synthetic impulse response that corresponds to the virtual position of the instrument in the room before all tracks are digitally summed. The database now contains the symbolic description in the form of MIDI commands and the auralized music performances. A polyphonic pitch model based on an array of autocorrelation functions for individual frequency bands is used to train a neural network and analyze the data [Work supported by IBM AIRC grant and NSF BCS-1539276.]This paper proposes methods for generation and implementation of uniform, large-scale data from auralized MIDI music files for use with deep learning networks for polyphonic pitch perception and impulse response recognition. This includes synthesis and sound source separation of large batches of multitrack MIDI files in non-real time, convolution with artificial binaural room impulse responses, and techniques for neural network training. Using ChucK, individual tracks for each MIDI file, containing the ground truth for pitch and other parameters, are processed concurrently with variable Synthesis ToolKit (STK) instruments, and the audio output is written to separate wave files in order to create multiple incoherent sound sources. Then, each track is convolved with a measured or synthetic impulse response that corresponds to the virtual position of the instrument in the room before all tracks are digitally summed. The database now contains the symbolic description in the form of MIDI commands and the aural...

OBJECTIVES/SPECIFIC AIMS: “Cure Quest” is an adventure quest game for mobile tablets that aims to teach the player about the complexities of discovery and development of new medicines. The game instills a sense of wonderment into the learning process, taking the player to a world of magic where a mysterious condition has affected the land and they must follow the steps of the discovery and development process to find a treatment. METHODS/STUDY POPULATION: The game is being developed through a collaboration between faculty and students at ISMMS and the Games and Simulation Arts and Science Program at Rensselaer Polytechnic Institute. The first target audience is 2nd–3rd year medical students, with the future goal of adapting the game to a broader population. RESULTS/ANTICIPATED RESULTS: The game is currently in development, but the project has yielded insight into the design process for serious games in medicine. We found that for a game of this type it is essential not just to have both designers and subject matter experts, but to enable cross-pollination of modes of thinking. Through multiple design iterations and focus groups, we found that a game design approach rooted in narrative and allegorical abstraction would have a better ability to engage the target audience than one focused only on realistic simulation. When complete, we anticipate that the game will improve understanding of the core concepts in drug discovery. DISCUSSION/SIGNIFICANCE OF IMPACT: If successful, the game-based learning approach can help fill key gaps in current formal medical and scientific training, as well as gaps in understanding among the general public. The design process serves as an informative model of evolving collaborative team science.

Salvia divinorum is a natural occurring hallucinogen that is traditionally used by the Mazatec Indians of central Mexico. The diterpene salvinorin A was identified as an active component of S. divinorum over 20 years ago, but only recently has biochemical screening indicated that a molecular target of salvinorin A in vitro is the kappa-opioid receptor. We have examined whether salvinorin A, the C2-substituted derivative salvinorinyl-2-propionate, and salvinorin B can act as kappa-opioid receptor agonists in vivo. We found that following intracerebroventricular injection over a dose range of 1 to 30 microg of both salvinorin A and salvinorinyl-2-propionate produces antinociception in wild-type mice but not in a novel strain of kappa-opioid receptor knockout mice. Moreover, both salvinorin A and salvinorinyl-2-propionate reduce rectal body temperature, similar to conventional kappa-opioid receptor agonists, in a genotype-dependent manner. In addition, we determined that salvinorin A has high affinity for kappa 1- but not kappa 2-opioid receptors, demonstrating selectivity for this receptor subclass. Finally, treatment over the same dose range with salvinorin B, which is inactive in vitro, produced neither antinociceptive nor hypothermic effects in wild-type mice. These data demonstrate that salvinorin A is the active component of S. divinorum, selective for kappa(1)-opioid receptors, and that salvinorin A and specific structurally related analogs produce behavioral effects that require the kappa-opioid receptor.

Following up on our previous findings that the skin possesses steroidogenic activity from progesterone, we now show widespread cutaneous expression of the full cytochrome P450 side-chain cleavage (P450scc) system required for the intracellular catalytic production of pregnenolone, i.e. the genes and proteins for P450scc enzyme, adrenodoxin, adrenodoxin reductase and MLN64. Functionality of the system was confirmed in mitochondria from skin cells. Moreover, purified mammalian P450scc enzyme and, most importantly, mitochondria isolated from placenta and adrenals produced robust transformation of 7-dehydrocholesterol (7-DHC; precursor to cholesterol and vitamin D3) to 7-dehydropregnenolone (7-DHP). Product identity was confirmed by comparison with the chemically synthesized standard and chromatographic, MS and NMR analyses. Reaction kinetics for the conversion of 7-DHC into 7-DHP were similar to those for cholesterol conversion into pregnenolone. Thus, 7-DHC can form 7-DHP through P450scc side-chain cleavage, which may serve as a substrate for further conversions into hydroxy derivatives through existing steroidogenic enzymes. In the skin, 5,7-steroidal dienes (7-DHP and its hydroxy derivatives), whether synthesized locally or delivered by the circulation, may undergo UVB-induced intramolecular rearrangements to vitamin D3-like derivatives. This novel pathway has the potential to generate a variety of molecules depending on local steroidogenic activity and access to UVB.

Introduction: Chronic graft versus host disease (cGVHD) remains a major source of morbidity and mortality following allogeneic transplantation. While corticosteroids remain first line therapy for cGVHD, they are associated with significant toxicity, and a substantial proportion of patients fail to completely respond. Treatments for steroid-refractory cGVHD are limited. While the pathophysiology of chronic GVHD is complex, activated T cells play a critical role, driven by allo-antigen stimulation. As such, inhibition of T cell activation via blockade of co-stimulation has potential as a therapeutic target in cGVHD. Abatacept is a recombinant fusion protein consisting of the extracellular domain of human CTLA-4 and a fragment of the Fc domain of human IgG1 that has been modified to prevent complement fixation and antibody-dependent cellular cytotoxicity. Abatacept is the first drug in a class of agents termed "selective co-stimulation modulators." The CTLA-4 moiety of Abatacept binds specifically to CD80 and CD86 and down-modulates the CD28-mediated co-stimulation of T cells. We conducted a phase I clinical trial was conducted to evaluate the safety, clinical and immune effects of Abatacept in patients with steroid-refractory cGVHD. Methods: The study followed a 3+3 design with two escalating doses of Abatacept to determine the maximum tolerated dose (MTD): 3 mg/kg and 10 mg/kg. Dose-limiting toxicities (DLTs) were defined as Grade 3 or 4 toxicities judged to be probably or definitely related to Abatacept. Infection was not considered a DLT. Abatacept was administered for a total of 6 doses. Doses 1-3 were administered at two-week intervals. One month following Dose 3, Abatacept was given at four-week intervals for three doses (Doses 4-6). Inclusion criteria included recipients of allogeneic bone marrow or stem cell transplantation with myeloablative or reduced intensity conditioning, with cGVHD defined by NIH consensus criteria. Patients must have had treatment with ≥ 0.5 mg/kg/day of prednisone for at least 4 weeks. Patients with active malignant disease relapse or other active malignancy and patients with uncontrolled infection were excluded. Peripheral blood was drawn prior to each dose of Abatacept and following completion of therapy to assess the effect of treatment on circulating T cells. PD-1 expression on circulating T cells, and T cell expression of interferon gamma versus IL-10 was assessed by multichannel FACS analysis. Results: 17 subjects were treated. Three patients were treated at a dose of 3 mg/kg without DLT. Three evaluable patients completed treatment on cohort 2, at a dose of 10mg/kg without DLT. A forth participant withdrew consent following one dose of treatment and therefore is not evaluable. Ten patients were treated on an expansion cohort at a dose of 10mg/kg. We observed one grade 4 pulmonary infection, and three grade 3 pulmonary infections which resolved. Other Abatacept related adverse events included grade 2 gastritis (n=1), grade 2 pain (n=1), and grade 1 diarrhea (n=2), fatigue (n=2), rash (n=1), and skin pain (n=1). Of the 16 evaluable patients, 7 (44%) achieved a clinical partial response as defined by improvement of two disease systems based on the 2011 NIH consensus criteria. Abatacept resulted in a 51.3% reduction in prednisone usage in clinical responders with a mean baseline dose of 27mg compared to a mean dose of 14mg 1 month following the 6th dose of Abatacept (p = 0.01). PD-1 expression on circulating CD4+ and CD8+ T cells increased from a mean of 3.4% and 2.7% respectively at baseline to a mean of 8.9% and 7.6% respectively at one month following the 6thdose of Abatacept in clinical responders (n=3; p Conclusion: Abatacept is well-tolerated in the treatment of steroid-refractory cGVHD. Abatacept resulted in the improvement in NIH cGVHD scores in 44% of patients with steroid-refractory GVHD with a significant decrease in prednisone dose. An increase in PD-1 expression and a skewing toward Th2 cytokines was observed in clinical responders. Based on this promising data, a phase II trial is being initiated. Disclosures Soiffer: GentiumSpA/Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees. Arnason:Gilead: Consultancy. Avigan:Astex: Research Funding; DCPrime: Research Funding. Rosenblatt:Astex: Research Funding; BMS: Research Funding; DCPrime: Research Funding.

Solar domestic hot water (SDHW) can be used to reduce energy bills and greenhouse gas emissions associated with heating domestic water. However, one of the most significant barriers to further deployment of solar thermal applications is the space and weight required for storage of the energy collected. Phase change materials (PCMs) are advantageous for daily energy storage with SDHW due to their high storage density and isothermal operation during phase transitions, and would overcome these obstacles. The aim of this paper is to outline the initial steps in the development of a SDHW energy storage system using PCMs, with emphasis on the numerical and experimental studies used to access the phase change and thermal behaviour of the selected PCM. Lauric acid was selected as the PCM based on the melting temperature range which was targeted by studying solar data from an existing solar hot water system in Halifax, Nova Scotia, Canada. Due to the low thermal conductivity of PCMs, additional work is required to develop and validate a design to enhance heat transfer to the storage material using fins. The selected design will be built and installed in an existing large scale solar thermal system on an apartment building in Halifax. The system will be instrumented in order to acquire continuous data (temperatures, flow rates, pressures, etc.) to fully characterize the system.

Heavy metal contamination of herbal products is a major concern in the herbal and dietary supplement industry. Heavy metal exposure is well-documented to cause a variety of adverse human health effects and to negatively impact our environment. The Final Rule for Dietary Supplements for current good manufacturing practice regulation, 21 U.S. Food and Drug Administration Code of Federal Regulations 111, requires dietary supplement manufacturers to establish herbal purity limits for heavy metal contaminants considered safe for human consumption. Heavy metals may enter into the herbal manufacturing process via bioaccumulation from the harvest site or during postharvest processing phases, such as drying and/or liquid extraction. Traditionally, herbalists have used hydroethanolic solvents to extract herbal biomasses in pure food-grade ethanolwater combinations with solvent polarities capable of removing a wide range of hydrophilic and lipophilic constituents. The presented data demonstrate that hydroethanolic solvents are not completely efficient in the extraction of heavy metal accumulations from plant matrixes; and can act as an effective decontamination step in herbal product processing.

Novel semisynthetic analogs of salvinorin A, a full agonist having extraordinary affinity as well as selectivity for the κ-opioid receptor (KOR), were obtained in good yields. The derivatives are remarkable for their unusual and unique hemiacetal structure in the salvinorin series of compounds. The formation of the hemiacetal occurs with epimerization at C-12, thus preserving the original configuration of salvinorin A. The dimethyl ester derivative of the hemiacetal was found to have an affinity for both KOR and MOR (μ-opioid receptor).

Cryopreserved, transiently transfected HepG2 cells were compared to freshly transfected HepG2 cells for use in a pregnane X receptor (PXR) transactivation assay. Assay performance was similar for both cell preparations; however, cryopreserved cells demonstrated less interassay variation. Validation with drugs of different PXR activation potencies and efficacies demonstrated an excellent correlation (r2 > 0.95) between cryopreserved and fresh cells. Cryopreservation did not change the effect of known CYP3A4 inducers that have poor cell permeability, indicating that cryopreservation had little effect on membrane permeability. In addition, cryopreserved HepG2 cells did not exhibit enhanced susceptibility to cytotoxic compounds compared to transiently transfected control cells. The use of cryopreserved cells enables this assay to run with enhanced efficiency.

This thesis draws on the work of a wide range of theorists, philosophers, and educators in order to examine corporate sponsored curriculum used in the Canadian public school system. The main aim of this thesis is to determine whether or not corporate sponsored curriculum is, in fact, advertising. Does the classroom become a marketing medium through the use of corporate sponsored curriculum? Two case studies, of the Bank of Montreal's my money Investment Kit and the Tampax Health Education Program On Puberty And Menstrual Health, will be used as models for this thesis. The curriculum will be examined through both proponents and critics of adverting via four main perspectives. These perspectives include: (1) the view that advertising is a form of information, (2) the view that advertising is a form of persuasion, (3) the view that advertising is a form of symbolism, and (4) the critical cultural view of advertising. The findings will be entrenched in the socio-historical context of the current role played by the system of public education. This role is then contrasted with the aims and desires of marketing organizations and corporations. The thesis concludes with a synthesis of the findings and combines them with theoretical, philosophical, and contemporary views of education and society. Source: Masters Abstracts International, Volume: 39-02, page: 0372. Adviser: Myles Ruggles. Thesis (M.A.)--University of Windsor (Canada), 2000.

In this thesis we present an algorithm for the precise determination of Fermi-Dirac (FD) integral functions, for arbitrary values of the parameter and the argument. The FD integrals are a class of functions that are used extensively in the modeling of semiconductor devices, e.g., when the charge carriers are in a strongly quantum, degenerate regime, such as in heavily doped semiconductors. The determination of FD integrals has a long history. Our approach to evaluating these functions is two-fold. First, we develop exact power series expansions of the integral. These series, however, converge too slowly to be a practical means of evaluating the integral. The second aspect of our approach is to apply numerical series acceleration methods to improve significantly the rate of convergence of these series expansions. The result is a computer program that provides efficient, accurate values of the FD integral. http://archive.org/details/highspeednumeric109458472 Lieutenant, United States Navy Approved for public release; distribution is unlimited.