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Sample records for achieve maximal therapeutic

  1. Maximizing the Therapeutic Potential of Hsp90 Inhibitors

    PubMed Central

    Butler, Lisa M.; Ferraldeschi, Roberta; Armstrong, Heather K.; Centenera, Margaret M.; Workman, Paul

    2015-01-01

    Hsp90 is required for maintaining the stability and activity of a diverse group of client proteins, including protein kinases, transcription factors and steroid hormone receptors involved in cell signaling, proliferation, survival, oncogenesis and cancer progression. Inhibition of Hsp90 alters the Hsp90-client protein complex, leading to reduced activity, misfolding, ubiquitination and, ultimately, proteasomal degradation of client proteins. Hsp90 inhibitors have demonstrated significant antitumor activity in a wide variety of preclinical models with evidence of selectivity for cancer versus normal cells. In the clinic however, the efficacy of this class of therapeutic agents has been relatively limited to date, with promising responses mainly observed in breast and lung cancer, but no major activity seen in other tumor types. In addition, adverse events and some significant toxicities have been documented. Key to improving these clinical outcomes is a better understanding of the cellular consequences of inhibiting Hsp90 that may underlie treatment response or resistance. This review considers the recent progress that has been made in the study of Hsp90 and its inhibitors, and highlights new opportunities to maximize their therapeutic potential. PMID:26219697

  2. Curriculum and Testing Strategies to Maximize Special Education STAAR Achievement

    ERIC Educational Resources Information Center

    Johnson, William L.; Johnson, Annabel M.; Johnson, Jared W.

    2015-01-01

    This document is from a presentation at the 2015 annual conference of the Science Teachers Association of Texas (STAT). The two sessions (each listed as feature sessions at the state conference) examined classroom strategies the presenter used in his chemistry classes to maximize Texas end-of-course chemistry test scores for his special population…

  3. Achieving transparency and maximizing scattering with metamaterial-coated conducting cylinders.

    PubMed

    Irci, Erdinc; Ertürk, Vakur B

    2007-11-01

    In this work, the electromagnetic interaction of plane waves with infinitely long metamaterial-coated conducting cylinders is considered. Different from "conjugate" pairing of double-positive (DPS) and double-negative (DNG) or epsilon-negative (ENG) and mu-negative (MNG) concentric cylinders, achieving transparency and maximizing scattering are separately achieved by covering perfect electric conductor (PEC) cylinders with simple (i.e., homogeneous, isotropic, and linear) metamaterial coatings. The appropriate constitutive parameters of such metamaterials are investigated for Transverse Magnetic (TM) and in particular for Transverse Electric (TE) polarizations. For TE polarization it is found out that the metamaterial-coating permittivity has to be in the 0achieve transparency, and in the -epsilon0achieve scattering maximization. However, unlike the "conjugate" pairing of DPS-DNG or ENG-MNG cases, when the transparency for metamaterial-coated PEC cylinders are considered, the analytically found relation between epsilonc and the ratio of core-coating radii, gamma, should be modified in a sense that scattering from the PEC core is canceled by the coating. Furthermore, replacing epsilon by mu (and vice versa) does not lead to the same conclusions for TM polarization unless the PEC cylinder is replaced by a perfect magnetic conductor (PMC) cylinder. On the other hand, scattering maximization can also be achieved in the TM polarization case when coating permeability muc<0, whereas transparency requires large |muc| for this polarization. Numerical results in the form of normalized monostatic and bistatic echo widths, which demonstrate the transparency and scattering maximization phenomena, are given and possible application areas are discussed.

  4. Maximal Oxygen Uptake Is Achieved in Hypoxia but Not Normoxia during an Exhaustive Severe Intensity Run

    PubMed Central

    Black, Matthew I.; Potter, Christopher R.; Corbett, Jo; Clark, Cain C. T.; Draper, Stephen B.

    2017-01-01

    Highly aerobically trained individuals are unable to achieve maximal oxygen uptake (V˙O2max) during exhaustive running lasting ~2 min, instead V˙O2 plateaus below V˙O2max after ~1 min. Hypoxia offers the opportunity to study the (V˙O2) response to an exhaustive run relative to a hypoxia induced reduction in V˙O2max. The aim of this study was to explore whether there is a difference in the percentage of V˙O2max achieved (during a 2 min exhaustive run) in normoxia and hypoxia. Fourteen competitive middle distance runners (normoxic V˙O2max 67.0 ± 5.2 ml.kg−1.min−1) completed exhaustive treadmill ramp tests and constant work rate (CWR) tests in normoxia and hypoxia (FiO2 0.13). The V˙O2 data from the CWR tests were modeled using a single exponential function. End exercise normoxic CWR V˙O2 was less than normoxic V˙O2max (86 ± 6% ramp, P < 0.001). During the hypoxic CWR test, hypoxic V˙O2max was achieved (102 ± 8% ramp, P = 0.490). The phase II time constant was greater in hypoxia (12.7 ± 2.8 s) relative to normoxia (10.4 ± 2.6 s) (P = 0.029). The results demonstrate that highly aerobically trained individuals cannot achieve V˙O2max during exhaustive severe intensity treadmill running in normoxia, but can achieve the lower V˙O2max in hypoxia despite a slightly slower V˙O2 response. PMID:28270770

  5. Maximal Oxygen Uptake Is Achieved in Hypoxia but Not Normoxia during an Exhaustive Severe Intensity Run.

    PubMed

    Black, Matthew I; Potter, Christopher R; Corbett, Jo; Clark, Cain C T; Draper, Stephen B

    2017-01-01

    Highly aerobically trained individuals are unable to achieve maximal oxygen uptake ([Formula: see text]) during exhaustive running lasting ~2 min, instead [Formula: see text] plateaus below [Formula: see text] after ~1 min. Hypoxia offers the opportunity to study the ([Formula: see text]) response to an exhaustive run relative to a hypoxia induced reduction in [Formula: see text]. The aim of this study was to explore whether there is a difference in the percentage of [Formula: see text] achieved (during a 2 min exhaustive run) in normoxia and hypoxia. Fourteen competitive middle distance runners (normoxic [Formula: see text] 67.0 ± 5.2 ml.kg(-1).min(-1)) completed exhaustive treadmill ramp tests and constant work rate (CWR) tests in normoxia and hypoxia (F i O2 0.13). The [Formula: see text] data from the CWR tests were modeled using a single exponential function. End exercise normoxic CWR [Formula: see text] was less than normoxic [Formula: see text] (86 ± 6% ramp, P < 0.001). During the hypoxic CWR test, hypoxic [Formula: see text] was achieved (102 ± 8% ramp, P = 0.490). The phase II time constant was greater in hypoxia (12.7 ± 2.8 s) relative to normoxia (10.4 ± 2.6 s) (P = 0.029). The results demonstrate that highly aerobically trained individuals cannot achieve [Formula: see text] during exhaustive severe intensity treadmill running in normoxia, but can achieve the lower [Formula: see text] in hypoxia despite a slightly slower [Formula: see text] response.

  6. New strategies to maximize therapeutic opportunities for NAMPT inhibitors in oncology

    PubMed Central

    Roulston, Anne; Shore, Gordon C.

    2016-01-01

    ABSTRACT Nicotinamide phosphoribosyltransferase (NAMPT) is crucial for nicotinamide adenine dinucleotide (NAD+) biosynthesis in mammalian cells. NAMPT inhibitors represent multifunctional anticancer agents that act on NAD+ metabolism to shut down glycolysis, nucleotide biosynthesis, and ATP generation and act indirectly as PARP and sirtuin inhibitors. The selectivity of NAMPT inhibitors preys on the increased metabolic requirements to replenish NAD+ in cancer cells. Although initial clinical studies with NAMPT inhibitors did not achieve single-agent therapeutic levels before dose-limiting toxicities were reached, a new understanding of alternative rescue pathways and a biomarker that can be used to select patients provides new opportunities to widen the therapeutic window and achieve efficacious doses in the clinic. Recent work has also illustrated the potential for drug combination strategies to further enhance the therapeutic opportunities. This review summarizes recent discoveries in NAD+/NAMPT inhibitor biology in the context of exploiting this new knowledge to optimize the clinical outcomes for this promising new class of agents. PMID:27308565

  7. Maximal Levels of Aspiration, Minimal Boundary Goals, and Their Relationships with Academic Achievement: The Case of Secondary-School Students

    ERIC Educational Resources Information Center

    Hodis, Flaviu A.; Johnston, Michael; Meyer, Luanna H.; McClure, John; Hodis, Georgeta M.; Starkey, Louise

    2015-01-01

    Maximising educational attainment is important for both individuals and societies. However, understanding of why some students achieve better than others is far from complete. Motivation and achievement data from a sample of 782 secondary-school students in New Zealand reveal that two specific types of outcome goals, namely "maximal levels of…

  8. Strategic administration of enrofloxacin in poultry to achieve higher maximal serum concentrations.

    PubMed

    Sumano, L H; Gutierrez, O L; Zamora, Q M

    2003-03-01

    To achieve a higher maximal serum concentration (Cs(max)) of enrofloxacin after oral administration of 10mg/kg/day of three commercial preparations of enrofloxacin to chickens, two concentrations of the drug were tested (0.1 and 0.2%), under controlled laboratory conditions. A single oral bolus dose was delivered directly into the proventriculus of each of 240 chickens, which were equally divided into six groups: three received the customary concentration (0.1%), and three received the higher concentration. A quantitative/qualitative microbiological analytical method to determine serum concentrations of enrofloxacin and a software program to obtain pharmacokinetic variables, revealed that time vs. concentration relationships best fitted double peak shape curves, Cs(max1) and Cs(max2). Statistically significant (P>0.01) increments were obtained when 0.2% enrofloxacin oral solutions from the three different commercial preparations were administered. The increments ranged from 175% to 338% for Cs(max1) and 69% to 342% for Cs(max2). Optimal bactericidal concentrations of enrofloxacin are usually twice the value of their minimal inhibitory concentration. Although clinical trials are now required, it would appear that increments in the serum concentration of enrofloxacin may reduce to the rate at which bacterial resistance occurs and so increase clinical efficacy without affecting the cost per treatment.

  9. Achieving high mass-throughput of therapeutic proteins through parvovirus retentive filters.

    PubMed

    Bolton, Glen R; Basha, Jonida; Lacasse, Daniel P

    2010-01-01

    Parvovirus retentive filters that assure removal of viruses and virus-like particles during the production of therapeutic proteins significantly contribute to total manufacturing costs. Operational approaches that can increase throughput and reduce filtration area would result in a significant cost savings. A combination of methods was used to achieve high throughputs of an antibody or therapeutic protein solution through three parvovirus retentive filters. These methods included evaluation of diatomaceous earth or size-based prefilters, the addition of additives, and the optimization of protein concentration, temperature, buffer composition, and solution pH. An optimum temperature of 35°C was found for maximizing throughput through the Virosart CPV and Viresolve Pro filters. Mass-throughput values of 7.3, 26.4, and 76.2 kg/m(2) were achieved through the Asahi Planova 20N, Virosart CPV, and Viresolve Pro filters, respectively, in 4 h of processing. Mass-throughput values of 73, 137, and 192 kg/m(2) were achieved through a Millipore Viresolve Pro filter in 4.0, 8.8, and 22.1 h of processing, respectively, during a single experiment. However, large-scale parvovirus filtration operations are typically controlled to limit volumetric throughput to below the level achieved during small-scale virus spiking experiments. The virus spike may cause significant filter plugging, limiting throughput. Therefore newer parvovirus filter spiking strategies should be adopted that may lead to more representative viral clearance data and higher utilization of large-scale filter capacity.

  10. Reallocating Human Resources to Maximize Student Achievement: A Critical Case Study of a Southern California School District

    ERIC Educational Resources Information Center

    Glazener, Adrianna Kathleen

    2013-01-01

    This study applied the Evidence-Based Model (Odden & Picus, 2008) as a framework for determining how district leadership could potentially reallocate human resources to maximize the opportunity for student achievement, relying heavily on the ten strategies for doubling student performance (Odden, 2009; Odden & Archibald, 2009) and the…

  11. Individualizing amikacin regimens: accurate method to achieve therapeutic concentrations.

    PubMed

    Zaske, D E; Cipolle, R J; Rotschafer, J C; Kohls, P R; Strate, R G

    1991-11-01

    Amikacin's pharmacokinetics and dosage requirements were studied in 98 patients receiving treatment for gram-negative infections. A wide interpatient variation in the kinetic parameters of the drug occurred in all patients and in patients who had normal serum creatinine levels or normal creatinine clearance. The half-life ranged from 0.7 to 14.4 h in 74 patients who had normal serum creatinine levels and from 0.7 to 7.2 h in 37 patients who had normal creatinine clearance. The necessary daily dose to obtain therapeutic serum concentrations ranged from 1.25 to 57 mg/kg in patients with normal serum creatinine levels and from 10 to 57 mg/kg in patients with normal creatinine clearance. In four patients (4%), a significant change in baseline serum creatinine level (greater than 0.5 mg/dl) occurred during or after treatment, which may have been amikacin-associated toxicity. Overt ototoxicity occurred in one patient. The method of individualizing dosage regimens provided a clinically useful means of rapidly attaining therapeutic peak and trough serum concentrations.

  12. Matching achievement contexts with implicit theories to maximize motivation after failure: a congruence model.

    PubMed

    El-Alayli, Amani

    2006-12-01

    Previous research has shown that matching person variables with achievement contexts can produce the best motivational outcomes. The current study examines whether this is also true when matching entity and incremental beliefs with the appropriate motivational climate. Participants were led to believe that a personal attribute was fixed (entity belief) or malleable (incremental belief). After thinking that they failed a test that assessed the attribute, participants performed a second (related) task in a context that facilitated the pursuit of either performance or learning goals. Participants were expected to exhibit greater effort on the second task in the congruent conditions (entity belief plus performance goal climate and incremental belief plus learning goal climate) than in the incongruent conditions. These results were obtained, but only for participants who either valued competence on the attribute or had high achievement motivation. Results are discussed in terms of developing strategies for optimizing motivation in achievement settings.

  13. Achievable rate maximization for decode-and-forward MIMO-OFDM networks with an energy harvesting relay.

    PubMed

    Du, Guanyao; Yu, Jianjun

    2016-01-01

    This paper investigates the system achievable rate for the multiple-input multiple-output orthogonal frequency division multiplexing (MIMO-OFDM) system with an energy harvesting (EH) relay. Firstly we propose two protocols, time switching-based decode-and-forward relaying (TSDFR) and a flexible power splitting-based DF relaying (PSDFR) protocol by considering two practical receiver architectures, to enable the simultaneous information processing and energy harvesting at the relay. In PSDFR protocol, we introduce a temporal parameter to describe the time division pattern between the two phases which makes the protocol more flexible and general. In order to explore the system performance limit, we discuss the system achievable rate theoretically and formulate two optimization problems for the proposed protocols to maximize the system achievable rate. Since the problems are non-convex and difficult to solve, we first analyze them theoretically and get some explicit results, then design an augmented Lagrangian penalty function (ALPF) based algorithm for them. Numerical results are provided to validate the accuracy of our analytical results and the effectiveness of the proposed ALPF algorithm. It is shown that, PSDFR outperforms TSDFR to achieve higher achievable rate in such a MIMO-OFDM relaying system. Besides, we also investigate the impacts of the relay location, the number of antennas and the number of subcarriers on the system performance. Specifically, it is shown that, the relay position greatly affects the system performance of both protocols, and relatively worse achievable rate is achieved when the relay is placed in the middle of the source and the destination. This is different from the MIMO-OFDM DF relaying system without EH. Moreover, the optimal factor which indicates the time division pattern between the two phases in the PSDFR protocol is always above 0.8, which means that, the common division of the total transmission time into two equal phases in

  14. Alcohol liver disease: A review of current therapeutic approaches to achieve long-term abstinence

    PubMed Central

    García, María Luisa Gutiérrez; Blasco-Algora, Sara; Fernández-Rodríguez, Conrado M

    2015-01-01

    Harmful alcohol drinking may lead to significant damage on any organ or system of the body. Alcoholic liver disease (ALD) is the most prevalent cause of advanced liver disease in Europe. In ALD, only alcohol abstinence was associated with a better long-term survival. Therefore, current effective therapeutic strategy should be oriented towards achieving alcohol abstinence or a significant reduction in alcohol consumption. Screening all primary care patients to detect those cases with alcohol abuse has been proposed as population-wide preventive intervention in primary care. It has been suggested that in patients with mild alcohol use disorder the best approach is brief intervention in the primary care setting with the ultimate goal being abstinence, whereas patients with moderate-to-severe alcohol use disorder must be referred to specialized care where detoxification and medical treatment of alcohol dependence must be undertaken. PMID:26229395

  15. HDAC4 as a potential therapeutic target in neurodegenerative diseases: a summary of recent achievements

    PubMed Central

    Mielcarek, Michal; Zielonka, Daniel; Carnemolla, Alisia; Marcinkowski, Jerzy T.; Guidez, Fabien

    2015-01-01

    For the past decade protein acetylation has been shown to be a crucial post-transcriptional modification involved in the regulation of protein functions. Histone acetyltransferases (HATs) mediate acetylation of histones which results in the nucleosomal relaxation associated with gene expression. The reverse reaction, histone deacetylation, is mediated by histone deacetylases (HDACs) leading to chromatin condensation followed by transcriptional repression. HDACs are divided into distinct classes: I, IIa, IIb, III, and IV, on the basis of size and sequence homology, as well as formation of distinct repressor complexes. Implications of HDACs in many diseases, such as cancer, heart failure, and neurodegeneration, have identified these molecules as unique and attractive therapeutic targets. The emergence of HDAC4 among the members of class IIa family as a major player in synaptic plasticity raises important questions about its functions in the brain. The characterization of HDAC4 specific substrates and molecular partners in the brain will not only provide a better understanding of HDAC4 biological functions but also might help to develop new therapeutic strategies to target numerous malignancies. In this review we highlight and summarize recent achievements in understanding the biological role of HDAC4 in neurodegenerative processes. PMID:25759639

  16. Gaps Between Aims and Achievements in Therapeutic Modification of Neuronal Damage ("Neuroprotection").

    PubMed

    Wiendl, Heinz; Elger, Christian; Förstl, Hans; Hartung, Hans-Peter; Oertel, Wolfgang; Reichmann, Heinz; Schwab, Stefan

    2015-04-01

    The term "neuroprotection" is often misused, overused, or misunderstood. A reasonable definition of neuroprotection refers to the preservation of "neuronal structure and/or function." Although our knowledge about the cellular and molecular mechanisms of neurodegeneration has expanded, experimental systems and animal models that mimic the process or allow translation into clinical success remain limited. This editorial discusses reasons for this gap and strategies to close it. Experimental models can only mirror certain aspects of disease mechanisms in humans. Therefore, findings in these models need to be linked with patient data to improve real-life relevance. Successful neuroprotection depends on finding the right "window of opportunity" which varies from very short (stroke) to very long (Alzheimer's disease), necessitating the need to focus on strategies for very early disease recognition. This need challenges the strategies to be chosen, trial approaches and methodologies, and the allocation of resources. Additionally, outcome measures are often not well suited to assess neuroprotection. To this end, surrogate measures, including biomarkers, are useful endpoints to demonstrate evidence of target directed therapeutic utility. Finally, studies have shown that neuroprotection is not likely to succeed when targeting only one pathway. These obstacles have reduced the level of enthusiasm for neuroprotection in certain disease areas (e.g., stroke). Academia, industry, regulatory authorities, funding agencies and patient organizations have to cooperate to a greater extent in order to overcome these impediments and to encourage nonclassical concepts. These concepts will be interdisciplinary in order to achieve meaningful disease modification.

  17. Pre-Type 1 Diabetes Dysmetabolism: Maximal sensitivity achieved with Both Oral and Intravenous Glucose Tolerance Testing

    PubMed Central

    Barker, Jennifer M.; McFann, Kim; Harrison, Leonard C.; Fourlanos, Spiros; Krischer, Jeffrey; Cuthbertson, David; Chase, H. Peter; Eisenbarth, George S.; Group, the DPT-1 Study

    2007-01-01

    Objective To determine the relationship of intravenous (IVGTT) and oral (OGTT) glucose tolerance tests abnormalities to diabetes development in a high-risk pre-diabetic cohort and identify an optimal testing strategy for detecting pre-clinical diabetes. Study design Diabetes Prevention Trial Type 1 randomized subjects to oral (n=372) and parenteral (n=339) insulin prevention trials. Subjects were followed with IVGTTs and OGTTs. Factors associated with progression to diabetes were evaluated. Results Survival analysis revealed that higher quartiles of 2-hour glucose and lower quartiles of FPIR at baseline were associated with decreased diabetes-free survival. Cox proportional hazards modeling showed that baseline BMI, FPIR and 2-hour glucose levels were significantly associated with an increased hazard for diabetes. On testing performed within 6 months of diabetes diagnosis, 3% (1/32) had normal first phase insulin response (FPIR) and normal 2-hour glucose on OGTT. The sensitivities for impaired glucose tolerance (IGT) and low FPIR performed within 6 months of diabetes diagnosis were equivalent (76% vs. 73%). Conclusions Most (97%) subjects had abnormal IVGTTs and/or OGTTs prior to the development of diabetes. The highest sensitivity is achieved using both tests. PMID:17188609

  18. Preferences for Analgesic Treatments Are Influenced by Probability of the Occurrence of Adverse Effects and the Time to Reach Maximal Therapeutic Effects

    PubMed Central

    Lin, Chia-Shu; Wu, Shih-Yun; Wu, Long-Ting

    2015-01-01

    Research on shared medical decision-making suggested that both the potency of a treatment and the probability of it being successful influence individual treatment preferences. Patients also need to consider the negative attributes of treatments, such as the occurrence of adverse effects or a slow start to the therapeutic effects. It remains unclear how these attributes influence individual treatment preferences. We investigated how the analgesic effect, the adverse effect, and the time-course effect influenced the preference of analgesic treatments. Forty-five healthy volunteers participated in three hypothetical analgesic decision-making tasks. They were instructed to imagine that they were experiencing pain and choose between two hypothetical analgesic treatments: the more potent radical treatment and the less potent conservative treatment. The potency of a treatment was countered by the following attributes: the probability of working successfully, the probability of inducing an adverse effect, and the time required for the treatment to reach its maximal effect. We found that (a) when the overall probability that a treatment would induce an adverse effect decreased, the participants changed their preference from a conservative treatment to a radical treatment; (b) when the time-course for a treatment to reach its maximal effect was shortened, the participants changed their preference from a conservative treatment to a radical treatment, and (c) individual differences in prior clinical pain and the degree of imagined pain relief were associated with preferences. The findings showed that the adverse effects and the time course of treatments guide the analgesic treatment preferences, highlighting the importance of sharing information about negative attributes of treatments in pain management. The findings imply that patients may over-emphasize the occurrence of adverse effect or a slow time-course of treatment effect. In terms of shared medical decision

  19. Delivery methods for site-specific nucleases: Achieving the full potential of therapeutic gene editing.

    PubMed

    Liu, Jia; Shui, Sai-Lan

    2016-12-28

    The advent of site-specific nucleases, particularly CRISPR/Cas9, provides researchers with the unprecedented ability to manipulate genomic sequences. These nucleases are used to create model cell lines, engineer metabolic pathways, produce transgenic animals and plants, perform genome-wide functional screen and, most importantly, treat human diseases that are difficult to tackle by traditional medications. Considerable efforts have been devoted to improving the efficiency and specificity of nucleases for clinical applications. However, safe and efficient delivery methods remain the major obstacle for therapeutic gene editing. In this review, we summarize the recent progress on nuclease delivery methods, highlight their impact on the outcomes of gene editing and discuss the potential of different delivery approaches for therapeutic gene editing.

  20. [Update of planning tables of cholesterol-lowering therapy orientated to achieve LDL therapeutic targets].

    PubMed

    Masana, Luis; Plana, Núria

    2015-01-01

    This is the third update of a planning-table for use in cholesterol-lowering therapy, so as to obtain LDLc objectives. This is an easy to use laptop tool to help choose the best statin or combination therapy (statin plus ezetimibe) depending on the current LDL concentration of the patient, and the LDLc objective to achieve. It is based on a colour code that indicates the drugs that are efficient enough to help patients to achieve their LDL goal. Along with the table, recommendations are given for the best strategy in order to implement the optimal therapy in a maximum of two clinical encounters.

  1. Magnetic Heating of Nanoparticles: The Importance of Particle Clustering to Achieve Therapeutic Temperatures.

    PubMed

    Pearce, John; Giustini, Andrew; Stigliano, Robert; Jack Hoopes, P

    2013-02-01

    Hyperthermia therapy for cancer treatment seeks to destroy tumors through heating alone or combined with other therapies at elevated temperatures between 41.8 and 48 °C. Various forms of cell death including apoptosis and necrosis occur depending on temperature and heating time. Effective tumoricidal effects can also be produced by inducing damage to the tissue vasculature and stroma; however, surrounding normal tissue must be spared to a large extent. Magnetic nanoparticles have been under experimental investigation in recent years as a means to provide a favorable therapeutic ratio for local hyperthermia; however, practical numerical models that can be used to study the underlying mechanisms in realistic geometries have not previously appeared to our knowledge. Useful numerical modeling of these experiments is made extremely difficult by the many orders of magnitude in the geometries: from nanometers to centimeters. What has been missing is a practical numerical modeling approach that can be used to more deeply understand the experiments. We develop and present numerical models that reveal the extent and dominance of the local heat transfer boundary conditions, and provide a new approach that may simplify the numerical problem sufficiently to make ordinary computing machinery capable of generating useful predictions. The objectives of this paper are to place the discussion in a convenient interchangeable classical electromagnetic formulation, and to develop useful engineering approximations to the larger multiscale numerical modeling problem that can potentially be used in experiment evaluation; and eventually, may prove useful in treatment planning. We cast the basic heating mechanisms in the framework of classical electromagnetic field theory and provide calibrating analytical calculations and preliminary experimental results on BNF-Starch(®) nanoparticles in a mouse tumor model for perspective.

  2. In patients with extensive subcutaneous emphysema, which technique achieves maximal clinical resolution: infraclavicular incisions, subcutaneous drain insertion or suction on in situ chest drain?

    PubMed

    Johnson, Charles H N; Lang, Sommer A; Bilal, Haris; Rammohan, Kandadai S

    2014-06-01

    A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was: 'In patients with extensive subcutaneous emphysema, which technique achieves maximal clinical resolution: infraclavicular incisions, subcutaneous drain insertion or suction on in situ chest drain?'. Altogether more than 200 papers were found using the reported search, of which 14 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. Subcutaneous emphysema is usually a benign, self-limiting condition only requiring conservative management. Interventions are useful in the context of severe patient discomfort, respiratory distress or persistent air leak. In the absence of any comparative study, it is not possible to choose definitively between infraclavicular incisions, drain insertion and increasing suction on an in situ drain as the best method for managing severe subcutaneous emphysema. All the three techniques described have been shown to provide effective relief. Increasing suction on a chest tube already in situ provided rapid relief in patients developing SE following pulmonary resection. A retrospective study showed resolution in 66%, increasing to 98% in those who underwent video-assisted thoracic surgery with identification and closure of the leak. Insertion of a drain into the subcutaneous tissue also provided rapid sustained relief. Several studies aided drainage by using regular compressive massage. Infraclavicular incisions were also shown to provide rapid relief, but were noted to be more invasive and carried the potential for cosmetic defect. No major complications were illustrated.

  3. Designer Self-Assemble Peptides Maximize the Therapeutic Benefits of Neural Stem Cell Transplantation for Alzheimer's Disease via Enhancing Neuron Differentiation and Paracrine Action.

    PubMed

    Cui, Guo-hong; Shao, Shui-jin; Yang, Jia-jun; Liu, Jian-ren; Guo, Hai-dong

    2016-03-01

    maximize the therapeutic benefits of NSC transplantation for AD through improving the survival and differentiation of transplanted stem cells and promoting the effects of neuroprotection, anti-neuroinflammatory and paracrine action. Our results may have important clinical implications for the design of future NSC-based strategies using the biomaterials for various neurodegenerative diseases including AD.

  4. The Achievement of Therapeutic Objectives Scale: Interrater Reliability and Sensitivity to Change in Short-Term Dynamic Psychotherapy and Cognitive Therapy

    ERIC Educational Resources Information Center

    Valen, Jakob; Ryum, Truls; Svartberg, Martin; Stiles, Tore C.; McCullough, Leigh

    2011-01-01

    This study examined interrater reliability and sensitivity to change of the Achievement of Therapeutic Objectives Scale (ATOS; McCullough, Larsen, et al., 2003) in short-term dynamic psychotherapy (STDP) and cognitive therapy (CT). The ATOS is a process scale originally developed to assess patients' achievements of treatment objectives in STDP,…

  5. Analysis of the first therapeutic-target-achieving time of warfarin therapy and associated factors in patients with pulmonary embolism

    PubMed Central

    Gong, Xiaowei; Wang, Haiyan; Yuan, Yadong

    2016-01-01

    The present study aimed to investigate the factors affecting the first therapeutic-target-achieving (TTA) time of warfarin therapy in patients with acute pulmonary embolism (PTE). Between January 2008 and June 2013, patients with PTE confirmed by transpulmonary arterial enhanced computed tomographic pulmonary angiography or pulmonary ventilation perfusion scanning were included in the present study. Data collected included demographic information, history of tobacco and alcohol intake, basic diseases (stable and unstable hypertension, diabetes, heart failure, cancer/cerebral infarction, old myocardial infarction and atrial fibrillation), liver and kidney function, the haemoglobin and platelet count of the blood, international normalized ratio monitoring, warfarin dosage adjustment and medication combinations. Dynamic changes in international normalized ratio, anticoagulant efficacy, and adverse events within 90 days were monitored and analyzed. Univariate analysis demonstrated that the following factors affect the first TTA time: Initial dose, body mass index (BMI), liver function, heart failure, and the administration of levofloxacin, cephalosporins, and blood circulation-activating drugs. Logistic regression analysis revealed that the following were independent factors of the first TTA time: Initial dose, BMI, liver function, heart failure and levofloxacin. Therefore, the results of the present study demonstrated that various factors may affect the first TTA time of warfarin therapy, including the initial dose, BMI, liver function, heart function and concomitant medication. PMID:27698722

  6. Multipoint-likelihood maximization mapping on 4 segregating populations to achieve an integrated framework map for QTL analysis in pot azalea (Rhododendron simsii hybrids)

    PubMed Central

    2010-01-01

    Background Azalea (Rhododendron simsii hybrids) is the most important flowering pot plant produced in Belgium, being exported world-wide. In the breeding program, flower color is the main feature for selection, only in later stages cultivation related plant quality traits are evaluated. As a result, plants with attractive flowering are kept too long in the breeding cycle. The inheritance of flower color has been well studied; information on the heritability of cultivation related quality traits is lacking. For this purpose, QTL mapping in diverse genetic backgrounds appeared to be a must and therefore 4 mapping populations were made and analyzed. Results An integrated framework map on four individual linkage maps in Rhododendron simsii hybrids was constructed. For genotyping, mainly dominant scored AFLP (on average 364 per population) and MYB-based markers (15) were combined with co-dominant SSR (23) and EST markers (12). Linkage groups were estimated in JoinMap. A consensus grouping for the 4 mapping populations was made and applied in each individual mapping population. Finally, 16 stable linkage groups were set for the 4 populations; the azalea chromosome number being 13. A combination of regression mapping (JoinMap) and multipoint-likelihood maximization (Carthagène) enabled the construction of 4 maps and their alignment. A large portion of loci (43%) was common to at least two populations and could therefore serve as bridging markers. The different steps taken for map optimization and integration into a reference framework map for QTL mapping are discussed. Conclusions This is the first map of azalea up to our knowledge. AFLP and SSR markers are used as a reference backbone and functional markers (EST and MYB) were added as candidate genes for QTL analysis. The alignment of the 4 maps on the basis of framework markers will facilitate in turn the alignment of QTL regions detected in each of the populations. The approach we took is thoroughly different than the

  7. Treatment-naïve Gaucher disease patients achieve therapeutic goals and normalization with velaglucerase alfa by 4years in phase 3 trials.

    PubMed

    Zimran, Ari; Elstein, Deborah; Gonzalez, Derlis E; Lukina, Elena A; Qin, Yulin; Dinh, Quinn; Turkia, Hadhami Ben

    2016-10-21

    Gaucher disease is an inherited metabolic disease characterized by β-glucocerebrosidase deficiency and commonly treated with enzyme replacement therapy (ERT). The efficacy of ERT with velaglucerase alfa was assessed based on the achievement of published therapeutic goals and the normalization of disease parameters in 39 treatment-naïve patients with type 1 Gaucher disease, 6 to 62years of age, enrolled in phase 3 clinical trials. After 4years of ERT, therapeutic goals for thrombocytopenia and splenomegaly had been achieved in 100% of patients; goals for anemia and hepatomegaly had been achieved in 95% and 94% of patients, respectively. Consistent with the goal for bone mineral density, lumbar spine bone density improved in 87% of patients ≥18years of age. At year 4, compared with clinical ranges for healthy individuals, 86% of patients with a low baseline hemoglobin concentration had normalized, 60% with a low baseline platelet count had normalized, 67% with baseline splenomegaly had normalized, 58% with hepatomegaly had normalized, and lumbar spine bone density had normalized in 53% of adults. The decade-old therapeutic goals do not reflect the potential for normalization of clinical parameters in ERT-treated patients. Goals consistent with normalization or near-normalization should be considered. ClinicalTrials.gov identifiers: NCT00430625, NCT00553631, NCT00635427.

  8. Currently used dosage regimens of vancomycin fail to achieve therapeutic levels in approximately 40% of intensive care unit patients

    PubMed Central

    Obara, Vitor Yuzo; Zacas, Carolina Petrus; Carrilho, Claudia Maria Dantas de Maio; Delfino, Vinicius Daher Alvares

    2016-01-01

    Objective This study aimed to assess whether currently used dosages of vancomycin for treatment of serious gram-positive bacterial infections in intensive care unit patients provided initial therapeutic vancomycin trough levels and to examine possible factors associated with the presence of adequate initial vancomycin trough levels in these patients. Methods A prospective descriptive study with convenience sampling was performed. Nursing note and medical record data were collected from September 2013 to July 2014 for patients who met inclusion criteria. Eighty-three patients were included. Initial vancomycin trough levels were obtained immediately before vancomycin fourth dose. Acute kidney injury was defined as an increase of at least 0.3mg/dL in serum creatinine within 48 hours. Results Considering vancomycin trough levels recommended for serious gram-positive infection treatment (15 - 20µg/mL), patients were categorized as presenting with low, adequate, and high vancomycin trough levels (35 [42.2%], 18 [21.7%], and 30 [36.1%] patients, respectively). Acute kidney injury patients had significantly greater vancomycin trough levels (p = 0.0055, with significance for a trend, p = 0.0023). Conclusion Surprisingly, more than 40% of the patients did not reach an effective initial vancomycin trough level. Studies on pharmacokinetic and dosage regimens of vancomycin in intensive care unit patients are necessary to circumvent this high proportion of failures to obtain adequate initial vancomycin trough levels. Vancomycin use without trough serum level monitoring in critically ill patients should be discouraged. PMID:28099635

  9. Variability in protein binding of teicoplanin and achievement of therapeutic drug monitoring targets in critically ill patients: lessons from the DALI Study.

    PubMed

    Roberts, J A; Stove, V; De Waele, J J; Sipinkoski, B; McWhinney, B; Ungerer, J P J; Akova, M; Bassetti, M; Dimopoulos, G; Kaukonen, K-M; Koulenti, D; Martin, C; Montravers, P; Rello, J; Rhodes, A; Starr, T; Wallis, S C; Lipman, J

    2014-05-01

    The aims of this study were to describe the variability in protein binding of teicoplanin in critically ill patients as well as the number of patients achieving therapeutic target concentrations. This report is part of the multinational pharmacokinetic DALI Study. Patients were sampled on a single day, with blood samples taken both at the midpoint and the end of the dosing interval. Total and unbound teicoplanin concentrations were assayed using validated chromatographic methods. The lower therapeutic range of teicoplanin was defined as total trough concentrations from 10 to 20 mg/L and the higher range as 10-30 mg/L. Thirteen critically ill patients were available for analysis. The following are the median (interquartile range) total and free concentrations (mg/L): midpoint, total 13.6 (11.2-26.0) and free 1.5 (0.7-2.5); trough, total 11.9 (10.2-22.7) and free 1.8 (0.6-2.6). The percentage free teicoplanin for the mid-dose and trough time points was 6.9% (4.5-15.6%) and 8.2% (5.5-16.4%), respectively. The correlation between total and free antibiotic concentrations was moderate for both the midpoint (ρ = 0.79, P = 0.0021) and trough (ρ = 0.63, P = 0.027). Only 42% and 58% of patients were in the lower and higher therapeutic ranges, respectively. In conclusion, use of standard dosing for teicoplanin leads to inappropriate concentrations in a high proportion of critically ill patients. Variability in teicoplanin protein binding is very high, placing significant doubt on the validity of total concentrations for therapeutic drug monitoring in critically ill patients.

  10. Systemic Administration of Glibenclamide Fails to Achieve Therapeutic Levels in the Brain and Cerebrospinal Fluid of Rodents

    PubMed Central

    Lahmann, Carolina; Kramer, Holger B.; Ashcroft, Frances M.

    2015-01-01

    Activating mutations in the Kir6.2 (KCNJ11) subunit of the ATP-sensitive potassium channel cause neonatal diabetes (ND). Patients with severe mutations also suffer from neurological complications. Glibenclamide blocks the open KATP channels and is the treatment of choice for ND. However, although glibenclamide successfully restores normoglycaemia, it has a far more limited effect on the neurological problems. To assess the extent to which glibenclamide crosses the blood-brain barrier (BBB) in vivo, we quantified glibenclamide concentrations in plasma, cerebrospinal fluid (CSF), and brain tissue of rats, control mice, and mice expressing a human neonatal diabetes mutation (Kir6.2-V59M) selectively in neurones (nV59M mice). As only small sample volumes can be obtained from rodents, we developed a highly sensitive method of analysis, using liquid chromatography tandem mass spectrometry acquisition with pseudo-selected reaction monitoring, achieving a quantification limit of 10ng/ml (20nM) glibenclamide in a 30μl sample. Glibenclamide was not detectable in the CSF or brain of rats after implantation with subcutaneous glibenclamide pellets, despite high plasma concentrations. Further, one hour after a suprapharmacological glibenclamide dose was administered directly into the lateral ventricle of the brain, the plasma concentration was twice that of the CSF. This suggests the drug is rapidly exported from the CSF. Elacridar, an inhibitor of P-glycoprotein and breast cancer resistance protein (major multidrug resistance transporters at the BBB), did not affect glibenclamide levels in CSF and brain tissue. We also identified a reduced sensitivity to volatile anaesthetics in nV59M mice and showed this was not reversed by systemic delivery of glibenclamide. Our results therefore suggest that little glibenclamide reaches the central nervous system when given systemically, that glibenclamide is rapidly removed across the BBB when given intracranioventricularly, and that any

  11. Patients’ empowerment, physicians’ perceptions, and achievement of therapeutic goals in patients with type 1 and type 2 diabetes mellitus in Mexico

    PubMed Central

    Lavalle-González, Fernando J; Chiquete, Erwin

    2016-01-01

    Background Physicians’ perception may not parallel objective measures of therapeutic targets in patients with diabetes. This is an issue rarely addressed in the medical literature. We aimed to analyze physicians’ perception and characteristics of adequate control of patients with diabetes. Patients and methods We studied information on physicians and their patients who participated in the third wave of the International Diabetes Management Practices Study registry in Mexico. This analysis was performed on 2,642 patients, 203 with type 1 diabetes mellitus (T1DM) and 2,439 with type 2 diabetes mellitus (T2DM), treated by 200 physicians. Results The patients perceived at target had lower hemoglobin A1c (HbA1c) and fasting blood glucose than those considered not at target. However, overestimation of the frequency of patients with HbA1c <7% was 41.5% in patients with T1DM and 31.7% in patients with T2DM (underestimation: 2.8% and 8.0%, respectively). The agreement between the physicians’ perception and the class of HbA1c was suboptimal (κ: 0.612). Diabetologists and endocrinologists tested HbA1c more frequently than primary care practitioners, internists, or cardiologists; however, no differences were observed in mean HbA1c, for both T1DM (8.4% vs 7.2%, P=0.42) and T2DM (8.03% vs 8.01%, P=0.87) patients. Nevertheless, insulin users perceived at target, who practiced self-monitoring and self-adjustment of insulin, had a lower mean HbA1c than patients without these characteristics (mean HbA1c in T1DM: 6.8% vs 9.6%, respectively; mean HbA1c in T2DM: 7.0% vs 10.1%, respectively). Conclusion Although there is a significant physicians’ overestimation about the optimal glycemic control, this global impression and characteristics of patients’ empowerment, such as self-monitoring and self-adjustment of insulin, are associated with the achievement of targets. PMID:27555751

  12. How To: Maximize Google

    ERIC Educational Resources Information Center

    Branzburg, Jeffrey

    2004-01-01

    Google is shaking out to be the leading Web search engine, with recent research from Nielsen NetRatings reporting about 40 percent of all U.S. households using the tool at least once in January 2004. This brief article discusses how teachers and students can maximize their use of Google.

  13. Quantum-Inspired Maximizer

    NASA Technical Reports Server (NTRS)

    Zak, Michail

    2008-01-01

    A report discusses an algorithm for a new kind of dynamics based on a quantum- classical hybrid-quantum-inspired maximizer. The model is represented by a modified Madelung equation in which the quantum potential is replaced by different, specially chosen 'computational' potential. As a result, the dynamics attains both quantum and classical properties: it preserves superposition and entanglement of random solutions, while allowing one to measure its state variables, using classical methods. Such optimal combination of characteristics is a perfect match for quantum-inspired computing. As an application, an algorithm for global maximum of an arbitrary integrable function is proposed. The idea of the proposed algorithm is very simple: based upon the Quantum-inspired Maximizer (QIM), introduce a positive function to be maximized as the probability density to which the solution is attracted. Then the larger value of this function will have the higher probability to appear. Special attention is paid to simulation of integer programming and NP-complete problems. It is demonstrated that the problem of global maximum of an integrable function can be found in polynomial time by using the proposed quantum- classical hybrid. The result is extended to a constrained maximum with applications to integer programming and TSP (Traveling Salesman Problem).

  14. Achieving therapeutic goals in insulin-using diabetic patients with non-insulin-dependent diabetes mellitus. A weight reduction-exercise-oral agent approach.

    PubMed

    Lucas, C P; Patton, S; Stepke, T; Kinhal, V; Darga, L L; Carroll-Michals, L; Spafford, T R; Kasim, S

    1987-09-18

    Non-insulin-dependent diabetes mellitus (NIDDM) is the most common form of diabetes in the civilized world. Its consequences include microvascular and macrovascular disease, both of which appear to evolve from a common background of obesity and physical inactivity. The current study was undertaken in obese patients with NIDDM to see whether improvements could be made in glycemic control as well as in many cardiovascular risk factors (obesity, hypertension, lipid abnormalities, and physical inactivity) that are typical of this condition. Fifteen obese insulin-using patients with NIDDM (average body mass index, 34.0) were treated with a 500-calorie formula diet for eight to 12 weeks. Administration of insulin and diuretics was discontinued at the onset of the study. A eucaloric diet was begun at eight to 12 weeks and maintained until Week 24. A behaviorally oriented nutrition-exercise program was instituted at the beginning of the study. Glipizide or placebo was added (randomized) at Week 15 if the fasting plasma glucose level in patients exceeded 115 mg/dl. Patients lost an average of 22 pounds over the course of 24 weeks. Frequency and duration of physical activity increased significantly from baseline, as did the maximal oxygen consumption rate. Glycemic control by 15 weeks (without insulin) was similar to baseline (with insulin). With the addition of glipizide at Week 15, both fasting plasma glucose and glucose tolerance improved significantly. This improvement was not observed with placebo. In addition, both systolic and diastolic blood pressure decreased by about 10 mm Hg. There were no significant changes in the levels of serum lipids or glycosylated hemoglobin. In conclusion, a multifaceted intervention program, employing weight reduction, exercise, diet, and glipizide therapy, can be instituted in insulin-using patients with NIDDM, with improvement in glycemic control and in certain risk factors (hypertension, obesity, physical inactivity) for cardiovascular

  15. Use of boron cluster-containing redox nanoparticles with ROS scavenging ability in boron neutron capture therapy to achieve high therapeutic efficiency and low adverse effects.

    PubMed

    Gao, Zhenyu; Horiguchi, Yukichi; Nakai, Kei; Matsumura, Akira; Suzuki, Minoru; Ono, Koji; Nagasaki, Yukio

    2016-10-01

    A boron delivery system with high therapeutic efficiency and low adverse effects is crucial for a successful boron neutron capture therapy (BNCT). In this study, we developed boron cluster-containing redox nanoparticles (BNPs) via polyion complex (PIC) formation, using a newly synthesized poly(ethylene glycol)-polyanion (PEG-polyanion, possessing a (10)B-enriched boron cluster as a side chain of one of its segments) and PEG-polycation (possessing a reactive oxygen species (ROS) scavenger as a side chain of one of its segments). The BNPs exhibited high colloidal stability, selective uptake in tumor cells, specific accumulation, and long retention in tumor tissue and ROS scavenging ability. After thermal neutron irradiation, significant suppression of tumor growth was observed in the BNP-treated group, with only 5-ppm (10)B in tumor tissues, whereas at least 20-ppm (10)B is generally required for low molecular weight (LMW) (10)B agents. In addition, increased leukocyte levels were observed in the LMW (10)B agent-treated group after thermal neutron irradiation, and not in BNP-treated group, which might be attributed to its ROS scavenging ability. No visual metastasis of tumor cells to other organs was observed 1 month after irradiation in the BNP-treated group. These results suggest that BNPs are promising for enhancing the BNCT performance.

  16. Maximizing the Effective Use of Formative Assessments

    ERIC Educational Resources Information Center

    Riddell, Nancy B.

    2016-01-01

    In the current age of accountability, teachers must be able to produce tangible evidence of students' concept mastery. This article focuses on implementation of formative assessments before, during, and after instruction in order to maximize teachers' ability to effectively monitor student achievement. Suggested strategies are included to help…

  17. Ehrenfest's Lottery--Time and Entropy Maximization

    ERIC Educational Resources Information Center

    Ashbaugh, Henry S.

    2010-01-01

    Successful teaching of the Second Law of Thermodynamics suffers from limited simple examples linking equilibrium to entropy maximization. I describe a thought experiment connecting entropy to a lottery that mixes marbles amongst a collection of urns. This mixing obeys diffusion-like dynamics. Equilibrium is achieved when the marble distribution is…

  18. Maximizing the Motivated Mind for Emergent Giftedness.

    ERIC Educational Resources Information Center

    Rea, Dan

    2001-01-01

    This article explains how the theory of the motivated mind conceptualizes the productive interaction of intelligence, creativity, and achievement motivation and how this theory can help educators to maximize students' emergent potential for giftedness. It discusses the integration of cold-order thinking and hot-chaotic thinking into fluid-adaptive…

  19. Curriculum and Testing Strategies to Maximize STAAR Achievement

    ERIC Educational Resources Information Center

    Johnson, William L.; Johnson, Annabel M.; Johnson, Jared W.

    2014-01-01

    The document is from a presentation at the 2014 annual conference of the Science Teachers Association of Texas (STAT). The presenter noted that the 2001 No Child Left Behind (NCLB) law was the most far-reaching education legislation in over four decades. To address the requirements of this legislation, the presenter examined the third-generation…

  20. Maximally Expressive Modeling

    NASA Technical Reports Server (NTRS)

    Jaap, John; Davis, Elizabeth; Richardson, Lea

    2004-01-01

    Planning and scheduling systems organize tasks into a timeline or schedule. Tasks are logically grouped into containers called models. Models are a collection of related tasks, along with their dependencies and requirements, that when met will produce the desired result. One challenging domain for a planning and scheduling system is the operation of on-board experiments for the International Space Station. In these experiments, the equipment used is among the most complex hardware ever developed; the information sought is at the cutting edge of scientific endeavor; and the procedures are intricate and exacting. Scheduling is made more difficult by a scarcity of station resources. The models to be fed into the scheduler must describe both the complexity of the experiments and procedures (to ensure a valid schedule) and the flexibilities of the procedures and the equipment (to effectively utilize available resources). Clearly, scheduling International Space Station experiment operations calls for a maximally expressive modeling schema.

  1. Maximally Expressive Task Modeling

    NASA Technical Reports Server (NTRS)

    Japp, John; Davis, Elizabeth; Maxwell, Theresa G. (Technical Monitor)

    2002-01-01

    Planning and scheduling systems organize "tasks" into a timeline or schedule. The tasks are defined within the scheduling system in logical containers called models. The dictionary might define a model of this type as "a system of things and relations satisfying a set of rules that, when applied to the things and relations, produce certainty about the tasks that are being modeled." One challenging domain for a planning and scheduling system is the operation of on-board experiment activities for the Space Station. The equipment used in these experiments is some of the most complex hardware ever developed by mankind, the information sought by these experiments is at the cutting edge of scientific endeavor, and the procedures for executing the experiments are intricate and exacting. Scheduling is made more difficult by a scarcity of space station resources. The models to be fed into the scheduler must describe both the complexity of the experiments and procedures (to ensure a valid schedule) and the flexibilities of the procedures and the equipment (to effectively utilize available resources). Clearly, scheduling space station experiment operations calls for a "maximally expressive" modeling schema. Modeling even the simplest of activities cannot be automated; no sensor can be attached to a piece of equipment that can discern how to use that piece of equipment; no camera can quantify how to operate a piece of equipment. Modeling is a human enterprise-both an art and a science. The modeling schema should allow the models to flow from the keyboard of the user as easily as works of literature flowed from the pen of Shakespeare. The Ground Systems Department at the Marshall Space Flight Center has embarked on an effort to develop a new scheduling engine that is highlighted by a maximally expressive modeling schema. This schema, presented in this paper, is a synergy of technological advances and domain-specific innovations.

  2. Prevalence of Obesity and Its Influence on Achievement of Cardiometabolic Therapeutic Goals in Chinese Type 2 Diabetes Patients: An Analysis of the Nationwide, Cross-Sectional 3B Study

    PubMed Central

    Zhou, Xianghai; Ji, Linong; Ran, Xingwu; Su, Benli; Ji, Qiuhe; Pan, Changyu; Weng, Jianping; Ma, Changsheng; Hao, Chuanming; Zhang, Danyi; Hu, Dayi

    2016-01-01

    Background There are few data on the prevalence of obesity and its influence on achieving blood glucose, blood pressure, and blood lipid (3B) goals in Chinese type 2 diabetes outpatients. Methods Patient demographic data, anthropometric measurements, medications, and blood glucose and lipid profiles of 24,512 type 2 diabetes patients from a large, geographically diverse study (CCMR-3B) were analyzed. Using cut-points for body mass index (BMI) and waist circumference (WC) recommended by the Working Group on Obesity in China, overweight and obesity were defined as BMIs of 24–27.9kg/m2 and ≥28.0kg/m2. Central obesity was defined as a waist circumference ≥80cm in women and ≥85cm in men. The 3B therapeutic goals were HbA1c<7.0%, BP<140/90mmHg and LDL-C<2.6mmol/L. Results Overall, 43.0% of type 2 diabetes patients were overweight and 16.7% were obese; 13.3% of overweight and and10.1% of obese patients achieved all the 3B target goals. Overweight or obese patients were less likely to achieve 3B goals than those with normal BMIs. More than a half the overweight or obese patients (69.6%) were centrally obese. Patients with abdominal obesity were less likely to achieve cardiometabolic targets than those without abdominal obesity. In multivariate logistic regression analysis, female, higher BMI and waist circumference, smoking, drinking, sedentary lifestyle, and longer diabetes duration were significantly correlated with failure to achieve 3B control goals. Conclusions Obesity is highly prevalent and associated with poor 3B control in Chinese type 2 diabetes patients. In clinical practice, more attention and resources should focus on weight loss for such patients. PMID:26726883

  3. Formation Control for the Maxim Mission.

    NASA Technical Reports Server (NTRS)

    Luquette, Richard J.; Leitner, Jesse; Gendreau, Keith; Sanner, Robert M.

    2004-01-01

    Over the next twenty years, a wave of change is occurring in the spacebased scientific remote sensing community. While the fundamental limits in the spatial and angular resolution achievable in spacecraft have been reached, based on today's technology, an expansive new technology base has appeared over the past decade in the area of Distributed Space Systems (DSS). A key subset of the DSS technology area is that which covers precision formation flying of space vehicles. Through precision formation flying, the baselines, previously defined by the largest monolithic structure which could fit in the largest launch vehicle fairing, are now virtually unlimited. Several missions including the Micro-Arcsecond X-ray Imaging Mission (MAXIM), and the Stellar Imager will drive the formation flying challenges to achieve unprecedented baselines for high resolution, extended-scene, interferometry in the ultraviolet and X-ray regimes. This paper focuses on establishing the feasibility for the formation control of the MAXIM mission. The Stellar Imager mission requirements are on the same order of those for MAXIM. This paper specifically addresses: (1) high-level science requirements for these missions and how they evolve into engineering requirements; (2) the formation control architecture devised for such missions; (3) the design of the formation control laws to maintain very high precision relative positions; and (4) the levels of fuel usage required in the duration of these missions. Specific preliminary results are presented for two spacecraft within the MAXIM mission.

  4. COPD: maximization of bronchodilation.

    PubMed

    Nardini, Stefano; Camiciottoli, Gianna; Locicero, Salvatore; Maselli, Rosario; Pasqua, Franco; Passalacqua, Giovanni; Pela, Riccardo; Pesci, Alberto; Sebastiani, Alfredo; Vatrella, Alessandro

    2014-01-01

    The most recent guidelines define COPD in a multidimensional way, nevertheless the diagnosis is still linked to the limitation of airflow, usually measured by the reduction in the FEV1/FVC ratio below 70%. However, the severity of obstruction is not directly correlated to symptoms or to invalidity determined by COPD. Thus, besides respiratory function, COPD should be evaluated based on symptoms, frequency and severity of exacerbations, patient's functional status and health related quality of life (HRQoL). Therapy is mainly aimed at increasing exercise tolerance and reducing dyspnea, with improvement of daily activities and HRQoL. This can be accomplished by a drug-induced reduction of pulmonary hyperinflation and exacerbations frequency and severity. All guidelines recommend bronchodilators as baseline therapy for all stages of COPD, and long-acting inhaled bronchodilators, both beta-2 agonist (LABA) and antimuscarinic (LAMA) drugs, are the most effective in regular treatment in the clinically stable phase. The effectiveness of bronchodilators should be evaluated in terms of functional (relief of bronchial obstruction and pulmonary hyperinflation), symptomatic (exercise tolerance and HRQoL), and clinical improvement (reduction in number or severity of exacerbations), while the absence of a spirometric response is not a reason for interrupting treatment, if there is subjective improvement in symptoms. Because LABA and LAMA act via different mechanisms of action, when administered in combination they can exert additional effects, thus optimizing (i.e. maximizing) sustained bronchodilation in COPD patients with severe airflow limitation, who cannot benefit (or can get only partial benefit) by therapy with a single bronchodilator. Recently, a fixed combination of ultra LABA/LAMA (indacaterol/glycopyrronium) has shown that it is possible to get a stable and persistent bronchodilation, which can help in avoiding undesirable fluctuations of bronchial calibre.

  5. Formation Control for the MAXIM Mission

    NASA Technical Reports Server (NTRS)

    Luquette, Richard J.; Leitner, Jesse; Gendreau, Keith; Sanner, Robert M.

    2004-01-01

    Over the next twenty years, a wave of change is occurring in the space-based scientific remote sensing community. While the fundamental limits in the spatial and angular resolution achievable in spacecraft have been reached, based on today s technology, an expansive new technology base has appeared over the past decade in the area of Distributed Space Systems (DSS). A key subset of the DSS technology area is that which covers precision formation flying of space vehicles. Through precision formation flying, the baselines, previously defined by the largest monolithic structure which could fit in the largest launch vehicle fairing, are now virtually unlimited. Several missions including the Micro-Arcsecond X-ray Imaging Mission (MAXIM), and the Stellar Imager will drive the formation flying challenges to achieve unprecedented baselines for high resolution, extended-scene, interferometry in the ultraviolet and X-ray regimes. This paper focuses on establishing the feasibility for the formation control of the MAXIM mission. MAXIM formation flying requirements are on the order of microns, while Stellar Imager mission requirements are on the order of nanometers. This paper specifically addresses: (1) high-level science requirements for these missions and how they evolve into engineering requirements; and (2) the development of linearized equations of relative motion for a formation operating in an n-body gravitational field. Linearized equations of motion provide the ground work for linear formation control designs.

  6. Combination therapeutics in complex diseases.

    PubMed

    He, Bing; Lu, Cheng; Zheng, Guang; He, Xiaojuan; Wang, Maolin; Chen, Gao; Zhang, Ge; Lu, Aiping

    2016-12-01

    The biological redundancies in molecular networks of complex diseases limit the efficacy of many single drug therapies. Combination therapeutics, as a common therapeutic method, involve pharmacological intervention using several drugs that interact with multiple targets in the molecular networks of diseases and may achieve better efficacy and/or less toxicity than monotherapy in practice. The development of combination therapeutics is complicated by several critical issues, including identifying multiple targets, targeting strategies and the drug combination. This review summarizes the current achievements in combination therapeutics, with a particular emphasis on the efforts to develop combination therapeutics for complex diseases.

  7. Ependymoma in children: molecular considerations and therapeutic insights.

    PubMed

    Kim, J-H; Huang, Y; Griffin, A S; Rajappa, P; Greenfield, J P

    2013-10-01

    A multi-modality approach that encompasses maximal surgical resection in combination with adjuvant therapy is critical for achieving optimal disease control in children with ependymoma. In view of its complex biology and variable response to therapy, ependymoma remains a challenge for clinicians involved in the care of these patients. Meanwhile, translation of molecular findings can characterize unique features of childhood ependymoma and their natural history. Furthermore, understanding the biology of pediatric ependymoma serves as a platform for development of future targeted therapies. In line with these goals, we review the molecular basis of pediatric ependymoma and its prognostic implications, as well as novel therapeutic advances in the management of ependymoma in children.

  8. Maximizing TDRS Command Load Lifetime

    NASA Technical Reports Server (NTRS)

    Brown, Aaron J.

    2002-01-01

    was therefore the key to achieving this goal. This goal was eventually realized through development of an Excel spreadsheet tool called EMMIE (Excel Mean Motion Interactive Estimation). EMMIE utilizes ground ephemeris nodal data to perform a least-squares fit to inferred mean anomaly as a function of time, thus generating an initial estimate for mean motion. This mean motion in turn drives a plot of estimated downtrack position difference versus time. The user can then manually iterate the mean motion, and determine an optimal value that will maximize command load lifetime. Once this optimal value is determined, the mean motion initially calculated by the command builder tool is overwritten with the new optimal value, and the command load is built for uplink to ISS. EMMIE also provides the capability for command load lifetime to be tracked through multiple TORS ephemeris updates. Using EMMIE, TORS command load lifetimes of approximately 30 days have been achieved.

  9. Maximization, learning, and economic behavior

    PubMed Central

    Erev, Ido; Roth, Alvin E.

    2014-01-01

    The rationality assumption that underlies mainstream economic theory has proved to be a useful approximation, despite the fact that systematic violations to its predictions can be found. That is, the assumption of rational behavior is useful in understanding the ways in which many successful economic institutions function, although it is also true that actual human behavior falls systematically short of perfect rationality. We consider a possible explanation of this apparent inconsistency, suggesting that mechanisms that rest on the rationality assumption are likely to be successful when they create an environment in which the behavior they try to facilitate leads to the best payoff for all agents on average, and most of the time. Review of basic learning research suggests that, under these conditions, people quickly learn to maximize expected return. This review also shows that there are many situations in which experience does not increase maximization. In many cases, experience leads people to underweight rare events. In addition, the current paper suggests that it is convenient to distinguish between two behavioral approaches to improve economic analyses. The first, and more conventional approach among behavioral economists and psychologists interested in judgment and decision making, highlights violations of the rational model and proposes descriptive models that capture these violations. The second approach studies human learning to clarify the conditions under which people quickly learn to maximize expected return. The current review highlights one set of conditions of this type and shows how the understanding of these conditions can facilitate market design. PMID:25024182

  10. Maximization, learning, and economic behavior.

    PubMed

    Erev, Ido; Roth, Alvin E

    2014-07-22

    The rationality assumption that underlies mainstream economic theory has proved to be a useful approximation, despite the fact that systematic violations to its predictions can be found. That is, the assumption of rational behavior is useful in understanding the ways in which many successful economic institutions function, although it is also true that actual human behavior falls systematically short of perfect rationality. We consider a possible explanation of this apparent inconsistency, suggesting that mechanisms that rest on the rationality assumption are likely to be successful when they create an environment in which the behavior they try to facilitate leads to the best payoff for all agents on average, and most of the time. Review of basic learning research suggests that, under these conditions, people quickly learn to maximize expected return. This review also shows that there are many situations in which experience does not increase maximization. In many cases, experience leads people to underweight rare events. In addition, the current paper suggests that it is convenient to distinguish between two behavioral approaches to improve economic analyses. The first, and more conventional approach among behavioral economists and psychologists interested in judgment and decision making, highlights violations of the rational model and proposes descriptive models that capture these violations. The second approach studies human learning to clarify the conditions under which people quickly learn to maximize expected return. The current review highlights one set of conditions of this type and shows how the understanding of these conditions can facilitate market design.

  11. Postactivation Potentiation Biases Maximal Isometric Strength Assessment

    PubMed Central

    Lima, Leonardo Coelho Rabello; Oliveira, Felipe Bruno Dias; Oliveira, Thiago Pires; Assumpção, Claudio de Oliveira; Greco, Camila Coelho; Cardozo, Adalgiso Croscato; Denadai, Benedito Sérgio

    2014-01-01

    Postactivation potentiation (PAP) is known to enhance force production. Maximal isometric strength assessment protocols usually consist of two or more maximal voluntary isometric contractions (MVCs). The objective of this study was to determine if PAP would influence isometric strength assessment. Healthy male volunteers (n = 23) performed two five-second MVCs separated by a 180-seconds interval. Changes in isometric peak torque (IPT), time to achieve it (tPTI), contractile impulse (CI), root mean square of the electromyographic signal during PTI (RMS), and rate of torque development (RTD), in different intervals, were measured. Significant increases in IPT (240.6 ± 55.7 N·m versus 248.9 ± 55.1 N·m), RTD (746 ± 152 N·m·s−1versus 727 ± 158 N·m·s−1), and RMS (59.1 ± 12.2% RMSMAX  versus 54.8 ± 9.4% RMSMAX) were found on the second MVC. tPTI decreased significantly on the second MVC (2373 ± 1200 ms versus 2784 ± 1226 ms). We conclude that a first MVC leads to PAP that elicits significant enhancements in strength-related variables of a second MVC performed 180 seconds later. If disconsidered, this phenomenon might bias maximal isometric strength assessment, overestimating some of these variables. PMID:25133157

  12. Maximizing strain in miniaturized dielectric elastomer actuators

    NASA Astrophysics Data System (ADS)

    Rosset, Samuel; Araromi, Oluwaseun; Shea, Herbert

    2015-04-01

    We present a theoretical model to optimise the unidirectional motion of a rigid object bonded to a miniaturized dielectric elastomer actuator (DEA), a configuration found for example in AMI's haptic feedback devices, or in our tuneable RF phase shifter. Recent work has shown that unidirectional motion is maximized when the membrane is both anistropically prestretched and subjected to a dead load in the direction of actuation. However, the use of dead weights for miniaturized devices is clearly highly impractical. Consequently smaller devices use the membrane itself to generate the opposing force. Since the membrane covers the entire frame, one has the same prestretch condition in the active (actuated) and passive zones. Because the passive zone contracts when the active zone expands, it does not provide a constant restoring force, reducing the maximum achievable actuation strain. We have determined the optimal ratio between the size of the electrode (active zone) and the passive zone, as well as the optimal prestretch in both in-plane directions, in order to maximize the absolute displacement of the rigid object placed at the active/passive border. Our model and experiments show that the ideal active ratio is 50%, with a displacement twice smaller than what can be obtained with a dead load. We expand our fabrication process to also show how DEAs can be laser-post-processed to remove carefully chosen regions of the passive elastomer membrane, thereby increasing the actuation strain of the device.

  13. Spiders Tune Glue Viscosity to Maximize Adhesion.

    PubMed

    Amarpuri, Gaurav; Zhang, Ci; Diaz, Candido; Opell, Brent D; Blackledge, Todd A; Dhinojwala, Ali

    2015-11-24

    Adhesion in humid conditions is a fundamental challenge to both natural and synthetic adhesives. Yet, glue from most spider species becomes stickier as humidity increases. We find the adhesion of spider glue, from five diverse spider species, maximizes at very different humidities that matches their foraging habitats. By using high-speed imaging and spreading power law, we find that the glue viscosity varies over 5 orders of magnitude with humidity for each species, yet the viscosity at maximal adhesion for each species is nearly identical, 10(5)-10(6) cP. Many natural systems take advantage of viscosity to improve functional response, but spider glue's humidity responsiveness is a novel adaptation that makes the glue stickiest in each species' preferred habitat. This tuning is achieved by a combination of proteins and hygroscopic organic salts that determines water uptake in the glue. We therefore anticipate that manipulation of polymer-salts interaction to control viscosity can provide a simple mechanism to design humidity responsive smart adhesives.

  14. Therapeutic Recreation

    ERIC Educational Resources Information Center

    Parks and Recreation, 1971

    1971-01-01

    Graphic profiles of (1) the professional membership of the National Therapeutic Recreation Society, (2) state-level employment opportunities in the field, and (3) educational opportunities at U.S. colleges and universities. (MB)

  15. Matching Pupils and Teachers to Maximize Expected Outcomes.

    ERIC Educational Resources Information Center

    Ward, Joe H., Jr.; And Others

    To achieve a good teacher-pupil match, it is necessary (1) to predict the learning outcomes that will result when each student is instructed by each teacher, (2) to use the predicted performance to compute an Optimality Index for each teacher-pupil combination to indicate the quality of each combination toward maximizing learning for all students,…

  16. Mentoring as Professional Development for Novice Entrepreneurs: Maximizing the Learning

    ERIC Educational Resources Information Center

    St-Jean, Etienne

    2012-01-01

    Mentoring can be seen as relevant if not essential in the continuing professional development of entrepreneurs. In the present study, we seek to understand how to maximize the learning that occurs through the mentoring process. To achieve this, we consider various elements that the literature suggested are associated with successful mentoring and…

  17. Polycrystalline configurations that maximize electrical resistivity

    NASA Astrophysics Data System (ADS)

    Nesi, Vincenzo; Milton, Graeme W.

    A lower bound on the effective conductivity tensor of polycrystalline aggregates formed from a single basic crystal of conductivity σ was recently established by Avellaneda. Cherkaev, Lurie and Milton. The bound holds for any basic crystal, but for isotropic aggregates of a uniaxial crystal, the bound is achieved by a sphere assemblage model of Schulgasser. This left open the question of attainability of the bound when the crystal is not uniaxial. The present work establishes that the bound is always attained by a rather large class of polycrystalline materials. These polycrystalline materials, with maximal electrical resistivity, are constructed by sequential lamination of the basic crystal and rotations of itself on widely separated length scales. The analysis is facilitated by introducing a tensor S = 0( 0I + σ) -1 where 0 > 0 is chosen so that Tr S = 1. This tensor s is related to the electric field in the optimal polycrystalline configurations.

  18. Multivariate residues and maximal unitarity

    NASA Astrophysics Data System (ADS)

    Søgaard, Mads; Zhang, Yang

    2013-12-01

    We extend the maximal unitarity method to amplitude contributions whose cuts define multidimensional algebraic varieties. The technique is valid to all orders and is explicitly demonstrated at three loops in gauge theories with any number of fermions and scalars in the adjoint representation. Deca-cuts realized by replacement of real slice integration contours by higher-dimensional tori encircling the global poles are used to factorize the planar triple box onto a product of trees. We apply computational algebraic geometry and multivariate complex analysis to derive unique projectors for all master integral coefficients and obtain compact analytic formulae in terms of tree-level data.

  19. Target Homework to Maximize Learning

    ERIC Educational Resources Information Center

    Heitzmann, Ray

    2007-01-01

    Targeted homework is based upon the belief that homework can make a significant contribution to student achievement in the areas of knowledge, skills, and values. It centers on the notion that homework achieves maximum effectiveness when teachers share the school's homework policy as well as their policy with students and parents or guardians. The…

  20. Knowledge discovery by accuracy maximization

    PubMed Central

    Cacciatore, Stefano; Luchinat, Claudio; Tenori, Leonardo

    2014-01-01

    Here we describe KODAMA (knowledge discovery by accuracy maximization), an unsupervised and semisupervised learning algorithm that performs feature extraction from noisy and high-dimensional data. Unlike other data mining methods, the peculiarity of KODAMA is that it is driven by an integrated procedure of cross-validation of the results. The discovery of a local manifold’s topology is led by a classifier through a Monte Carlo procedure of maximization of cross-validated predictive accuracy. Briefly, our approach differs from previous methods in that it has an integrated procedure of validation of the results. In this way, the method ensures the highest robustness of the obtained solution. This robustness is demonstrated on experimental datasets of gene expression and metabolomics, where KODAMA compares favorably with other existing feature extraction methods. KODAMA is then applied to an astronomical dataset, revealing unexpected features. Interesting and not easily predictable features are also found in the analysis of the State of the Union speeches by American presidents: KODAMA reveals an abrupt linguistic transition sharply separating all post-Reagan from all pre-Reagan speeches. The transition occurs during Reagan’s presidency and not from its beginning. PMID:24706821

  1. Maximizing exosome colloidal stability following electroporation.

    PubMed

    Hood, Joshua L; Scott, Michael J; Wickline, Samuel A

    2014-03-01

    Development of exosome-based semisynthetic nanovesicles for diagnostic and therapeutic purposes requires novel approaches to load exosomes with cargo. Electroporation has previously been used to load exosomes with RNA. However, investigations into exosome colloidal stability following electroporation have not been considered. Herein, we report the development of a unique trehalose pulse media (TPM) that minimizes exosome aggregation following electroporation. Dynamic light scattering (DLS) and RNA absorbance were employed to determine the extent of exosome aggregation and electroextraction post electroporation in TPM compared to common PBS pulse media or sucrose pulse media (SPM). Use of TPM to disaggregate melanoma exosomes post electroporation was dependent on both exosome concentration and electric field strength. TPM maximized exosome dispersal post electroporation for both homogenous B16 melanoma and heterogeneous human serum-derived populations of exosomes. Moreover, TPM enabled heavy cargo loading of melanoma exosomes with 5nm superparamagnetic iron oxide nanoparticles (SPION5) while maintaining original exosome size and minimizing exosome aggregation as evidenced by transmission electron microscopy. Loading exosomes with SPION5 increased exosome density on sucrose gradients. This provides a simple, label-free means of enriching exogenously modified exosomes and introduces the potential for MRI-driven theranostic exosome investigations in vivo.

  2. Maximizing Exosome Colloidal Stability Following Electroporation

    PubMed Central

    Hood, Joshua L.; Scott, Michael J.; Wickline, Samuel A.

    2014-01-01

    Development of exosome based semi-synthetic nanovesicles for diagnostic and therapeutic purposes requires novel approaches to load exosomes with cargo. Electroporation has previously been used to load exosomes with RNA. However, investigations into exosome colloidal stability following electroporation have not been considered. Herein, we report the development of a unique trehalose pulse media (TPM) that minimizes exosome aggregation following electroporation. Dynamic light scattering (DLS) and RNA absorbance were employed to determine the extent of exosome aggregation and electroextraction post electroporation in TPM compared to common PBS pulse media or sucrose pulse media (SPM). Use of TPM to disaggregate melanoma exosomes post electroporation was dependent on both exosome concentration and electric field strength. TPM maximized exosome dispersal post electroporation for both homogenous B16 melanoma and heterogeneous human serum derived populations of exosomes. Moreover, TPM enabled heavy cargo loading of melanoma exosomes with 5 nm superparamagnetic iron oxide nanoparticles (SPION5) while maintaining original exosome size and minimizing exosome aggregation as evidenced by transmission electron microscopy. Loading exosomes with SPION5 increased exosome density on sucrose gradients. This provides a simple, label free means to enrich exogenously modified exosomes and introduces the potential for MRI driven theranostic exosome investigations in vivo. PMID:24333249

  3. MACROMOLECULAR THERAPEUTICS

    PubMed Central

    Yang, Jiyuan; Kopeček, Jindřich

    2014-01-01

    This review covers water-soluble polymer-drug conjugates and macromolecules that possess biological activity without attached low molecular weight drugs. The main design principles of traditional and backbone degradable polymer-drug conjugates as well as the development of a new paradigm in nanomedicines – (low molecular weight) drug-free macromolecular therapeutics are discussed. To address the biological features of cancer, macromolecular therapeutics directed to stem/progenitor cells and the tumor microenvironment are deliberated. Finally, the future perspectives of the field are briefly debated. PMID:24747162

  4. Macromolecular therapeutics.

    PubMed

    Yang, Jiyuan; Kopeček, Jindřich

    2014-09-28

    This review covers water-soluble polymer-drug conjugates and macromolecules that possess biological activity without attached low molecular weight drugs. The main design principles of traditional and backbone degradable polymer-drug conjugates as well as the development of a new paradigm in nanomedicines - (low molecular weight) drug-free macromolecular therapeutics are discussed. To address the biological features of cancer, macromolecular therapeutics directed to stem/progenitor cells and the tumor microenvironment are deliberated. Finally, the future perspectives of the field are briefly debated.

  5. Natural selection maximizes Fisher information.

    PubMed

    Frank, S A

    2009-02-01

    In biology, information flows from the environment to the genome by the process of natural selection. However, it has not been clear precisely what sort of information metric properly describes natural selection. Here, I show that Fisher information arises as the intrinsic metric of natural selection and evolutionary dynamics. Maximizing the amount of Fisher information about the environment captured by the population leads to Fisher's fundamental theorem of natural selection, the most profound statement about how natural selection influences evolutionary dynamics. I also show a relation between Fisher information and Shannon information (entropy) that may help to unify the correspondence between information and dynamics. Finally, I discuss possible connections between the fundamental role of Fisher information in statistics, biology and other fields of science.

  6. Therapeutic Nanodevices

    NASA Astrophysics Data System (ADS)

    Lee, Stephen C.; Ruegsegger, Mark; Barnes, Philip D.; Smith, Bryan R.; Ferrari, Mauro

    Therapeutic nanotechnology offers minimally invasive therapies with high densities of function concentrated in small volumes, features that may reduce patient morbidity and mortality. Unlike other areas of nanotechnology, novel physical properties associated with nanoscale dimensionality are not the raison d'etre of therapeutic nanotechnology, whereas the aggregation of multiple biochemical (or comparably precise) functions into controlled nanoarchitectures is. Multifunctionality is a hallmark of emerging nanotherapeutic devices, and multifunctionality can allow nanotherapeutic devices to perform multi-step work processes, with each functional component contributing to one or more nanodevice subroutine such that, in aggregate, subroutines sum to a cogent work process. Cannonical nanotherapeutic subroutines include tethering (targeting) to sites of disease, dispensing measured doses of drug (or bioactive compound), detection of residual disease after therapy and communication with an external clinician/operator. Emerging nanotherapeutics thus blur the boundaries between medical devices and traditional pharmaceuticals. Assembly of therapeutic nanodevices generally exploits either (bio)material self assembly properties or chemoselective bioconjugation techniques, or both. Given the complexity, composition, and the necessity for their tight chemical and structural definition inherent in the nature of nanotherapeutics, their cost of goods (COGs) might exceed that of (already expensive) biologics. Early therapeutic nanodevices will likely be applied to disease states which exhibit significant unmet patient need (cancer and cardiovascular disease), while application to other disease states well-served by conventional therapy may await perfection of nanotherapeutic design and assembly protocols.

  7. Therapeutic Nanodevices

    NASA Astrophysics Data System (ADS)

    Lee, Stephen; Ruegsegger, Mark; Barnes, Philip; Smith, Bryan; Ferrari, Mauro

    Therapeutic nanotechnology offers minimally invasive therapies with high densities of function concentrated in small volumes, features that may reduce patient morbidity and mortality. Unlike other areas of nanotechnology, novel physical properties associated with nanoscale dimensionality are not the raison d'être of therapeutic nanotechnology, whereas the aggregation of multiple biochemical (or comparably precise) functions into controlled nanoarchitectures is. Multifunctionality is a hallmark of emerging nanotherapeutic devices, and multifunctionality can allow nanotherapeutic devices to perform multistep work processes, with each functional component contributing to one or more nanodevice subroutine such that, in aggregate, subroutines sum to a cogent work process. Cannonical nanotherapeutic subroutines include tethering (targeting) to sites of disease, dispensing measured doses of drug (or bioactive compound), detection of residual disease after therapy and communication with an external clinician/operator. Emerging nanotherapeutics thus blur the boundaries between medical devices and traditional pharmaceuticals. Assembly of therapeutic nanodevices generally exploits either (bio)material self-assembly properties or chemoselective bioconjugation techniques, or both. Given the complexity, composition, and the necessity for their tight chemical and structural definition inherent in the nature of nanotherapeutics, their cost of goods (COGs) might exceed that of (already expensive) biologics. Early therapeutic nanodevices will likely be applied to disease states which exhibit significant unmet patient need (cancer and cardiovascular disease), while application to other disease states well-served by conventional therapy may await perfection of nanotherapeutic design and assembly protocols.

  8. Therapeutic proteins.

    PubMed

    Dimitrov, Dimiter S

    2012-01-01

    Protein-based therapeutics are highly successful in clinic and currently enjoy unprecedented recognition of their potential. More than 100 genuine and similar number of modified therapeutic proteins are approved for clinical use in the European Union and the USA with 2010 sales of US$108 bln; monoclonal antibodies (mAbs) accounted for almost half (48%) of the sales. Based on their pharmacological activity, they can be divided into five groups: (a) replacing a protein that is deficient or abnormal; (b) augmenting an existing pathway; (c) providing a novel function or activity; (d) interfering with a molecule or organism; and (e) delivering other compounds or proteins, such as a radionuclide, cytotoxic drug, or effector proteins. Therapeutic proteins can also be grouped based on their molecular types that include antibody-based drugs, Fc fusion proteins, anticoagulants, blood factors, bone morphogenetic proteins, engineered protein scaffolds, enzymes, growth factors, hormones, interferons, interleukins, and thrombolytics. They can also be classified based on their molecular mechanism of activity as (a) binding non-covalently to target, e.g., mAbs; (b) affecting covalent bonds, e.g., enzymes; and (c) exerting activity without specific interactions, e.g., serum albumin. Most protein therapeutics currently on the market are recombinant and hundreds of them are in clinical trials for therapy of cancers, immune disorders, infections, and other diseases. New engineered proteins, including bispecific mAbs and multispecific fusion proteins, mAbs conjugated with small molecule drugs, and proteins with optimized pharmacokinetics, are currently under development. However, in the last several decades, there are no conceptually new methodological developments comparable, e.g., to genetic engineering leading to the development of recombinant therapeutic proteins. It appears that a paradigm change in methodologies and understanding of mechanisms is needed to overcome major

  9. Maximally symmetric stabilizer MUBs in even prime-power dimensions

    NASA Astrophysics Data System (ADS)

    Carmeli, Claudio; Schultz, Jussi; Toigo, Alessandro

    2017-03-01

    One way to construct a maximal set of mutually unbiased bases (MUBs) in a prime-power dimensional Hilbert space is by means of finite phase-space methods. MUBs obtained in this way are covariant with respect to some subgroup of the group of all affine symplectic phase-space transformations. However, this construction is not canonical: as a consequence, many different choices of covariance subgroups are possible. In particular, when the Hilbert space is 2n dimensional, it is known that covariance with respect to the full group of affine symplectic phase-space transformations can never be achieved. Here we show that in this case there exist two essentially different choices of maximal subgroups admitting covariant MUBs. For both of them, we explicitly construct a family of 2n covariant MUBs. We thus prove that, contrary to the odd dimensional case, maximally covariant MUBs are very far from being unique in even prime-power dimensions.

  10. Maximal dinucleotide and trinucleotide circular codes.

    PubMed

    Michel, Christian J; Pellegrini, Marco; Pirillo, Giuseppe

    2016-01-21

    We determine here the number and the list of maximal dinucleotide and trinucleotide circular codes. We prove that there is no maximal dinucleotide circular code having strictly less than 6 elements (maximum size of dinucleotide circular codes). On the other hand, a computer calculus shows that there are maximal trinucleotide circular codes with less than 20 elements (maximum size of trinucleotide circular codes). More precisely, there are maximal trinucleotide circular codes with 14, 15, 16, 17, 18 and 19 elements and no maximal trinucleotide circular code having less than 14 elements. We give the same information for the maximal self-complementary dinucleotide and trinucleotide circular codes. The amino acid distribution of maximal trinucleotide circular codes is also determined.

  11. Disk Density Tuning of a Maximal Random Packing

    PubMed Central

    Ebeida, Mohamed S.; Rushdi, Ahmad A.; Awad, Muhammad A.; Mahmoud, Ahmed H.; Yan, Dong-Ming; English, Shawn A.; Owens, John D.; Bajaj, Chandrajit L.; Mitchell, Scott A.

    2016-01-01

    We introduce an algorithmic framework for tuning the spatial density of disks in a maximal random packing, without changing the sizing function or radii of disks. Starting from any maximal random packing such as a Maximal Poisson-disk Sampling (MPS), we iteratively relocate, inject (add), or eject (remove) disks, using a set of three successively more-aggressive local operations. We may achieve a user-defined density, either more dense or more sparse, almost up to the theoretical structured limits. The tuned samples are conflict-free, retain coverage maximality, and, except in the extremes, retain the blue noise randomness properties of the input. We change the density of the packing one disk at a time, maintaining the minimum disk separation distance and the maximum domain coverage distance required of any maximal packing. These properties are local, and we can handle spatially-varying sizing functions. Using fewer points to satisfy a sizing function improves the efficiency of some applications. We apply the framework to improve the quality of meshes, removing non-obtuse angles; and to more accurately model fiber reinforced polymers for elastic and failure simulations. PMID:27563162

  12. Maximizing Potential: The Parents' Role.

    ERIC Educational Resources Information Center

    Dyer, Shirley Poindexter

    The mother of a 16-year-old daughter with autism offers a parental perspective on coping with a child's disability. The paper emphasizes that through direct interaction with the child and the child's teacher and through taking an active role in the child's activities and achievements, the child's potential can be discovered and the child can be…

  13. Maximizing Teaching through Brain Research

    ERIC Educational Resources Information Center

    Pattridge, Gregory C.

    2009-01-01

    Teachers and parents who read about the brain on the Internet should do so critically to determine fact from opinion. Are the assertions real about certain methods/strategies that claim to be based on brain research? Will they make a difference in their teaching and in achievement levels? Turning theory into fact take time and replication of solid…

  14. A maximally supersymmetric Kondo model

    NASA Astrophysics Data System (ADS)

    Harrison, Sarah; Kachru, Shamit; Torroba, Gonzalo

    2012-10-01

    We study the maximally supersymmetric Kondo model obtained by adding a fermionic impurity to N=4 supersymmetric Yang-Mills theory. While the original Kondo problem describes a defect interacting with a free Fermi liquid of itinerant electrons, here the ambient theory is an interacting CFT, and this introduces qualitatively new features into the system. The model arises in string theory by considering the intersection of a stack of M D5-branes with a stack of N D3-branes, at a point in the D3 worldvolume. We analyze the theory holographically, and propose a dictionary between the Kondo problem and antisymmetric Wilson loops in N=4 SYM. We perform an explicit calculation of the D5 fluctuations in the D3 geometry and determine the spectrum of defect operators. This establishes the stability of the Kondo fixed point together with its basic thermodynamic properties. Known supergravity solutions for Wilson loops allow us to go beyond the probe approximation: the D5s disappear and are replaced by three-form flux piercing a new topologically non-trivial S3 in the corrected geometry. This describes the Kondo model in terms of a geometric transition. A dual matrix model reflects the basic properties of the corrected gravity solution in its eigenvalue distribution.

  15. Maximizing the optical network capacity

    PubMed Central

    Bayvel, Polina; Maher, Robert; Liga, Gabriele; Shevchenko, Nikita A.; Lavery, Domaniç; Killey, Robert I.

    2016-01-01

    Most of the digital data transmitted are carried by optical fibres, forming the great part of the national and international communication infrastructure. The information-carrying capacity of these networks has increased vastly over the past decades through the introduction of wavelength division multiplexing, advanced modulation formats, digital signal processing and improved optical fibre and amplifier technology. These developments sparked the communication revolution and the growth of the Internet, and have created an illusion of infinite capacity being available. But as the volume of data continues to increase, is there a limit to the capacity of an optical fibre communication channel? The optical fibre channel is nonlinear, and the intensity-dependent Kerr nonlinearity limit has been suggested as a fundamental limit to optical fibre capacity. Current research is focused on whether this is the case, and on linear and nonlinear techniques, both optical and electronic, to understand, unlock and maximize the capacity of optical communications in the nonlinear regime. This paper describes some of them and discusses future prospects for success in the quest for capacity. PMID:26809572

  16. A Maximally Supersymmetric Kondo Model

    SciTech Connect

    Harrison, Sarah; Kachru, Shamit; Torroba, Gonzalo; /Stanford U., Phys. Dept. /SLAC

    2012-02-17

    We study the maximally supersymmetric Kondo model obtained by adding a fermionic impurity to N = 4 supersymmetric Yang-Mills theory. While the original Kondo problem describes a defect interacting with a free Fermi liquid of itinerant electrons, here the ambient theory is an interacting CFT, and this introduces qualitatively new features into the system. The model arises in string theory by considering the intersection of a stack of M D5-branes with a stack of N D3-branes, at a point in the D3 worldvolume. We analyze the theory holographically, and propose a dictionary between the Kondo problem and antisymmetric Wilson loops in N = 4 SYM. We perform an explicit calculation of the D5 fluctuations in the D3 geometry and determine the spectrum of defect operators. This establishes the stability of the Kondo fixed point together with its basic thermodynamic properties. Known supergravity solutions for Wilson loops allow us to go beyond the probe approximation: the D5s disappear and are replaced by three-form flux piercing a new topologically non-trivial S3 in the corrected geometry. This describes the Kondo model in terms of a geometric transition. A dual matrix model reflects the basic properties of the corrected gravity solution in its eigenvalue distribution.

  17. Maximal switchability of centralized networks

    NASA Astrophysics Data System (ADS)

    Vakulenko, Sergei; Morozov, Ivan; Radulescu, Ovidiu

    2016-08-01

    We consider continuous time Hopfield-like recurrent networks as dynamical models for gene regulation and neural networks. We are interested in networks that contain n high-degree nodes preferably connected to a large number of N s weakly connected satellites, a property that we call n/N s -centrality. If the hub dynamics is slow, we obtain that the large time network dynamics is completely defined by the hub dynamics. Moreover, such networks are maximally flexible and switchable, in the sense that they can switch from a globally attractive rest state to any structurally stable dynamics when the response time of a special controller hub is changed. In particular, we show that a decrease of the controller hub response time can lead to a sharp variation in the network attractor structure: we can obtain a set of new local attractors, whose number can increase exponentially with N, the total number of nodes of the nework. These new attractors can be periodic or even chaotic. We provide an algorithm, which allows us to design networks with the desired switching properties, or to learn them from time series, by adjusting the interactions between hubs and satellites. Such switchable networks could be used as models for context dependent adaptation in functional genetics or as models for cognitive functions in neuroscience.

  18. Ischemic preconditioning of the muscle improves maximal exercise performance but not maximal oxygen uptake in humans.

    PubMed

    Crisafulli, Antonio; Tangianu, Flavio; Tocco, Filippo; Concu, Alberto; Mameli, Ombretta; Mulliri, Gabriele; Caria, Marcello A

    2011-08-01

    Brief episodes of nonlethal ischemia, commonly known as "ischemic preconditioning" (IP), are protective against cell injury induced by infarction. Moreover, muscle IP has been found capable of improving exercise performance. The aim of the study was the comparison of standard exercise performances carried out in normal conditions with those carried out following IP, achieved by brief muscle ischemia at rest (RIP) and after exercise (EIP). Seventeen physically active, healthy male subjects performed three incremental, randomly assigned maximal exercise tests on a cycle ergometer up to exhaustion. One was the reference (REF) test, whereas the others were performed after the RIP and EIP sessions. Total exercise time (TET), total work (TW), and maximal power output (W(max)), oxygen uptake (VO(2max)), and pulmonary ventilation (VE(max)) were assessed. Furthermore, impedance cardiography was used to measure maximal heart rate (HR(max)), stroke volume (SV(max)), and cardiac output (CO(max)). A subgroup of volunteers (n = 10) performed all-out tests to assess their anaerobic capacity. We found that both RIP and EIP protocols increased in a similar fashion TET, TW, W(max), VE(max), and HR(max) with respect to the REF test. In particular, W(max) increased by ∼ 4% in both preconditioning procedures. However, preconditioning sessions failed to increase traditionally measured variables such as VO(2max), SV(max,) CO(max), and anaerobic capacity(.) It was concluded that muscle IP improves performance without any difference between RIP and EIP procedures. The mechanism of this effect could be related to changes in fatigue perception.

  19. Dynamically Disordered Quantum Walk as a Maximal Entanglement Generator

    NASA Astrophysics Data System (ADS)

    Vieira, Rafael; Amorim, Edgard P. M.; Rigolin, Gustavo

    2013-11-01

    We show that the entanglement between the internal (spin) and external (position) degrees of freedom of a qubit in a random (dynamically disordered) one-dimensional discrete time quantum random walk (QRW) achieves its maximal possible value asymptotically in the number of steps, outperforming the entanglement attained by using ordered QRW. The disorder is modeled by introducing an extra random aspect to QRW, a classical coin that randomly dictates which quantum coin drives the system’s time evolution. We also show that maximal entanglement is achieved independently of the initial state of the walker, study the number of steps the system must move to be within a small fixed neighborhood of its asymptotic limit, and propose two experiments where these ideas can be tested.

  20. Inflation in maximal gauged supergravities

    SciTech Connect

    Kodama, Hideo; Nozawa, Masato

    2015-05-18

    We discuss the dynamics of multiple scalar fields and the possibility of realistic inflation in the maximal gauged supergravity. In this paper, we address this problem in the framework of recently discovered 1-parameter deformation of SO(4,4) and SO(5,3) dyonic gaugings, for which the base point of the scalar manifold corresponds to an unstable de Sitter critical point. In the gauge-field frame where the embedding tensor takes the value in the sum of the 36 and 36’ representations of SL(8), we present a scheme that allows us to derive an analytic expression for the scalar potential. With the help of this formalism, we derive the full potential and gauge coupling functions in analytic forms for the SO(3)×SO(3)-invariant subsectors of SO(4,4) and SO(5,3) gaugings, and argue that there exist no new critical points in addition to those discovered so far. For the SO(4,4) gauging, we also study the behavior of 6-dimensional scalar fields in this sector near the Dall’Agata-Inverso de Sitter critical point at which the negative eigenvalue of the scalar mass square with the largest modulus goes to zero as the deformation parameter s approaches a critical value s{sub c}. We find that when the deformation parameter s is taken sufficiently close to the critical value, inflation lasts more than 60 e-folds even if the initial point of the inflaton allows an O(0.1) deviation in Planck units from the Dall’Agata-Inverso critical point. It turns out that the spectral index n{sub s} of the curvature perturbation at the time of the 60 e-folding number is always about 0.96 and within the 1σ range n{sub s}=0.9639±0.0047 obtained by Planck, irrespective of the value of the η parameter at the critical saddle point. The tensor-scalar ratio predicted by this model is around 10{sup −3} and is close to the value in the Starobinsky model.

  1. Computing Maximally Supersymmetric Scattering Amplitudes

    NASA Astrophysics Data System (ADS)

    Stankowicz, James Michael, Jr.

    This dissertation reviews work in computing N = 4 super-Yang--Mills (sYM) and N = 8 maximally supersymmetric gravity (mSUGRA) scattering amplitudes in D = 4 spacetime dimensions in novel ways. After a brief introduction and overview in Ch. 1, the various techniques used to construct amplitudes in the remainder of the dissertation are discussed in Ch. 2. This includes several new concepts such as d log and pure integrand bases, as well as how to construct the amplitude using exactly one kinematic point where it vanishes. Also included in this chapter is an outline of the Mathematica package on shell diagrams and numerics.m (osdn) that was developed for the computations herein. The rest of the dissertation is devoted to explicit examples. In Ch. 3, the starting point is tree-level sYM amplitudes that have integral representations with residues that obey amplitude relations. These residues are shown to have corresponding residue numerators that allow a double copy prescription that results in mSUGRA residues. In Ch. 4, the two-loop four-point sYM amplitude is constructed in several ways, showcasing many of the techniques of Ch. 2; this includes an example of how to use osdn. The two-loop five-point amplitude is also presented in a pure integrand representation with comments on how it was constructed from one homogeneous cut of the amplitude. On-going work on the two-loop n-point amplitude is presented at the end of Ch. 4. In Ch. 5, the three-loop four-point amplitude is presented in the d log representation and in the pure integrand representation. In Ch. 6, there are several examples of four- through seven-loop planar diagrams that illustrate how considerations of the singularity structure of the amplitude underpin dual-conformal invariance. Taken with the previous examples, this is additional evidence that the structure known to exist in the planar sector extends to the full theory. At the end of this chapter is a proof that all mSUGRA amplitudes have a pole at

  2. Platelet-delivered therapeutics.

    PubMed

    Lyde, R; Sabatino, D; Sullivan, S K; Poncz, M

    2015-06-01

    We have proposed that modified platelets could potentially be used to correct intrinsic platelet defects as well as for targeted delivery of therapeutic molecules to sights of vascular injury. Ectopic expression of proteins within α-granules prior to platelet activation has been achieved for several proteins, including urokinase, factor (F) VIII, and partially for FIX. Potential uses of platelet-directed therapeutics will be discussed, focusing on targeted delivery of urokinase as a thromboprophylactic agent and FVIII for the treatment of hemophilia A patients with intractable inhibitors. This presentation will discuss new strategies that may be useful in the care of patients with vascular injury as well as remaining challenges and limitations of these approaches.

  3. Specificity of a Maximal Step Exercise Test

    ERIC Educational Resources Information Center

    Darby, Lynn A.; Marsh, Jennifer L.; Shewokis, Patricia A.; Pohlman, Roberta L.

    2007-01-01

    To adhere to the principle of "exercise specificity" exercise testing should be completed using the same physical activity that is performed during exercise training. The present study was designed to assess whether aerobic step exercisers have a greater maximal oxygen consumption (max VO sub 2) when tested using an activity specific, maximal step…

  4. Diurnal Variations in Maximal Oxygen Uptake.

    ERIC Educational Resources Information Center

    McClellan, Powell D.

    A study attempted to determine if diurnal (daily cyclical) variations were present during maximal exercise. The subjects' (30 female undergraduate physical education majors) oxygen consumption and heart rates were monitored while they walked on a treadmill on which the grade was raised every minute. Each subject was tested for maximal oxygen…

  5. Statistical mechanics of maximal independent sets

    NASA Astrophysics Data System (ADS)

    Dall'Asta, Luca; Pin, Paolo; Ramezanpour, Abolfazl

    2009-12-01

    The graph theoretic concept of maximal independent set arises in several practical problems in computer science as well as in game theory. A maximal independent set is defined by the set of occupied nodes that satisfy some packing and covering constraints. It is known that finding minimum and maximum-density maximal independent sets are hard optimization problems. In this paper, we use cavity method of statistical physics and Monte Carlo simulations to study the corresponding constraint satisfaction problem on random graphs. We obtain the entropy of maximal independent sets within the replica symmetric and one-step replica symmetry breaking frameworks, shedding light on the metric structure of the landscape of solutions and suggesting a class of possible algorithms. This is of particular relevance for the application to the study of strategic interactions in social and economic networks, where maximal independent sets correspond to pure Nash equilibria of a graphical game of public goods allocation.

  6. [Normal or high maximal oxygen uptake: a target in health].

    PubMed

    Ben-Dov, Issahar; Segel, Michael

    2012-02-01

    To achieve the predicted maximal oxygen consumption, many organs need to increase their output in a synchronized fashion. Therefore, maximal oxygen consumption is the single most reliable parameter predicting fitness, morbidity and mortality. Peak O2 uptake can be measured from noninvasive ventilatory parameters during short, incremental, cardiopulmonary exercise test (CPET) on a cycle ergometer or on a treadmill. Commercial systems are available and all enable breath by breath measurement of ventilation, exhaled gas concentration, oxygen saturation and additional cardiorespiratory parameters. Performance of the test requires adherence to strict guidelines and experienced technicians and physicians, although their qualification has not yet been defined by the national health authorities. There are well defined indications and benefits from CPET, among them are, determination of the anaerobic threshold, defining the cause of dyspnea, the timing for heart transplantation, exercise prescription for training and rehabilitation purposes and follow-up on disease progression or response to pharmacological or other modes of therapy. Measuring maximal oxygen consumption should be encouraged in health and disease and normal maximal oxygen consumption should be defined as a health target.

  7. Should academic therapeutic patents go to the highest bidder?

    PubMed

    Collinsworth, Bryan; Crager, Sara E

    2014-05-01

    Universities conduct biomedical research with the self-stated goal of disseminating the benefits to the global public. Licensing therapeutic patents to the highest bidder is counterproductive to this aim, as it prioritizes income maximization over dissemination. We believe that licensing strategies focused on promoting broad access to university-discovered therapeutics better serve both the mission of universities and the public good.

  8. Maximal aerobic power measurement in runners and swimmers.

    PubMed Central

    Corry, I.; Powers, N.

    1982-01-01

    Five cross-country runners and five competitive swimmers performed a pulling exercise with elastic shock cords and a treadmill run to exhaustion. The mean VO2 max related to lean body mass of the runners was significantly higher than the swimmers on the treadmill (p less than 0.05) while, on the pulling test, the mean VO2 max of the swimmers was significantly higher than the runners (p less 0.01). The maximum heart rates achieved pulling were 95% of the running maximum by runners and 96% by swimmers with no significant difference between them. Their mean oxygen pulse was almost the same for maximal running but the swimmers had a significantly higher oxygen pulse than the runners for maximal pulling (p less than 0.01). The swimmers could reach about 79% of their running VO2 max by pulling while the runners used 53% of their running VO2 max. Images Fig. 1 Fig. 3 PMID:7139226

  9. The effects of strenuous exercises on resting heart rate, blood pressure, and maximal oxygen uptake.

    PubMed

    Oh, Deuk-Ja; Hong, Hyeon-Ok; Lee, Bo-Ae

    2016-02-01

    The purpose of this study is to investigate the effects of strenuous exercises on resting heart rate, blood pressure, and maximal oxygen uptake. To achieve the purpose of the study, a total of 30 subjects were selected, including 15 people who performed continued regular exercises and 15 people as the control group. With regard to data processing, the IBM SPSS Statistics ver. 21.0 was used to calculate the mean and standard deviation. The difference of mean change between groups was verified through an independent t-test. As a result, there were significant differences in resting heart rate, maximal heart rate, maximal systolic blood pressure, and maximal oxygen uptake. However, the maximal systolic blood pressure was found to be an exercise-induced high blood pressure. Thus, it is thought that a risk diagnosis for it through a regular exercise stress test is necessary.

  10. Polarity related influence maximization in signed social networks.

    PubMed

    Li, Dong; Xu, Zhi-Ming; Chakraborty, Nilanjan; Gupta, Anika; Sycara, Katia; Li, Sheng

    2014-01-01

    Influence maximization in social networks has been widely studied motivated by applications like spread of ideas or innovations in a network and viral marketing of products. Current studies focus almost exclusively on unsigned social networks containing only positive relationships (e.g. friend or trust) between users. Influence maximization in signed social networks containing both positive relationships and negative relationships (e.g. foe or distrust) between users is still a challenging problem that has not been studied. Thus, in this paper, we propose the polarity-related influence maximization (PRIM) problem which aims to find the seed node set with maximum positive influence or maximum negative influence in signed social networks. To address the PRIM problem, we first extend the standard Independent Cascade (IC) model to the signed social networks and propose a Polarity-related Independent Cascade (named IC-P) diffusion model. We prove that the influence function of the PRIM problem under the IC-P model is monotonic and submodular Thus, a greedy algorithm can be used to achieve an approximation ratio of 1-1/e for solving the PRIM problem in signed social networks. Experimental results on two signed social network datasets, Epinions and Slashdot, validate that our approximation algorithm for solving the PRIM problem outperforms state-of-the-art methods.

  11. Maximally reliable spatial filtering of steady state visual evoked potentials.

    PubMed

    Dmochowski, Jacek P; Greaves, Alex S; Norcia, Anthony M

    2015-04-01

    Due to their high signal-to-noise ratio (SNR) and robustness to artifacts, steady state visual evoked potentials (SSVEPs) are a popular technique for studying neural processing in the human visual system. SSVEPs are conventionally analyzed at individual electrodes or linear combinations of electrodes which maximize some variant of the SNR. Here we exploit the fundamental assumption of evoked responses--reproducibility across trials--to develop a technique that extracts a small number of high SNR, maximally reliable SSVEP components. This novel spatial filtering method operates on an array of Fourier coefficients and projects the data into a low-dimensional space in which the trial-to-trial spectral covariance is maximized. When applied to two sample data sets, the resulting technique recovers physiologically plausible components (i.e., the recovered topographies match the lead fields of the underlying sources) while drastically reducing the dimensionality of the data (i.e., more than 90% of the trial-to-trial reliability is captured in the first four components). Moreover, the proposed technique achieves a higher SNR than that of the single-best electrode or the Principal Components. We provide a freely-available MATLAB implementation of the proposed technique, herein termed "Reliable Components Analysis".

  12. Formation Control of the MAXIM L2 Libration Orbit Mission

    NASA Technical Reports Server (NTRS)

    Folta, David; Hartman, Kate; Howell, Kathleen; Marchand, Belinda

    2004-01-01

    The Micro-Arcsecond Imaging Mission (MAXIM), a proposed concept for the Structure and Evolution of the Universe (SEU) Black Hole Imaging mission, is designed to make a ten million-fold improvement in X-ray image clarity of celestial objects by providing better than 0.1 microarcsecond imaging. To achieve mission requirements, MAXIM will have to improve on pointing by orders of magnitude. This pointing requirement impacts the control and design of the formation. Currently the architecture is comprised of 25 spacecraft, which will form the sparse apertures of a grazing incidence X-ray interferometer covering the 0.3-10 keV bandpass. This configuration will deploy 24 spacecraft as optics modules and one as the detector. The formation must allow for long duration continuous science observations and also for reconfiguration that permits re-pointing of the formation. In this paper, we provide analysis and trades of several control efforts that are dependent upon the pointing requirements and the configuration and dimensions of the MAXIM formation. We emphasize the utilization of natural motions in the Lagrangian regions that minimize the control efforts and we address both continuous and discrete control via LQR and feedback linearization. Results provide control cost, configuration options, and capabilities as guidelines for the development of this complex mission.

  13. Formation Control of the MAXIM L2 Libration Orbit Mission

    NASA Technical Reports Server (NTRS)

    Folta, David; Hartman, Kate; Howell, Kathleen; Marchand, Belinda

    2004-01-01

    The Micro-Arcsecond X-ray Imaging Mission (MAXIM), a proposed concept for the Structure and Evolution of the Universe (SEU) Black Hole Imager mission, is designed to make a ten million-fold improvement in X-ray image clarity of celestial objects by providing better than 0.1 micro-arcsecond imaging. Currently the mission architecture comprises 25 spacecraft, 24 as optics modules and one as the detector, which will form sparse sub-apertures of a grazing incidence X-ray interferometer covering the 0.3-10 keV bandpass. This formation must allow for long duration continuous science observations and also for reconfiguration that permits re-pointing of the formation. To achieve these mission goals, the formation is required to cooperatively point at desired targets. Once pointed, the individual elements of the MAXIM formation must remain stable, maintaining their relative positions and attitudes below a critical threshold. These pointing and formation stability requirements impact the control and design of the formation. In this paper, we provide analysis of control efforts that are dependent upon the stability and the configuration and dimensions of the MAXIM formation. We emphasize the utilization of natural motions in the Lagrangian regions to minimize the control efforts and we address continuous control via input feedback linearization (IFL). Results provide control cost, configuration options, and capabilities as guidelines for the development of this complex mission.

  14. Maximal likelihood correspondence estimation for face recognition across pose.

    PubMed

    Li, Shaoxin; Liu, Xin; Chai, Xiujuan; Zhang, Haihong; Lao, Shihong; Shan, Shiguang

    2014-10-01

    Due to the misalignment of image features, the performance of many conventional face recognition methods degrades considerably in across pose scenario. To address this problem, many image matching-based methods are proposed to estimate semantic correspondence between faces in different poses. In this paper, we aim to solve two critical problems in previous image matching-based correspondence learning methods: 1) fail to fully exploit face specific structure information in correspondence estimation and 2) fail to learn personalized correspondence for each probe image. To this end, we first build a model, termed as morphable displacement field (MDF), to encode face specific structure information of semantic correspondence from a set of real samples of correspondences calculated from 3D face models. Then, we propose a maximal likelihood correspondence estimation (MLCE) method to learn personalized correspondence based on maximal likelihood frontal face assumption. After obtaining the semantic correspondence encoded in the learned displacement, we can synthesize virtual frontal images of the profile faces for subsequent recognition. Using linear discriminant analysis method with pixel-intensity features, state-of-the-art performance is achieved on three multipose benchmarks, i.e., CMU-PIE, FERET, and MultiPIE databases. Owe to the rational MDF regularization and the usage of novel maximal likelihood objective, the proposed MLCE method can reliably learn correspondence between faces in different poses even in complex wild environment, i.e., labeled face in the wild database.

  15. Polarity Related Influence Maximization in Signed Social Networks

    PubMed Central

    Li, Dong; Xu, Zhi-Ming; Chakraborty, Nilanjan; Gupta, Anika; Sycara, Katia; Li, Sheng

    2014-01-01

    Influence maximization in social networks has been widely studied motivated by applications like spread of ideas or innovations in a network and viral marketing of products. Current studies focus almost exclusively on unsigned social networks containing only positive relationships (e.g. friend or trust) between users. Influence maximization in signed social networks containing both positive relationships and negative relationships (e.g. foe or distrust) between users is still a challenging problem that has not been studied. Thus, in this paper, we propose the polarity-related influence maximization (PRIM) problem which aims to find the seed node set with maximum positive influence or maximum negative influence in signed social networks. To address the PRIM problem, we first extend the standard Independent Cascade (IC) model to the signed social networks and propose a Polarity-related Independent Cascade (named IC-P) diffusion model. We prove that the influence function of the PRIM problem under the IC-P model is monotonic and submodular Thus, a greedy algorithm can be used to achieve an approximation ratio of 1-1/e for solving the PRIM problem in signed social networks. Experimental results on two signed social network datasets, Epinions and Slashdot, validate that our approximation algorithm for solving the PRIM problem outperforms state-of-the-art methods. PMID:25061986

  16. Reference values of maximal oxygen uptake for polish rowers.

    PubMed

    Klusiewicz, Andrzej; Starczewski, Michał; Ładyga, Maria; Długołęcka, Barbara; Braksator, Wojciech; Mamcarz, Artur; Sitkowski, Dariusz

    2014-12-09

    The aim of this study was to characterize changes in maximal oxygen uptake over several years and to elaborate current reference values of this index based on determinations carried out in large and representative groups of top Polish rowers. For this study 81 female and 159 male rowers from the sub-junior to senior categories were recruited from the Polish National Team and its direct backup. All the subjects performed an incremental exercise test on a rowing ergometer. During the test maximal oxygen uptake was measured with the BxB method. The calculated reference values for elite Polish junior and U23 rowers allowed to evaluate the athletes' fitness level against the respective reference group and may aid the coach in controlling the training process. Mean values of VO2max achieved by members of the top Polish rowing crews who over the last five years competed in the Olympic Games or World Championships were also presented. The results of the research on the "trainability" of the maximal oxygen uptake may lead to a conclusion that the growth rate of the index is larger in case of high-level athletes and that the index (in absolute values) increases significantly between the age of 19-22 years (U23 category).

  17. Maximizing Complementary Quantities by Projective Measurements

    NASA Astrophysics Data System (ADS)

    M. Souza, Leonardo A.; Bernardes, Nadja K.; Rossi, Romeu

    2017-04-01

    In this work, we study the so-called quantitative complementarity quantities. We focus in the following physical situation: two qubits ( q A and q B ) are initially in a maximally entangled state. One of them ( q B ) interacts with a N-qubit system ( R). After the interaction, projective measurements are performed on each of the qubits of R, in a basis that is chosen after independent optimization procedures: maximization of the visibility, the concurrence, and the predictability. For a specific maximization procedure, we study in detail how each of the complementary quantities behave, conditioned on the intensity of the coupling between q B and the N qubits. We show that, if the coupling is sufficiently "strong," independent of the maximization procedure, the concurrence tends to decay quickly. Interestingly enough, the behavior of the concurrence in this model is similar to the entanglement dynamics of a two qubit system subjected to a thermal reservoir, despite that we consider finite N. However, the visibility shows a different behavior: its maximization is more efficient for stronger coupling constants. Moreover, we investigate how the distinguishability, or the information stored in different parts of the system, is distributed for different couplings.

  18. Accolades or Achievement? Addressing the Unforeseen Consequences of Therapeutic Pedagogy

    ERIC Educational Resources Information Center

    McWilliam, Erica

    2015-01-01

    In June this year, Wellesley High School became a focus of attention worldwide, following a graduation speech made by a teacher at the school. Departing from the traditional rhetoric of such ceremonies, English teacher David McCullough told the assembled graduates that they were neither special nor exceptional, but may well believe they were…

  19. Ethics Audit of a Therapeutic Recreation Course

    ERIC Educational Resources Information Center

    Nisbett, Nancy; Hinton, Jennifer

    2008-01-01

    The purpose of this study was to enhance awareness of the presence of ethics education within the allied health discipline of therapeutic recreation. To achieve this end, a curriculum audit was conducted in a therapeutic recreation course to determine the existence of ethics education within the course. Included topics, methods of delivery, and…

  20. Lipidome determinants of maximal lifespan in mammals.

    PubMed

    Bozek, Katarzyna; Khrameeva, Ekaterina E; Reznick, Jane; Omerbašić, Damir; Bennett, Nigel C; Lewin, Gary R; Azpurua, Jorge; Gorbunova, Vera; Seluanov, Andrei; Regnard, Pierrick; Wanert, Fanelie; Marchal, Julia; Pifferi, Fabien; Aujard, Fabienne; Liu, Zhen; Shi, Peng; Pääbo, Svante; Schroeder, Florian; Willmitzer, Lothar; Giavalisco, Patrick; Khaitovich, Philipp

    2017-12-01

    Maximal lifespan of mammalian species, even if closely related, may differ more than 10-fold, however the nature of the mechanisms that determine this variability is unresolved. Here, we assess the relationship between maximal lifespan duration and concentrations of more than 20,000 lipid compounds, measured in 669 tissue samples from 6 tissues of 35 species representing three mammalian clades: primates, rodents and bats. We identify lipids associated with species' longevity across the three clades, uncoupled from other parameters, such as basal metabolic rate, body size, or body temperature. These lipids clustered in specific lipid classes and pathways, and enzymes linked to them display signatures of greater stabilizing selection in long-living species, and cluster in functional groups related to signaling and protein-modification processes. These findings point towards the existence of defined molecular mechanisms underlying variation in maximal lifespan among mammals.

  1. An information maximization model of eye movements

    NASA Technical Reports Server (NTRS)

    Renninger, Laura Walker; Coughlan, James; Verghese, Preeti; Malik, Jitendra

    2005-01-01

    We propose a sequential information maximization model as a general strategy for programming eye movements. The model reconstructs high-resolution visual information from a sequence of fixations, taking into account the fall-off in resolution from the fovea to the periphery. From this framework we get a simple rule for predicting fixation sequences: after each fixation, fixate next at the location that minimizes uncertainty (maximizes information) about the stimulus. By comparing our model performance to human eye movement data and to predictions from a saliency and random model, we demonstrate that our model is best at predicting fixation locations. Modeling additional biological constraints will improve the prediction of fixation sequences. Our results suggest that information maximization is a useful principle for programming eye movements.

  2. Balanced crossmodal excitation and inhibition essential for maximizing multisensory gain.

    PubMed

    Hoshino, Osamu

    2014-07-01

    We examined whether and how the balancing of crossmodal excitation and inhibition affects intersensory facilitation. A neural network model, comprising lower-order unimodal networks (X, Y) and a higher-order multimodal network (M), was simulated. Crossmodal excitation was made by direct activation of principal cells of the X network by the Y network. Crossmodal inhibition was made in an indirect manner: the Y network activated glial cells of the X network. This let glial plasma membrane transporters export GABA molecules into the extracellular space and increased the level of ambient GABA. The ambient GABA molecules were accepted by extrasynaptic GABAa receptors and tonically inhibited principal cells of the X network. Namely, crossmodal inhibition was made through GABAergic gliotransmission. Intersensory facilitation was assessed in terms of multisensory gain: the difference between the numbers of spikes evoked by multisensory (XY) stimulation and unisensory (X-alone) stimulation. The maximal multisensory gain (XY-X) could be achieved at an intermediate noise level by balancing crossmodal excitation and inhibition. This result supports an experimentally derived conclusion: intersensory facilitation under noisy environmental conditions is not necessarily in accord with the principle of inverse effectiveness; rather, multisensory gain is maximal at intermediate signal-to-noise ratio (SNR) levels. The maximal multisensory gain was available at the weakest signal if noise was not present, indicating that the principle of inverse effectiveness is a special case of the intersensory facilitation model proposed here. We suggest that the balancing of crossmodal excitation and inhibition may be crucial for intersensory facilitation. The GABAergic glio-transmission-mediated crossmodal inhibitory mechanism effectively works for intersensory facilitation and on determining the maximal multisensory gain in the entire SNR range between the two extremes: low and high SNRs.

  3. Singularity structure of maximally supersymmetric scattering amplitudes.

    PubMed

    Arkani-Hamed, Nima; Bourjaily, Jacob L; Cachazo, Freddy; Trnka, Jaroslav

    2014-12-31

    We present evidence that loop amplitudes in maximally supersymmetric (N=4) Yang-Mills theory (SYM) beyond the planar limit share some of the remarkable structures of the planar theory. In particular, we show that through two loops, the four-particle amplitude in full N=4 SYM has only logarithmic singularities and is free of any poles at infinity--properties closely related to uniform transcendentality and the UV finiteness of the theory. We also briefly comment on implications for maximal (N=8) supergravity theory (SUGRA).

  4. Understanding violations of Gricean maxims in preschoolers and adults

    PubMed Central

    Okanda, Mako; Asada, Kosuke; Moriguchi, Yusuke; Itakura, Shoji

    2015-01-01

    This study used a revised Conversational Violations Test to examine Gricean maxim violations in 4- to 6-year-old Japanese children and adults. Participants' understanding of the following maxims was assessed: be informative (first maxim of quantity), avoid redundancy (second maxim of quantity), be truthful (maxim of quality), be relevant (maxim of relation), avoid ambiguity (second maxim of manner), and be polite (maxim of politeness). Sensitivity to violations of Gricean maxims increased with age: 4-year-olds' understanding of maxims was near chance, 5-year-olds understood some maxims (first maxim of quantity and maxims of quality, relation, and manner), and 6-year-olds and adults understood all maxims. Preschoolers acquired the maxim of relation first and had the greatest difficulty understanding the second maxim of quantity. Children and adults differed in their comprehension of the maxim of politeness. The development of the pragmatic understanding of Gricean maxims and implications for the construction of developmental tasks from early childhood to adulthood are discussed. PMID:26191018

  5. How to Generate Good Profit Maximization Problems

    ERIC Educational Resources Information Center

    Davis, Lewis

    2014-01-01

    In this article, the author considers the merits of two classes of profit maximization problems: those involving perfectly competitive firms with quadratic and cubic cost functions. While relatively easy to develop and solve, problems based on quadratic cost functions are too simple to address a number of important issues, such as the use of…

  6. Robust Utility Maximization Under Convex Portfolio Constraints

    SciTech Connect

    Matoussi, Anis; Mezghani, Hanen Mnif, Mohamed

    2015-04-15

    We study a robust maximization problem from terminal wealth and consumption under a convex constraints on the portfolio. We state the existence and the uniqueness of the consumption–investment strategy by studying the associated quadratic backward stochastic differential equation. We characterize the optimal control by using the duality method and deriving a dynamic maximum principle.

  7. Maximizing the Spectacle of Water Fountains

    ERIC Educational Resources Information Center

    Simoson, Andrew J.

    2009-01-01

    For a given initial speed of water from a spigot or jet, what angle of the jet will maximize the visual impact of the water spray in the fountain? This paper focuses on fountains whose spigots are arranged in circular fashion, and couches the measurement of the visual impact in terms of the surface area and the volume under the fountain's natural…

  8. Maximal dinucleotide comma-free codes.

    PubMed

    Fimmel, Elena; Strüngmann, Lutz

    2016-01-21

    The problem of retrieval and maintenance of the correct reading frame plays a significant role in RNA transcription. Circular codes, and especially comma-free codes, can help to understand the underlying mechanisms of error-detection in this process. In recent years much attention has been paid to the investigation of trinucleotide circular codes (see, for instance, Fimmel et al., 2014; Fimmel and Strüngmann, 2015a; Michel and Pirillo, 2012; Michel et al., 2012, 2008), while dinucleotide codes had been touched on only marginally, even though dinucleotides are associated to important biological functions. Recently, all maximal dinucleotide circular codes were classified (Fimmel et al., 2015; Michel and Pirillo, 2013). The present paper studies maximal dinucleotide comma-free codes and their close connection to maximal dinucleotide circular codes. We give a construction principle for such codes and provide a graphical representation that allows them to be visualized geometrically. Moreover, we compare the results for dinucleotide codes with the corresponding situation for trinucleotide maximal self-complementary C(3)-codes. Finally, the results obtained are discussed with respect to Crick׳s hypothesis about frame-shift-detecting codes without commas.

  9. DNA solution of the maximal clique problem.

    PubMed

    Ouyang, Q; Kaplan, P D; Liu, S; Libchaber, A

    1997-10-17

    The maximal clique problem has been solved by means of molecular biology techniques. A pool of DNA molecules corresponding to the total ensemble of six-vertex cliques was built, followed by a series of selection processes. The algorithm is highly parallel and has satisfactory fidelity. This work represents further evidence for the ability of DNA computing to solve NP-complete search problems.

  10. Maximizing Resource Utilization in Video Streaming Systems

    ERIC Educational Resources Information Center

    Alsmirat, Mohammad Abdullah

    2013-01-01

    Video streaming has recently grown dramatically in popularity over the Internet, Cable TV, and wire-less networks. Because of the resource demanding nature of video streaming applications, maximizing resource utilization in any video streaming system is a key factor to increase the scalability and decrease the cost of the system. Resources to…

  11. Why Contextual Preference Reversals Maximize Expected Value

    PubMed Central

    2016-01-01

    Contextual preference reversals occur when a preference for one option over another is reversed by the addition of further options. It has been argued that the occurrence of preference reversals in human behavior shows that people violate the axioms of rational choice and that people are not, therefore, expected value maximizers. In contrast, we demonstrate that if a person is only able to make noisy calculations of expected value and noisy observations of the ordinal relations among option features, then the expected value maximizing choice is influenced by the addition of new options and does give rise to apparent preference reversals. We explore the implications of expected value maximizing choice, conditioned on noisy observations, for a range of contextual preference reversal types—including attraction, compromise, similarity, and phantom effects. These preference reversal types have played a key role in the development of models of human choice. We conclude that experiments demonstrating contextual preference reversals are not evidence for irrationality. They are, however, a consequence of expected value maximization given noisy observations. PMID:27337391

  12. A Model of College Tuition Maximization

    ERIC Educational Resources Information Center

    Bosshardt, Donald I.; Lichtenstein, Larry; Zaporowski, Mark P.

    2009-01-01

    This paper develops a series of models for optimal tuition pricing for private colleges and universities. The university is assumed to be a profit maximizing, price discriminating monopolist. The enrollment decision of student's is stochastic in nature. The university offers an effective tuition rate, comprised of stipulated tuition less financial…

  13. Managing the innovation supply chain to maximize personalized medicine.

    PubMed

    Waldman, S A; Terzic, A

    2014-02-01

    Personalized medicine epitomizes an evolving model of care tailored to the individual patient. This emerging paradigm harnesses radical technological advances to define each patient's molecular characteristics and decipher his or her unique pathophysiological processes. Translated into individualized algorithms, personalized medicine aims to predict, prevent, and cure disease without producing therapeutic adverse events. Although the transformative power of personalized medicine is generally recognized by physicians, patients, and payers, the complexity of translating discoveries into new modalities that transform health care is less appreciated. We often consider the flow of innovation and technology along a continuum of discovery, development, regulation, and application bridging the bench with the bedside. However, this process also can be viewed through a complementary prism, as a necessary supply chain of services and providers, each making essential contributions to the development of the final product to maximize value to consumers. Considering personalized medicine in this context of supply chain management highlights essential points of vulnerability and/or scalability that can ultimately constrain translation of the biological revolution or potentiate it into individualized diagnostics and therapeutics for optimized value creation and delivery.

  14. Administration of ciprofloxacin and capsaicin in rats to achieve higher maximal serum concentrations.

    PubMed

    Sumano-López, Héctor; Gutiérrez-Olvera, Lilia; Aguilera-Jiménez, Rita; Gutiérrez-Olvera, Carlos; Jiménez-Gómez, Francisco

    2007-01-01

    To test if capsaicin could improve the bioavailability of ciprofloxacin (1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylic acid, CAS 85721-33-1, Bay q 3939) in rats, 0.01, 0.1, 0.5 and 1% capsaicin ((E)-N-[(4-hydroxy-3-methoxyphenyl)methyl]-8-methyl-6-nonenamide, trans-8-methyl-N-vanillyl-6-nonenamide, CAS 404-86-4) dissolved in ethanol and mixed with 20 mg/kg of ciprofloxacin were orally administered to groups of 10 rats each. Control groups were dosed with capsaicin-free, ethanol-containing or ethanol-free ciprofloxacin. Reference intravenous pharmacokinetics of ciprofloxacin was also established. The results revealed that capsaicin increased ciprofloxacin bioavailability by approximately 70% in groups receiving preparations containing capsaicin at a rate of 0.01, 0.1 and 0.5%. Higher concentrations failed to further increase bioavailability. However, capsaicin appears to have little or no impact on the rate of absorption or clearance of ciprofloxacin. Considering that 0.01% or 0.1% capsaicin are unlikely to upset the gastrointestinal tract, it may be worth attempting to study if a similar effect occurs in man, and to evaluate if the addition of capsaicin can be used as a method to increase the area under the curve/minimum inhibitory concentration rate, a key variable to improve clinical efficacy of ciprofloxacin.

  15. Adapting Grouping Patterns to Maximize Reading Achievement within an Elementary School Classroom.

    ERIC Educational Resources Information Center

    Wiesendanger, Katherine D.; Birlem, Ellen D.

    The results of a survey of 225 primary school teachers indicate that a high proportion of children in the primary grades are in classrooms that use the basal reader approach. In addition, it is apparent that the vast majority are assigned to either a high, medium, or low group. Once this assignment is made, it becomes difficult for a child to be…

  16. Future Tactical Truck System Maximization: A Achieving Objective Force Sustainment and Distribution Requirements

    DTIC Science & Technology

    2007-11-02

    automatically execute a convoy standing operating procedure that creates the convoy chain of command and S/V team roles in the convoy for execution of...responsibility for their assigned vehicle. Soldiers are culturally indoctrinated to understand their individual S/V team role in the greater sustainment

  17. The 5 Essentials of Organizational Excellence: Maximizing Schoolwide Student Achievement and Performance.

    ERIC Educational Resources Information Center

    Marazza, Lawrence L.

    This book explores the necessity for building strong relationships among administrators, teachers, parents, and the community by applying what the book calls the five essentials of organizational excellence. The five essentials are planning strategically; benchmarking for excellence; leading collaboratively; engaging the community; and governing…

  18. Maximizing Achievement in Computer-Based Training (CBT): The Role of the Instructor and Other Variables

    DTIC Science & Technology

    1991-07-01

    reviewed and is approved for publication. J . SCOTT NEW OMB HENDRICK W. RUCK, Technical Director Contract Monit r Technical Training Research Division...TX 78235-5000 9 11. SUPPLEMENTARY NOTES Armstrong Laboratory Tb,;hnical Monitor: J . Scott Newcomb, (512) 536-3992 12a. DISTRIBUTIONAVAILABIUTY

  19. Role of the Instructor in Maximizing Academic Achievement in Computer-Based Training

    DTIC Science & Technology

    1990-07-01

    nationals. This paper has been reviewed and is approved for publication. J . SCOTT NEWCOMB Contract Monitor HENDRICK W. RUCK, Technical Advisor Training...Reviewed and submitted for publication by J . Scott Newcomb, Chief Training Technology Branch This publication is primarily a working paper. It is

  20. Graded Achievement, Tested Achievement, and Validity

    ERIC Educational Resources Information Center

    Brookhart, Susan M.

    2015-01-01

    Twenty-eight studies of grades, over a century, were reviewed using the argument-based approach to validity suggested by Kane as a theoretical framework. The review draws conclusions about the meaning of graded achievement, its relation to tested achievement, and changes in the construct of graded achievement over time. "Graded…

  1. An information-theoretic analysis of return maximization in reinforcement learning.

    PubMed

    Iwata, Kazunori

    2011-12-01

    We present a general analysis of return maximization in reinforcement learning. This analysis does not require assumptions of Markovianity, stationarity, and ergodicity for the stochastic sequential decision processes of reinforcement learning. Instead, our analysis assumes the asymptotic equipartition property fundamental to information theory, providing a substantially different view from that in the literature. As our main results, we show that return maximization is achieved by the overlap of typical and best sequence sets, and we present a class of stochastic sequential decision processes with the necessary condition for return maximization. We also describe several examples of best sequences in terms of return maximization in the class of stochastic sequential decision processes, which satisfy the necessary condition.

  2. Modularity maximization using completely positive programming

    NASA Astrophysics Data System (ADS)

    Yazdanparast, Sakineh; Havens, Timothy C.

    2017-04-01

    Community detection is one of the most prominent problems of social network analysis. In this paper, a novel method for Modularity Maximization (MM) for community detection is presented which exploits the Alternating Direction Augmented Lagrangian (ADAL) method for maximizing a generalized form of Newman's modularity function. We first transform Newman's modularity function into a quadratic program and then use Completely Positive Programming (CPP) to map the quadratic program to a linear program, which provides the globally optimal maximum modularity partition. In order to solve the proposed CPP problem, a closed form solution using the ADAL merged with a rank minimization approach is proposed. The performance of the proposed method is evaluated on several real-world data sets used for benchmarks community detection. Simulation results shows the proposed technique provides outstanding results in terms of modularity value for crisp partitions.

  3. Maximally discordant mixed states of two qubits

    SciTech Connect

    Galve, Fernando; Giorgi, Gian Luca; Zambrini, Roberta

    2011-01-15

    We study the relative strength of classical and quantum correlations, as measured by discord, for two-qubit states. Quantum correlations appear only in the presence of classical correlations, while the reverse is not always true. We identify the family of states that maximize the discord for a given value of the classical correlations and show that the largest attainable discord for mixed states is greater than for pure states. The difference between discord and entanglement is emphasized by the remarkable fact that these states do not maximize entanglement and are, in some cases, even separable. Finally, by random generation of density matrices uniformly distributed over the whole Hilbert space, we quantify the frequency of the appearance of quantum and classical correlations for different ranks.

  4. Hamiltonian formalism and path entropy maximization

    NASA Astrophysics Data System (ADS)

    Davis, Sergio; González, Diego

    2015-10-01

    Maximization of the path information entropy is a clear prescription for constructing models in non-equilibrium statistical mechanics. Here it is shown that, following this prescription under the assumption of arbitrary instantaneous constraints on position and velocity, a Lagrangian emerges which determines the most probable trajectory. Deviations from the probability maximum can be consistently described as slices in time by a Hamiltonian, according to a nonlinear Langevin equation and its associated Fokker-Planck equation. The connections unveiled between the maximization of path entropy and the Langevin/Fokker-Planck equations imply that missing information about the phase space coordinate never decreases in time, a purely information-theoretical version of the second law of thermodynamics. All of these results are independent of any physical assumptions, and thus valid for any generalized coordinate as a function of time, or any other parameter. This reinforces the view that the second law is a fundamental property of plausible inference.

  5. Nondecoupling of maximal supergravity from the superstring.

    PubMed

    Green, Michael B; Ooguri, Hirosi; Schwarz, John H

    2007-07-27

    We consider the conditions necessary for obtaining perturbative maximal supergravity in d dimensions as a decoupling limit of type II superstring theory compactified on a (10-d) torus. For dimensions d=2 and d=3, it is possible to define a limit in which the only finite-mass states are the 256 massless states of maximal supergravity. However, in dimensions d>or=4, there are infinite towers of additional massless and finite-mass states. These correspond to Kaluza-Klein charges, wound strings, Kaluza-Klein monopoles, or branes wrapping around cycles of the toroidal extra dimensions. We conclude that perturbative supergravity cannot be decoupled from string theory in dimensions>or=4. In particular, we conjecture that pure N=8 supergravity in four dimensions is in the Swampland.

  6. Experimental implementation of maximally synchronizable networks

    NASA Astrophysics Data System (ADS)

    Sevilla-Escoboza, R.; Buldú, J. M.; Boccaletti, S.; Papo, D.; Hwang, D.-U.; Huerta-Cuellar, G.; Gutiérrez, R.

    2016-04-01

    Maximally synchronizable networks (MSNs) are acyclic directed networks that maximize synchronizability. In this paper, we investigate the feasibility of transforming networks of coupled oscillators into their corresponding MSNs. By tuning the weights of any given network so as to reach the lowest possible eigenratio λN /λ2, the synchronized state is guaranteed to be maintained across the longest possible range of coupling strengths. We check the robustness of the resulting MSNs with an experimental implementation of a network of nonlinear electronic oscillators and study the propagation of the synchronization errors through the network. Importantly, a method to study the effects of topological uncertainties on the synchronizability is proposed and explored both theoretically and experimentally.

  7. Profit Maximization Models for Exponential Decay Processes.

    DTIC Science & Technology

    1980-08-01

    assumptions could easily be analyzed in similar fashion. References [1] Bensoussan, A., Hurst , E.G. and Nislund, B., Management Applications of Modern...TVIPe OF r 04PORNT A i M0 CiH O .V9RAE PROFIT MAXIMIZATION .ODELS FOR EXPONENT IAL Technical Report DECAY PROCESSES August 1990 ~~~I. PtA’OR~idNG ONqG

  8. Maximal respiratory pressures among adolescent swimmers.

    PubMed

    Rocha Crispino Santos, M A; Pinto, M L; Couto Sant'Anna, C; Bernhoeft, M

    2011-01-01

    Maximal inspiratory pressures (MIP) and maximal expiratory pressures (MEP) are useful indices of respiratory muscle strength in athletes. The aims of this study were: to describe the strength of the respiratory muscles of Olympic junior swim team, at baseline and after a standard physical training; and to determine if there is a differential inspiratory and expiratory pressure response to the physical training. A cross-sectional study evaluated 28 international-level swimmers with ages ranging from 15 to 17 years, 19 (61 %) being males. At baseline, MIP was found to be lower in females (P = .001). The mean values reached by males and females were: MIP(cmH2O) = M: 100.4 (± 26.5)/F: 67.8 (± 23.2); MEP (cmH2O) = M: 87.4 (± 20.7)/F: 73.9 (± 17.3). After the physical training they reached: MIP (cmH2O) = M: 95.3 (± 30.3)/F: 71.8 (± 35.6); MEP (cmH2O) = M: 82.8 (± 26.2)/F: 70.4 (± 8.3). No differential pressure responses were observed in either males or females. These results suggest that swimmers can sustain the magnitude of the initial maximal pressures. Other studies should be developed to clarify if MIP and MEP could be used as a marker of an athlete's performance.

  9. A Geometric-Structure Theory for Maximally Random Jammed Packings

    PubMed Central

    Tian, Jianxiang; Xu, Yaopengxiao; Jiao, Yang; Torquato, Salvatore

    2015-01-01

    Maximally random jammed (MRJ) particle packings can be viewed as prototypical glasses in that they are maximally disordered while simultaneously being mechanically rigid. The prediction of the MRJ packing density ϕMRJ, among other packing properties of frictionless particles, still poses many theoretical challenges, even for congruent spheres or disks. Using the geometric-structure approach, we derive for the first time a highly accurate formula for MRJ densities for a very wide class of two-dimensional frictionless packings, namely, binary convex superdisks, with shapes that continuously interpolate between circles and squares. By incorporating specific attributes of MRJ states and a novel organizing principle, our formula yields predictions of ϕMRJ that are in excellent agreement with corresponding computer-simulation estimates in almost the entire α-x plane with semi-axis ratio α and small-particle relative number concentration x. Importantly, in the monodisperse circle limit, the predicted ϕMRJ = 0.834 agrees very well with the very recently numerically discovered MRJ density of 0.827, which distinguishes it from high-density “random-close packing” polycrystalline states and hence provides a stringent test on the theory. Similarly, for non-circular monodisperse superdisks, we predict MRJ states with densities that are appreciably smaller than is conventionally thought to be achievable by standard packing protocols. PMID:26568437

  10. Maximally spaced projection sequencing in electron paramagnetic resonance imaging

    PubMed Central

    Redler, Gage; Epel, Boris; Halpern, Howard J.

    2015-01-01

    Electron paramagnetic resonance imaging (EPRI) provides 3D images of absolute oxygen concentration (pO2) in vivo with excellent spatial and pO2 resolution. When investigating such physiologic parameters in living animals, the situation is inherently dynamic. Improvements in temporal resolution and experimental versatility are necessary to properly study such a system. Uniformly distributed projections result in efficient use of data for image reconstruction. This has dictated current methods such as equal-solid-angle (ESA) spacing of projections. However, acquisition sequencing must still be optimized to achieve uniformity throughout imaging. An object-independent method for uniform acquisition of projections, using the ESA uniform distribution for the final set of projections, is presented. Each successive projection maximizes the distance in the gradient space between itself and prior projections. This maximally spaced projection sequencing (MSPS) method improves image quality for intermediate images reconstructed from incomplete projection sets, enabling useful real-time reconstruction. This method also provides improved experimental versatility, reduced artifacts, and the ability to adjust temporal resolution post factum to best fit the data and its application. The MSPS method in EPRI provides the improvements necessary to more appropriately study a dynamic system. PMID:26185490

  11. A criterion to maximize the irreversible efficiency in heat engines

    NASA Astrophysics Data System (ADS)

    Aragón-González, G.; Canales-Palma, A.; León-Galicia, A.; Musharrafie-Martínez, M.

    2003-02-01

    The purpose of this work is to obtain a more precise calculation of the effective limits to the efficiency, of several cyclic heat engines. This calculation is based, first, on the equations describing the irreversible efficiency, and second, on a method which results from a general criterion to maximize this efficiency, applicable to several heat engines. With this method, we apply the criterion to maximize efficiencies; establish lower and upper bounds, corresponding to the efficiencies of Curzon-Ahlborn-like and Carnot-like heat engines; and, finally, find analytical or numerical expressions for the efficiencies etame and etamax. etamax is the maximum irreversible efficiency; etame is the efficiency in which the irreversible efficiency achieves its maximum, in a similar way to the Curzon-Ahlborn efficiency (maximum work or power). The method was applied to a Brayton cycle, presenting internal dissipations of the working fluid and irreversibilities due to the finite-rate heat transfer between the heat engine and its reservoirs. Also, we applied this method to a Carnot cycle including the irreversibilities of a finite-rate heat transfer between the heat engine and its reservoirs, heat leak between the reservoirs, and internal dissipations of the working fluid. The results obtained for the Brayton cycle are more general and useful than those in the relevant literature.

  12. A Brief Review of Effective Teaching Practices That Maximize Student Engagement

    ERIC Educational Resources Information Center

    Harbour, Kristin E.; Evanovich, Lauren L.; Sweigart, Chris A.; Hughes, Lindsay E.

    2015-01-01

    What teachers do and how students perform intersect, making teachers a critical factor for determining student success. When teachers use effective practices, they maximize the probability that students will be actively engaged in instruction. Student engagement is one of the most well-established predictors of achievement; when students are more…

  13. Maximizing the Performance and Job-Related Behaviors of Contract and Permanent IT Workers

    ERIC Educational Resources Information Center

    Pai, Tanusree

    2010-01-01

    As the use of contracting for Information Technology (IT) services steadily increases, IT managers are challenged with reconciling the need for flexibility achieved through the use of contract workers, with the need to understand the factors that maximize the performance and behaviors of contract and permanent IT workers. While several research…

  14. Maximizing Learning from Rehearsal Activity in Web-Based Distance Learning

    ERIC Educational Resources Information Center

    Wallace, Tary; Grinnell, Lynn; Carey, Lou; Carey, James

    2006-01-01

    Faculty teaching distance courses continuously seek ways to maximize learning for students. Two practice with feedback strategies were examined in this study for their impact on students' achievement and attitudes in an upper-division university level web-based course. One format contained higher structure and dialog creating lower transactional…

  15. Nonimaging optics maximizing exergy for hybrid solar system

    NASA Astrophysics Data System (ADS)

    Winston, Roland; Jiang, Lun; Abdelhamid, Mahmoud; Widyolar, Bennett K.; Ferry, Jonathan; Cygan, David; Abbasi, Hamid; Kozlov, Alexandr; Kirk, Alexander; Elarde, Victor; Osowski, Mark

    2016-09-01

    The project team of University of California at Merced (UC-Merced), Gas Technology Institute (GTI) and MicroLink Devices Inc. (MicroLink) are developing a hybrid solar system using a nonimaging compound parabolic concentrator (CPC) that maximizes the exergy by delivering direct electricity and on-demand heat. The hybrid solar system technology uses secondary optics in a solar receiver to achieve high efficiency at high temperature, collects heat in particles and uses reflective liftoff cooled double junction (2J) InGaP/GaAs solar cells with backside infrared (IR) reflectors on the secondary optical element to raise exergy efficiency. The nonimaging optics provides additional concentration towards the high temperature thermal stream and enables it to operate efficiently at 650 °C while the solar cell is maintained at 40 °C to operate as efficiently as possible.

  16. Auctions with Dynamic Populations: Efficiency and Revenue Maximization

    NASA Astrophysics Data System (ADS)

    Said, Maher

    We study a stochastic sequential allocation problem with a dynamic population of privately-informed buyers. We characterize the set of efficient allocation rules and show that a dynamic VCG mechanism is both efficient and periodic ex post incentive compatible; we also show that the revenue-maximizing direct mechanism is a pivot mechanism with a reserve price. We then consider sequential ascending auctions in this setting, both with and without a reserve price. We construct equilibrium bidding strategies in this indirect mechanism where bidders reveal their private information in every period, yielding the same outcomes as the direct mechanisms. Thus, the sequential ascending auction is a natural institution for achieving either efficient or optimal outcomes.

  17. KATTS: a framework for maximizing NCLEX-RN performance.

    PubMed

    McDowell, Betsy M

    2008-04-01

    A key indicator of the quality of a nursing education program is the performance of its graduates as first-time takers of the NCLEX-RN. As a result, nursing schools are open to strategies that strengthen the performance of their graduates on the examination. The Knowledge base, Anxiety control, Test-Taking Skills (KATTS) framework focuses on the three components of achieving a maximum score on an examination. In KATTS, all three components must be present and in proper balance to maximize a test taker's score. By strengthening not just one but all of these components, graduates can improve their overall test scores significantly. Suggested strategies for strengthening each component of KATTS are provided. This framework has been used successfully in designing remedial tutoring programs and in assisting first-time NCLEX test takers in preparing for the licensing examination.

  18. Accurate and efficient maximal ball algorithm for pore network extraction

    NASA Astrophysics Data System (ADS)

    Arand, Frederick; Hesser, Jürgen

    2017-04-01

    The maximal ball (MB) algorithm is a well established method for the morphological analysis of porous media. It extracts a network of pores and throats from volumetric data. This paper describes structural modifications to the algorithm, while the basic concepts are preserved. Substantial improvements to accuracy and efficiency are achieved as follows: First, all calculations are performed on a subvoxel accurate distance field, and no approximations to discretize balls are made. Second, data structures are simplified to keep memory usage low and improve algorithmic speed. Third, small and reasonable adjustments increase speed significantly. In volumes with high porosity, memory usage is improved compared to classic MB algorithms. Furthermore, processing is accelerated more than three times. Finally, the modified MB algorithm is verified by extracting several network properties from reference as well as real data sets. Runtimes are measured and compared to literature.

  19. Maximizing versus satisficing: happiness is a matter of choice.

    PubMed

    Schwartz, Barry; Ward, Andrew; Monterosso, John; Lyubomirsky, Sonja; White, Katherine; Lehman, Darrin R

    2002-11-01

    Can people feel worse off as the options they face increase? The present studies suggest that some people--maximizers--can. Study 1 reported a Maximization Scale, which measures individual differences in desire to maximize. Seven samples revealed negative correlations between maximization and happiness, optimism, self-esteem, and life satisfaction, and positive correlations between maximization and depression, perfectionism, and regret. Study 2 found maximizers less satisfied than nonmaximizers (satisficers) with consumer decisions, and more likely to engage in social comparison. Study 3 found maximizers more adversely affected by upward social comparison. Study 4 found maximizers more sensitive to regret and less satisfied in an ultimatum bargaining game. The interaction between maximizing and choice is discussed in terms of regret, adaptation, and self-blame.

  20. Electromagnetically induced grating with maximal atomic coherence

    SciTech Connect

    Carvalho, Silvania A.; Araujo, Luis E. E. de

    2011-10-15

    We describe theoretically an atomic diffraction grating that combines an electromagnetically induced grating with a coherence grating in a double-{Lambda} atomic system. With the atom in a condition of maximal coherence between its lower levels, the combined gratings simultaneously diffract both the incident probe beam as well as the signal beam generated through four-wave mixing. A special feature of the atomic grating is that it will diffract any beam resonantly tuned to any excited state of the atom accessible by a dipole transition from its ground state.

  1. Maximizing algebraic connectivity in air transportation networks

    NASA Astrophysics Data System (ADS)

    Wei, Peng

    In air transportation networks the robustness of a network regarding node and link failures is a key factor for its design. An experiment based on the real air transportation network is performed to show that the algebraic connectivity is a good measure for network robustness. Three optimization problems of algebraic connectivity maximization are then formulated in order to find the most robust network design under different constraints. The algebraic connectivity maximization problem with flight routes addition or deletion is first formulated. Three methods to optimize and analyze the network algebraic connectivity are proposed. The Modified Greedy Perturbation Algorithm (MGP) provides a sub-optimal solution in a fast iterative manner. The Weighted Tabu Search (WTS) is designed to offer a near optimal solution with longer running time. The relaxed semi-definite programming (SDP) is used to set a performance upper bound and three rounding techniques are discussed to find the feasible solution. The simulation results present the trade-off among the three methods. The case study on two air transportation networks of Virgin America and Southwest Airlines show that the developed methods can be applied in real world large scale networks. The algebraic connectivity maximization problem is extended by adding the leg number constraint, which considers the traveler's tolerance for the total connecting stops. The Binary Semi-Definite Programming (BSDP) with cutting plane method provides the optimal solution. The tabu search and 2-opt search heuristics can find the optimal solution in small scale networks and the near optimal solution in large scale networks. The third algebraic connectivity maximization problem with operating cost constraint is formulated. When the total operating cost budget is given, the number of the edges to be added is not fixed. Each edge weight needs to be calculated instead of being pre-determined. It is illustrated that the edge addition and the

  2. Approximation Algorithms for Free-Label Maximization

    NASA Astrophysics Data System (ADS)

    de Berg, Mark; Gerrits, Dirk H. P.

    Inspired by air traffic control and other applications where moving objects have to be labeled, we consider the following (static) point labeling problem: given a set P of n points in the plane and labels that are unit squares, place a label with each point in P in such a way that the number of free labels (labels not intersecting any other label) is maximized. We develop efficient constant-factor approximation algorithms for this problem, as well as PTASs, for various label-placement models.

  3. Maximizing results in reconstruction of cheek defects.

    PubMed

    Mureau, Marc A M; Hofer, Stefan O P

    2009-07-01

    The face is exceedingly important, as it is the medium through which individuals interact with the rest of society. Reconstruction of cheek defects after trauma or surgery is a continuing challenge for surgeons who wish to reliably restore facial function and appearance. Important in aesthetic facial reconstruction are the aesthetic unit principles, by which the face can be divided in central facial units (nose, lips, eyelids) and peripheral facial units (cheeks, forehead, chin). This article summarizes established options for reconstruction of cheek defects and provides an overview of several modifications as well as tips and tricks to avoid complications and maximize aesthetic results.

  4. Developing maximal neuromuscular power: part 2 - training considerations for improving maximal power production.

    PubMed

    Cormie, Prue; McGuigan, Michael R; Newton, Robert U

    2011-02-01

    This series of reviews focuses on the most important neuromuscular function in many sport performances: the ability to generate maximal muscular power. Part 1, published in an earlier issue of Sports Medicine, focused on the factors that affect maximal power production while part 2 explores the practical application of these findings by reviewing the scientific literature relevant to the development of training programmes that most effectively enhance maximal power production. The ability to generate maximal power during complex motor skills is of paramount importance to successful athletic performance across many sports. A crucial issue faced by scientists and coaches is the development of effective and efficient training programmes that improve maximal power production in dynamic, multi-joint movements. Such training is referred to as 'power training' for the purposes of this review. Although further research is required in order to gain a deeper understanding of the optimal training techniques for maximizing power in complex, sports-specific movements and the precise mechanisms underlying adaptation, several key conclusions can be drawn from this review. First, a fundamental relationship exists between strength and power, which dictates that an individual cannot possess a high level of power without first being relatively strong. Thus, enhancing and maintaining maximal strength is essential when considering the long-term development of power. Second, consideration of movement pattern, load and velocity specificity is essential when designing power training programmes. Ballistic, plyometric and weightlifting exercises can be used effectively as primary exercises within a power training programme that enhances maximal power. The loads applied to these exercises will depend on the specific requirements of each particular sport and the type of movement being trained. The use of ballistic exercises with loads ranging from 0% to 50% of one-repetition maximum (1RM) and

  5. Development of new RNAi therapeutics.

    PubMed

    Liu, G; Wong-Staal, F; Li, Q-X

    2007-02-01

    RNAi-mediated gene inactivation has become a cornerstone of the present day gene function studies that are the foundation of mechanism and target based drug discovery and development, which could potentially shorten the otherwise long process of drug development. In particular, the coming of age of "RNAi drug" could provide new promising therapeutics bypassing traditional approaches. However, there are technological hurdles need to overcome and the biological limitations need to consider for achieving effective therapeutics. Major hurdles include the intrinsic poor pharmacokinetic property of siRNA and major biological restrictions include off-target effects, interferon response and the interference with endogenous miRNA. Recent innovations in nucleic acid chemistry, formulations and delivery methods have gradually rendered it possible to develop effective RNAi-based therapeutics. Careful design based on the newest RNAi/miRNA biology can also help to minimize the potential tissue toxicity. If successful with systemic application, RNAi drug will no doubt revolutionize the whole drug development process. This review attempts to describe the progress in this area, including applications in preclinical models and recent favorable experience in a number of human trials of local diseases, along with the discussion on the potential limitations of RNAi therapeutics.

  6. Optimizing Population Variability to Maximize Benefit

    PubMed Central

    Izu, Leighton T.; Bányász, Tamás; Chen-Izu, Ye

    2015-01-01

    Variability is inherent in any population, regardless whether the population comprises humans, plants, biological cells, or manufactured parts. Is the variability beneficial, detrimental, or inconsequential? This question is of fundamental importance in manufacturing, agriculture, and bioengineering. This question has no simple categorical answer because research shows that variability in a population can have both beneficial and detrimental effects. Here we ask whether there is a certain level of variability that can maximize benefit to the population as a whole. We answer this question by using a model composed of a population of individuals who independently make binary decisions; individuals vary in making a yes or no decision, and the aggregated effect of these decisions on the population is quantified by a benefit function (e.g. accuracy of the measurement using binary rulers, aggregate income of a town of farmers). Here we show that an optimal variance exists for maximizing the population benefit function; this optimal variance quantifies what is often called the “right mix” of individuals in a population. PMID:26650247

  7. Fractional stereo matching using expectation-maximization.

    PubMed

    Xiong, Wei; Chung, Hin Shun; Jia, Jiaya

    2009-03-01

    In our fractional stereo matching problem, a foreground object with a fractional boundary is blended with a background scene using unknown transparencies. Due to the spatially varying disparities in different layers, one foreground pixel may be blended with different background pixels in stereo images, making the color constancy commonly assumed in traditional stereo matching not hold any more. To tackle this problem, in this paper, we introduce a probabilistic framework constraining the matching of pixel colors, disparities, and alpha values in different layers, and propose an automatic optimization method to solve a Maximizing a Posterior (MAP) problem using Expectation-Maximization (EM), given only a short-baseline stereo input image pair. Our method encodes the effect of background occlusion by layer blending without requiring a special detection process. The alpha computation process in our unified framework can be regarded as a new approach by natural image matting, which handles appropriately the situation when the background color is similar to that of the foreground object. We demonstrate the efficacy of our method by experimenting with challenging stereo images and making comparisons with state-of-the-art methods.

  8. Maximal liquid bridges between horizontal cylinders.

    PubMed

    Cooray, Himantha; Huppert, Herbert E; Neufeld, Jerome A

    2016-08-01

    We investigate two-dimensional liquid bridges trapped between pairs of identical horizontal cylinders. The cylinders support forces owing to surface tension and hydrostatic pressure that balance the weight of the liquid. The shape of the liquid bridge is determined by analytically solving the nonlinear Laplace-Young equation. Parameters that maximize the trapping capacity (defined as the cross-sectional area of the liquid bridge) are then determined. The results show that these parameters can be approximated with simple relationships when the radius of the cylinders is small compared with the capillary length. For such small cylinders, liquid bridges with the largest cross-sectional area occur when the centre-to-centre distance between the cylinders is approximately twice the capillary length. The maximum trapping capacity for a pair of cylinders at a given separation is linearly related to the separation when it is small compared with the capillary length. The meniscus slope angle of the largest liquid bridge produced in this regime is also a linear function of the separation. We additionally derive approximate solutions for the profile of a liquid bridge, using the linearized Laplace-Young equation. These solutions analytically verify the above-mentioned relationships obtained for the maximization of the trapping capacity.

  9. Maximal liquid bridges between horizontal cylinders

    NASA Astrophysics Data System (ADS)

    Cooray, Himantha; Huppert, Herbert E.; Neufeld, Jerome A.

    2016-08-01

    We investigate two-dimensional liquid bridges trapped between pairs of identical horizontal cylinders. The cylinders support forces owing to surface tension and hydrostatic pressure that balance the weight of the liquid. The shape of the liquid bridge is determined by analytically solving the nonlinear Laplace-Young equation. Parameters that maximize the trapping capacity (defined as the cross-sectional area of the liquid bridge) are then determined. The results show that these parameters can be approximated with simple relationships when the radius of the cylinders is small compared with the capillary length. For such small cylinders, liquid bridges with the largest cross-sectional area occur when the centre-to-centre distance between the cylinders is approximately twice the capillary length. The maximum trapping capacity for a pair of cylinders at a given separation is linearly related to the separation when it is small compared with the capillary length. The meniscus slope angle of the largest liquid bridge produced in this regime is also a linear function of the separation. We additionally derive approximate solutions for the profile of a liquid bridge, using the linearized Laplace-Young equation. These solutions analytically verify the above-mentioned relationships obtained for the maximization of the trapping capacity.

  10. Maximal lactate steady state in Judo

    PubMed Central

    de Azevedo, Paulo Henrique Silva Marques; Pithon-Curi, Tania; Zagatto, Alessandro Moura; Oliveira, João; Perez, Sérgio

    2014-01-01

    Summary Background: the purpose of this study was to verify the validity of respiratory compensation threshold (RCT) measured during a new single judo specific incremental test (JSIT) for aerobic demand evaluation. Methods: to test the validity of the new test, the JSIT was compared with Maximal Lactate Steady State (MLSS), which is the gold standard procedure for aerobic demand measuring. Eight well-trained male competitive judo players (24.3 ± 7.9 years; height of 169.3 ± 6.7cm; fat mass of 12.7 ± 3.9%) performed a maximal incremental specific test for judo to assess the RCT and performed on 30-minute MLSS test, where both tests were performed mimicking the UchiKomi drills. Results: the intensity at RCT measured on JSIT was not significantly different compared to MLSS (p=0.40). In addition, it was observed high and significant correlation between MLSS and RCT (r=0.90, p=0.002), as well as a high agreement. Conclusions: RCT measured during JSIT is a valid procedure to measure the aerobic demand, respecting the ecological validity of Judo. PMID:25332923

  11. Optimizing Population Variability to Maximize Benefit.

    PubMed

    Izu, Leighton T; Bányász, Tamás; Chen-Izu, Ye

    2015-01-01

    Variability is inherent in any population, regardless whether the population comprises humans, plants, biological cells, or manufactured parts. Is the variability beneficial, detrimental, or inconsequential? This question is of fundamental importance in manufacturing, agriculture, and bioengineering. This question has no simple categorical answer because research shows that variability in a population can have both beneficial and detrimental effects. Here we ask whether there is a certain level of variability that can maximize benefit to the population as a whole. We answer this question by using a model composed of a population of individuals who independently make binary decisions; individuals vary in making a yes or no decision, and the aggregated effect of these decisions on the population is quantified by a benefit function (e.g. accuracy of the measurement using binary rulers, aggregate income of a town of farmers). Here we show that an optimal variance exists for maximizing the population benefit function; this optimal variance quantifies what is often called the "right mix" of individuals in a population.

  12. Maximal coherence in a generic basis

    NASA Astrophysics Data System (ADS)

    Yao, Yao; Dong, G. H.; Ge, Li; Li, Mo; Sun, C. P.

    2016-12-01

    Since quantum coherence is an undoubted characteristic trait of quantum physics, the quantification and application of quantum coherence has been one of the long-standing central topics in quantum information science. Within the framework of a resource theory of quantum coherence proposed recently, a fiducial basis should be preselected for characterizing the quantum coherence in specific circumstances, namely, the quantum coherence is a basis-dependent quantity. Therefore, a natural question is raised: what are the maximum and minimum coherences contained in a certain quantum state with respect to a generic basis? While the minimum case is trivial, it is not so intuitive to verify in which basis the quantum coherence is maximal. Based on the coherence measure of relative entropy, we indicate the particular basis in which the quantum coherence is maximal for a given state, where the Fourier matrix (or more generally, complex Hadamard matrices) plays a critical role in determining the basis. Intriguingly, though we can prove that the basis associated with the Fourier matrix is a stationary point for optimizing the l1 norm of coherence, numerical simulation shows that it is not a global optimal choice.

  13. Designing phage therapeutics.

    PubMed

    Goodridge, Lawrence D

    2010-01-01

    Phage therapy is the application of phages to bodies, substances, or environments to effect the biocontrol of pathogenic or nuisance bacteria. To be effective, phages, minimally, must be capable of attaching to bacteria (adsorption), killing those bacteria (usually associated with phage infection), and otherwise surviving (resisting decay) until they achieve attachment and subsequent killing. While a strength of phage therapy is that phages that possess appropriate properties can be chosen from a large diversity of naturally occurring phages, a more rational approach to phage therapy also can include post-isolation manipulation of phages genetically, phenotypically, or in terms of combining different products into a single formulation. Genetic manipulation, especially in these modern times, can involve genetic engineering, though a more traditional approach involves the selection of spontaneously occurring phage mutants during serial transfer protocols. While genetic modification typically is done to give rise to phenotypic changes in phages, phage phenotype alone can also be modified in vitro, prior to phage application for therapeutic purposes, as for the sake of improving phage lethality (such as by linking phage virions to antibacterial chemicals such as chloramphenicol) or survival capabilities (e.g., via virion PEGylation). Finally, phages, both naturally occurring isolates or otherwise modified constructs, can be combined into cocktails which provide collectively enhanced capabilities such as expanded overall host range. Generally these strategies represent different routes towards improving phage therapy formulations and thereby efficacy through informed design.

  14. Leader as achiever.

    PubMed

    Dienemann, Jacqueline

    2002-01-01

    This article examines one outcome of leadership: productive achievement. Without achievement one is judged to not truly be a leader. Thus, the ideal leader must be a visionary, a critical thinker, an expert, a communicator, a mentor, and an achiever of organizational goals. This article explores the organizational context that supports achievement, measures of quality nursing care, fiscal accountability, leadership development, rewards and punishments, and the educational content and teaching strategies to prepare graduates to be achievers.

  15. Phase estimation for a phased array therapeutic interstitial ultrasound probe.

    PubMed

    Yang, Zhenya; Dillenseger, Jean-Louis

    2012-01-01

    This paper deals about high intensity ultrasound interstitial therapy simulation. The simulated phased array ultrasound probe allows a dynamic electronic focusing of the therapeutic beam. In order to maximize the power deposit at the focal point we propose a method which allows to optimally defining the phase shift of the electrical control signal for each individual element.

  16. Steroid hormone receptors and prostate cancer: role of structural dynamics in therapeutic targeting

    PubMed Central

    Kumar, Raj

    2016-01-01

    Steroid hormone receptors (SHRs) act in cell type- and gene-specific manner through interactions with coregulatory proteins to regulate numerous physiological and pathological processes at the level of gene regulation. Binding of steroid receptor modulator (SRM) ligand leads to allosteric changes in SHR to exert positive or negative effects on the expression of target genes. Due, in part, to the fact that current SRMs generally target ligand binding domain (LBD)/AF2 and neglect intrinsically disordered (ID) N-terminal domain (NTD)/AF1, clinically relevant SRMs lack selectivity and are also prone to the development of resistance over time. Therefore, to maximize the efficacy of SHR-based therapeutics, the possibility of developing unique modulators that act to control AF1 activity must be considered. Recent studies targeting androgen receptor's (AR's) ID AF1 domain for the castration-resistant prostate cancer has provided the possibility of therapeutically targeting ID NTD/AF1 surfaces by allosteric modulations to achieve desired effects. In this review article, we discuss how inter- and intra- molecular allosteric regulations controlled by AR's structural flexibility and dynamics particularly the ID NTD/AF1 is an emerging area of investigation, which could be exploited for drug development and therapeutic targeting of prostate cancer. PMID:27364545

  17. Maximal energy extraction under discrete diffusive exchange

    SciTech Connect

    Hay, M. J.; Schiff, J.; Fisch, N. J.

    2015-10-15

    Waves propagating through a bounded plasma can rearrange the densities of states in the six-dimensional velocity-configuration phase space. Depending on the rearrangement, the wave energy can either increase or decrease, with the difference taken up by the total plasma energy. In the case where the rearrangement is diffusive, only certain plasma states can be reached. It turns out that the set of reachable states through such diffusive rearrangements has been described in very different contexts. Building upon those descriptions, and making use of the fact that the plasma energy is a linear functional of the state densities, the maximal extractable energy under diffusive rearrangement can then be addressed through linear programming.

  18. Maximal energy extraction under discrete diffusive exchange

    NASA Astrophysics Data System (ADS)

    Hay, M. J.; Schiff, J.; Fisch, N. J.

    2015-10-01

    Waves propagating through a bounded plasma can rearrange the densities of states in the six-dimensional velocity-configuration phase space. Depending on the rearrangement, the wave energy can either increase or decrease, with the difference taken up by the total plasma energy. In the case where the rearrangement is diffusive, only certain plasma states can be reached. It turns out that the set of reachable states through such diffusive rearrangements has been described in very different contexts. Building upon those descriptions, and making use of the fact that the plasma energy is a linear functional of the state densities, the maximal extractable energy under diffusive rearrangement can then be addressed through linear programming.

  19. Multipartite maximally entangled states in symmetric scenarios

    NASA Astrophysics Data System (ADS)

    González-Guillén, Carlos E.

    2012-08-01

    We consider the class of (N+1)-partite states suitable for protocols where there is a powerful party, the authority, and the other N parties play the same role, namely, the state of their system lies in the symmetric Hilbert space. We show that, within this scenario, there is a “maximally entangled state” that can be transform by a local operations and classical communication protocol into any other state. In addition, we show how to use the protocol efficiently, including the construction of the state, and discuss security issues for possible applications to cryptographic protocols. As an immediate consequence we recover a sequential protocol that implements the 1-to-N symmetric cloning.

  20. Dispatch Scheduling to Maximize Exoplanet Detection

    NASA Astrophysics Data System (ADS)

    Johnson, Samson; McCrady, Nate; MINERVA

    2016-01-01

    MINERVA is a dedicated exoplanet detection telescope array using radial velocity measurements of nearby stars to detect planets. MINERVA will be a completely robotic facility, with a goal of maximizing the number of exoplanets detected. MINERVA requires a unique application of queue scheduling due to its automated nature and the requirement of high cadence observations. A dispatch scheduling algorithm is employed to create a dynamic and flexible selector of targets to observe, in which stars are chosen by assigning values through a weighting function. I designed and have begun testing a simulation which implements the functions of a dispatch scheduler and records observations based on target selections through the same principles that will be used at the commissioned site. These results will be used in a larger simulation that incorporates weather, planet occurrence statistics, and stellar noise to test the planet detection capabilities of MINERVA. This will be used to heuristically determine an optimal observing strategy for the MINERVA project.

  1. Characterizing maximally singular phase-space distributions

    NASA Astrophysics Data System (ADS)

    Sperling, J.

    2016-07-01

    Phase-space distributions are widely applied in quantum optics to access the nonclassical features of radiations fields. In particular, the inability to interpret the Glauber-Sudarshan distribution in terms of a classical probability density is the fundamental benchmark for quantum light. However, this phase-space distribution cannot be directly reconstructed for arbitrary states, because of its singular behavior. In this work, we perform a characterization of the Glauber-Sudarshan representation in terms of distribution theory. We address important features of such distributions: (i) the maximal degree of their singularities is studied, (ii) the ambiguity of representation is shown, and (iii) their dual space for nonclassicality tests is specified. In this view, we reconsider the methods for regularizing the Glauber-Sudarshan distribution for verifying its nonclassicality. This treatment is supported with comprehensive examples and counterexamples.

  2. Robust determination of maximally localized Wannier functions

    NASA Astrophysics Data System (ADS)

    Cancès, Éric; Levitt, Antoine; Panati, Gianluca; Stoltz, Gabriel

    2017-02-01

    We propose an algorithm to determine maximally localized Wannier functions (MLWFs). This algorithm, based on recent theoretical developments, does not require any physical input such as initial guesses for the Wannier functions, unlike popular schemes based on the projection method. We discuss how the projection method can fail on fine grids when the initial guesses are too far from MLWFs. We demonstrate that our algorithm is able to find localized Wannier functions through tests on two-dimensional systems, simplified models of semiconductors, and realistic DFT systems by interfacing with the wannier90 code. We also test our algorithm on the Haldane and Kane-Mele models to examine how it fails in the presence of topological obstructions.

  3. Maximally reliable Markov chains under energy constraints.

    PubMed

    Escola, Sean; Eisele, Michael; Miller, Kenneth; Paninski, Liam

    2009-07-01

    Signal-to-noise ratios in physical systems can be significantly degraded if the outputs of the systems are highly variable. Biological processes for which highly stereotyped signal generations are necessary features appear to have reduced their signal variabilities by employing multiple processing steps. To better understand why this multistep cascade structure might be desirable, we prove that the reliability of a signal generated by a multistate system with no memory (i.e., a Markov chain) is maximal if and only if the system topology is such that the process steps irreversibly through each state, with transition rates chosen such that an equal fraction of the total signal is generated in each state. Furthermore, our result indicates that by increasing the number of states, it is possible to arbitrarily increase the reliability of the system. In a physical system, however, an energy cost is associated with maintaining irreversible transitions, and this cost increases with the number of such transitions (i.e., the number of states). Thus, an infinite-length chain, which would be perfectly reliable, is infeasible. To model the effects of energy demands on the maximally reliable solution, we numerically optimize the topology under two distinct energy functions that penalize either irreversible transitions or incommunicability between states, respectively. In both cases, the solutions are essentially irreversible linear chains, but with upper bounds on the number of states set by the amount of available energy. We therefore conclude that a physical system for which signal reliability is important should employ a linear architecture, with the number of states (and thus the reliability) determined by the intrinsic energy constraints of the system.

  4. Does Maximizing Information at the Cut Score Always Maximize Classification Accuracy and Consistency?

    ERIC Educational Resources Information Center

    Wyse, Adam E.; Babcock, Ben

    2016-01-01

    A common suggestion made in the psychometric literature for fixed-length classification tests is that one should design tests so that they have maximum information at the cut score. Designing tests in this way is believed to maximize the classification accuracy and consistency of the assessment. This article uses simulated examples to illustrate…

  5. Anaerobic contribution during maximal anaerobic running test: correlation with maximal accumulated oxygen deficit.

    PubMed

    Zagatto, A; Redkva, P; Loures, J; Kalva Filho, C; Franco, V; Kaminagakura, E; Papoti, M

    2011-12-01

    The aims of this study were: (i) to measure energy system contributions in maximal anaerobic running test (MART); and (ii) to verify any correlation between MART and maximal accumulated oxygen deficit (MAOD). Eleven members of the armed forces were recruited for this study. Participants performed MART and MAOD, both accomplished on a treadmill. MART consisted of intermittent exercise, 20 s effort with 100 s recovery, after each spell of effort exercise. Energy system contributions by MART were also determined by excess post-exercise oxygen consumption, lactate response, and oxygen uptake measurements. MAOD was determined by five submaximal intensities and one supramaximal intensity exercises corresponding to 120% at maximal oxygen uptake intensity. Energy system contributions were 65.4±1.1% to aerobic; 29.5±1.1% to anaerobic a-lactic; and 5.1±0.5% to anaerobic lactic system throughout the whole test, while only during effort periods the anaerobic contribution corresponded to 73.5±1.0%. Maximal power found in MART corresponded to 111.25±1.33 mL/kg/min but did not significantly correlate with MAOD (4.69±0.30 L and 70.85±4.73 mL/kg). We concluded that the anaerobic a-lactic system is the main energy system in MART efforts and this test did not significantly correlate to MAOD.

  6. From entropy-maximization to equality-maximization: Gauss, Laplace, Pareto, and Subbotin

    NASA Astrophysics Data System (ADS)

    Eliazar, Iddo

    2014-12-01

    The entropy-maximization paradigm of statistical physics is well known to generate the omnipresent Gauss law. In this paper we establish an analogous socioeconomic model which maximizes social equality, rather than physical disorder, in the context of the distributions of income and wealth in human societies. We show that-on a logarithmic scale-the Laplace law is the socioeconomic equality-maximizing counterpart of the physical entropy-maximizing Gauss law, and that this law manifests an optimized balance between two opposing forces: (i) the rich and powerful, striving to amass ever more wealth, and thus to increase social inequality; and (ii) the masses, struggling to form more egalitarian societies, and thus to increase social equality. Our results lead from log-Gauss statistics to log-Laplace statistics, yield Paretian power-law tails of income and wealth distributions, and show how the emergence of a middle-class depends on the underlying levels of socioeconomic inequality and variability. Also, in the context of asset-prices with Laplace-distributed returns, our results imply that financial markets generate an optimized balance between risk and predictability.

  7. Comparison of Maximal Wall Thickness in Hypertrophic Cardiomyopathy Differs Between Magnetic Resonance Imaging and Transthoracic Echocardiography.

    PubMed

    Bois, John P; Geske, Jeffrey B; Foley, Thomas A; Ommen, Steve R; Pellikka, Patricia A

    2017-02-15

    Left ventricular (LV) wall thickness is a prognostic marker in hypertrophic cardiomyopathy (HC). LV wall thickness ≥30 mm (massive hypertrophy) is independently associated with sudden cardiac death. Presence of massive hypertrophy is used to guide decision making for cardiac defibrillator implantation. We sought to determine whether measurements of maximal LV wall thickness differ between cardiac magnetic resonance imaging (MRI) and transthoracic echocardiography (TTE). Consecutive patients were studied who had HC without previous septal ablation or myectomy and underwent both cardiac MRI and TTE at a single tertiary referral center. Reported maximal LV wall thickness was compared between the imaging techniques. Patients with ≥1 technique reporting massive hypertrophy received subset analysis. In total, 618 patients were evaluated from January 1, 2003, to December 21, 2012 (mean [SD] age, 53 [15] years; 381 men [62%]). In 75 patients (12%), reported maximal LV wall thickness was identical between MRI and TTE. Median difference in reported maximal LV wall thickness between the techniques was 3 mm (maximum difference, 17 mm). Of the 63 patients with ≥1 technique measuring maximal LV wall thickness ≥30 mm, 44 patients (70%) had discrepant classification regarding massive hypertrophy. MRI identified 52 patients (83%) with massive hypertrophy; TTE, 30 patients (48%). Although guidelines recommend MRI or TTE imaging to assess cardiac anatomy in HC, this study shows discrepancy between the techniques for maximal reported LV wall thickness assessment. In conclusion, because this measure clinically affects prognosis and therapeutic decision making, efforts to resolve these discrepancies are critical.

  8. Therapeutic angiogenesis in cardiovascular disease

    PubMed Central

    Al Sabti, Hilal

    2007-01-01

    Atherosclerotic disease of the arteries is a major cause of coronary artery disease, peripheral vascular disease and stroke. Some patients are however not candidate for the standard treatment of angioplasty or bypass surgery. Hence there is tremendous enthusiasm for the utilization of angiogenesis as a therapeutic modality for atherosclerotic arterial disease. This augmentation of physiological neo-vascularization in cardiovascular disease can be achieved through different pathways. In this article we are reviewing the Use of Gene therapy, Protein therapy and cellular therapy. PMID:18021404

  9. Immediate return preference emerged from a synaptic learning rule for return maximization.

    PubMed

    Yamaguchi, Yoshiya; Aihara, Takeshi; Sakai, Yutaka

    2015-02-01

    Animals including human often prefer immediate returns to larger delayed returns. It holds true in the human communications. Standard interpretation of the immediate return preference is that an animal might subjectively discount the value of a delayed reward, and that might choose the larger valued one. The interpretation has been successfully applied to explain behavior of many species including human. However, the description is not necessarily sufficient to apply for interactions of individuals. This study adopts a different approach to seek a possibility that immediate return preference may be reproduced by learning rule to maximize objective outcomes. We show that a synaptic learning rule to achieve the temporal difference (TD) learning for outcome maximization fails the maximization and exhibits immediate return preference if the context is not properly represented as a internal state.

  10. Are running speeds maximized with simple-spring stance mechanics?

    PubMed

    Clark, Kenneth P; Weyand, Peter G

    2014-09-15

    Are the fastest running speeds achieved using the simple-spring stance mechanics predicted by the classic spring-mass model? We hypothesized that a passive, linear-spring model would not account for the running mechanics that maximize ground force application and speed. We tested this hypothesis by comparing patterns of ground force application across athletic specialization (competitive sprinters vs. athlete nonsprinters, n = 7 each) and running speed (top speeds vs. slower ones). Vertical ground reaction forces at 5.0 and 7.0 m/s, and individual top speeds (n = 797 total footfalls) were acquired while subjects ran on a custom, high-speed force treadmill. The goodness of fit between measured vertical force vs. time waveform patterns and the patterns predicted by the spring-mass model were assessed using the R(2) statistic (where an R(2) of 1.00 = perfect fit). As hypothesized, the force application patterns of the competitive sprinters deviated significantly more from the simple-spring pattern than those of the athlete, nonsprinters across the three test speeds (R(2) <0.85 vs. R(2) ≥ 0.91, respectively), and deviated most at top speed (R(2) = 0.78 ± 0.02). Sprinters attained faster top speeds than nonsprinters (10.4 ± 0.3 vs. 8.7 ± 0.3 m/s) by applying greater vertical forces during the first half (2.65 ± 0.05 vs. 2.21 ± 0.05 body wt), but not the second half (1.71 ± 0.04 vs. 1.73 ± 0.04 body wt) of the stance phase. We conclude that a passive, simple-spring model has limited application to sprint running performance because the swiftest runners use an asymmetrical pattern of force application to maximize ground reaction forces and attain faster speeds.

  11. Comparing Science Achievement Constructs: Targeted and Achieved

    ERIC Educational Resources Information Center

    Ferrara, Steve; Duncan, Teresa

    2011-01-01

    This article illustrates how test specifications based solely on academic content standards, without attention to other cognitive skills and item response demands, can fall short of their targeted constructs. First, the authors inductively describe the science achievement construct represented by a statewide sixth-grade science proficiency test.…

  12. Which Achievement Gap?

    ERIC Educational Resources Information Center

    Anderson, Sharon; Medrich, Elliott; Fowler, Donna

    2007-01-01

    From the halls of Congress to the local elementary school, conversations on education reform have tossed around the term "achievement gap" as though people all know precisely what that means. As it's commonly used, "achievement gap" refers to the differences in scores on state or national achievement tests between various…

  13. Exhaustive computation of exact duplications via super and non-nested local maximal repeats.

    PubMed

    Taillefer, Eddy; Miller, Jonathan

    2014-02-01

    We propose and implement a method to obtain all duplicated sequences (repeats) from a chromosome or whole genome. Unlike existing approaches our method makes it possible to simultaneously identify and classify repeats into super, local, and non-nested local maximal repeats. Computation verification demonstrates that maximal repeats for a genome of several gigabases can be identified in a reasonable time, enabling us to identified these maximal repeats for any sequenced genome. The algorithm used for the identification relies on enhanced suffix array data structure to achieve practical space and time efficiency, to identify and classify the maximal repeats, and to perform further post-processing on the identified duplicated sequences. The simplicity and effectiveness of the implementation makes the method readily extendible to more sophisticated computations. Maxmers can be exhaustively accounted for in few minutes for genome sequences of dozen megabases in length and in less than a day or two for genome sequences of few gigabases in length. One application of duplicated sequence identification is to the study of duplicated sequence length distributions, which our found to exhibit for large lengths a persistent power-law behavior. Variation of estimated exponents of this power law are studied among different species and successive assembly release versions of the same species. This makes the characterization of the power-law regime of sequenced genomes via maximal repeats identification and classification, an important task for the derivation of models that would help us to elucidate sequence duplication and genome evolution.

  14. Maximizing Information from Implementation of Innovative Courses.

    ERIC Educational Resources Information Center

    Churchman, David

    Discussed are four different approaches to the evaluation of the implementation of innovative courses. The first approach is that of Alkin and his associates at UCLA. This group emphasized the need to collect information on the degree to which an innovative course is implemented for the purpose of taking corrective action to achieve full…

  15. Trends in Therapeutic Recreation.

    ERIC Educational Resources Information Center

    Smith, Ralph W.

    1995-01-01

    Discusses the implications of the rapid, dramatic changes taking place in therapeutic recreation for individuals with physical disabilities. The article notes the impact of changes in managed care, examines programming trends in therapeutic recreation (adventure/outdoor education, competitive sports, handcycling, health enhancement activities, and…

  16. Therapeutic Recreation Practicum Manual.

    ERIC Educational Resources Information Center

    Schneegas, Kay

    This manual provides information on the practicum program offered by Moraine Valley Community College (MVCC) for students in its therapeutic recreation program. Sections I and II outline the rationale and goals for providing practical, on-the-job work experiences for therapeutic recreation students. Section III specifies MVCC's responsibilities…

  17. Chicanoizing the Therapeutic Community

    ERIC Educational Resources Information Center

    Aron, William S.; And Others

    1974-01-01

    Focusing on the drug addiction problem and its antecedent conditions in a Chicano population, the article examines several therapeutic interventions suggested by these conditions and indicates how they might be incorporated into a drug addiction Therapeutic Community treatment program designed to meet the needs of Chicano drug addicts. (Author/NQ)

  18. Impact of Therapeutic Camping

    ERIC Educational Resources Information Center

    Shniderman, Craig M.

    1974-01-01

    There has been little interest in, and only slight illumination of, the impact of therapeutic camping for emotionally disturbed children. This study seeks to validate the belief that camping is therapeutic. Subjects were 52 boys, 5 to 11 1/2 years of age. Results support the hypothesis. (Author/HMV)

  19. Therapeutic Strategies Based on Polymeric Microparticles

    PubMed Central

    Vilos, C.; Velasquez, L. A.

    2012-01-01

    The development of the field of materials science, the ability to perform multidisciplinary scientific work, and the need for novel administration technologies that maximize therapeutic effects and minimize adverse reactions to readily available drugs have led to the development of delivery systems based on microencapsulation, which has taken one step closer to the target of personalized medicine. Drug delivery systems based on polymeric microparticles are generating a strong impact on preclinical and clinical drug development and have reached a broad development in different fields supporting a critical role in the near future of medical practice. This paper presents the foundations of polymeric microparticles based on their formulation, mechanisms of drug release and some of their innovative therapeutic strategies to board multiple diseases. PMID:22665988

  20. Anticonvulsant effects of benzhydryl piperazines on maximal electroshock seizures in rats.

    PubMed

    Novack, G D; Stark, L G; Peterson, S L

    1979-03-01

    The anticonvulsant effects of four benzhydryl piperazines, SC-13504 (ropizine, an anticonvulsant), hydroxyzine (HDX, an anxiolytic), chlorcyclizine (CCZ, an antihistaminic) and buclizine (BUC, an antihistaminic), were investigated utilizing a modified maximal electroshock seizure test in rats. In addition to detecting the presence or absence of tonic hindlimb extension, the modified method quantified various phases of the seizure. All four benzhydryl piperazines exhibited anticonvulsant activity in maximal electroshock seizure, but SC-13504 was similar in efficacy to phenobarbital and phenytoin, and much more effective than HDX, CCZ or BUC. Additionally, SC-13504 possessed a therapeutic index much greater than any of the compounds tested. The duration of action of the benzhydryl piperazines, in hours was: SC-13504, 0.5 to 8; HDX, 0.5 to 2; CCZ, 0.5 to 16; and BUC, 2 to 8. Buc and CCZ are postulated to be converted to active anticonvulsant metabolites.

  1. Maximal and sub-maximal functional lifting performance at different platform heights.

    PubMed

    Savage, Robert J; Jaffrey, Mark A; Billing, Daniel C; Ham, Daniel J

    2015-01-01

    Introducing valid physical employment tests requires identifying and developing a small number of practical tests that provide broad coverage of physical performance across the full range of job tasks. This study investigated discrete lifting performance across various platform heights reflective of common military lifting tasks. Sixteen Australian Army personnel performed a discrete lifting assessment to maximal lifting capacity (MLC) and maximal acceptable weight of lift (MAWL) at four platform heights between 1.30 and 1.70 m. There were strong correlations between platform height and normalised lifting performance for MLC (R(2) = 0.76 ± 0.18, p < 0.05) and MAWL (R(2) = 0.73 ± 0.21, p < 0.05). The developed relationship allowed prediction of lifting capacity at one platform height based on lifting capacity at any of the three other heights, with a standard error of < 4.5 kg and < 2.0 kg for MLC and MAWL, respectively.

  2. Maximally Expressive Modeling of Operations Tasks

    NASA Technical Reports Server (NTRS)

    Jaap, John; Richardson, Lea; Davis, Elizabeth

    2002-01-01

    Planning and scheduling systems organize "tasks" into a timeline or schedule. The tasks are defined within the scheduling system in logical containers called models. The dictionary might define a model of this type as "a system of things and relations satisfying a set of rules that, when applied to the things and relations, produce certainty about the tasks that are being modeled." One challenging domain for a planning and scheduling system is the operation of on-board experiments for the International Space Station. In these experiments, the equipment used is among the most complex hardware ever developed, the information sought is at the cutting edge of scientific endeavor, and the procedures are intricate and exacting. Scheduling is made more difficult by a scarcity of station resources. The models to be fed into the scheduler must describe both the complexity of the experiments and procedures (to ensure a valid schedule) and the flexibilities of the procedures and the equipment (to effectively utilize available resources). Clearly, scheduling International Space Station experiment operations calls for a "maximally expressive" modeling schema.

  3. Maximal respiratory pressure in healthy Japanese children.

    PubMed

    Tagami, Miki; Okuno, Yukako; Matsuda, Tadamitsu; Kawamura, Kenta; Shoji, Ryosuke; Tomita, Kazuhide

    2017-03-01

    [Purpose] Normal values for respiratory muscle pressures during development in Japanese children have not been reported. The purpose of this study was to investigate respiratory muscle pressures in Japanese children aged 3-12 years. [Subjects and Methods] We measured respiratory muscle pressure values using a manovacuometer without a nose clip, with subjects in a sitting position. Data were collected for ages 3-6 (Group I: 68 subjects), 7-9 (Group II: 86 subjects), and 10-12 (Group III: 64 subjects) years. [Results] The values for respiratory muscle pressures in children were significantly higher with age in both sexes, and were higher in boys than in girls. Correlation coefficients were significant at values of 0.279 to 0.471 for each gender relationship between maximal respiratory pressure and age, height, and weight, respectively. [Conclusion] In this study, we showed pediatric respiratory muscle pressure reference value for each age. In the present study, values for respiratory muscle pressures were lower than Brazilian studies. This suggests that differences in respiratory muscle pressures vary with ethnicity.

  4. Maximally localized Wannier functions: Theory and applications

    NASA Astrophysics Data System (ADS)

    Marzari, Nicola; Mostofi, Arash A.; Yates, Jonathan R.; Souza, Ivo; Vanderbilt, David

    2012-10-01

    The electronic ground state of a periodic system is usually described in terms of extended Bloch orbitals, but an alternative representation in terms of localized “Wannier functions” was introduced by Gregory Wannier in 1937. The connection between the Bloch and Wannier representations is realized by families of transformations in a continuous space of unitary matrices, carrying a large degree of arbitrariness. Since 1997, methods have been developed that allow one to iteratively transform the extended Bloch orbitals of a first-principles calculation into a unique set of maximally localized Wannier functions, accomplishing the solid-state equivalent of constructing localized molecular orbitals, or “Boys orbitals” as previously known from the chemistry literature. These developments are reviewed here, and a survey of the applications of these methods is presented. This latter includes a description of their use in analyzing the nature of chemical bonding, or as a local probe of phenomena related to electric polarization and orbital magnetization. Wannier interpolation schemes are also reviewed, by which quantities computed on a coarse reciprocal-space mesh can be used to interpolate onto much finer meshes at low cost, and applications in which Wannier functions are used as efficient basis functions are discussed. Finally the construction and use of Wannier functions outside the context of electronic-structure theory is presented, for cases that include phonon excitations, photonic crystals, and cold-atom optical lattices.

  5. Inverting Monotonic Nonlinearities by Entropy Maximization

    PubMed Central

    López-de-Ipiña Pena, Karmele; Caiafa, Cesar F.

    2016-01-01

    This paper proposes a new method for blind inversion of a monotonic nonlinear map applied to a sum of random variables. Such kinds of mixtures of random variables are found in source separation and Wiener system inversion problems, for example. The importance of our proposed method is based on the fact that it permits to decouple the estimation of the nonlinear part (nonlinear compensation) from the estimation of the linear one (source separation matrix or deconvolution filter), which can be solved by applying any convenient linear algorithm. Our new nonlinear compensation algorithm, the MaxEnt algorithm, generalizes the idea of Gaussianization of the observation by maximizing its entropy instead. We developed two versions of our algorithm based either in a polynomial or a neural network parameterization of the nonlinear function. We provide a sufficient condition on the nonlinear function and the probability distribution that gives a guarantee for the MaxEnt method to succeed compensating the distortion. Through an extensive set of simulations, MaxEnt is compared with existing algorithms for blind approximation of nonlinear maps. Experiments show that MaxEnt is able to successfully compensate monotonic distortions outperforming other methods in terms of the obtained Signal to Noise Ratio in many important cases, for example when the number of variables in a mixture is small. Besides its ability for compensating nonlinearities, MaxEnt is very robust, i.e. showing small variability in the results. PMID:27780261

  6. Viral quasispecies assembly via maximal clique enumeration.

    PubMed

    Töpfer, Armin; Marschall, Tobias; Bull, Rowena A; Luciani, Fabio; Schönhuth, Alexander; Beerenwinkel, Niko

    2014-03-01

    Virus populations can display high genetic diversity within individual hosts. The intra-host collection of viral haplotypes, called viral quasispecies, is an important determinant of virulence, pathogenesis, and treatment outcome. We present HaploClique, a computational approach to reconstruct the structure of a viral quasispecies from next-generation sequencing data as obtained from bulk sequencing of mixed virus samples. We develop a statistical model for paired-end reads accounting for mutations, insertions, and deletions. Using an iterative maximal clique enumeration approach, read pairs are assembled into haplotypes of increasing length, eventually enabling global haplotype assembly. The performance of our quasispecies assembly method is assessed on simulated data for varying population characteristics and sequencing technology parameters. Owing to its paired-end handling, HaploClique compares favorably to state-of-the-art haplotype inference methods. It can reconstruct error-free full-length haplotypes from low coverage samples and detect large insertions and deletions at low frequencies. We applied HaploClique to sequencing data derived from a clinical hepatitis C virus population of an infected patient and discovered a novel deletion of length 357±167 bp that was validated by two independent long-read sequencing experiments. HaploClique is available at https://github.com/armintoepfer/haploclique. A summary of this paper appears in the proceedings of the RECOMB 2014 conference, April 2-5.

  7. Network channel allocation and revenue maximization

    NASA Astrophysics Data System (ADS)

    Hamalainen, Timo; Joutsensalo, Jyrki

    2002-09-01

    This paper introduces a model that can be used to share link capacity among customers under different kind of traffic conditions. This model is suitable for different kind of networks like the 4G networks (fast wireless access to wired network) to support connections of given duration that requires a certain quality of service. We study different types of network traffic mixed in a same communication link. A single link is considered as a bottleneck and the goal is to find customer traffic profiles that maximizes the revenue of the link. Presented allocation system accepts every calls and there is not absolute blocking, but the offered data rate/user depends on the network load. Data arrival rate depends on the current link utilization, user's payment (selected CoS class) and delay. The arrival rate is (i) increasing with respect to the offered data rate, (ii) decreasing with respect to the price, (iii) decreasing with respect to the network load, and (iv) decreasing with respect to the delay. As an example, explicit formula obeying these conditions is given and analyzed.

  8. Evolution of correlated multiplexity through stability maximization

    NASA Astrophysics Data System (ADS)

    Dwivedi, Sanjiv K.; Jalan, Sarika

    2017-02-01

    Investigating the relation between various structural patterns found in real-world networks and the stability of underlying systems is crucial to understand the importance and evolutionary origin of such patterns. We evolve multiplex networks, comprising antisymmetric couplings in one layer depicting predator-prey relationship and symmetric couplings in the other depicting mutualistic (or competitive) relationship, based on stability maximization through the largest eigenvalue of the corresponding adjacency matrices. We find that there is an emergence of the correlated multiplexity between the mirror nodes as the evolution progresses. Importantly, evolved values of the correlated multiplexity exhibit a dependence on the interlayer coupling strength. Additionally, the interlayer coupling strength governs the evolution of the disassortativity property in the individual layers. We provide analytical understanding to these findings by considering starlike networks representing both the layers. The framework discussed here is useful for understanding principles governing the stability as well as the importance of various patterns in the underlying networks of real-world systems ranging from the brain to ecology which consist of multiple types of interaction behavior.

  9. Predicting maximal grip strength using hand circumference.

    PubMed

    Li, Ke; Hewson, David J; Duchêne, Jacques; Hogrel, Jean-Yves

    2010-12-01

    The objective of this study was to analyze the correlations between anthropometric data and maximal grip strength (MGS) in order to establish a simple model to predict "normal" MGS. Randomized bilateral measurement of MGS was performed on a homogeneous population of 100 subjects. MGS was measured according to a standardized protocol with three dynamometers (Jamar, Myogrip and Martin Vigorimeter) for both dominant and non-dominant sides. Several anthropometric data were also measured: height; weight; hand, wrist and forearm circumference; hand and palm length. Among these data, hand circumference had the strongest correlation with MGS for all three dynamometers and for both hands (0.789 and 0.782 for Jamar; 0.829 and 0.824 for Myogrip; 0.663 and 0.730 for Vigorimeter). In addition, the only anthropometric variable systematically selected by a stepwise multiple linear regression analysis was also hand circumference. Based on this parameter alone, a predictive regression model presented good results (r(2) = 0.624 for Jamar; r(2) = 0.683 for Myogrip and r(2) = 0.473 for Vigorimeter; all adjusted r(2)). Moreover a single equation was predictive of MGS for both men and women and for both non-dominant and dominant hands. "Normal" MGS can be predicted using hand circumference alone.

  10. Maximal respiratory pressure in healthy Japanese children

    PubMed Central

    Tagami, Miki; Okuno, Yukako; Matsuda, Tadamitsu; Kawamura, Kenta; Shoji, Ryosuke; Tomita, Kazuhide

    2017-01-01

    [Purpose] Normal values for respiratory muscle pressures during development in Japanese children have not been reported. The purpose of this study was to investigate respiratory muscle pressures in Japanese children aged 3–12 years. [Subjects and Methods] We measured respiratory muscle pressure values using a manovacuometer without a nose clip, with subjects in a sitting position. Data were collected for ages 3–6 (Group I: 68 subjects), 7–9 (Group II: 86 subjects), and 10–12 (Group III: 64 subjects) years. [Results] The values for respiratory muscle pressures in children were significantly higher with age in both sexes, and were higher in boys than in girls. Correlation coefficients were significant at values of 0.279 to 0.471 for each gender relationship between maximal respiratory pressure and age, height, and weight, respectively. [Conclusion] In this study, we showed pediatric respiratory muscle pressure reference value for each age. In the present study, values for respiratory muscle pressures were lower than Brazilian studies. This suggests that differences in respiratory muscle pressures vary with ethnicity. PMID:28356644

  11. Reflection quasilattices and the maximal quasilattice

    NASA Astrophysics Data System (ADS)

    Boyle, Latham; Steinhardt, Paul J.

    2016-08-01

    We introduce the concept of a reflection quasilattice, the quasiperiodic generalization of a Bravais lattice with irreducible reflection symmetry. Among their applications, reflection quasilattices are the reciprocal (i.e., Bragg diffraction) lattices for quasicrystals and quasicrystal tilings, such as Penrose tilings, with irreducible reflection symmetry and discrete scale invariance. In a follow-up paper, we will show that reflection quasilattices can be used to generate tilings in real space with properties analogous to those in Penrose tilings, but with different symmetries and in various dimensions. Here we explain that reflection quasilattices only exist in dimensions two, three, and four, and we prove that there is a unique reflection quasilattice in dimension four: the "maximal reflection quasilattice" in terms of dimensionality and symmetry. Unlike crystallographic Bravais lattices, all reflection quasilattices are invariant under rescaling by certain discrete scale factors. We tabulate the complete set of scale factors for all reflection quasilattices in dimension d >2 , and for all those with quadratic irrational scale factors in d =2 .

  12. Enzyme therapeutics for systemic detoxification.

    PubMed

    Liu, Yang; Li, Jie; Lu, Yunfeng

    2015-08-01

    Life relies on numerous biochemical processes working synergistically and correctly. Certain substances disrupt these processes, inducing living organism into an abnormal state termed intoxication. Managing intoxication usually requires interventions, which is referred as detoxification. Decades of development on detoxification reveals the potential of enzymes as ideal therapeutics and antidotes, because their high substrate specificity and catalytic efficiency are essential for clearing intoxicating substances without adverse effects. However, intrinsic shortcomings of enzymes including low stability and high immunogenicity are major hurdles, which could be overcome by delivering enzymes with specially designed nanocarriers. Extensive investigations on protein delivery indicate three types of enzyme-nanocarrier architectures that show more promise than others for systemic detoxification, including liposome-wrapped enzymes, polymer-enzyme conjugates, and polymer-encapsulated enzymes. This review highlights recent advances in these nano-architectures and discusses their applications in systemic detoxifications. Therapeutic potential of various enzymes as well as associated challenges in achieving effective delivery of therapeutic enzymes will also be discussed.

  13. Engineered microRNA therapeutics.

    PubMed

    Gibson, N W

    2014-01-01

    Targeting of microRNAs that are overexpressed or replacement of microRNAs whose expression is lost are two distinct and novel approaches to treat disease(s) driven by microRNA dysregulation. This can be achieved by chemical modification of either a single stranded oligonucleotide called an antimiR or a double stranded nucleic acid molecule termed a microRNA mimic.With hundreds of microRNAs identified and knowledge of their role in disease becoming clearer there is the prospect, over the coming years, to harness engineered microRNA therapeutics to revolutionise the way diseases are treated.Both types of engineered microRNA therapeutics have advanced into clinical development with human proof of concept achieved with an anti-miR targeting miR-122 (one of the most abundant microRNAs in human hepatocytes that is utilised by the hepatitis C virus to enable its function and replication). Rather than targeting individual proteins or enzymes involved in human disease, an opportunity now exists to modulate multiple different proteins/enzymes which act in concert in the progression of disease.

  14. Rare flavor processes in Maximally Natural Supersymmetry

    NASA Astrophysics Data System (ADS)

    García, Isabel García; March-Russell, John

    2015-01-01

    We study CP-conserving rare flavor violating processes in the recently proposed theory of Maximally Natural Supersymmetry (MNSUSY). MNSUSY is an unusual supersymmetric (SUSY) extension of the Standard Model (SM) which, remarkably, is untuned at present LHC limits. It employs Scherk-Schwarz breaking of SUSY by boundary conditions upon compactifying an underlying 5-dimensional (5D) theory down to 4D, and is not well-described by softly-broken SUSY, with much different phenomenology than the Minimal Supersymmetric Standard Model (MSSM) and its variants. The usual CP-conserving SUSY-flavor problem is automatically solved in MNSUSY due to a residual almost exact U(1) R symmetry, naturally heavy and highly degenerate 1st- and 2nd-generation sfermions, and heavy gauginos and Higgsinos. Depending on the exact implementation of MNSUSY there exist important new sources of flavor violation involving gauge boson Kaluza-Klein (KK) excitations. The spatial localization properties of the matter multiplets, in particular the brane localization of the 3rd generation states, imply KK-parity is broken and tree-level contributions to flavor changing neutral currents are present in general. Nevertheless, we show that simple variants of the basic MNSUSY model are safe from present flavor constraints arising from kaon and B-meson oscillations, the rare decays B s, d → μ + μ -, μ → ēee and μ- e conversion in nuclei. We also briefly discuss some special features of the radiative decays μ → eγ and . Future experiments, especially those concerned with lepton flavor violation, should see deviations from SM predictions unless one of the MNSUSY variants with enhanced flavor symmetries is realized.

  15. Student academic achievement in college chemistry

    NASA Astrophysics Data System (ADS)

    Tabibzadeh, Kiana S.

    General Chemistry is required for variety of baccalaureate degrees, including all medical related fields, engineering, and science majors. Depending on the institution, the prerequisite requirement for college level General Chemistry varies. The success rate for this course is low. The purpose of this study is to examine the factors influencing student academic achievement and retention in General Chemistry at the college level. In this study student achievement is defined by those students who earned grades of "C" or better. The dissertation contains in-depth studies on influence of Intermediate Algebra as a prerequisite compared to Fundamental Chemistry for student academic achievement and student retention in college General Chemistry. In addition the study examined the extent and manner in which student self-efficacy influences student academic achievement in college level General Chemistry. The sample for this part of the study is 144 students enrolled in first semester college level General Chemistry. Student surveys determined student self-efficacy level. The statistical analyses of study demonstrated that Fundamental Chemistry is a better prerequisite for student academic achievement and student retention. The study also found that student self-efficacy has no influence on student academic achievement. The significance of this study will be to provide data for the purpose of establishing a uniform and most suitable prerequisite for college level General Chemistry. Finally the variables identified to influence student academic achievement and enhance student retention will support educators' mission to maximize the students' ability to complete their educational goal at institutions of higher education.

  16. Biomimetic Particles as Therapeutics

    PubMed Central

    Green, Jordan J.

    2015-01-01

    In recent years, there have been major advances in the development of novel nanoparticle and microparticle-based therapeutics. An emerging paradigm is the incorporation of biomimetic features into these synthetic therapeutic constructs to enable them to better interface with biological systems. Through the control of size, shape, and material consistency, particle cores have been generated that better mimic natural cells and viruses. In addition, there have been significant advances in biomimetic surface functionalization of particles through the integration of bio-inspired artificial cell membranes and naturally derived cell membranes. Biomimetic technologies enable therapeutic particles to have increased potency to benefit human health. PMID:26277289

  17. Biomimetic particles as therapeutics.

    PubMed

    Meyer, Randall A; Sunshine, Joel C; Green, Jordan J

    2015-09-01

    In recent years, there have been major advances in the development of novel nanoparticle- and microparticle-based therapeutics. An emerging paradigm is the incorporation of biomimetic features into these synthetic therapeutic constructs to enable them to better interface with biological systems. Through the control of size, shape, and material consistency, particle cores have been generated that better mimic natural cells and viruses. In addition, there have been significant advances in biomimetic surface functionalization of particles through the integration of bio-inspired artificial cell membranes and naturally derived cell membranes. Biomimetic technologies enable therapeutic particles to have increased potency to benefit human health.

  18. Range sidelobe elimination in maximal sequence phase coded C.W. radars

    NASA Astrophysics Data System (ADS)

    Metaxas, D. G.; Aitchison, C. S.

    Elimination of the range sidelobe of the autocorrelation of the periodic binary maximal sequence has been achieved. A new property of the m-sequence is defined. As a result the ambiguity function of an m-sequence PSK CW radar coincides with the ambiguity function of the equivalent pulse radar as far as the range and velocity resolution are concerned. The signal to noise deterioration due to the post-correlation implementation of the new property is insignificant.

  19. Maximality-Based Structural Operational Semantics for Petri Nets

    NASA Astrophysics Data System (ADS)

    Saīdouni, Djamel Eddine; Belala, Nabil; Bouneb, Messaouda

    2009-03-01

    The goal of this work is to exploit an implementable model, namely the maximality-based labeled transition system, which permits to express true-concurrency in a natural way without splitting actions on their start and end events. One can do this by giving a maximality-based structural operational semantics for the model of Place/Transition Petri nets in terms of maximality-based labeled transition systems structures.

  20. Parametric image alignment using enhanced correlation coefficient maximization.

    PubMed

    Evangelidis, Georgios D; Psarakis, Emmanouil Z

    2008-10-01

    In this work we propose the use of a modified version of the correlation coefficient as a performance criterion for the image alignment problem. The proposed modification has the desirable characteristic of being invariant with respect to photometric distortions. Since the resulting similarity measure is a nonlinear function of the warp parameters, we develop two iterative schemes for its maximization, one based on the forward additive approach and the second on the inverse compositional method. As it is customary in iterative optimization, in each iteration, the nonlinear objective function is approximated by an alternative expression for which the corresponding optimization is simple. In our case we propose an efficient approximation that leads to a closed-form solution (per iteration) which is of low computational complexity, the latter property being particularly strong in our inverse version. The proposed schemes are tested against the Forward Additive Lucas-Kanade and the Simultaneous Inverse Compositional (SIC) algorithm through simulations. Under noisy conditions and photometric distortions, our forward version achieves more accurate alignments and exhibits faster convergence whereas our inverse version has similar performance as the SIC algorithm but at a lower computational complexity.

  1. Symptom-limited maximal treadmill testing after myocardial infarction.

    PubMed

    Roberts, K C; Logan, R L

    1980-11-12

    In this paper we report our experience of routine symptom limited maximal treadmill assessment, and the methodology used with patients at the end of their convalescence after myocardial infarction. Sixty-one of 68 (90 percent) consecutive patients, mean age 55.7 years (21 to 69 years), were studied at the median time after infarction of six weeks (three to 16 weeks). No complications occurred during or after the tests. Fifty-six percent of the patients studied achieved a work capacity which was within the average range reported for healthy people of the smae age. Thirty-two percent experienced chest pain thought to be angina and 31 percent developed ST segment depression of at least 1 mm without chest pain. Although ventricular premature beats occurred in half the tests the only arrhythmia requiring any treatment was a supraventricular tachycardia. The assessment of work capacity and limiting symptoms in this way after myocardial infarction is safe and is of considerable help in patient management.

  2. Moderate Intra-Group Bias Maximizes Cooperation on Interdependent Populations

    PubMed Central

    Tang, Changbing; Wang, Zhen; Li, Xiang

    2014-01-01

    Evolutionary game theory on spatial structures has received increasing attention during the past decades. However, the majority of these achievements focuses on single and static population structures, which is not fully consistent with the fact that real structures are composed of many interactive groups. These groups are interdependent on each other and present dynamical features, in which individuals mimic the strategy of neighbors and switch their partnerships continually. It is however unclear how the dynamical and interdependent interactions among groups affect the evolution of collective behaviors. In this work, we employ the prisoner's dilemma game to investigate how the dynamics of structure influences cooperation on interdependent populations, where populations are represented by group structures. It is found that the more robust the links between cooperators (or the more fragile the links between cooperators and defectors), the more prevalent of cooperation. Furthermore, theoretical analysis shows that the intra-group bias can favor cooperation, which is only possible when individuals are likely to attach neighbors within the same group. Yet, interestingly, cooperation can be even inhibited for large intra-group bias, allowing the moderate intra-group bias maximizes the cooperation level. PMID:24533084

  3. Maximal atmospheric neutrino mixing in an SU(5) model

    NASA Astrophysics Data System (ADS)

    Grimus, W.; Lavoura, L.

    2003-05-01

    We show that maximal atmospheric and large solar neutrino mixing can be implemented in SU(5) gauge theories, by making use of the U(1) F symmetry associated with a suitably defined family number F, together with a Z2 symmetry which does not commute with F. U(1) F is softly broken by the mass terms of the right-handed neutrino singlets, which are responsible for the seesaw mechanism; in additio n, U(1) F is also spontaneously broken at the electroweak scale. In our scenario, lepton mixing stems exclusively from the right-handed-neutrino Majorana mass matrix, whereas the CKM matrix originates solely in the up-type-quark sector. We show that, despite the non-supersymmetric character of our model, unification of the gauge couplings can be achieved at a scale 1016 GeV < m U < 1019 GeV; indeed, we have found a particula r solution to this problem which yields results almost identical to the ones of the minimal supersymmetric standard model.

  4. 'No delays achiever'.

    PubMed

    2007-05-01

    The latest version of the NHS Institute for Innovation and Improvement's 'no delays achiever', a web based tool created to help NHS organisations achieve the 18-week target for GP referrals to first treatment, is available at www.nodelaysachiever.nhs.uk.

  5. Vicarious Achievement Orientation.

    ERIC Educational Resources Information Center

    Leavitt, Harold J.; And Others

    This study tests hypotheses about achievement orientation, particularly vicarious achievement. Undergraduate students (N=437) completed multiple-choice questionnaires, indicating likely responses of one person to the success of another. The sex of succeeder and observer, closeness of relationship, and setting (medical school or graduate school of…

  6. Heritability of Creative Achievement

    ERIC Educational Resources Information Center

    Piffer, Davide; Hur, Yoon-Mi

    2014-01-01

    Although creative achievement is a subject of much attention to lay people, the origin of individual differences in creative accomplishments remain poorly understood. This study examined genetic and environmental influences on creative achievement in an adult sample of 338 twins (mean age = 26.3 years; SD = 6.6 years). Twins completed the Creative…

  7. Confronting the Achievement Gap

    ERIC Educational Resources Information Center

    Gardner, David

    2007-01-01

    This article talks about the large achievement gap between children of color and their white peers. The reasons for the achievement gap are varied. First, many urban minorities come from a background of poverty. One of the detrimental effects of growing up in poverty is receiving inadequate nourishment at a time when bodies and brains are rapidly…

  8. Achievement-Based Resourcing.

    ERIC Educational Resources Information Center

    Fletcher, Mike; And Others

    1992-01-01

    This collection of seven articles examines achievement-based resourcing (ABR), the concept that the funding of educational institutions should be linked to their success in promoting student achievement, with a focus on the application of ABR to postsecondary education in the United Kingdom. The articles include: (1) "Introduction" (Mick…

  9. States Address Achievement Gaps.

    ERIC Educational Resources Information Center

    Christie, Kathy

    2002-01-01

    Summarizes 2 state initiatives to address the achievement gap: North Carolina's report by the Advisory Commission on Raising Achievement and Closing Gaps, containing an 11-point strategy, and Kentucky's legislation putting in place 10 specific processes. The North Carolina report is available at www.dpi.state.nc.us.closingthegap; Kentucky's…

  10. Maximizing a transport platform through computer technology.

    PubMed

    Hudson, Timothy L

    2003-01-01

    One of the most recent innovations coalescing computer technology and medical care is the further development of integrated medical component technology coupled with a computer subsystem. One such example is the self-contained patient transport system known as the Life Support for Trauma and Transport (LSTAT(tm)). The LSTAT creates a new transport platform that integrates the most current medical monitoring and therapeutic capabilities with computer processing capacity, creating the first "smart litter". The LSTAT is built around a computer system that is network capable and acts as the data hub for multiple medical devices and utilities, including data, power, and oxygen systems. The system logs patient and device data in a simultaneous, time-synchronized, continuous format, allowing electronic transmission, storage, and electronic documentation. The third-generation LSTAT includes an oxygen system, ventilator, clinical point-of-care blood analyzer, suction, defibrillator, infusion pump, and physiologic monitor, as well as on-board power and oxygen systems. The developers of LSTAT and other developers have the ability to further expand integrative component technology by developing and integrating clinical decision support systems.

  11. How many manoeuvres should be done to measure maximal inspiratory mouth pressure in patients with chronic airflow obstruction?

    PubMed Central

    Fiz, J A; Montserrat, J M; Picado, C; Plaza, V; Agusti-Vidal, A

    1989-01-01

    To determine the number of maximal mouth pressure manoeuvres needed to obtain a reproducible value of maximal inspiratory mouth pressure (MIP), we studied 44 patients with chronic airflow obstruction, with a mean (SD) % predicted FEV1 value of 53.9 (25), who were clinically stable. Maximal inspiratory mouth pressure was determined with an anaeroid manometer during maximal inspiratory efforts in a quasi static condition at residual volume. All patients performed 20 consecutive maximal inspiratory mouth manoeuvres, each one separated by 30-40 seconds. The mean (SD) values of MIP varied from 71.5 (25.5) cm H2O at the first measurement to 80.1 (27) cm H2O at the last measurement. Maximal values of MIP were usually achieved after nine determinations. It is concluded that to obtain a reproducible MIP value in patients with chronic airflow obstruction who are untrained and unexperienced in such manoeuvres a minimum of nine technically acceptable maximal mouth pressure manoeuvres should be performed. PMID:2763242

  12. Maximizing the safety of nonsteroidal anti-inflammatory drug use for postoperative dental pain: an evidence-based approach.

    PubMed Central

    Ong, K. S.; Seymour, R. A.

    2003-01-01

    This article reviews the use of nonsteroidal anti-inflammatory drugs (NSAIDs) for postoperative dental pain. An evidence-based approach is used to evaluate the clinical studies to date on the safe use of these drugs in dental patients. No drugs are without adverse effects or are perfectly safe, but their safe use in clinical practice would entail maximizing the therapeutic efficacy and minimizing the adverse effects. Therapeutic recommendations are made after reviewing the evidence for the safe use of NSAIDs in postoperative dental pain. PMID:12866802

  13. Achievability for telerobotic systems

    NASA Astrophysics Data System (ADS)

    Kress, Reid L.; Draper, John V.; Hamel, William R.

    2001-02-01

    Methods are needed to improve the capabilities of autonomous robots to perform tasks that are difficult for contemporary robots, and to identify those tasks that robots cannot perform. Additionally, in the realm of remote handling, methods are needed to assess which tasks and/or subtasks are candidates for automation. We are developing a new approach to understanding the capability of autonomous robotic systems. This approach uses formalized methods for determining the achievability of tasks for robots, that is, the likelihood that an autonomous robot or telerobot can successfully complete a particular task. Any autonomous system may be represented in achievability space by the volume describing that system's capabilities within the 3-axis space delineated by perception, cognition, and action. This volume may be thought of as a probability density with achievability decreasing as the distance from the centroid of the volume increases. Similarly, any task may be represented within achievability space. However, as tasks have more finite requirements for perception, cognition, and action, each may be represented as a point (or, more accurately, as a small sphere) within achievability space. Analysis of achievability can serve to identify, a priori, the survivability of robotic systems and the likelihood of mission success; it can be used to plan a mission or portions of a mission; it can be used to modify a mission plan to accommodate unpredicted occurrences; it can also serve to identify needs for modifications to robotic systems or tasks to improve achievability. .

  14. Maximizing the security of chaotic optical communications.

    PubMed

    Hou, T T; Yi, L L; Yang, X L; Ke, J X; Hu, Y; Yang, Q; Zhou, P; Hu, W S

    2016-10-03

    The practical application of chaotic optical communications has been limited by two aspects: the difficulty in concealing the time delay - a critical security parameter in feedback chaotic systems, and the difficulty of significantly enlarging the key space without complicating the implementation. Here we propose an architecture to break the above limits. By introducing a frequency-dependent group delay module with frequency tuning resolution of 1 MHz into the chaotic feedback loop, we demonstrate excellent time delay concealment effect, and an additional huge key space of 1048 can be achieved at the same time. The effectiveness is proved by both numerical simulation and experiment. Besides, the proposed scheme is compatible with the existing commercial optical communication systems, thus pave the way for high-speed secure optical communications.

  15. Method of making maximally dispersed heterogeneous catalysts

    DOEpatents

    Jennison, Dwight R.

    2005-11-15

    A method of making a catalyst with monolayer or sub-monolayer metal by controlling the wetting characteristics on the support surface and increasing the adhesion between the catalytic metal and an oxide layer. There are two methods that have been demonstrated by experiment and supported by theory. In the first method, which is useful for noble metals as well as others, a negatively-charged species is introduced to the surface of a support in sub-ML coverage. The layer-by-layer growth of metal deposited onto the oxide surface is promoted because the adhesion strength of the metal-oxide interface is increased. This method can also be used to achieve nanoislands of metal upon sub-ML deposition. The negatively-charged species can either be deposited onto the oxide surface or a compound can be deposited that dissociates on, or reacts with, the surface to form the negatively-charged species. The deposited metal adatoms can thereby bond laterally to the negatively-charged species as well as vertically to the oxide surface. Thus the negatively-charged species serve as anchors for the metal. In the second method, a chemical reaction that occurs when most metals are deposited on a fully hydroxylated oxide surface is used to create cationic metal species that bind strongly both to the substrate and to metallic metal atoms. These are incorporated into the top layer of the substrate and bind strongly both to the substrate and to metallic metal atoms. In this case, these oxidized metal atoms serve as the anchors. Here, as in the previous method, nanoislands of catalytic metal can be achieved to increase catalytic activity, or monolayers or bilayers of reactive metal can also be made.

  16. Culture and Achievement Motivation

    ERIC Educational Resources Information Center

    Maehr, Martin L.

    1974-01-01

    A framework is suggested for the cross-cultural study of motivation that stresses the importance of contextual conditions in eliciting achievement motivation and emphasizes cultural relativity in the definition of the concept. (EH)

  17. Achieving Salary Equity

    ERIC Educational Resources Information Center

    Nevill, Dorothy D.

    1975-01-01

    Three techniques are outlined for use by higher education institutions to achieve salary equity: salary prediction (using various statistical procedures), counterparting (comparing salaries of persons of similar rank), and grievance procedures. (JT)

  18. Pace's Maxims for Homegrown Library Projects. Coming Full Circle

    ERIC Educational Resources Information Center

    Pace, Andrew K.

    2005-01-01

    This article discusses six maxims by which to run library automation. The following maxims are discussed: (1) Solve only known problems; (2) Avoid changing data to fix display problems; (3) Aut viam inveniam aut faciam; (4) If you cannot make it yourself, buy something; (5) Kill the alligator closest to the boat; and (6) Just because yours is…

  19. The Negative Consequences of Maximizing in Friendship Selection.

    PubMed

    Newman, David B; Schug, Joanna; Yuki, Masaki; Yamada, Junko; Nezlek, John B

    2017-02-27

    Previous studies have shown that the maximizing orientation, reflecting a motivation to select the best option among a given set of choices, is associated with various negative psychological outcomes. In the present studies, we examined whether these relationships extend to friendship selection and how the number of options for friends moderated these effects. Across 5 studies, maximizing in selecting friends was negatively related to life satisfaction, positive affect, and self-esteem, and was positively related to negative affect and regret. In Study 1, a maximizing in selecting friends scale was created, and regret mediated the relationships between maximizing and well-being. In a naturalistic setting in Studies 2a and 2b, the tendency to maximize among those who participated in the fraternity and sorority recruitment process was negatively related to satisfaction with their selection, and positively related to regret and negative affect. In Study 3, daily levels of maximizing were negatively related to daily well-being, and these relationships were mediated by daily regret. In Study 4, we extended the findings to samples from the U.S. and Japan. When participants who tended to maximize were faced with many choices, operationalized as the daily number of friends met (Study 3) and relational mobility (Study 4), the opportunities to regret a decision increased and further diminished well-being. These findings imply that, paradoxically, attempts to maximize when selecting potential friends is detrimental to one's well-being. (PsycINFO Database Record

  20. Detrimental Relations of Maximization with Academic and Career Attitudes

    ERIC Educational Resources Information Center

    Dahling, Jason J.; Thompson, Mindi N.

    2013-01-01

    Maximization refers to a decision-making style that involves seeking the single best option when making a choice, which is generally dysfunctional because people are limited in their ability to rationally evaluate all options and identify the single best outcome. The vocational consequences of maximization are examined in two samples, college…

  1. Cardiorespiratory responses to maximal arm and leg exercise in national-class marathon runners.

    PubMed

    deJong, Adam T; Bonzheim, Kimberly; Franklin, Barry A; Saltarelli, William

    2009-06-01

    Marathon runners (MR) are among the most aerobically fit athletes in the world. Although aerobic capacity (VO(2)max) during arm exercise generally varies between 64% and 80% of leg VO(2)max (mean 70%) in healthy men, few data are available regarding the comparative arm fitness of MR. To clarify the relationship between arm and leg fitness in MR, we studied 10 national-class MR (mean + or - standard deviation age 30 + or - 4 years) whose best marathon times averaged < 2 hours and 40 minutes. Each MR underwent lower and upper body maximal exercise evaluations with measurement of cardiorespiratory variables using indirect calorimetry during treadmill testing (standard Bruce protocol) and arm-crank ergometry, respectively. Our subjects achieved VO(2)max levels equaling 75.8 + or - 7.1 mL/kg/min (5.2 + or - 0.6 L/min) during treadmill testing, which was significantly higher than the level of cardiorespiratory fitness achieved during maximal arm exercise (45.4 + or - 12.4 mL/kg/min [3.1 + or - 0.9 L/min]; P < 0.01). In addition, maximal heart rate (183.2 + or - 8.2 vs 163.7 + or - 10 bpm) and systolic blood pressure (201.8 + or - 10.1 vs 186.6 + or - 12.1 mm Hg) were significantly higher (P < 0.01 and P < 0.05, respectively) during maximal leg versus arm exercise. Relative arm fitness (arm VO(2)max/leg VO(2)max) was extremely variable (41%-76%), averaging 60% + or - 13%. Although MR are able to achieve significantly higher VO(2)max values during treadmill testing than those observed in the general population, their relative arm fitness appears to be slightly reduced. These findings add to and strongly support the specificity of measurement and training concept.

  2. Maximal power at different percentages of one repetition maximum: influence of resistance and gender.

    PubMed

    Thomas, Gwendolyn A; Kraemer, William J; Spiering, Barry A; Volek, Jeff S; Anderson, Jeffrey M; Maresh, Carl M

    2007-05-01

    National Collegiate Athletic Association Division I athletes were tested to determine the load at which maximal mechanical output is achieved. Athletes performed power testing at 30, 40, 50, 60, and 70% of individual 1 repetition maximum (1RM) in the squat jump, bench press, and hang pull exercises. Additionally, hang pull power testing was performed using free-form (i.e., barbell) and fixed-form (i.e., Smith machine) techniques. There were differences between genders in optimal power output during the squat jump (30-40% of 1RM for men; 30-50% of 1RM for women) and bench throw (30% of 1RM for men; 30-50% of 1RM for women) exercises. There were no gender or form interactions during the hang pull exercise; maximal power output during the hang pull occurred at 30-60% of 1RM. In conclusion, these results indicate that (a) gender differences exist in the load at which maximal power output occurs during the squat jump and bench throw; and (b) although no gender or form interactions occurred during the hang pull exercise, greater power could be generated during fixed-form exercise. In general, 30% of 1RM will elicit peak power outputs for both genders and all exercises used in this study, allowing this standard percentage to be used as a starting point in order to train maximal mechanical power output capabilities in these lifts in strength trained athletes.

  3. Dietary 2-oxoglutarate prevents bone loss caused by neonatal treatment with maximal dexamethasone dose.

    PubMed

    Dobrowolski, Piotr; Tomaszewska, Ewa; Muszyński, Siemowit; Blicharski, Tomasz; Pierzynowski, Stefan G

    2017-04-01

    Synthetic glucocorticoids (GCs) are widely used in the variety of dosages for treatment of premature infants with chronic lung disease, respiratory distress syndrome, allergies, asthma, and other inflammatory and autoimmune conditions. Yet, adverse effects such as glucocorticoid-induced osteoporosis and growth retardation are recognized. Conversely, 2-oxoglutarate (2-Ox), a precursor of glutamine, glutamate, and collagen amino acids, exerts protective effects on bone development. Our aim was to elucidate the effect of dietary administered 2-Ox on bone loss caused by neonatal treatment with clinically relevant maximal therapeutic dexamethasone (Dex) dose. Long bones of neonatal female piglets receiving Dex, Dex+2-Ox, or untreated were examined through measurements of mechanical properties, density, mineralization, geometry, histomorphometry, and histology. Selected hormones, bone turnover, and growth markers were also analyzed. Neonatal administration of clinically relevant maximal dose of Dex alone led to over 30% decrease in bone mass and the ultimate strength ( P < 0.001 for all). The length (13 and 7% for femur and humerus, respectively) and other geometrical parameters (13-45%) decreased compared to the control ( P < 0.001 for all). Dex impaired bone growth and caused hormonal imbalance. Dietary 2-Ox prevented Dex influence and vast majority of assessed bone parameters were restored almost to the control level. Piglets receiving 2-Ox had heavier, denser, and stronger bones; higher levels of growth hormone and osteocalcin concentration; and preserved microarchitecture of trabecular bone compared to the Dex group. 2-Ox administered postnatally had a potential to maintain bone structure of animals simultaneously treated with maximal therapeutic doses of Dex, which, in our opinion, may open up a new opportunity in developing combined treatment for children treated with GCs. Impact statement The present study has showed, for the first time, that dietary 2

  4. [Therapeutic drug monitoring of zonisamide].

    PubMed

    Verdier, Marie-Clémence; Bentué-Ferrer, Danièle; Tribut, Olivier

    2010-01-01

    Zonisamide is a second generation antiepileptic drug available in France since 2005. It provides a mechanism of action similar to those of phenytoin or carbamazepine. It is indicated in association in the treatment of partial epilepsy with or without secondary generalization. Zonisamide is well absorbed with maximum concentration achieved in 2 to 5 h. It is partly metabolized by the CYP3A4. Its elimination half-life is very long, around 60 h. Studies in adults and children show low concentration-efficacy and concentration-toxicity correlations, but a therapeutic range has been determined between 10 and 40 mg/L. Zonisamide is sensitive to the inductive molecules of CYP which will increase its clearance and decrease its half-life. A specific monitoring of patient is recommended in renal impairment. For this molecule, the interest of TDM has been evaluated: possibly useful.

  5. Host modulation by therapeutic agents

    PubMed Central

    Elavarasu, Sugumari; Sekar, Santhosh; Murugan, Thamaraiselvan

    2012-01-01

    Periodontal disease susceptible group present advanced periodontal breakdown even though they achieve a high standard of oral hygiene. Various destructive enzymes and inflammatory mediators are involved in destruction. These are elevated in case of periodontal destruction. Host modulation aims at bringing these enzymes and mediators to normal level. Doxycycline, nonsteroidal anti-inflammatory drugs (NSAIDs), bisphosphonates, nitrous oxide (NO) synthase inhibitors, recombinant human interleukin-11 (rhIL-11), omega-3 fatty acid, mouse anti-human interleukin-6 receptor antibody (MRA), mitogen-activated protein kinase (MAPK) inhibitors, nuclear factor-kappa B (NF-kb) inhibitors, osteoprotegerin, and tumor necrosis factor antagonist (TNF-α) are some of the therapeutic agents that have host modulation properties. PMID:23066265

  6. Therapeutic options for lip augmentation.

    PubMed

    Segall, Lorne; Ellis, David A F

    2007-11-01

    Aesthetic ideals vary with emerging fashion trends and within different cultures. However, over the past few decades, fuller lips have been considered a desirable trait. Many younger patients are presenting for lip augmentation to achieve the sought-after look commonly seen in many fashion magazines. In addition, as individuals age, they lose lip volume, with a thinning of the red lip, some effacement of the vermillion border, and elongation and flattening of the white portion of the lip. Rejuvenation of the lips plays a key role in restoring a more youthful appearance. As a result, lip augmentation appeals to a wide spectrum of patients who present with various different aesthetic goals and expectations. Numerous therapeutic options exist for aesthetic lip augmentation, ranging from temporary and permanent injectable fillers to implants and other surgical techniques.

  7. Recent advances in cancer therapeutics.

    PubMed

    Chessum, Nicola; Jones, Keith; Pasqua, Elisa; Tucker, Michael

    2015-01-01

    In the past 20 years, cancer therapeutics has undergone a paradigm shift away from the traditional cytotoxic drugs towards the targeting of proteins intimately involved in driving the cancer phenotype. The poster child for this alternative approach to the treatment of cancer is imatinib, a small-molecule kinase inhibitor designed to target chronic myeloid leukaemia driven by the BCR-ABL translocation in a defined patient population. The improvement in survival achieved by treatment of this patient cohort with imatinib is impressive. Thus, the aim is to provide efficacy but with low toxicity. The role of the medicinal chemist in oncology drug discovery is now closely aligned with the role in most other therapeutic areas with high-throughput and/or fragment-based screening, structure-based design, selectivity, pharmacokinetic optimisation and pharmacodynamic biomarker modulation, all playing a familiar part in the process. In this chapter, we selected four areas in which compounds are either approved drugs or in clinical trials. These are chaperone inhibitors, kinase inhibitors, histone deacetylase inhibitors and inhibitors of protein-protein interactions. Even within these areas, we have been selective, particularly for kinase inhibitors, and our aim has been to exemplify newer approaches and novel aspects of medicinal chemistry.

  8. General review of maximal aerobic velocity measurement at laboratory. Proposition of a new simplified protocol for maximal aerobic velocity assessment.

    PubMed

    Berthon, P; Fellmann, N

    2002-09-01

    The maximal aerobic velocity concept developed since eighties is considered as either the minimal velocity which elicits the maximal aerobic consumption or as the "velocity associated to maximal oxygen consumption". Different methods for measuring maximal aerobic velocity on treadmill in laboratory conditions have been elaborated, but all these specific protocols measure V(amax) either during a maximal oxygen consumption test or with an association of such a test. An inaccurate method presents a certain number of problems in the subsequent use of the results, for example in the elaboration of training programs, in the study of repeatability or in the determination of individual limit time. This study analyzes 14 different methods to understand their interests and limits in view to propose a general methodology for measuring V(amax). In brief, the test should be progressive and maximal without any rest period and of 17 to 20 min total duration. It should begin with a five min warm-up at 60-70% of the maximal aerobic power of the subjects. The beginning of the trial should be fixed so that four or five steps have to be run. The duration of the steps should be three min with a 1% slope and an increasing speed of 1.5 km x h(-1) until complete exhaustion. The last steps could be reduced at two min for a 1 km x h(-1) increment. The maximal aerobic velocity is adjusted in relation to duration of the last step.

  9. Pluristem Therapeutics, Inc.

    PubMed

    Prather, William

    2008-01-01

    Pluristem Therapeutics, Inc., based in Haifa, Israel, is a regenerative, biotherapeutics Company dedicated to the commercialization of nonpersonalized (allogeneic) cell therapy products. The Company is expanding noncontroversial placental-derived mesenchymal stem cells via a proprietary 3D process, named PluriX, into therapeutics for a variety of degenerative, malignant and autoimmune disorders. Pluristem will be conducting Phase I trials in the USA with its first product, PLX-I, which addresses the global shortfall of matched tissue for bone marrow transplantation by improving the engraftment of hematopoietic stem cells contained in umbilical cord blood.

  10. Therapeutics for cognitive aging.

    PubMed

    Shineman, Diana W; Salthouse, Timothy A; Launer, Lenore J; Hof, Patrick R; Bartzokis, George; Kleiman, Robin; Luine, Victoria; Buccafusco, Jerry J; Small, Gary W; Aisen, Paul S; Lowe, David A; Fillit, Howard M

    2010-04-01

    This review summarizes the scientific talks presented at the conference "Therapeutics for Cognitive Aging," hosted by the New York Academy of Sciences and the Alzheimer's Drug Discovery Foundation on May 15, 2009. Attended by scientists from industry and academia, as well as by a number of lay people-approximately 200 in all-the conference specifically tackled the many aspects of developing therapeutic interventions for cognitive impairment. Discussion also focused on how to define cognitive aging and whether it should be considered a treatable, tractable disease.

  11. DELIVERY OF THERAPEUTIC PROTEINS

    PubMed Central

    Pisal, Dipak S.; Kosloski, Matthew P.; Balu-Iyer, Sathy V.

    2009-01-01

    The safety and efficacy of protein therapeutics are limited by three interrelated pharmaceutical issues, in vitro and in vivo instability, immunogenicity and shorter half-lives. Novel drug modifications for overcoming these issues are under investigation and include covalent attachment of poly(ethylene glycol) (PEG), polysialic acid, or glycolic acid, as well as developing new formulations containing nanoparticulate or colloidal systems (e.g. liposomes, polymeric microspheres, polymeric nanoparticles). Such strategies have the potential to develop as next generation protein therapeutics. This review includes a general discussion on these delivery approaches. PMID:20049941

  12. Therapeutic Antioxidant Medical Gas

    PubMed Central

    Nakao, Atsunori; Sugimoto, Ryujiro; Billiar, Timothy R; McCurry, Kenneth R

    2009-01-01

    Medical gases are pharmaceutical gaseous molecules which offer solutions to medical needs and include traditional gases, such as oxygen and nitrous oxide, as well as gases with recently discovered roles as biological messenger molecules, such as carbon monoxide, nitric oxide and hydrogen sulphide. Medical gas therapy is a relatively unexplored field of medicine; however, a recent increasing in the number of publications on medical gas therapies clearly indicate that there are significant opportunities for use of gases as therapeutic tools for a variety of disease conditions. In this article, we review the recent advances in research on medical gases with antioxidant properties and discuss their clinical applications and therapeutic properties. PMID:19177183

  13. Strategies To Maximize Retention of a Sample of Young Adolescents in a Longitudinal Evaluation of "Healthy & Alive!"

    ERIC Educational Resources Information Center

    Simkin, Linda S.; Hirsch, Lesley; Radosh, Alice; Middlestadt, Susan E.; Kaiser, Javaid; Santelli, John S.

    2000-01-01

    Investigated the effectiveness of strategies to maximize cohort retention in a longitudinal evaluation of a middle school human immunodeficiency virus/sexually transmitted disease prevention intervention. Retention rates of 80 percent at 6 months and 73 percent at 18 months were achieved. This required joint, proactive problem solving at the…

  14. Design and manufacturing rules for maximizing the performance of polycrystalline piezoelectric bending actuators

    NASA Astrophysics Data System (ADS)

    Jafferis, Noah T.; Smith, Michael J.; Wood, Robert J.

    2015-06-01

    Increasing the energy and power density of piezoelectric actuators is very important for any weight-sensitive application, and is especially crucial for enabling autonomy in micro/milli-scale robots and devices utilizing this technology. This is achieved by maximizing the mechanical flexural strength and electrical dielectric strength through the use of laser-induced melting or polishing, insulating edge coating, and crack-arresting features, combined with features for rigid ground attachments to maximize force output. Manufacturing techniques have also been developed to enable mass customization, in which sheets of material are pre-stacked to form a laminate from which nearly arbitrary planar actuator designs can be fabricated using only laser cutting. These techniques have led to a 70% increase in energy density and an increase in mean lifetime of at least 15× compared to prior manufacturing methods. In addition, measurements have revealed a doubling of the piezoelectric coefficient when operating at the high fields necessary to achieve maximal energy densities, along with an increase in the Young’s modulus at the high compressive strains encountered—these two effects help to explain the higher performance of our actuators as compared to that predicted by linear models.

  15. Expanding the therapeutic index of radiation therapy by combining in situ gene therapy in the treatment of prostate cancer.

    PubMed

    Tetzlaff, Michael T; Teh, Bin S; Timme, Terry L; Fujita, Tetsuo; Satoh, Takefumi; Tabata, Ken-Ichi; Mai, Wei-Yuan; Vlachaki, Maria T; Amato, Robert J; Kadmon, Dov; Miles, Brian J; Ayala, Gustavo; Wheeler, Thomas M; Aguilar-Cordova, Estuardo; Thompson, Timothy C; Butler, E Brian

    2006-02-01

    The advances in radiotherapy (3D-CRT, IMRT) have enabled high doses of radiation to be delivered with the least possible associated toxicity. However, the persistence of cancer (local recurrence after radiotherapy) despite these increased doses as well as distant failure suggesting the existence of micro-metastases, especially in the case of higher risk disease, have underscored the need for continued improvement in treatment strategies to manage local and micro-metastatic disease as definitively as possible. This has prompted the idea that an increase in the therapeutic index of radiotherapy might be achieved by combining it with in situ gene therapy. The goal of these combinatorial therapies is to maximize the selective pressure against cancer cell growth while minimizing treatment-associated toxicity. Major efforts utilizing different gene therapy strategies have been employed in conjunction with radiotherapy. We reviewed our and other published clinical trials utilizing this combined radio-genetherapy approach including their associated pre-clinical in vitro and in vivo models. The use of in situ gene therapy as an adjuvant to radiation therapy dramatically reduced cell viability in vitro and tumor growth in vivo. No significant worsening of the toxicities normally observed in single-modality approaches were identified in Phase I/II clinical studies. Enhancement of both local and systemic T-cell activation was noted with this combined approach suggesting anti-tumor immunity. Early clinical outcome including biochemical and biopsy data was very promising. These results demonstrate the increased therapeutic efficacy achieved by combining in situ gene therapy with radiotherapy in the management of local prostate cancer. The combined approach maximizes tumor control, both local-regional and systemic through radio-genetherapy induced cytotoxicity and anti-tumor immunity.

  16. Can monkeys make investments based on maximized pay-off?

    PubMed

    Steelandt, Sophie; Dufour, Valérie; Broihanne, Marie-Hélène; Thierry, Bernard

    2011-03-10

    Animals can maximize benefits but it is not known if they adjust their investment according to expected pay-offs. We investigated whether monkeys can use different investment strategies in an exchange task. We tested eight capuchin monkeys (Cebus apella) and thirteen macaques (Macaca fascicularis, Macaca tonkeana) in an experiment where they could adapt their investment to the food amounts proposed by two different experimenters. One, the doubling partner, returned a reward that was twice the amount given by the subject, whereas the other, the fixed partner, always returned a constant amount regardless of the amount given. To maximize pay-offs, subjects should invest a maximal amount with the first partner and a minimal amount with the second. When tested with the fixed partner only, one third of monkeys learned to remove a maximal amount of food for immediate consumption before investing a minimal one. With both partners, most subjects failed to maximize pay-offs by using different decision rules with each partner' quality. A single Tonkean macaque succeeded in investing a maximal amount to one experimenter and a minimal amount to the other. The fact that only one of over 21 subjects learned to maximize benefits in adapting investment according to experimenters' quality indicates that such a task is difficult for monkeys, albeit not impossible.

  17. Oxygen uptake in maximal effort constant rate and interval running.

    PubMed

    Pratt, Daniel; O'Brien, Brendan J; Clark, Bradley

    2013-01-01

    This study investigated differences in average VO2 of maximal effort interval running to maximal effort constant rate running at lactate threshold matched for time. The average VO2 and distance covered of 10 recreational male runners (VO2max: 4158 ± 390 mL · min(-1)) were compared between a maximal effort constant-rate run at lactate threshold (CRLT), a maximal effort interval run (INT) consisting of 2 min at VO2max speed with 2 minutes at 50% of VO2 repeated 5 times, and a run at the average speed sustained during the interval run (CR submax). Data are presented as mean and 95% confidence intervals. The average VO2 for INT, 3451 (3269-3633) mL · min(-1), 83% VO2max, was not significantly different to CRLT, 3464 (3285-3643) mL · min(-1), 84% VO2max, but both were significantly higher than CR sub-max, 3464 (3285-3643) mL · min(-1), 76% VO2max. The distance covered was significantly greater in CLRT, 4431 (4202-3731) metres, compared to INT and CR sub-max, 4070 (3831-4309) metres. The novel finding was that a 20-minute maximal effort constant rate run uses similar amounts of oxygen as a 20-minute maximal effort interval run despite the greater distance covered in the maximal effort constant-rate run.

  18. Opportunities to maximize value with integrated palliative care

    PubMed Central

    Bergman, Jonathan; Laviana, Aaron A

    2016-01-01

    Palliative care involves aggressively addressing and treating psychosocial, spiritual, religious, and family concerns, as well as considering the overall psychosocial structures supporting a patient. The concept of integrated palliative care removes the either/or decision a patient needs to make: they need not decide if they want either aggressive chemotherapy from their oncologist or symptom-guided palliative care but rather they can be comanaged by several clinicians, including a palliative care clinician, to maximize the benefit to them. One common misconception about palliative care, and supportive care in general, is that it amounts to “doing nothing” or “giving up” on aggressive treatments for patients. Rather, palliative care involves very aggressive care, targeted at patient symptoms, quality-of-life, psychosocial needs, family needs, and others. Integrating palliative care into the care plan for individuals with advanced diseases does not necessarily imply that a patient must forego other treatment options, including those aimed at a cure, prolonging of life, or palliation. Implementing interventions to understand patient preferences and to ensure those preferences are addressed, including preferences related to palliative and supportive care, is vital in improving the patient-centeredness and value of surgical care. Given our aging population and the disproportionate cost of end-of-life care, this holds great hope in bending the cost curve of health care spending, ensuring patient-centeredness, and improving quality and value of care. Level 1 evidence supports this model, and it has been achieved in several settings; the next necessary step is to disseminate such models more broadly. PMID:27226721

  19. Therapeutic Angiogenesis in Critical Limb Ischemia

    PubMed Central

    Ouma, Geoffrey O.; Zafrir, Barak; Mohler, Emile R.; Flugelman, Moshe Y.

    2013-01-01

    Critical limb ischemia (CLI) is a severe form of peripheral artery disease associated with high morbidity and mortality. The primary therapeutic goals in treating CLI are to reduce the risk of adverse cardiovascular events, relieve ischemic pain, heal ulcers, prevent major amputation, and improve quality of life (QoL) and survival. These goals may be achieved by medical therapy, endovascular intervention, open surgery, or amputation and require a multidisciplinary approach including pain management, wound care, risk factors reduction, and treatment of comorbidities. No-option patients are potential candidates for the novel angiogenic therapies. The application of genetic, molecular, and cellular-based modalities, the so-called therapeutic angiogenesis, in the treatment of arterial obstructive diseases has not shown consistent efficacy. This article summarizes the current status related to the management of patients with CLI and discusses the current findings of the emerging modalities for therapeutic angiogenesis. PMID:23129733

  20. Therapeutic Recombinant Monoclonal Antibodies

    ERIC Educational Resources Information Center

    Bakhtiar, Ray

    2012-01-01

    During the last two decades, the rapid growth of biotechnology-derived techniques has led to a myriad of therapeutic recombinant monoclonal antibodies with significant clinical benefits. Recombinant monoclonal antibodies can be obtained from a number of natural sources such as animal cell cultures using recombinant DNA engineering. In contrast to…

  1. Developing Therapeutic Listening

    ERIC Educational Resources Information Center

    Lee, Billy; Prior, Seamus

    2013-01-01

    We present an experience-near account of the development of therapeutic listening in first year counselling students. A phenomenological approach was employed to articulate the trainees' lived experiences of their learning. Six students who had just completed a one-year postgraduate certificate in counselling skills were interviewed and the…

  2. Measuring Therapeutic Effectiveness.

    ERIC Educational Resources Information Center

    Callister, Sheldon L.

    In the recent past, there has been a great deal of effort directed toward developing techniques for documenting therapeutic outcome. Funding sources and the general public seem to be demanding more meaningful data which indicate, in a clear manner, whether or not the services they are paying for are of value. Mental health centers, like other…

  3. Antibody Therapeutics in Oncology

    PubMed Central

    Wold, Erik D; Smider, Vaughn V; Felding, Brunhilde H

    2016-01-01

    One of the newer classes of targeted cancer therapeutics is monoclonal antibodies. Monoclonal antibody therapeutics are a successful and rapidly expanding drug class due to their high specificity, activity, favourable pharmacokinetics, and standardized manufacturing processes. Antibodies are capable of recruiting the immune system to attack cancer cells through complement-dependent cytotoxicity or antibody dependent cellular cytotoxicity. In an ideal scenario the initial tumor cell destruction induced by administration of a therapeutic antibody can result in uptake of tumor associated antigens by antigen-presenting cells, establishing a prolonged memory effect. Mechanisms of direct tumor cell killing by antibodies include antibody recognition of cell surface bound enzymes to neutralize enzyme activity and signaling, or induction of receptor agonist or antagonist activity. Both approaches result in cellular apoptosis. In another and very direct approach, antibodies are used to deliver drugs to target cells and cause cell death. Such antibody drug conjugates (ADCs) direct cytotoxic compounds to tumor cells, after selective binding to cell surface antigens, internalization, and intracellular drug release. Efficacy and safety of ADCs for cancer therapy has recently been greatly advanced based on innovative approaches for site-specific drug conjugation to the antibody structure. This technology enabled rational optimization of function and pharmacokinetics of the resulting conjugates, and is now beginning to yield therapeutics with defined, uniform molecular characteristics, and unprecedented promise to advance cancer treatment. PMID:27081677

  4. On the Ribosomal Density that Maximizes Protein Translation Rate

    PubMed Central

    Zarai, Yoram; Margaliot, Michael; Tuller, Tamir

    2016-01-01

    During mRNA translation, several ribosomes attach to the same mRNA molecule simultaneously translating it into a protein. This pipelining increases the protein translation rate. A natural and important question is what ribosomal density maximizes the protein translation rate. Using mathematical models of ribosome flow along both a linear and a circular mRNA molecules we prove that typically the steady-state protein translation rate is maximized when the ribosomal density is one half of the maximal possible density. We discuss the implications of our results to endogenous genes under natural cellular conditions and also to synthetic biology. PMID:27861564

  5. Building hospital TQM teams: effective polarity analysis and maximization.

    PubMed

    Hurst, J B

    1996-09-01

    Building and maintaining teams require careful attention to and maximization of such polar opposites (¿polarities¿) as individual and team, directive and participatory leadership, task and process, and stability and change. Analyzing systematic elements of any polarity and listing blocks, supports, and flexible ways to maximize it will prevent the negative consequences that occur when treating a polarity like a solvable problem. Flexible, well-timed shifts from pole to pole result in the maximization of upside and minimization of downside consequences.

  6. SALT and Spelling Achievement.

    ERIC Educational Resources Information Center

    Nelson, Joan

    A study investigated the effects of suggestopedic accelerative learning and teaching (SALT) on the spelling achievement, attitudes toward school, and memory skills of fourth-grade students. Subjects were 20 male and 28 female students from two self-contained classrooms at Kennedy Elementary School in Rexburg, Idaho. The control classroom and the…

  7. Iowa Women of Achievement.

    ERIC Educational Resources Information Center

    Ohrn, Deborah Gore, Ed.

    1993-01-01

    This issue of the Goldfinch highlights some of Iowa's 20th century women of achievement. These women have devoted their lives to working for human rights, education, equality, and individual rights. They come from the worlds of politics, art, music, education, sports, business, entertainment, and social work. They represent Native Americans,…

  8. Schools Achieving Gender Equity.

    ERIC Educational Resources Information Center

    Revis, Emma

    This guide is designed to assist teachers presenting the Schools Achieving Gender Equity (SAGE) curriculum for vocational education students, which was developed to align gender equity concepts with the Kentucky Education Reform Act (KERA). Included in the guide are lesson plans for classes on the following topics: legal issues of gender equity,…

  9. Achieving Peace through Education.

    ERIC Educational Resources Information Center

    Clarken, Rodney H.

    While it is generally agreed that peace is desirable, there are barriers to achieving a peaceful world. These barriers are classified into three major areas: (1) an erroneous view of human nature; (2) injustice; and (3) fear of world unity. In a discussion of these barriers, it is noted that although the consciousness and conscience of the world…

  10. Explorations in achievement motivation

    NASA Technical Reports Server (NTRS)

    Helmreich, Robert L.

    1982-01-01

    Recent research on the nature of achievement motivation is reviewed. A three-factor model of intrinsic motives is presented and related to various criteria of performance, job satisfaction and leisure activities. The relationships between intrinsic and extrinsic motives are discussed. Needed areas for future research are described.

  11. Increasing Male Academic Achievement

    ERIC Educational Resources Information Center

    Jackson, Barbara Talbert

    2008-01-01

    The No Child Left Behind legislation has brought greater attention to the academic performance of American youth. Its emphasis on student achievement requires a closer analysis of assessment data by school districts. To address the findings, educators must seek strategies to remedy failing results. In a mid-Atlantic district of the Unites States,…

  12. Appraising Reading Achievement.

    ERIC Educational Resources Information Center

    Ediger, Marlow

    To determine quality sequence in pupil progress, evaluation approaches need to be used which guide the teacher to assist learners to attain optimally. Teachers must use a variety of procedures to appraise student achievement in reading, because no one approach is adequate. Appraisal approaches might include: (1) observation and subsequent…

  13. Cognitive Processes and Achievement.

    ERIC Educational Resources Information Center

    Hunt, Dennis; Randhawa, Bikkar S.

    For a group of 165 fourth- and fifth-grade students, four achievement test scores were correlated with success on nine tests designed to measure three cognitive functions: sustained attention, successive processing, and simultaneous processing. This experiment was designed in accordance with Luria's model of the three functional units of the…

  14. Graders' Mathematics Achievement

    ERIC Educational Resources Information Center

    Bond, John B.; Ellis, Arthur K.

    2013-01-01

    The purpose of this experimental study was to investigate the effects of metacognitive reflective assessment instruction on student achievement in mathematics. The study compared the performance of 141 students who practiced reflective assessment strategies with students who did not. A posttest-only control group design was employed, and results…

  15. Achieving All Our Ambitions

    ERIC Educational Resources Information Center

    Hartley, Tricia

    2009-01-01

    National learning and skills policy aims both to build economic prosperity and to achieve social justice. Participation in higher education (HE) has the potential to contribute substantially to both aims. That is why the Campaign for Learning has supported the ambition to increase the proportion of the working-age population with a Level 4…

  16. Improving Educational Achievement.

    ERIC Educational Resources Information Center

    New York University Education Quarterly, 1979

    1979-01-01

    This is a slightly abridged version of the report of the National Academy of Education panel, convened at the request of HEW Secretary Joseph Califano and Assistant Secretary for Education Mary F. Berry, to study recent declines in student achievement and methods of educational improvement. (SJL)

  17. The Achievement Club

    ERIC Educational Resources Information Center

    Rogers, Ibram

    2009-01-01

    When Gabrielle Carpenter became a guidance counselor in Northern Virginia nine years ago, she focused on the academic achievement gap and furiously tried to close it. At first, she was compelled by tremendous professional interest. However, after seeing her son lose his zeal for school, Carpenter joined forces with other parents to form an…

  18. Achievement in Problem Solving

    ERIC Educational Resources Information Center

    Friebele, David

    2010-01-01

    This Action Research Project is meant to investigate the effects of incorporating research-based instructional strategies into instruction and their subsequent effect on student achievement in the area of problem-solving. The two specific strategies utilized are the integration of manipulatives and increased social interaction on a regular basis.…

  19. Essays on Educational Achievement

    ERIC Educational Resources Information Center

    Ampaabeng, Samuel Kofi

    2013-01-01

    This dissertation examines the determinants of student outcomes--achievement, attainment, occupational choices and earnings--in three different contexts. The first two chapters focus on Ghana while the final chapter focuses on the US state of Massachusetts. In the first chapter, I exploit the incidence of famine and malnutrition that resulted to…

  20. Advancing Student Achievement

    ERIC Educational Resources Information Center

    Walberg, Herbert J.

    2010-01-01

    For the last half century, higher spending and many modern reforms have failed to raise the achievement of students in the United States to the levels of other economically advanced countries. A possible explanation, says Herbert Walberg, is that much current education theory is ill informed about scientific psychology, often drawing on fads and…

  1. NCLB: Achievement Robin Hood?

    ERIC Educational Resources Information Center

    Bracey, Gerald W.

    2008-01-01

    In his "Wall Street Journal" op-ed on the 25th of anniversary of "A Nation At Risk", former assistant secretary of education Chester E. Finn Jr. applauded the report for turning U.S. education away from equality and toward achievement. It was not surprising, then, that in mid-2008, Finn arranged a conference to examine the…

  2. A4 and CP symmetry and a model with maximal CP violation

    NASA Astrophysics Data System (ADS)

    Li, Cai-Chang; Lu, Jun-Nan; Ding, Gui-Jun

    2016-12-01

    We study a second CP symmetry compatible with the A4 flavor group, which interchanges the representations 1‧ and 1″. We analyze the lepton mixing patterns arising from the A4 and CP symmetry broken to residual subgroups Z3 and Z2 × CP in the charged lepton and neutrino sectors respectively. One phenomenologically viable mixing pattern is found, and it predicts maximal atmospheric mixing angle as well as maximal Dirac CP phase, trivial Majorana phases and the correlation sin2 ⁡θ12cos2 ⁡θ13 = 1 / 3. We construct a concrete model based on the A4 and CP symmetry, the above interesting mixing pattern is achieved, the observed charged lepton mass hierarchy is reproduced, and the reactor mixing angle θ13 is of the correct order.

  3. Maximizing information exchange between complex networks

    NASA Astrophysics Data System (ADS)

    West, Bruce J.; Geneston, Elvis L.; Grigolini, Paolo

    2008-10-01

    Science is not merely the smooth progressive interaction of hypothesis, experiment and theory, although it sometimes has that form. More realistically the scientific study of any given complex phenomenon generates a number of explanations, from a variety of perspectives, that eventually requires synthesis to achieve a deep level of insight and understanding. One such synthesis has created the field of out-of-equilibrium statistical physics as applied to the understanding of complex dynamic networks. Over the past forty years the concept of complexity has undergone a metamorphosis. Complexity was originally seen as a consequence of memory in individual particle trajectories, in full agreement with a Hamiltonian picture of microscopic dynamics and, in principle, macroscopic dynamics could be derived from the microscopic Hamiltonian picture. The main difficulty in deriving macroscopic dynamics from microscopic dynamics is the need to take into account the actions of a very large number of components. The existence of events such as abrupt jumps, considered by the conventional continuous time random walk approach to describing complexity was never perceived as conflicting with the Hamiltonian view. Herein we review many of the reasons why this traditional Hamiltonian view of complexity is unsatisfactory. We show that as a result of technological advances, which make the observation of single elementary events possible, the definition of complexity has shifted from the conventional memory concept towards the action of non-Poisson renewal events. We show that the observation of crucial processes, such as the intermittent fluorescence of blinking quantum dots as well as the brain’s response to music, as monitored by a set of electrodes attached to the scalp, has forced investigators to go beyond the traditional concept of complexity and to establish closer contact with the nascent field of complex networks. Complex networks form one of the most challenging areas of

  4. Engineered Hybrid Nanoparticles for On-Demand Diagnostics and Therapeutics.

    PubMed

    Nguyen, Kim Truc; Zhao, Yanli

    2015-12-15

    Together with the simultaneous development of nanomaterials and molecular biology, the bionano interface brings about various applications of hybrid nanoparticles in nanomedicine. The hybrid nanoparticles not only present properties of the individual components but also show synergistic effects for specialized applications. Thus, the development of advanced hybrid nanoparticles for targeted and on-demand diagnostics and therapeutics of diseases has rapidly become a hot research topic in nanomedicine. The research focus is to fabricate novel classes of programmable hybrid nanoparticles that are precisely engineered to maximize drug concentrations in diseased cells, leading to enhanced efficacy and reduced side effects of chemotherapy for the disease treatment. In particular, the hybrid nanoparticle platforms can simultaneously target diseased cells, enable the location to be imaged by optical methods, and release therapeutic drugs to the diseased cells by command. This Account specially discusses the rational fabrication of integrated hybrid nanoparticles and their applications in diagnostics and therapeutics. For diagnostics applications, hybrid nanoparticles can be utilized as imaging agents that enable detailed visualization at the molecular level. By the use of suitable targeting ligands incorporated on the nanoparticles, targeted optical imaging may be feasible with improved performance. Novel imaging techniques such as multiphoton excitation and photoacoustic imaging using near-infrared light have been developed using the intrinsic properties of particular nanoparticles. The use of longer-wavelength excitation sources allows deeper penetration into the human body for disease diagnostics and at the same time reduces the adverse effects on normal tissues. Furthermore, multimodal imaging techniques have been achieved by combining several types of components in nanoparticles, offering higher accuracy and better spatial views, with the aim of detecting life

  5. Therapeutic targets in malignant glioblastoma microenvironment.

    PubMed

    Barcellos-Hoff, Mary Helen; Newcomb, Elizabeth W; Zagzag, David; Narayana, Ashwatha

    2009-07-01

    There is considerable evidence that the tissue microenvironment can suppress cancer and that microenvironment disruption is required for cancer growth and progression. Distortion of the microenvironment by tumor cells can promote growth, recruit nonmalignant cells that provide physiological resources, and facilitate invasion. Compared with the variable routes taken by cells to become cancers, the response of normal tissue to cancer is relatively consistent such that controlling cancer may be more readily achieved indirectly via the microenvironment. Here, we discuss 3 ideas about how the microenvironment, consisting of a vasculature, inflammatory cells, immune cells, growth factors, and extracellular matrix, might provide therapeutic targets in glioblastoma (GBM) in the context of radiotherapy (RT): (1) viable therapeutic targets exist in the GBM microenvironment, (2) RT alters the microenvironment of tissues and tumors; and (3) a potential benefit may be achieved by targeting the microenvironments induced by RT.

  6. How fast-growing bacteria robustly tune their ribosome concentration to approximate growth-rate maximization.

    PubMed

    Bosdriesz, Evert; Molenaar, Douwe; Teusink, Bas; Bruggeman, Frank J

    2015-05-01

    Maximization of growth rate is an important fitness strategy for bacteria. Bacteria can achieve this by expressing proteins at optimal concentrations, such that resources are not wasted. This is exemplified for Escherichia coli by the increase of its ribosomal protein-fraction with growth rate, which precisely matches the increased protein synthesis demand. These findings and others have led to the hypothesis that E. coli aims to maximize its growth rate in environments that support growth. However, what kind of regulatory strategy is required for a robust, optimal adjustment of the ribosome concentration to the prevailing condition is still an open question. In the present study, we analyze the ppGpp-controlled mechanism of ribosome expression used by E. coli and show that this mechanism maintains the ribosomes saturated with its substrates. In this manner, overexpression of the highly abundant ribosomal proteins is prevented, and limited resources can be redirected to the synthesis of other growth-promoting enzymes. It turns out that the kinetic conditions for robust, optimal protein-partitioning, which are required for growth rate maximization across conditions, can be achieved with basic biochemical interactions. We show that inactive ribosomes are the most suitable 'signal' for tracking the intracellular nutritional state and for adjusting gene expression accordingly, as small deviations from optimal ribosome concentration cause a huge fractional change in ribosome inactivity. We expect to find this control logic implemented across fast-growing microbial species because growth rate maximization is a common selective pressure, ribosomes are typically highly abundant and thus costly, and the required control can be implemented by a small, simple network.

  7. Resistance Training for Explosive and Maximal Strength: Effects on Early and Late Rate of Force Development

    PubMed Central

    Oliveira, Felipe B.D.; Oliveira, Anderson S.C.; Rizatto, Guilherme F.; Denadai, Benedito S.

    2013-01-01

    The aim of the present study was to verify whether strength training designed to improve explosive and maximal strength would influence rate of force development (RFD). Nine men participated in a 6-week knee extensors resistance training program and 9 matched subjects participated as controls. Throughout the training sessions, subjects were instructed to perform isometric knee extension as fast and forcefully as possible, achieving at least 90% maximal voluntary contraction as quickly as possible, hold it for 5 s, and relax. Fifteen seconds separated each repetition (6-10), and 2 min separated each set (3). Pre- and post-training measurements were maximal isometric knee extensor (MVC), RFD, and RFD relative to MVC (i.e., %MVC·s-1) in different time-epochs varying from 10 to 250 ms from the contraction onset. The MVC (Nm) increased by 19% (275.8 ± 64.9 vs. 329.8 ± 60.4, p < 0.001) after training. In addition, RFD (Nm·s-1) increased by 22-28% at time epochs up to 20 ms from the contraction onset (0-10 ms = 1679. 1 ± 597.1 vs. 2159.2 ± 475.2, p < 0.001; 0-20 ms = 1958.79 ± 640.3 vs. 2398.4 ± 479.6, p < 0. 01), with no changes verified in later time epochs. However, no training effects on RFD were found for the training group when RFD was normalized to MVC. No changes were found in the control group. In conclusion, very early and late RFD responded differently to a short period of resistance training for explosive and maximal strength. This time-specific RFD adaptation highlight that resistance training programs should consider the specific neuromuscular demands of each sport. Key Points The time-specific RFD adaptation evoked by resistance training highlight that the method of analyzing RFD is essential for the interpretation of results. Confirming previous data, maximal contractile RFD and maximal force can be differently influenced by resistance training. Thus, the resistance training programs should consider the specific neuromuscular demands of each sport

  8. Sensitivity to conversational maxims in deaf and hearing children.

    PubMed

    Surian, Luca; Tedoldi, Mariantonia; Siegal, Michael

    2010-09-01

    We investigated whether access to a sign language affects the development of pragmatic competence in three groups of deaf children aged 6 to 11 years: native signers from deaf families receiving bimodal/bilingual instruction, native signers from deaf families receiving oralist instruction and late signers from hearing families receiving oralist instruction. The performance of these children was compared to a group of hearing children aged 6 to 7 years on a test designed to assess sensitivity to violations of conversational maxims. Native signers with bimodal/bilingual instruction were as able as the hearing children to detect violations that concern truthfulness (Maxim of Quality) and relevance (Maxim of Relation). On items involving these maxims, they outperformed both the late signers and native signers attending oralist schools. These results dovetail with previous findings on mindreading in deaf children and underscore the role of early conversational experience and instructional setting in the development of pragmatics.

  9. Optimizing Air Force Depot Programming to Maximize Operational Capability

    DTIC Science & Technology

    2014-03-27

    34 vii LINGO Component... LINGO Code with Notional Data by Model .................................. 45 RAND Formulation to Maximize Operational Capability...Minimize Cost ...................................................................................... 49 Appendix B –Final LINGO Code by Model

  10. Interpreting Negative Results in an Angle Maximization Problem.

    ERIC Educational Resources Information Center

    Duncan, David R.; Litwiller, Bonnie H.

    1995-01-01

    Presents a situation in which differential calculus is used with inverse trigonometric tangent functions to maximize an angle measure. A negative distance measure ultimately results, requiring a reconsideration of assumptions inherent in the initial figure. (Author/MKR)

  11. Exploring the interplay between the motivational climate and goal orientation in predicting maximal oxygen uptake.

    PubMed

    Buch, Robert; Nerstad, Christina G L; Aandstad, Anders; Säfvenbom, Reidar

    2016-01-01

    Drawing upon achievement goal theory, this study explored the interplay between the perceived motivational climate, achievement goals and objective measurements of maximal oxygen uptake (VO2max). The results of a study of 123 individuals from three Norwegian military academies revealed that under the condition of a high-performance orientation there is a stronger positive relationship between performance climate and VO2max for individuals reporting a low (rather than high)-mastery orientation. Furthermore, we found that for individuals with a high-mastery orientation there is a stronger positive relationship between mastery climate and VO2max for individuals reporting a low (rather than high)-performance orientation. These findings contribute to achievement goal theory by providing support for an interactionist person-environment fit perspective. Implications for future research and practice are discussed.

  12. On maximal parabolic regularity for non-autonomous parabolic operators

    NASA Astrophysics Data System (ADS)

    Disser, Karoline; ter Elst, A. F. M.; Rehberg, Joachim

    2017-02-01

    We consider linear inhomogeneous non-autonomous parabolic problems associated to sesquilinear forms, with discontinuous dependence of time. We show that for these problems, the property of maximal parabolic regularity can be extrapolated to time integrability exponents r ≠ 2. This allows us to prove maximal parabolic Lr-regularity for discontinuous non-autonomous second-order divergence form operators in very general geometric settings and to prove existence results for related quasilinear equations.

  13. Power Converters Maximize Outputs Of Solar Cell Strings

    NASA Technical Reports Server (NTRS)

    Frederick, Martin E.; Jermakian, Joel B.

    1993-01-01

    Microprocessor-controlled dc-to-dc power converters devised to maximize power transferred from solar photovoltaic strings to storage batteries and other electrical loads. Converters help in utilizing large solar photovoltaic arrays most effectively with respect to cost, size, and weight. Main points of invention are: single controller used to control and optimize any number of "dumb" tracker units and strings independently; power maximized out of converters; and controller in system is microprocessor.

  14. [Maximal anaerobic capacity of man in a modified Wingate test].

    PubMed

    Ushakov, B B; Chelnokova, E V

    1992-01-01

    We studied the possibility of using a 380B Siemens-Elema (Sweden) bicycle ergometer to determine the maximal anaerobic capacity of healthy subjects during a modified Wingate test. Exercise was performed under stable moment conditions, with calculation of braking resistance on the basis of the subjects lean body mass. The values of total work performed and maximal power may be used for comparative evaluation of physical work capacity in participants of training and rehabilitation programs.

  15. Maximally Permissive Composition of Actors in Ptolemy II

    DTIC Science & Technology

    2013-03-20

    Maximally Permissive Composition of Actors in Ptolemy II Marten Lohstroh Electrical Engineering and Computer Sciences University of California at...3. DATES COVERED 00-00-2013 to 00-00-2013 4. TITLE AND SUBTITLE Maximally Permissive Composition of Actors in Ptolemy II 5a. CONTRACT NUMBER...addresses the problem of handling dynamic data, in the statically typed, actor-oriented modeling environment called Ptolemy II. It explores the possibilities

  16. A new augmentation based algorithm for extracting maximal chordal subgraphs

    SciTech Connect

    Bhowmick, Sanjukta; Chen, Tzu-Yi; Halappanavar, Mahantesh

    2014-10-18

    If every cycle of a graph is chordal length greater than three then it contains an edge between non-adjacent vertices. Chordal graphs are of interest both theoretically, since they admit polynomial time solutions to a range of NP-hard graph problems, and practically, since they arise in many applications including sparse linear algebra, computer vision, and computational biology. A maximal chordal subgraph is a chordal subgraph that is not a proper subgraph of any other chordal subgraph. Existing algorithms for computing maximal chordal subgraphs depend on dynamically ordering the vertices, which is an inherently sequential process and therefore limits the algorithms’ parallelizability. In our paper we explore techniques to develop a scalable parallel algorithm for extracting a maximal chordal subgraph. We demonstrate that an earlier attempt at developing a parallel algorithm may induce a non-optimal vertex ordering and is therefore not guaranteed to terminate with a maximal chordal subgraph. We then give a new algorithm that first computes and then repeatedly augments a spanning chordal subgraph. After proving that the algorithm terminates with a maximal chordal subgraph, we then demonstrate that this algorithm is more amenable to parallelization and that the parallel version also terminates with a maximal chordal subgraph. That said, the complexity of the new algorithm is higher than that of the previous parallel algorithm, although the earlier algorithm computes a chordal subgraph which is not guaranteed to be maximal. Finally, we experimented with our augmentation-based algorithm on both synthetic and real-world graphs. We provide scalability results and also explore the effect of different choices for the initial spanning chordal subgraph on both the running time and on the number of edges in the maximal chordal subgraph.

  17. A new augmentation based algorithm for extracting maximal chordal subgraphs

    DOE PAGES

    Bhowmick, Sanjukta; Chen, Tzu-Yi; Halappanavar, Mahantesh

    2014-10-18

    If every cycle of a graph is chordal length greater than three then it contains an edge between non-adjacent vertices. Chordal graphs are of interest both theoretically, since they admit polynomial time solutions to a range of NP-hard graph problems, and practically, since they arise in many applications including sparse linear algebra, computer vision, and computational biology. A maximal chordal subgraph is a chordal subgraph that is not a proper subgraph of any other chordal subgraph. Existing algorithms for computing maximal chordal subgraphs depend on dynamically ordering the vertices, which is an inherently sequential process and therefore limits the algorithms’more » parallelizability. In our paper we explore techniques to develop a scalable parallel algorithm for extracting a maximal chordal subgraph. We demonstrate that an earlier attempt at developing a parallel algorithm may induce a non-optimal vertex ordering and is therefore not guaranteed to terminate with a maximal chordal subgraph. We then give a new algorithm that first computes and then repeatedly augments a spanning chordal subgraph. After proving that the algorithm terminates with a maximal chordal subgraph, we then demonstrate that this algorithm is more amenable to parallelization and that the parallel version also terminates with a maximal chordal subgraph. That said, the complexity of the new algorithm is higher than that of the previous parallel algorithm, although the earlier algorithm computes a chordal subgraph which is not guaranteed to be maximal. Finally, we experimented with our augmentation-based algorithm on both synthetic and real-world graphs. We provide scalability results and also explore the effect of different choices for the initial spanning chordal subgraph on both the running time and on the number of edges in the maximal chordal subgraph.« less

  18. Faculty achievement tracking tool.

    PubMed

    Pettus, Sarah; Reifschneider, Ellen; Burruss, Nancy

    2009-03-01

    Faculty development and scholarship is an expectation of nurse educators. Accrediting institutions, such as the Commission on Collegiate Nursing Education, the National League for Nursing Accrediting Commission, and the Higher Learning Commission, all have criteria regarding faculty achievement. A faculty achievement tracking tool (FATT) was developed to facilitate documentation of accreditation criteria attainment. Based on criteria from accrediting organizations, the roles that are addressed include scholarship, service, and practice. Definitions and benchmarks for the faculty as an aggregate are included. Undergoing reviews from different accrediting organizations, the FATT has been used once for accreditation of the undergraduate program and once for accreditation of the graduate program. The FATT is easy to use and has become an excellent adjunct for the preparation for accreditation reports. In addition, the FATT may be used for yearly evaluations, advancement, and merit.

  19. Project ACHIEVE final report

    SciTech Connect

    1997-06-13

    Project ACHIEVE was a math/science academic enhancement program aimed at first year high school Hispanic American students. Four high schools -- two in El Paso, Texas and two in Bakersfield, California -- participated in this Department of Energy-funded program during the spring and summer of 1996. Over 50 students, many of whom felt they were facing a nightmare future, were given the opportunity to work closely with personal computers and software, sophisticated calculators, and computer-based laboratories -- an experience which their regular academic curriculum did not provide. Math and science projects, exercises, and experiments were completed that emphasized independent and creative applications of scientific and mathematical theories to real world problems. The most important outcome was the exposure Project ACHIEVE provided to students concerning the college and technical-field career possibilities available to them.

  20. [Diagnostic and therapeutic management of Gram-negative infections].

    PubMed

    Bassetti, Matteo; Repetto, Ernestina

    2008-04-01

    Among Gram negative bacteria, Pseudomonas aeruginosa, the extended spectrum beta-lactamases (ESBL)-producing strains, Acinetobacter spp, in particular the multiresistant Acinetobacter baumannii, and Stenotrophomonas maltophilia are the most implicated micrororganisms in the ever more increasing problem of bacterial resistance. Possible solutions have to be searched, on one hand, in the use of new drugs but, on the other hand, in the re-evaluation of those already available drugs, possibly considering a new role for old drugs such as colistine and fosfomycin. Concerning ESBL-producing strains, the most recent data provided by EARSS report, in Italy, an incidence rate of 10-25 percent. The insurgence of an infection sustained by an ESBL+ve strain is strictly related to some well known risk factors, like the hospital stay itself, the disease severity, the length of stay in ICU, intubation and mechanical ventilation, catheterization, urinary or artery, and the past exposure to antibiotics. The raise in ESBL producing strains is closely related to the increasing use of cephalosporins. In the setting of a Gram negative infection, the combination therapy guarantees a higher coverage by reducing insurgence of possible resistance mechanisms, possibly resulting synergistic, and allowing a de-escalation therapy, although to this latter other problems, such as tolerability, costs and compliance, can be related. Another basic aspect to take into account of, in order to achieve the maximal efficacy of the antibiotic treatment, is the right dosage. In the idea to look for the best approach for the antibiotic treatment of a severe infection in a hospital setting, when a Gram negative aetiology is implicated, it can be possibly presumed that the right way consists in avoiding inappropriate antibiotic therapies, making therapeutic choices based on guidelines resulted from local epidemiological data, initiating the therapy promptly, avoiding excessive use of antibiotics, possibly

  1. Multistage vector (MSV) therapeutics.

    PubMed

    Wolfram, Joy; Shen, Haifa; Ferrari, Mauro

    2015-12-10

    One of the greatest challenges in the field of medicine is obtaining controlled distribution of systemically administered therapeutic agents within the body. Indeed, biological barriers such as physical compartmentalization, pressure gradients, and excretion pathways adversely affect localized delivery of drugs to pathological tissue. The diverse nature of these barriers requires the use of multifunctional drug delivery vehicles that can overcome a wide range of sequential obstacles. In this review, we explore the role of multifunctionality in nanomedicine by primarily focusing on multistage vectors (MSVs). The MSV is an example of a promising therapeutic platform that incorporates several components, including a microparticle, nanoparticles, and small molecules. In particular, these components are activated in a sequential manner in order to successively address transport barriers.

  2. Multistage vector (MSV) therapeutics

    PubMed Central

    Wolfram, Joy; Shen, Haifa; Ferrari, Mauro

    2015-01-01

    One of the greatest challenges in the field of medicine is obtaining controlled distribution of systemically administered therapeutic agents within the body. Indeed, biological barriers such as physical compartmentalization, pressure gradients, and excretion pathways adversely affect localized delivery of drugs to pathological tissue. The diverse nature of these barriers requires the use of multifunctional drug delivery vehicles that can overcome a wide range of sequential obstacles. In this review, we explore the role of multifunctionality in nanomedicine by primarily focusing on multistage vectors (MSVs). The MSV is an example of a promising therapeutic platform that incorporates several components, including a microparticle, nanoparticles, and small molecules. In particular, these components are activated in a sequential manner in order to successively address transport barriers. PMID:26264836

  3. Therapeutic Hypothermia for Neuroprotection

    PubMed Central

    Karnatovskaia, Lioudmila V.; Wartenberg, Katja E.

    2014-01-01

    The earliest recorded application of therapeutic hypothermia in medicine spans about 5000 years; however, its use has become widespread since 2002, following the demonstration of both safety and efficacy of regimens requiring only a mild (32°C-35°C) degree of cooling after cardiac arrest. We review the mechanisms by which hypothermia confers neuroprotection as well as its physiological effects by body system and its associated risks. With regard to clinical applications, we present evidence on the role of hypothermia in traumatic brain injury, intracranial pressure elevation, stroke, subarachnoid hemorrhage, spinal cord injury, hepatic encephalopathy, and neonatal peripartum encephalopathy. Based on the current knowledge and areas undergoing or in need of further exploration, we feel that therapeutic hypothermia holds promise in the treatment of patients with various forms of neurologic injury; however, additional quality studies are needed before its true role is fully known. PMID:24982721

  4. Therapeutic cancer vaccines

    PubMed Central

    Melief, Cornelis J.M.; van Hall, Thorbald; Arens, Ramon; Ossendorp, Ferry; van der Burg, Sjoerd H.

    2015-01-01

    The clinical benefit of therapeutic cancer vaccines has been established. Whereas regression of lesions was shown for premalignant lesions caused by HPV, clinical benefit in cancer patients was mostly noted as prolonged survival. Suboptimal vaccine design and an immunosuppressive cancer microenvironment are the root causes of the lack of cancer eradication. Effective cancer vaccines deliver concentrated antigen to both HLA class I and II molecules of DCs, promoting both CD4 and CD8 T cell responses. Optimal vaccine platforms include DNA and RNA vaccines and synthetic long peptides. Antigens of choice include mutant sequences, selected cancer testis antigens, and viral antigens. Drugs or physical treatments can mitigate the immunosuppressive cancer microenvironment and include chemotherapeutics, radiation, indoleamine 2,3-dioxygenase (IDO) inhibitors, inhibitors of T cell checkpoints, agonists of selected TNF receptor family members, and inhibitors of undesirable cytokines. The specificity of therapeutic vaccination combined with such immunomodulation offers an attractive avenue for the development of future cancer therapies. PMID:26214521

  5. Antioxidant therapeutics for schizophrenia.

    PubMed

    Reddy, Ravinder; Reddy, Rajiv

    2011-10-01

    Pharmaceutical treatment for millions worldwide who have schizophrenia is limited to a handful of antipsychotics. Despite the proven efficacy of these drugs, the overall outcome for schizophrenia remains suboptimal. Thus, alternative treatment options are urgently needed. One possible approach may be antioxidant therapy. The extant evidence for the role of oxidative stress in the pathophysiology of schizophrenia offers a hypothesis-derived therapeutic approach in the form of antioxidants. Vitamins C and E, for example, are suitable for human clinical trials because they are readily available, inexpensive, and relatively safe. Research into the therapeutic use of antioxidants in schizophrenia can be grouped into two main clusters: for psychopathology and for side effects. Of these studies, some have been carefully conducted, but majority are open label. Use of antioxidants for treatment-related side effects has been more extensively investigated. The totality of the evidence to date suggests that specific antioxidants, such as N-acetyl cysteine, may offer tangible benefits for the clinical syndrome of schizophrenia, and vitamin E may offer salutary effects on glycemic effects of antipsychotics. However, a great deal of fundamental clinical research remains to be done before antioxidants can be routinely used therapeutically for schizophrenia and treatment-related complications.

  6. Polycyclic peptide therapeutics.

    PubMed

    Baeriswyl, Vanessa; Heinis, Christian

    2013-03-01

    Owing to their excellent binding properties, high stability, and low off-target toxicity, polycyclic peptides are an attractive molecule format for the development of therapeutics. Currently, only a handful of polycyclic peptides are used in the clinic; examples include the antibiotic vancomycin, the anticancer drugs actinomycin D and romidepsin, and the analgesic agent ziconotide. All clinically used polycyclic peptide drugs are derived from natural sources, such as soil bacteria in the case of vancomycin, actinomycin D and romidepsin, or the venom of a fish-hunting coil snail in the case of ziconotide. Unfortunately, nature provides peptide macrocyclic ligands for only a small fraction of therapeutic targets. For the generation of ligands of targets of choice, researchers have inserted artificial binding sites into natural polycyclic peptide scaffolds, such as cystine knot proteins, using rational design or directed evolution approaches. More recently, large combinatorial libraries of genetically encoded bicyclic peptides have been generated de novo and screened by phage display. In this Minireview, the properties of existing polycyclic peptide drugs are discussed and related to their interesting molecular architectures. Furthermore, technologies that allow the development of unnatural polycyclic peptide ligands are discussed. Recent application of these technologies has generated promising results, suggesting that polycyclic peptide therapeutics could potentially be developed for a broad range of diseases.

  7. Proteases as therapeutics

    PubMed Central

    Craik, Charles S.; Page, Michael J.; Madison, Edwin L.

    2015-01-01

    Proteases are an expanding class of drugs that hold great promise. The U.S. FDA (Food and Drug Administration) has approved 12 protease therapies, and a number of next generation or completely new proteases are in clinical development. Although they are a well-recognized class of targets for inhibitors, proteases themselves have not typically been considered as a drug class despite their application in the clinic over the last several decades; initially as plasma fractions and later as purified products. Although the predominant use of proteases has been in treating cardiovascular disease, they are also emerging as useful agents in the treatment of sepsis, digestive disorders, inflammation, cystic fibrosis, retinal disorders, psoriasis and other diseases. In the present review, we outline the history of proteases as therapeutics, provide an overview of their current clinical application, and describe several approaches to improve and expand their clinical application. Undoubtedly, our ability to harness proteolysis for disease treatment will increase with our understanding of protease biology and the molecular mechanisms responsible. New technologies for rationally engineering proteases, as well as improved delivery options, will expand greatly the potential applications of these enzymes. The recognition that proteases are, in fact, an established class of safe and efficacious drugs will stimulate investigation of additional therapeutic applications for these enzymes. Proteases therefore have a bright future as a distinct therapeutic class with diverse clinical applications. PMID:21406063

  8. Therapeutic antibody engineering

    PubMed Central

    Parren, Paul W.H.I.; Lugovskoy, Alexey A.

    2013-01-01

    It is an important event in any knowledge area when an authority in the field decides that it is time to share all accumulated knowledge and learnings by writing a text book. This does not occur often in the biopharmaceutical industry, likely due to both the highly dynamic environment with tight timelines and policies and procedures at many pharmaceutical companies that hamper knowledge sharing. To take on a task like this successfully, a strong drive combined with a desire and talent to teach, but also an accommodating and stimulating environment is required. Luckily for those interested in therapeutic monoclonal antibodies, Dr. William R. Strohl decided about two years ago that the time was right to write a book about the past, present and future of these fascinating molecules. Dr. Strohl’s great expertise and passion for biotechnology is evident from his life story and his strong academic and industry track record. Dr. Strohl pioneered natural product biotechnology, first in academia as a full professor of microbiology and biochemistry at Ohio State University in Columbus, Ohio and later in industry while at Merck. Despite his notable advances in recombinant natural products, industry interest in this area waned and in 2001 Dr. Strohl sought new opportunities by entering the field of antibody therapeutics. He initiated antibody discovery through phage display at Merck, and then moved to Centocor Research and Development Inc. (now Janssen Biotech, Inc.) in 2008 to head Biologics Research, where he now directs the discovery of innovative therapeutic antibody candidates.

  9. In vivo muscle force and muscle power during near-maximal frog jumps

    PubMed Central

    Leonard, Timothy R.; Kaya, Motoshi; Herzog, Walter

    2017-01-01

    Frogs’ outstanding jumping ability has been associated with a high power output from the leg extensor muscles. Two main theories have emerged to explain the high power output of the frog leg extensor muscles, either (i) the contractile conditions of all leg extensor muscles are optimized in terms of muscle length and speed of shortening, or (ii) maximal power is achieved through a dynamic catch mechanism that uncouples fibre shortening from the corresponding muscle-tendon unit shortening. As in vivo instantaneous power generation in frog hind limb muscles during jumping has never been measured directly, it is hard to distinguish between the two theories. In this study, we determined the instantaneous variable power output of the plantaris longus (PL) of Lithobates pipiens (also known as Rana pipiens), by directly measuring the in vivo force, length change, and speed of muscle and fibre shortening in near maximal jumps. Fifteen near maximal jumps (> 50cm in horizontal distance) were analyzed. High instantaneous peak power in PL (536 ± 47 W/kg) was achieved by optimizing the contractile conditions in terms of the force-length but not the force-velocity relationship, and by a dynamic catch mechanism that decouples fascicle shortening from muscle-tendon unit shortening. We also found that the extra-muscular free tendon likely amplifies the peak power output of the PL by modulating fascicle shortening length and shortening velocity for optimum power output, but not by releasing stored energy through recoiling as the tendon only started recoiling after peak PL power had been achieved. PMID:28282405

  10. Asparaginase pharmacokinetics and implications of therapeutic drug monitoring.

    PubMed

    Asselin, Barbara; Rizzari, Carmelo

    2015-01-01

    Asparaginase is widely used in chemotherapeutic regimens for the treatment of acute lymphoblastic leukemia (ALL) and has led to a substantial improvement in cure rates, especially in children. Optimal therapeutic effects depend on a complete and sustained depletion of serum asparagine. However, pronounced interpatient variability, differences in pharmacokinetic properties between asparaginases and the formation of asparaginase antibodies make it difficult to predict the degree of asparagine depletion that will result from a given dose of asparaginase. The pharmacological principles underlying asparaginase therapy in the treatment of ALL are summarized in this article. A better understanding of the many factors that influence asparaginase activity and subsequent asparagine depletion may allow physicians to tailor treatment to the individual, maximizing therapeutic effect and minimizing treatment-related toxicity. Therapeutic drug monitoring provides a means of assessing a patient's current depletion status and can be used to better evaluate the potential benefit of treatment adjustments.

  11. Wind tunnel testing of a closed-loop wake deflection controller for wind farm power maximization

    NASA Astrophysics Data System (ADS)

    Campagnolo, Filippo; Petrović, Vlaho; Schreiber, Johannes; Nanos, Emmanouil M.; Croce, Alessandro; Bottasso, Carlo L.

    2016-09-01

    This paper presents results from wind tunnel tests aimed at evaluating a closed- loop wind farm controller for wind farm power maximization by wake deflection. Experiments are conducted in a large boundary layer wind tunnel, using three servo-actuated and sensorized wind turbine scaled models. First, we characterize the impact on steady-state power output of wake deflection, achieved by yawing the upstream wind turbines. Next, we illustrate the capability of the proposed wind farm controller to dynamically driving the upstream wind turbines to the optimal yaw misalignment setting.

  12. Further reduction of minimal first-met bad markings for the computationally efficient synthesis of a maximally permissive controller

    NASA Astrophysics Data System (ADS)

    Liu, GaiYun; Chao, Daniel Yuh

    2015-08-01

    To date, research on the supervisor design for flexible manufacturing systems focuses on speeding up the computation of optimal (maximally permissive) liveness-enforcing controllers. Recent deadlock prevention policies for systems of simple sequential processes with resources (S3PR) reduce the computation burden by considering only the minimal portion of all first-met bad markings (FBMs). Maximal permissiveness is ensured by not forbidding any live state. This paper proposes a method to further reduce the size of minimal set of FBMs to efficiently solve integer linear programming problems while maintaining maximal permissiveness using a vector-covering approach. This paper improves the previous work and achieves the simplest structure with the minimal number of monitors.

  13. Understanding the Causal Path between Action, Learning, and Solutions: Maximizing the Power of Action Learning to Achieve Great Results

    ERIC Educational Resources Information Center

    Leonard, H. Skipton

    2015-01-01

    Clients and practitioners alike are often confused about the ultimate purpose of action learning (AL). Because of the title of the method, many believe the primary goal of AL is to generate learning. This article clarifies the relationship between action, learning, and solutions. It also provides historical evidence to support the conclusion that…

  14. Maximizing the Achievement of African American Children in Kanawha (MAACK): Assessing Laboratory Support of a Community Initiative

    ERIC Educational Resources Information Center

    Hughes, Georgia K.

    2005-01-01

    The No Child Left Behind Act of 2001 (NCLB) began, upon its institution in 2002, to hold states more directly accountable for the progress of all students, including students of color and students of low socioeconomic status (SES). These groups of students have historically performed less well than their White or upper-class peers. In 2001, prior…

  15. The Therapeutic Roller Coaster

    PubMed Central

    CHU, JAMES A.

    1992-01-01

    Survivors of severe childhood abuse often encounter profound difficulties. In addition to posttraumatic and dissociative symptomatology, abuse survivors frequently have characterologic problems, particularly regarding self-care and maintaining relationships. Backgrounds of abuse, abandonment, and betrayal are often recapitulated and reenacted in therapy, making the therapeutic experience arduous and confusing for therapists and patients. Efforts must be directed at building an adequate psychotherapeutic foundation before undertaking exploration and abreaction of past traumatic experiences. This discussion sets out a model for treatment of childhood abuse survivors, describing stages of treatment and suggesting interventions. Common treatment dilemmas or "traps" are discussed, with recommendations for their resolution. PMID:22700116

  16. Achieving closure at Fernald

    SciTech Connect

    Bradburne, John; Patton, Tisha C.

    2001-02-25

    When Fluor Fernald took over the management of the Fernald Environmental Management Project in 1992, the estimated closure date of the site was more than 25 years into the future. Fluor Fernald, in conjunction with DOE-Fernald, introduced the Accelerated Cleanup Plan, which was designed to substantially shorten that schedule and save taxpayers more than $3 billion. The management of Fluor Fernald believes there are three fundamental concerns that must be addressed by any contractor hoping to achieve closure of a site within the DOE complex. They are relationship management, resource management and contract management. Relationship management refers to the interaction between the site and local residents, regulators, union leadership, the workforce at large, the media, and any other interested stakeholder groups. Resource management is of course related to the effective administration of the site knowledge base and the skills of the workforce, the attraction and retention of qualified a nd competent technical personnel, and the best recognition and use of appropriate new technologies. Perhaps most importantly, resource management must also include a plan for survival in a flat-funding environment. Lastly, creative and disciplined contract management will be essential to effecting the closure of any DOE site. Fluor Fernald, together with DOE-Fernald, is breaking new ground in the closure arena, and ''business as usual'' has become a thing of the past. How Fluor Fernald has managed its work at the site over the last eight years, and how it will manage the new site closure contract in the future, will be an integral part of achieving successful closure at Fernald.

  17. Revisiting age-predicted maximal heart rate: Can it be used as a valid measure of effort?

    PubMed Central

    Arena, Ross; Myers, Jonathan; Kaminsky, Leonard A.

    2016-01-01

    Introduction Despite high error ranges, age-predicted maximal heart rate (APMHR) is frequently used to gauge the achievement of adequate effort during an exercise test. The current analysis revisits this issue using the Fitness Registry and the Importance of Exercise: National Database (FRIEND Registry). Methods A total of 4,796 (63% male) apparently healthy subjects underwent a maximal cardiopulmonary exercise test on a treadmill. The mean age, maximal heart rate (HR), and maximal aerobic capacity of the cohort were 43 ± 12 years, 178 ± 15 beats per minute, and 36.1 ± 10.6 mlO2 · kg−1 · min−1, respectively. All subjects reached or surpassed a peak respiratory exchange ratio of 1.10. A linear regression equation using age to predict maximal HR was validated in 3,796 subjects and cross-validated in the remaining 1,000 (randomly assigned). Results The APMHR equation in the validation cohort was as follows: 209.3 – 0.72(age). The r value and standard error of estimate for this regression was 0.61 (P < .001) and 11.35 beats/min, respectively. A 1-sample t test revealed that the mean difference between actual maximal HR and APMHR was not significantly different from 0 (mean difference = 0.32, P = .43). However, Bland-Altman revealed high limits of agreement (upper 25.31 and lower −24.67) and a significant proportional bias. Discussion The APMHR equation derived from this analysis included a large cohort of apparently healthy individuals with maximal exercise effort validated by the criterion standard (ie, peak respiratory exchange ratio). Using APMHR in this capacity should be discouraged, and new approaches to gauging an individual's exercise effort should be explored. PMID:26920596

  18. Determination of maximal oxygen uptake using the bruce or a novel athlete-led protocol in a mixed population.

    PubMed

    Hamlin, Michael J; Draper, Nick; Blackwell, Gavin; Shearman, Jeremy P; Kimber, Nicholas E

    2012-03-01

    Treadmill tests for maximal oxygen uptake (V̇O2max) have traditionally used set speed and incline increments regardless of participants training or exercise background. The aim of this study was to determine the validity of a novel athlete-led protocol for determining maximal aerobic fitness in adults. Twenty-nine participants (21 male, 8 female, age 29.8 ± 9.5 y, BMI 24.4 ± 3.1, mean ± SD) from a variety of exercise backgrounds were asked to complete two maximal treadmill running tests (using the standard Bruce or a novel athlete-led protocol [ALP]) to volitional failure in a counter-balanced randomised cross-over trial one week apart. We found no substantial difference in maximal oxygen uptake (47.0 ± 9.1 and 46.8 ± 10.7 ml·kg(-1)·min(-1), mean ± SD for the ALP and Bruce protocols respectively), evidenced by the Spearman correlation coefficient of 0.93 (90% confidence limits, 0.88-0.96). However, compared to the Bruce protocol, participants completing the ALP protocol attained a substantially higher maximal heart rate (ALP = 182.8 ± 10.5, Bruce = 179.7 ± 8.7 beats·min(-1)). Additionally, using the Bruce protocol took a longer period of time (23.2 ± 17.0 s) compared to the ALP protocol. It seems that using either treadmill protocol will give you similar maximal oxygen uptake results. We suggest the ALP protocol which is simpler, quicker and probably better at achieving maximal heart rates is a useful alternative to the traditional Bruce protocol.

  19. Ventromedial frontal lobe damage disrupts value maximization in humans.

    PubMed

    Camille, Nathalie; Griffiths, Cathryn A; Vo, Khoi; Fellows, Lesley K; Kable, Joseph W

    2011-05-18

    Recent work in neuroeconomics has shown that regions in orbitofrontal and medial prefrontal cortex encode the subjective value of different options during choice. However, these electrophysiological and neuroimaging studies cannot demonstrate whether such signals are necessary for value-maximizing choices. Here we used a paradigm developed in experimental economics to empirically measure and quantify violations of utility theory in humans with damage to the ventromedial frontal lobe (VMF). We show that people with such damage are more likely to make choices that violate the generalized axiom of revealed preference, which is the one necessary and sufficient condition for choices to be consistent with value maximization. These results demonstrate that the VMF plays a critical role in value-maximizing choice.

  20. Evaluation of maximal respiratory pressures in myasthenia gravis. Prognostic value.

    PubMed

    Muñoz Fernández, Carmen; Díez Tejedor, Exuperio; Frank Garcia, Ana; Pino, Jose María; Pérez Conde, Concepción; Barreiro Tella, Pablo

    2004-01-01

    We assess the prognosis of mild forms of myasthenia gravis (MG) by maximal respiratory pressures (MRP) and single fiber electromyography (SFEMG). Fifty MG patients (12 form I, 21 form IIa and 17 form IIb) are valued by MRP [maximal expiratory pressure (MEP) and maximal inspiratory pressure (MIP)] and SFEMG, and are followed-up clinically. We have found in form I patients developing form IIa and form IIa worsening to form IIb, MEP and MIP mean relative values significantly lower than the rest. Inversely, IIb form patients improving to IIa form display MIP mean relative values higher than the rest; no difference appears with MEP. A reduction under 50% of fifth-percentile implies clinical deterioration in forms I and IIa, while its surpassing in IIb form suggests a tendency to improvement. No evident differences are found by SFEMG. MRP allow the follow-up of MG patients and could warn us of a clinical prognosis.

  1. Viscosity and density dependence during maximal flow in man.

    PubMed

    Staats, B A; Wilson, T A; Lai-Fook, S J; Rodarte, J R; Hyatt, R E

    1980-02-01

    Maximal expiratory flow curves were obtained from ten healthy subjects white breathing air and three other gas mixtures with different densities and viscosities. From these data, the magnitudes of the dependence of maximal flow on gas density and viscosity were obtained. The scaling laws of fluid mechanics, together with a model for the flow-limiting mechanism, were used to obtain a prediction of the relationship between the density dependence and the viscosity dependence of maximal flow. Although the data for individual subjects were too variable to allow a precise comparison with this prediction, the relationship between the mean density dependence and the mean viscosity dependence of all usbjects agreed with the theoretic prediction. This agreement supports the assumption, which is frequently made, that flow resistance rather than tissue visoelasticity is the dominant contributor to peripheral resistance. Information on the relationships between the pressure drop to the flow-limiting segment and flow, gas density and viscosity, and lung volume were also obtained.

  2. Matching and maximizing with variable-time schedules.

    PubMed Central

    DeCarlo, L T

    1985-01-01

    Pigeons were offered choices between a variable-time schedule that arranged reinforcers throughout the session and a variable-time schedule that arranged reinforcers only when the pigeon was spending time on it. The subjects could maximize the overall rate of reinforcement in this situation by biasing their time allocation towards the latter schedule. This arrangement provides an alternative to concurrent variable-interval variable-ratio schedules for testing whether animals maximize overall rates or match relative rates, and has the advantage of being free of the asymmetrical response requirements present with those schedules. The results were contrary to those predicted by maximizing: The bias it predicts did not appear. PMID:3981085

  3. Mechanisms of Plasma Therapeutics

    NASA Astrophysics Data System (ADS)

    Graves, David

    2015-09-01

    In this talk, I address research directed towards biomedical applications of atmospheric pressure plasma such as sterilization, surgery, wound healing and anti-cancer therapy. The field has seen remarkable growth in the last 3-5 years, but the mechanisms responsible for the biomedical effects have remained mysterious. It is known that plasmas readily create reactive oxygen species (ROS) and reactive nitrogen species (RNS). ROS and RNS (or RONS), in addition to a suite of other radical and non-radical reactive species, are essential actors in an important sub-field of aerobic biology termed ``redox'' (or oxidation-reduction) biology. It is postulated that cold atmospheric plasma (CAP) can trigger a therapeutic shielding response in tissue in part by creating a time- and space-localized, burst-like form of oxy-nitrosative stress on near-surface exposed cells through the flux of plasma-generated RONS. RONS-exposed surface layers of cells communicate to the deeper levels of tissue via a form of the ``bystander effect,'' similar to responses to other forms of cell stress. In this proposed model of CAP therapeutics, the plasma stimulates a cellular survival mechanism through which aerobic organisms shield themselves from infection and other challenges.

  4. Therapeutic endoscopy in gastroenterology.

    PubMed

    Celiński, K; Cichoz-Lach, H

    2007-08-01

    The role of therapeutic endoscopy in current gastroenterology is very important. Therapuetic endoscopy is useful in treatment of gastrointestinal bleeding. Endoscopic control of gastrointestinal bleeding includes the following procedures of haemostasis techniques: photocoagulation, electrocoagulation, thermocoagulation and injection method. Owing to these procedures mortality has significantly decreased. Endoscopic hemostasis eliminates the risk of surgery, is less expensive and better tolerated by patients. Colonoscopic polypectomy is a widely used technique. By removal of polyps the incidence of colon cancer can be decreased. The "hot biopsy" forceps can be used to excise polyps of up to 6 mm. Larger polyps can be removed safely by snare electrocautery and retrieved for histologic study. Endoscopic retrograde cholangiopancreatography has a therapeutic application designed to cut the sphincter of Oddi fibers of the distal common bile duct, what is indicated currently in choledocholithiasis and papillary stenosis with ascending cholangitis, acute gallstone pancreatitis. Endoscopic sphincterotomy in now an established procedure that is indicated in patients with common bile duct calculi. Endoscopic decompression of the biliary tree - dilatation benign structures of the biliary tree with baloon catheters and placement an internal endoprothesis allows the nonoperative decompression and significant palliation for patients with obstructing tumors.

  5. Person-centered Therapeutics

    PubMed Central

    Cloninger, C. Robert; Cloninger, Kevin M.

    2015-01-01

    A clinician’s effectiveness in treatment depends substantially on his or her attitude toward -- and understanding of -- the patient as a person endowed with self-awareness and the will to direct his or her own future. The assessment of personality in the therapeutic encounter is a crucial foundation for forming an effective working alliance with shared goals. Helping a person to reflect on their personality provides a mirror image of their strengths and weaknesses in adapting to life’s many challenges. The Temperament and Character Inventory (TCI) provides an effective way to describe personality thoroughly and to predict both the positive and negative aspects of health. Strengths and weaknesses in TCI personality traits allow strong predictions of individual differences of all aspects of well-being. Diverse therapeutic techniques, such as diet, exercise, mood self-regulation, meditation, or acts of kindness, influence health and personality development in ways that are largely indistinguishable from one another or from effective allopathic treatments. Hence the development of well-being appears to be the result of activating a synergistic set of mechanisms of well-being, which are expressed as fuller functioning, plasticity, and virtue in adapting to life’s challenges PMID:26052429

  6. Engineering therapeutic protein disaggregases

    PubMed Central

    Shorter, James

    2016-01-01

    Therapeutic agents are urgently required to cure several common and fatal neurodegenerative disorders caused by protein misfolding and aggregation, including amyotrophic lateral sclerosis (ALS), Parkinson’s disease (PD), and Alzheimer’s disease (AD). Protein disaggregases that reverse protein misfolding and restore proteins to native structure, function, and localization could mitigate neurodegeneration by simultaneously reversing 1) any toxic gain of function of the misfolded form and 2) any loss of function due to misfolding. Potentiated variants of Hsp104, a hexameric AAA+ ATPase and protein disaggregase from yeast, have been engineered to robustly disaggregate misfolded proteins connected with ALS (e.g., TDP-43 and FUS) and PD (e.g., α-synuclein). However, Hsp104 has no metazoan homologue. Metazoa possess protein disaggregase systems distinct from Hsp104, including Hsp110, Hsp70, and Hsp40, as well as HtrA1, which might be harnessed to reverse deleterious protein misfolding. Nevertheless, vicissitudes of aging, environment, or genetics conspire to negate these disaggregase systems in neurodegenerative disease. Thus, engineering potentiated human protein disaggregases or isolating small-molecule enhancers of their activity could yield transformative therapeutics for ALS, PD, and AD. PMID:27255695

  7. Nitrones as Therapeutics

    PubMed Central

    Floyd, Robert A.; Kopke, Richard D.; Choi, Chul-Hee; Foster, Steven B.; Doblas, Sabrina; Towner, Rheal A.

    2008-01-01

    Nitrones have the general chemical formula X-CH=NO-Y. They were first used to trap free radicals in chemical systems and then subsequently in biochemical systems. More recently several nitrones including PBN (α-phenyl-tert-butylnitrone) have been shown to have potent biological activity in many experimental animal models. Many diseases of aging including stroke, cancer development, Parkinson’s disease and Alzheimer’s disease are known to have enhanced levels of free radicals and oxidative stress. Some derivatives of PBN are significantly more potent than PBN and have undergone extensive commercial development in stroke. Recent research has shown that PBN-related nitrones also have anti-cancer activity in several experimental cancer models and have potential as therapeutics in some cancers. Also in recent observations nitrones have been shown to act synergistically in combination with antioxidants in the prevention of acute acoustic noise induced hearing loss. The mechanistic basis of the potent biological activity of PBN-related nitrones is not known. Even though PBN-related nitrones do decrease oxidative stress and oxidative damage, their potent biological anti-inflammatory activity and their ability to alter cellular signaling processes can not readily be explained by conventional notions of free radical trapping biochemistry. This review is focused on our observations and others where the use of selected nitrones as novel therapeutics have been evaluated in experimental models in the context of free radical biochemical and cellular processes considered important in pathologic conditions and age-related diseases. PMID:18793715

  8. Therapeutic targeting of replicative immortality.

    PubMed

    Yaswen, Paul; MacKenzie, Karen L; Keith, W Nicol; Hentosh, Patricia; Rodier, Francis; Zhu, Jiyue; Firestone, Gary L; Matheu, Ander; Carnero, Amancio; Bilsland, Alan; Sundin, Tabetha; Honoki, Kanya; Fujii, Hiromasa; Georgakilas, Alexandros G; Amedei, Amedeo; Amin, Amr; Helferich, Bill; Boosani, Chandra S; Guha, Gunjan; Ciriolo, Maria Rosa; Chen, Sophie; Mohammed, Sulma I; Azmi, Asfar S; Bhakta, Dipita; Halicka, Dorota; Niccolai, Elena; Aquilano, Katia; Ashraf, S Salman; Nowsheen, Somaira; Yang, Xujuan

    2015-12-01

    One of the hallmarks of malignant cell populations is the ability to undergo continuous proliferation. This property allows clonal lineages to acquire sequential aberrations that can fuel increasingly autonomous growth, invasiveness, and therapeutic resistance. Innate cellular mechanisms have evolved to regulate replicative potential as a hedge against malignant progression. When activated in the absence of normal terminal differentiation cues, these mechanisms can result in a state of persistent cytostasis. This state, termed "senescence," can be triggered by intrinsic cellular processes such as telomere dysfunction and oncogene expression, and by exogenous factors such as DNA damaging agents or oxidative environments. Despite differences in upstream signaling, senescence often involves convergent interdependent activation of tumor suppressors p53 and p16/pRB, but can be induced, albeit with reduced sensitivity, when these suppressors are compromised. Doses of conventional genotoxic drugs required to achieve cancer cell senescence are often much lower than doses required to achieve outright cell death. Additional therapies, such as those targeting cyclin dependent kinases or components of the PI3K signaling pathway, may induce senescence specifically in cancer cells by circumventing defects in tumor suppressor pathways or exploiting cancer cells' heightened requirements for telomerase. Such treatments sufficient to induce cancer cell senescence could provide increased patient survival with fewer and less severe side effects than conventional cytotoxic regimens. This positive aspect is countered by important caveats regarding senescence reversibility, genomic instability, and paracrine effects that may increase heterogeneity and adaptive resistance of surviving cancer cells. Nevertheless, agents that effectively disrupt replicative immortality will likely be valuable components of new combinatorial approaches to cancer therapy.

  9. Therapeutic targeting of replicative immortality

    PubMed Central

    Yaswen, Paul; MacKenzie, Karen L.; Keith, W. Nicol; Hentosh, Patricia; Rodier, Francis; Zhu, Jiyue; Firestone, Gary L.; Matheu, Ander; Carnero, Amancio; Bilsland, Alan; Sundin, Tabetha; Honoki, Kanya; Fujii, Hiromasa; Georgakilas, Alexandros G.; Amedei, Amedeo; Amin, Amr; Helferich, Bill; Boosani, Chandra S.; Guha, Gunjan; Ciriolo, Maria Rosa; Chen, Sophie; Mohammed, Sulma I.; Azmi, Asfar S.; Bhakta, Dipita; Halicka, Dorota; Niccolai, Elena; Aquilano, Katia; Ashraf, S. Salman; Nowsheen, Somaira; Yang, Xujuan

    2015-01-01

    One of the hallmarks of malignant cell populations is the ability to undergo continuous proliferation. This property allows clonal lineages to acquire sequential aberrations that can fuel increasingly autonomous growth, invasiveness, and therapeutic resistance. Innate cellular mechanisms have evolved to regulate replicative potential as a hedge against malignant progression. When activated in the absence of normal terminal differentiation cues, these mechanisms can result in a state of persistent cytostasis. This state, termed “senescence,” can be triggered by intrinsic cellular processes such as telomere dysfunction and oncogene expression, and by exogenous factors such as DNA damaging agents or oxidative environments. Despite differences in upstream signaling, senescence often involves convergent interdependent activation of tumor suppressors p53 and p16/pRB, but can be induced, albeit with reduced sensitivity, when these suppressors are compromised. Doses of conventional genotoxic drugs required to achieve cancer cell senescence are often much lower than doses required to achieve outright cell death. Additional therapies, such as those targeting cyclin dependent kinases or components of the PI3K signaling pathway, may induce senescence specifically in cancer cells by circumventing defects in tumor suppressor pathways or exploiting cancer cells’ heightened requirements for telomerase. Such treatments sufficient to induce cancer cell senescence could provide increased patient survival with fewer and less severe side effects than conventional cytotoxic regimens. This positive aspect is countered by important caveats regarding senescence reversibility, genomic instability, and paracrine effects that may increase heterogeneity and adaptive resistance of surviving cancer cells. Nevertheless, agents that effectively disrupt replicative immortality will likely be valuable components of new combinatorial approaches to cancer therapy. PMID:25869441

  10. Influence of central obesity in estimating maximal oxygen uptake

    PubMed Central

    de Souza e Silva, Christina Grüne; Franklin, Barry A.; de Araújo, Claudio Gil Soares

    2016-01-01

    OBJECTIVE: To assess the influence of central obesity on the magnitude of the error of estimate of maximal oxygen uptake in maximal cycling exercise testing. METHOD: A total of 1,715 adults (68% men) between 18-91 years of age underwent cardiopulmonary exercise testing using a progressive protocol to volitional fatigue. Subjects were stratified by central obesity into three quartile ranges: Q1, Q2-3 and Q4. Maximal oxygen uptake [mL.(kg.min)-1] was estimated by the attained maximal workload and body weight using gender- and population-specific equations. The error of estimate [mL.(kg.min)-1] and percent error between measured and estimated maximal oxygen uptake values were compared among obesity quartile ranges. RESULTS: The error of estimate and percent error differed (mean ± SD) for men (Q1=1.3±3.7 and 2.0±10.4; Q2-3=0.5±3.1 and -0.5±13.0; and Q4=-0.3±2.8 and -4.5±15.8 (p<0.05)) and for women (Q1=1.6±3.3 and 3.6±10.2; Q2-3=0.4±2.7 and -0.4±11.8; and Q4=-0.9±2.3 and -10.0±22.7 (p<0.05)). CONCLUSION: Central obesity directly influences the magnitude of the error of estimate of maximal oxygen uptake and should be considered when direct expired gas analysis is unavailable. PMID:27982162

  11. Cardiovascular consequences of bed rest: effect on maximal oxygen uptake

    NASA Technical Reports Server (NTRS)

    Convertino, V. A.

    1997-01-01

    Maximal oxygen uptake (VO2max) is reduced in healthy individuals confined to bed rest, suggesting it is independent of any disease state. The magnitude of reduction in VO2max is dependent on duration of bed rest and the initial level of aerobic fitness (VO2max), but it appears to be independent of age or gender. Bed rest induces an elevated maximal heart rate which, in turn, is associated with decreased cardiac vagal tone, increased sympathetic catecholamine secretion, and greater cardiac beta-receptor sensitivity. Despite the elevation in heart rate, VO2max is reduced primarily from decreased maximal stroke volume and cardiac output. An elevated ejection fraction during exercise following bed rest suggests that the lower stroke volume is not caused by ventricular dysfunction but is primarily the result of decreased venous return associated with lower circulating blood volume, reduced central venous pressure, and higher venous compliance in the lower extremities. VO2max, stroke volume, and cardiac output are further compromised by exercise in the upright posture. The contribution of hypovolemia to reduced cardiac output during exercise following bed rest is supported by the close relationship between the relative magnitude (% delta) and time course of change in blood volume and VO2max during bed rest, and also by the fact that retention of plasma volume is associated with maintenance of VO2max after bed rest. Arteriovenous oxygen difference during maximal exercise is not altered by bed rest, suggesting that peripheral mechanisms may not contribute significantly to the decreased VO2max. However reduction in baseline and maximal muscle blood flow, red blood cell volume, and capillarization in working muscles represent peripheral mechanisms that may contribute to limited oxygen delivery and, subsequently, lowered VO2max. Thus, alterations in cardiac and vascular functions induced by prolonged confinement to bed rest contribute to diminution of maximal oxygen uptake

  12. Materials innovation for co-delivery of diverse therapeutic cargos

    PubMed Central

    Godsey, Megan E; Suryaprakash, Smruthi; Leong, Kam W

    2014-01-01

    Co-delivery is a rapidly growing sector of drug delivery that aspires to enhance therapeutic efficacy through controlled delivery of diverse therapeutic cargoes with synergistic activities. It requires the design of carriers capable of simultaneously transporting to and releasing multiple therapeutics at a disease site. Co-delivery has arisen from the emerging trend of combination therapy, where treatment with two or more therapeutics at the same time can succeed where single therapeutics fail. However, conventional combination therapy offers little control over achieving an optimized therapeutic ratio at the target site. Co-delivery via inclusion of multiple therapeutic cargos within the same carrier addresses this issue by not only ensuring delivery of both therapeutics to the same cell, but also offering a platform for control of the delivery process, from loading to release. Co-delivery systems have been formulated using a number of carriers previously developed for single-therapeutic delivery. Liposomes, polymeric micelles, PLGA nanoparticles, and dendrimers have all been adapted for co-delivery. Much of the effort focuses on dealing with drugs having dissimilar properties, increasing loading efficiencies, and controlling loading and release ratios. In this review, we highlight the innovations in carrier designs and formulations to deliver combination cargoes of drug/drug, drug/siRNA, and drug/pDNA toward disease therapy. With rapid advances in mechanistic understanding of interrelating molecular pathways and development of molecular medicine, the future of co-delivery will become increasingly promising and prominent. PMID:24818000

  13. Achievement Goals and Achievement Emotions: A Meta-Analysis

    ERIC Educational Resources Information Center

    Huang, Chiungjung

    2011-01-01

    This meta-analysis synthesized 93 independent samples (N = 30,003) in 77 studies that reported in 78 articles examining correlations between achievement goals and achievement emotions. Achievement goals were meaningfully associated with different achievement emotions. The correlations of mastery and mastery approach goals with positive achievement…

  14. Classification of maximally supersymmetric backgrounds in supergravity theories

    NASA Astrophysics Data System (ADS)

    Louis, Jan; Lüst, Severin

    2017-02-01

    We study maximally supersymmetric solutions of all gauged or deformed supergravity theories in D ≥ 3 space-time dimensions. For vanishing background fluxes the space-time background has to be either Minkowski or anti-de Sitter. We derive a simple criterion for the existence of solutions with non-trivial fluxes and determine all supergravities that satisfy it. We show that their solutions coincide with those of the corresponding ungauged theories and conclude that the known list of maximally supersymmetric solutions is exhaustive.

  15. Maximizing the Divergence from a Hierarchical Model of Quantum States

    NASA Astrophysics Data System (ADS)

    Weis, Stephan; Knauf, Andreas; Ay, Nihat; Zhao, Ming-Jing

    2015-03-01

    We study many-party correlations quantified in terms of the Umegaki relative entropy (divergence) from a Gibbs family known as a hierarchical model. We derive these quantities from the maximum-entropy principle which was used earlier to define the closely related irreducible correlation. We point out the differences between quantum states and probability vectors which exist in hierarchical models, in the divergence from a hierarchical model and in local maximizers of this divergence. The differences are, respectively, missing factorization, discontinuity and reduction of uncertainty. We discuss global maximizers of the mutual information of separable qubit states.

  16. Remarks on the information entropy maximization method and extended thermodynamics

    NASA Astrophysics Data System (ADS)

    Eu, Byung Chan

    1998-04-01

    The information entropy maximization method was applied by Jou et al. [J. Phys. A 17, 2799 (1984)] to heat conduction in the past. Advancing this method one more step, Nettleton [J. Chem. Phys. 106, 10311 (1997)] combined the method with a projection operator technique to derive a set of evolution equations for macroscopic variables from the Liouville equation for a simple liquid, and a claim was made that the method provides a statistical mechanical theory basis of irreversible processes and, in particular, of extended thermodynamics which is consistent with the laws of thermodynamics. This line of information entropy maximization method is analyzed from the viewpoint of the laws of thermodynamics in this paper.

  17. The relationship between patients' educational level and therapeutic process in an acute patient therapeutic community.

    PubMed

    Isohanni, I; Nieminen, P; Isohanni, M

    1997-01-01

    Traditional custodial care in mental hospitals has given way to brief hospitalizations and a variety of active inpatient treatment milieus, eg, therapeutic communities. But can only well-educated patients utilize this kind of complex, even demanding form of psychosocial care? A total of 1,538 patients and their first admissions from 1977 to 1993 at a closed therapeutic community ward at the Department of Psychiatry, University of Oulu (Finland) were assessed to analyze the association of the patient's educational level with some treatment and outcome characteristics. Educational levels were non-professional education (46% of all patients), lower professional (39%) and higher professional education (15%). There were no statistically significant differences in the treatment and outcome variables of patients in any educational level. The result indicates the achievement of one treatment goal on the therapeutic community model, ie, patient equality in spite of different educational status. This result may be especially important for less educated persons.

  18. Therapeutic interventions in acute stroke.

    PubMed Central

    Lees, K R

    1992-01-01

    1. Potential therapies for ischaemic stroke include agents to reduce oedema, to improve cerebral perfusion, to reduce excitotoxic damage, to minimise free-radical induced injury and to reduce complications such as deep venous thrombosis. 2. Of the anti-oedema drugs, steroids are ineffective and possibly dangerous; intravenous glycerol is unproven. 3. Haemodilution to reduce whole blood viscosity and improve perfusion is ineffective. Thrombolytic drugs have not been adequately tested but several randomised multicentre trials are now commencing. Early treatment and CT scanning are essential. 4. Anticoagulants and antiplatelet drugs may have wide applicability but have not been tested in the acute phase of stroke. A multi-centre trial will address this issue. 5. Neuronal cytoprotection offers exciting prospects for acute stroke treatment. Antagonists of glutamate at the NMDA receptor, calcium and sodium channel blocking agents and free radical scavenging drugs have potent effects experimentally. Several agents are now reaching clinical trials. The calcium antagonist nimodipine has been disappointing in large scale trials but some studies were flawed by late treatment. 6. Successful treatment of acute stroke is likely to combine several approaches. 7. Therapeutic trials in stroke must include CT scanning, early treatment and a multicentre approach to achieve large numbers of patients. PMID:1493080

  19. A six sigma approach to maximizing productivity in the cardiac cath lab.

    PubMed

    LeBlanc, Faye; McLauglin, Sandy; Freedman, John; Sager, Rosalie; Weissman, Marie

    2004-01-01

    Cardiac catheterization laboratories represent one of the most significant capital investments for hospitals. Historically, hospitals could achieve an economic return fairly rapidly on this capital investment because of the relatively high contribution margin on many of the procedures performed in the department. However, recent changes in DRG assignments, declines in Medicare reimbursement, and the advent of new technologies, such as drug-coated stents, pose a threat to achieving planned economic return. In response, many hospitals are pursuing strategies to improve throughput in the cardiac cath lab and maximize the number of procedures performed. The case example in this article describes how a busy cardiac catheterization lab in the southeastern United States successfully applied the Six Sigma methodology to improving productivity and increasing available capacity.

  20. Algal biofuels from urban wastewaters: maximizing biomass yield using nutrients recycled from hydrothermal processing of biomass.

    PubMed

    Selvaratnam, T; Pegallapati, A K; Reddy, H; Kanapathipillai, N; Nirmalakhandan, N; Deng, S; Lammers, P J

    2015-04-01

    Recent studies have proposed algal cultivation in urban wastewaters for the dual purpose of waste treatment and bioenergy production from the resulting biomass. This study proposes an enhancement to this approach that integrates cultivation of an acidophilic strain, Galdieria sulphuraria 5587.1, in a closed photobioreactor (PBR); hydrothermal liquefaction (HTL) of the wet algal biomass; and recirculation of the nutrient-rich aqueous product (AP) of HTL to the PBR to achieve higher biomass productivity than that could be achieved with raw wastewater. The premise is that recycling nutrients in the AP can maintain optimal C, N and P levels in the PBR to maximize biomass growth to increase energy returns. Growth studies on the test species validated growth on AP derived from HTL at temperatures from 180 to 300°C. Doubling N and P concentrations over normal levels in wastewater resulted in biomass productivity gains of 20-25% while N and P removal rates also doubled.

  1. Optimal Battery Utilization Over Lifetime for Parallel Hybrid Electric Vehicle to Maximize Fuel Economy

    SciTech Connect

    Patil, Chinmaya; Naghshtabrizi, Payam; Verma, Rajeev; Tang, Zhijun; Smith, Kandler; Shi, Ying

    2016-08-01

    This paper presents a control strategy to maximize fuel economy of a parallel hybrid electric vehicle over a target life of the battery. Many approaches to maximizing fuel economy of parallel hybrid electric vehicle do not consider the effect of control strategy on the life of the battery. This leads to an oversized and underutilized battery. There is a trade-off between how aggressively to use and 'consume' the battery versus to use the engine and consume fuel. The proposed approach addresses this trade-off by exploiting the differences in the fast dynamics of vehicle power management and slow dynamics of battery aging. The control strategy is separated into two parts, (1) Predictive Battery Management (PBM), and (2) Predictive Power Management (PPM). PBM is the higher level control with slow update rate, e.g. once per month, responsible for generating optimal set points for PPM. The considered set points in this paper are the battery power limits and State Of Charge (SOC). The problem of finding the optimal set points over the target battery life that minimize engine fuel consumption is solved using dynamic programming. PPM is the lower level control with high update rate, e.g. a second, responsible for generating the optimal HEV energy management controls and is implemented using model predictive control approach. The PPM objective is to find the engine and battery power commands to achieve the best fuel economy given the battery power and SOC constraints imposed by PBM. Simulation results with a medium duty commercial hybrid electric vehicle and the proposed two-level hierarchical control strategy show that the HEV fuel economy is maximized while meeting a specified target battery life. On the other hand, the optimal unconstrained control strategy achieves marginally higher fuel economy, but fails to meet the target battery life.

  2. Learning to maximize reward rate: a model based on semi-Markov decision processes

    PubMed Central

    Khodadadi, Arash; Fakhari, Pegah; Busemeyer, Jerome R.

    2014-01-01

    When animals have to make a number of decisions during a limited time interval, they face a fundamental problem: how much time they should spend on each decision in order to achieve the maximum possible total outcome. Deliberating more on one decision usually leads to more outcome but less time will remain for other decisions. In the framework of sequential sampling models, the question is how animals learn to set their decision threshold such that the total expected outcome achieved during a limited time is maximized. The aim of this paper is to provide a theoretical framework for answering this question. To this end, we consider an experimental design in which each trial can come from one of the several possible “conditions.” A condition specifies the difficulty of the trial, the reward, the penalty and so on. We show that to maximize the expected reward during a limited time, the subject should set a separate value of decision threshold for each condition. We propose a model of learning the optimal value of decision thresholds based on the theory of semi-Markov decision processes (SMDP). In our model, the experimental environment is modeled as an SMDP with each “condition” being a “state” and the value of decision thresholds being the “actions” taken in those states. The problem of finding the optimal decision thresholds then is cast as the stochastic optimal control problem of taking actions in each state in the corresponding SMDP such that the average reward rate is maximized. Our model utilizes a biologically plausible learning algorithm to solve this problem. The simulation results show that at the beginning of learning the model choses high values of decision threshold which lead to sub-optimal performance. With experience, however, the model learns to lower the value of decision thresholds till finally it finds the optimal values. PMID:24904252

  3. Learning to maximize reward rate: a model based on semi-Markov decision processes.

    PubMed

    Khodadadi, Arash; Fakhari, Pegah; Busemeyer, Jerome R

    2014-01-01

    WHEN ANIMALS HAVE TO MAKE A NUMBER OF DECISIONS DURING A LIMITED TIME INTERVAL, THEY FACE A FUNDAMENTAL PROBLEM: how much time they should spend on each decision in order to achieve the maximum possible total outcome. Deliberating more on one decision usually leads to more outcome but less time will remain for other decisions. In the framework of sequential sampling models, the question is how animals learn to set their decision threshold such that the total expected outcome achieved during a limited time is maximized. The aim of this paper is to provide a theoretical framework for answering this question. To this end, we consider an experimental design in which each trial can come from one of the several possible "conditions." A condition specifies the difficulty of the trial, the reward, the penalty and so on. We show that to maximize the expected reward during a limited time, the subject should set a separate value of decision threshold for each condition. We propose a model of learning the optimal value of decision thresholds based on the theory of semi-Markov decision processes (SMDP). In our model, the experimental environment is modeled as an SMDP with each "condition" being a "state" and the value of decision thresholds being the "actions" taken in those states. The problem of finding the optimal decision thresholds then is cast as the stochastic optimal control problem of taking actions in each state in the corresponding SMDP such that the average reward rate is maximized. Our model utilizes a biologically plausible learning algorithm to solve this problem. The simulation results show that at the beginning of learning the model choses high values of decision threshold which lead to sub-optimal performance. With experience, however, the model learns to lower the value of decision thresholds till finally it finds the optimal values.

  4. Spatiotemporal laser speckle contrast analysis for blood flow imaging with maximized speckle contrast.

    PubMed

    Qiu, Jianjun; Li, Pengcheng; Luo, Weihua; Wang, Jia; Zhang, Hongyan; Luo, Qingming

    2010-01-01

    Laser speckle contrast imaging is a technique used for imaging blood flow without scanning. Though several studies have attempted to combine spatial and temporal statistics of laser speckle images for reducing image noise as well as preserving acceptable spatiotemporal resolution, the statistical accuracy of these spatiotemporal methods has not been thoroughly compared. Through numerical simulation and animal experiments, this study investigates the changes in the mean speckle contrast values and the relative noise of the speckle contrast images computed by these methods with various numbers of frames and spatial windows. The simulation results show that the maximum relative error of the mean speckle contrast computed by the spatiotemporal laser speckle contrast analysis (STLASCA) method, in which the speckle contrast images are computed by analyzing the 3-D spatiotemporal speckle image cube, is approximately 5%, while it is higher than 13% for other methods. Changes in the mean speckle contrast values and the relative noise computed by these methods for animal experiment data are consistent with the simulation results. Our results demonstrate that STLASCA achieves more accurate speckle contrast, and suggest that STLASCA most effectively utilizes the number of pixels, thus achieving maximized speckle contrast, and thereby maximizing the variation of the laser speckle contrast image.

  5. Spatiotemporal laser speckle contrast analysis for blood flow imaging with maximized speckle contrast

    NASA Astrophysics Data System (ADS)

    Qiu, Jianjun; Li, Pengcheng; Luo, Weihua; Wang, Jia; Zhang, Hongyan; Luo, Qingming

    2010-01-01

    Laser speckle contrast imaging is a technique used for imaging blood flow without scanning. Though several studies have attempted to combine spatial and temporal statistics of laser speckle images for reducing image noise as well as preserving acceptable spatiotemporal resolution, the statistical accuracy of these spatiotemporal methods has not been thoroughly compared. Through numerical simulation and animal experiments, this study investigates the changes in the mean speckle contrast values and the relative noise of the speckle contrast images computed by these methods with various numbers of frames and spatial windows. The simulation results show that the maximum relative error of the mean speckle contrast computed by the spatiotemporal laser speckle contrast analysis (STLASCA) method, in which the speckle contrast images are computed by analyzing the 3-D spatiotemporal speckle image cube, is approximately 5%, while it is higher than 13% for other methods. Changes in the mean speckle contrast values and the relative noise computed by these methods for animal experiment data are consistent with the simulation results. Our results demonstrate that STLASCA achieves more accurate speckle contrast, and suggest that STLASCA most effectively utilizes the number of pixels, thus achieving maximized speckle contrast, and thereby maximizing the variation of the laser speckle contrast image.

  6. Different types of compression clothing do not increase sub-maximal and maximal endurance performance in well-trained athletes.

    PubMed

    Sperlich, Billy; Haegele, Matthias; Achtzehn, Silvia; Linville, John; Holmberg, Hans-Christer; Mester, Joachim

    2010-04-01

    Three textiles with increasing compressive surface were compared with non-compressive conventional clothing on physiological and perceptual variables during sub-maximal and maximal running. Fifteen well-trained endurance athletes (mean+/-s: age 27.1+/-4.8 years, VO(2max) 63.7+/-4.9 ml x min(-1) x kg(-1)) performed four sub-maximal (approximately 70% VO(2max)) and maximal tests with and without different compression stockings, tights, and whole-body compression suits. Arterial lactate concentration, oxygen saturation and partial pressure, pH, oxygen uptake, and ratings of muscle soreness were recorded before, during, and after all tests. In addition, we assessed time to exhaustion. Sub-maximal (P=0.22) and maximal oxygen uptake (P=0.26), arterial lactate concentration (P=0.16; 0.20), pH (P=0.23; 0.46), oxygen saturation (P=0.13; 0.26), and oxygen partial pressure (P=0.09; 0.20) did not differ between the types of clothing (effect sizes=0.00-0.45). Ratings of perceived exertion (P=0.10; 0.15), muscle soreness (P=0.09; 0.10) and time to exhaustion (P=0.16) were also unaffected by the different clothing (effect sizes=0.28-0.85). This was the first study to evaluate the effect on endurance performance of different types of compression clothing with increasing amounts of compressive surface. Overall, there were no performance benefits when using the compression garments.

  7. Therapeutic oligonucleotides and delivery technologies: Research topics in Japan.

    PubMed

    Murakami, Masahiro

    2016-01-01

    Oligonucleotides have been gaining considerable attention as promising and effective candidate therapeutics against various diseases. This special issue is aimed at providing a better understanding of the recent progress in the development of oligonucleotide-based therapeutics to encourage further research and innovation in this field to achieve these advancements. Several Japanese scientists have been invited to contribute to this issue by describing their recent findings, overviews, insights, or commentaries on rational designing of therapeutic oligonucleotide molecules and their novel delivery technologies, especially nanocarrier systems.

  8. Fairy tales as a trance experience: possible therapeutic uses.

    PubMed

    Stevens-Guille, M E; Boersma, F J

    1992-04-01

    The psychological literature contains little documentation of the therapeutic use of fairy tales. We suggest that fairy tales are uniquely suitable for hypnotherapy and for helping clients reframe existential issues. We propose that the structure of fairy tales allows the meaning of the story to be applied personally and that they also stimulate unconscious search. We examine the way in which hypnosis is achieved when fairy tales are read to children, as well as possible therapeutic uses of this learning set in therapy with both children and adults. We conclude by suggesting that fairy tales need to be given serious consideration as an alternative therapeutic trance procedure.

  9. Antibody Engineering and Therapeutics

    PubMed Central

    Almagro, Juan Carlos; Gilliland, Gary L; Breden, Felix; Scott, Jamie K; Sok, Devin; Pauthner, Matthias; Reichert, Janice M; Helguera, Gustavo; Andrabi, Raiees; Mabry, Robert; Bléry, Mathieu; Voss, James E; Laurén, Juha; Abuqayyas, Lubna; Barghorn, Stefan; Ben-Jacob, Eshel; Crowe, James E; Huston, James S; Johnston, Stephen Albert; Krauland, Eric; Lund-Johansen, Fridtjof; Marasco, Wayne A; Parren, Paul WHI; Xu, Kai Y

    2014-01-01

    The 24th Antibody Engineering & Therapeutics meeting brought together a broad range of participants who were updated on the latest advances in antibody research and development. Organized by IBC Life Sciences, the gathering is the annual meeting of The Antibody Society, which serves as the scientific sponsor. Preconference workshops on 3D modeling and delineation of clonal lineages were featured, and the conference included sessions on a wide variety of topics relevant to researchers, including systems biology; antibody deep sequencing and repertoires; the effects of antibody gene variation and usage on antibody response; directed evolution; knowledge-based design; antibodies in a complex environment; polyreactive antibodies and polyspecificity; the interface between antibody therapy and cellular immunity in cancer; antibodies in cardiometabolic medicine; antibody pharmacokinetics, distribution and off-target toxicity; optimizing antibody formats for immunotherapy; polyclonals, oligoclonals and bispecifics; antibody discovery platforms; and antibody-drug conjugates. PMID:24589717

  10. Outpatient therapeutic nuclear oncology.

    PubMed

    Turner, J Harvey

    2012-05-01

    In the beginning, nuclear medicine was radionuclide therapy, which has evolved into molecular tumour-targeted control of metastatic cancer. Safe, efficacious, clinical practice of therapeutic nuclear oncology may now be based upon accurate personalised dosimetry by quantitative gamma SPECT/CT imaging to prescribe tumoricidal activities without critical organ toxicity. Preferred therapy radionuclides possess gamma emission of modest energy and abundance to enable quantitative SPECT/CT imaging for calculation of the beta therapy dosimetry, without radiation exposure risk to hospital personnel, carers, family or members of the public. The safety of outpatient radiopharmaceutical therapy of cancer with Iodine-131, Samarium-153, Holmium-166, Rhenium-186, Rhenium-188, Lutetium-177 and Indium-111 is reviewed. Measured activity release rates and radiation exposure to carers and the public are all within recommendations and guidelines of international regulatory agencies and, when permitted by local regulatory authorities allow cost-effective, safe, outpatient radionuclide therapy of cancer without isolation in hospital.

  11. Mitochondrial Energetics and Therapeutics

    PubMed Central

    Wallace, Douglas C.; Fan, Weiwei; Procaccio, Vincent

    2011-01-01

    Mitochondrial dysfunction has been linked to a wide range of degenerative and metabolic diseases, cancer, and aging. All these clinical manifestations arise from the central role of bioenergetics in cell biology. Although genetic therapies are maturing as the rules of bioenergetic genetics are clarified, metabolic therapies have been ineffectual. This failure results from our limited appreciation of the role of bioenergetics as the interface between the environment and the cell. A systems approach, which, ironically, was first successfully applied over 80 years ago with the introduction of the ketogenic diet, is required. Analysis of the many ways that a shift from carbohydrate glycolytic metabolism to fatty acid and ketone oxidative metabolism may modulate metabolism, signal transduction pathways, and the epigenome gives us an appreciation of the ketogenic diet and the potential for bioenergetic therapeutics. PMID:20078222

  12. Antimicrobial peptides: therapeutic potentials.

    PubMed

    Kang, Su-Jin; Park, Sung Jean; Mishig-Ochir, Tsogbadrakh; Lee, Bong-Jin

    2014-12-01

    The increasing appearance of multidrug-resistant pathogens has created an urgent need for suitable alternatives to current antibiotics. Antimicrobial peptides (AMPs), which act as defensive weapons against microbes, have received great attention because of broad-spectrum activities, unique action mechanisms and rare antibiotic-resistant variants. Despite desirable characteristics, they have shown limitations in pharmaceutical development due to toxicity, stability and manufacturing costs. Because of these drawbacks, only a few AMPs have been tested in Phase III clinical trials and no AMPs have been approved by the US FDA yet. However, these obstacles could be overcome by well-known methods such as changing physicochemical characteristics and introducing nonnatural amino acids, acetylation or amidation, as well as modern techniques like molecular targeted AMPs, liposomal formulations and drug delivery systems. Thus, the current challenge in this field is to develop therapeutic AMPs at a reasonable cost as well as to overcome the limitations.

  13. Aptamers in Therapeutics

    PubMed Central

    2016-01-01

    Aptamers are single strand DNA or RNA molecules, selected by an iterative process known as Systematic Evolution of Ligands by Exponential Enrichment (SELEX). Due to various advantages of aptamers such as high temperature stability, animal free, cost effective production and its high affinity and selectivity for its target make them attractive alternatives to monoclonal antibody for use in diagnostic and therapeutic purposes. Aptamer has been generated against vesicular endothelial growth factor 165 involved in age related macular degeneracy. Macugen was the first FDA approved aptamer based drug that was commercialized. Later other aptamers were also developed against blood clotting proteins, cancer proteins, antibody E, agents involved in diabetes nephropathy, autoantibodies involved in autoimmune disorders, etc. Aptamers have also been developed against viruses and could work with other antiviral agents in treating infections. PMID:27504277

  14. Microfabricated therapeutic actuators

    DOEpatents

    Lee, Abraham P.; Northrup, M. Allen; Ciarlo, Dino R.; Krulevitch, Peter A.; Benett, William J.

    1999-01-01

    Microfabricated therapeutic actuators are fabricated using a shape memory polymer (SMP), a polyurethane-based material that undergoes a phase transformation at a specified temperature (Tg). At a temperature above temperature Tg material is soft and can be easily reshaped into another configuration. As the temperature is lowered below temperature Tg the new shape is fixed and locked in as long as the material stays below temperature Tg. Upon reheating the material to a temperature above Tg, the material will return to its original shape. By the use of such SMP material, SMP microtubing can be used as a release actuator for the delivery of embolic coils through catheters into aneurysms, for example. The microtubing can be manufactured in various sizes and the phase change temperature Tg is determinate for an intended temperature target and intended use.

  15. Microfabricated therapeutic actuators

    DOEpatents

    Lee, A.P.; Northrup, M.A.; Ciarlo, D.R.; Krulevitch, P.A.; Benett, W.J.

    1999-06-15

    Microfabricated therapeutic actuators are fabricated using a shape memory polymer (SMP), a polyurethane-based material that undergoes a phase transformation at a specified temperature (Tg). At a temperature above temperature Tg material is soft and can be easily reshaped into another configuration. As the temperature is lowered below temperature Tg the new shape is fixed and locked in as long as the material stays below temperature Tg. Upon reheating the material to a temperature above Tg, the material will return to its original shape. By the use of such SMP material, SMP microtubing can be used as a release actuator for the delivery of embolic coils through catheters into aneurysms, for example. The microtubing can be manufactured in various sizes and the phase change temperature Tg is determinate for an intended temperature target and intended use. 8 figs.

  16. Race-based therapeutics.

    PubMed

    Yancy, Clyde W

    2008-08-01

    The issue of race in medicine is problematic. Race is not a physiologic grouping, and all persons of a given race do not necessarily share the same clinical phenotype or genetic substrate. Despite clear signals that certain risk factors and diseases vary as a function of race, translating those differences into race-based therapeutics has been awkward and has done little to change the natural history of cardiovascular disease as it affects special populations. Among the varied special populations, the African American population appears to have the most significant and adverse variances for cardiovascular disease as well as worrisome signals that drug responsiveness varies. Recent guideline statements have now acknowledged certain treatment options that are most appropriate for African Americans with cardiovascular disease, especially hypertension and heart failure. As more physiologic markers of disease and drug responsiveness become available, the need for racial designations in medicine may lessen, and therapies can be optimized for all patients without regard to race or ethnicity.

  17. A panic attack in therapeutic recreation over being considered therapeutic.

    PubMed

    Lee, L L

    1987-01-01

    Ancillary professions have been called upon to account for therapeutic benefits from their services or be eliminated from the health care system. A singular focus on therapy, however, would negate the unique contribution of therapeutic recreation within, while simultaneously restricting services to health care settings. It is proposed that panic over therapeutic recreation services meeting health care goals has hindered evaluation and solidification of the leisure-based philosophy presented in the NTRS Philosophical Position Statement (NTRS, 1982). It is argued that emphasizing the leisure orientation of the philosophical position statement can secure therapeutic recreation's position within, yet, not deny services to those outside of the health care system. An overview is presented on the adequacy of the position statement philosophy for therapeutic recreation. A potential danger of attempting to explain therapeutic recreation in terms of non-leisure based philosophies is also discussed.

  18. Maximizing the Online Learning Experience: Suggestions for Educators and Students

    ERIC Educational Resources Information Center

    Cicco, Gina

    2011-01-01

    This article will discuss ways of maximizing the online course experience for teachers- and counselors-in-training. The widespread popularity of online instruction makes it a necessary learning experience for future teachers and counselors (Ash, 2011). New teachers and counselors take on the responsibility of preparing their students for real-life…

  19. Maximizing Thermal Efficiency and Optimizing Energy Management (Fact Sheet)

    SciTech Connect

    Not Available

    2012-03-01

    Researchers at the Thermal Test Facility (TTF) on the campus of the U.S. Department of Energy's National Renewable Energy Laboratory (NREL) in Golden, Colorado, are addressing maximizing thermal efficiency and optimizing energy management through analysis of efficient heating, ventilating, and air conditioning (HVAC) strategies, automated home energy management (AHEM), and energy storage systems.

  20. On Adaptation, Maximization, and Reinforcement Learning among Cognitive Strategies

    ERIC Educational Resources Information Center

    Erev, Ido; Barron, Greg

    2005-01-01

    Analysis of binary choice behavior in iterated tasks with immediate feedback reveals robust deviations from maximization that can be described as indications of 3 effects: (a) a payoff variability effect, in which high payoff variability seems to move choice behavior toward random choice; (b) underweighting of rare events, in which alternatives…

  1. Optoelectronic plethysmography compared to spirometry during maximal exercise.

    PubMed

    Layton, Aimee M; Moran, Sienna L; Garber, Carol Ewing; Armstrong, Hilary F; Basner, Robert C; Thomashow, Byron M; Bartels, Matthew N

    2013-01-15

    The purpose of this study was to compare simultaneous measurements of tidal volume (Vt) by optoelectronic plethysmography (OEP) and spirometry during a maximal cycling exercise test to quantify possible differences between methods. Vt measured simultaneously by OEP and spirometry was collected during a maximal exercise test in thirty healthy participants. The two methods were compared by linear regression and Bland-Altman analysis at submaximal and maximal exercise. The average difference between the two methods and the mean percentage discrepancy were calculated. Submaximal exercise (SM) and maximal exercise (M) Vt measured by OEP and spirometry had very good correlation, SM R=0.963 (p<0.001), M R=0.982 (p<0.001) and high degree of common variance, SM R(2)=0.928, M R(2)=0.983. Bland-Altman analysis demonstrated that during SM, OEP could measure exercise Vt as much as 0.134 L above and -0.025 L below that of spirometry. OEP could measure exercise Vt as much as 0.188 L above and -0.017 L below that of spirometry. The discrepancy between measurements was -2.0 ± 7.2% at SM and -2.4 ± 3.9% at M. In conclusion, Vt measurements at during exercise by OEP and spirometry are closely correlated and the difference between measurements was insignificant.

  2. Fertilizer placement to maximize nitrogen use by fescue

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The method of fertilizer nitrogen(N) application can affect N uptake in tall fescue and therefore its yield and quality. Subsurface-banding (knife) of fertilizer maximizes fescue N uptake in the poorly-drained clay–pan soils of southeastern Kansas. This study was conducted to determine if knifed N r...

  3. Using Debate to Maximize Learning Potential: A Case Study

    ERIC Educational Resources Information Center

    Firmin, Michael W.; Vaughn, Aaron; Dye, Amanda

    2007-01-01

    Following a review of the literature, an educational case study is provided for the benefit of faculty preparing college courses. In particular, we provide a transcribed debate utilized in a General Psychology course as a best practice example of how to craft a debate which maximizes student learning. The work is presented as a model for the…

  4. Modifying Softball for Maximizing Learning Outcomes in Physical Education

    ERIC Educational Resources Information Center

    Brian, Ali; Ward, Phillip; Goodway, Jacqueline D.; Sutherland, Sue

    2014-01-01

    Softball is taught in many physical education programs throughout the United States. This article describes modifications that maximize learning outcomes and that address the National Standards and safety recommendations. The modifications focus on tasks and equipment, developmentally appropriate motor-skill acquisition, increasing number of…

  5. Maximal regularity for perturbed integral equations on periodic Lebesgue spaces

    NASA Astrophysics Data System (ADS)

    Lizama, Carlos; Poblete, Verónica

    2008-12-01

    We characterize the maximal regularity of periodic solutions for an additive perturbed integral equation with infinite delay in the vector-valued Lebesgue spaces. Our method is based on operator-valued Fourier multipliers. We also study resonances, characterizing the existence of solutions in terms of a compatibility condition on the forcing term.

  6. Apportioning Program Evaluation Resources to Maximize Information Yield.

    ERIC Educational Resources Information Center

    Sadler, D. Royce

    1982-01-01

    Not all data for a program evaluation may be equally valuable, and costs of collection may vary when using several methods to obtain data from several sources. An approach to maximize information yield for a fixed, limited budget using a mathematical technique known as linear programming is described and generalized. (Author/CM)

  7. Formulation of Maximized Weighted Averages in URTURIP Technique

    DTIC Science & Technology

    2001-10-25

    Formulation of Maximized Weighted Averages in URTURIP Technique Bruno Migeon, Philippe Deforge, Pierre Marché Laboratoire Vision et Robotique ...Organization Name(s) and Address(es) Laboratoire Vision et Robotique 63, avenue de Lattre de Tassigny, 18020 Bourges Cedex - France Performing Organization

  8. A Maximal Flow Approach to Dynamic Routing in Communication Networks,

    DTIC Science & Technology

    1980-05-01

    of nodes. In Appendix B we provide a computer program in Fortran for finding the maximal flow in these networks, based on the algorithm of Edmons and... Edmons and Karp is implemented by a Fortran Subroutine called MAXFL. The algorithm finds the shortest path between source and destination on which an

  9. Maximizing the Benefits of an Administrative Internship: Some Practical Advice.

    ERIC Educational Resources Information Center

    Oldfield, Kenneth; Ayers, Nancy

    Recommendations to help student interns in administrative positions maximize their educational opportunities vis-a-vis the "real world" and to also help them avoid certain placement-associated problems. The suggestions may be helpful to both new and established internship directors as well. Attention is focused on governmental administrative…

  10. Maximizing grain sorghum water use efficiency under deficit irrigation

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Development and evaluation of sustainable and efficient irrigation strategies is a priority for producers faced with water shortages resulting from aquifer depletion, reduced base flows, and reallocation of water to non-agricultural sectors. Under a limited water supply, yield maximization may not b...

  11. Maximizing Access, Equity, and Inclusion in General and Special Education

    ERIC Educational Resources Information Center

    Obiakor, Festus E.

    2011-01-01

    The goal of any educational program is to help its students to maximize their fullest potential in inclusive environments. For many students with disabilities, having an inclusive environment seems to be an ideal policy. Ironically, this policy continues to be debatable and controversial. Sometimes, the controversy or debate dominates the real…

  12. Optimal technique for maximal forward rotating vaults in men's gymnastics.

    PubMed

    Hiley, Michael J; Jackson, Monique I; Yeadon, Maurice R

    2015-08-01

    In vaulting a gymnast must generate sufficient linear and angular momentum during the approach and table contact to complete the rotational requirements in the post-flight phase. This study investigated the optimization of table touchdown conditions and table contact technique for the maximization of rotation potential for forwards rotating vaults. A planar seven-segment torque-driven computer simulation model of the contact phase in vaulting was evaluated by varying joint torque activation time histories to match three performances of a handspring double somersault vault by an elite gymnast. The closest matching simulation was used as a starting point to maximize post-flight rotation potential (the product of angular momentum and flight time) for a forwards rotating vault. It was found that the maximized rotation potential was sufficient to produce a handspring double piked somersault vault. The corresponding optimal touchdown configuration exhibited hip flexion in contrast to the hyperextended configuration required for maximal height. Increasing touchdown velocity and angular momentum lead to additional post-flight rotation potential. By increasing the horizontal velocity at table touchdown, within limits obtained from recorded performances, the handspring double somersault tucked with one and a half twists, and the handspring triple somersault tucked became theoretically possible.

  13. Maximizing plant density affects broccoli yield and quality

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Increased demand for fresh market bunch broccoli (Brassica oleracea L. var. italica) has led to increased production along the United States east coast. Maximizing broccoli yields is a primary concern for quickly expanding southeastern commercial markets. This broccoli plant density study was carr...

  14. Emotional Control and Instructional Effectiveness: Maximizing a Timeout

    ERIC Educational Resources Information Center

    Andrews, Staci R.

    2015-01-01

    This article provides recommendations for best practices for basketball coaches to maximize the instructional effectiveness of a timeout during competition. Practical applications are derived from research findings linking emotional intelligence to effective coaching behaviors. Additionally, recommendations are based on the implications of the…

  15. How to Maximize Learning for Gifted Math Students

    ERIC Educational Resources Information Center

    Chamberlin, Scott A.

    2008-01-01

    Having a gifted math or science student in the family or classroom is a fascination as well as a significant challenge and responsibility for many parents and teachers. In order to help maximize student learning, several questions need to be asked. What should be the role of technology? How well do traditional schools serve gifted students? What…

  16. Nursing Students' Awareness and Intentional Maximization of Their Learning Styles

    ERIC Educational Resources Information Center

    Mayfield, Linda Riggs

    2012-01-01

    This small, descriptive, pilot study addressed survey data from four levels of nursing students who had been taught to maximize their learning styles in a first-semester freshman success skills course. Bandura's Agency Theory supports the design. The hypothesis was that without reinforcing instruction, the students' recall and application of that…

  17. The Profit-Maximizing Firm: Old Wine in New Bottles.

    ERIC Educational Resources Information Center

    Felder, Joseph

    1990-01-01

    Explains and illustrates a simplified use of graphical analysis for analyzing the profit-maximizing firm. Believes that graphical analysis helps college students gain a deeper understanding of marginalism and an increased ability to formulate economic problems in marginalist terms. (DB)

  18. Maximally entangled mixed-state generation via local operations

    SciTech Connect

    Aiello, A.; Puentes, G.; Voigt, D.; Woerdman, J. P.

    2007-06-15

    We present a general theoretical method to generate maximally entangled mixed states of a pair of photons initially prepared in the singlet polarization state. This method requires only local operations upon a single photon of the pair and exploits spatial degrees of freedom to induce decoherence. We report also experimental confirmation of these theoretical results.

  19. A Method for Maximizing Split-Half Reliability Coefficients

    ERIC Educational Resources Information Center

    Callender, John C.; Osburn, H. G.

    1977-01-01

    An efficient algorithm for maximizing split-half reliability coefficients is described. Coefficients derived by the algorithm were found to be generally larger than odd-even split-half coefficients or other internal consistency measures and nearly as large as the largest split half coefficients. MSPLIT, Odd-Even, and Kuder-Richardson-20…

  20. Hardy-Littlewood maximal operator in generalized grand Lebesgue spaces

    NASA Astrophysics Data System (ADS)

    Umarkhadzhiev, Salaudin M.

    2014-12-01

    We obtain sufficient conditions and necessary conditions for the maximal operator to be bounded in the generalized grand Lebesgue space on an open set Ω ∈ Rn which is not necessarily bounded. The sufficient conditions coincide with necessary conditions for instance in the case where Ω is bounded and the standard definition of the grand space is used.

  1. Teacher Praise: Maximizing the Motivational Impact. Teaching Strategies.

    ERIC Educational Resources Information Center

    McVey, Mary D.

    2001-01-01

    Recognizes the influence of praise on human behavior, and provides specific suggestions on how to maximize the positive effects of praise when intended as positive reinforcement. Examines contingency, specificity, and selectivity aspects of praise. Cautions teachers to avoid the controlling effects of praise and the possibility that praise may…

  2. Quantum state space as a maximal consistent set

    NASA Astrophysics Data System (ADS)

    Tabia, Gelo Noel

    2012-02-01

    Measurement statistics in quantum theory are obtained from the Born rule and the uniqueness of the probability measure it assigns through quantum states is guaranteed by Gleason's theorem. Thus, a possible systematic way of exploring the geometry of quantum state space expresses quantum states in terms of outcome probabilities of a symmetric informationally complete measurement. This specific choice for representing quantum states is motivated by how the associated probability space provides a natural venue for characterizing the set of quantum states as a geometric construct called a maximal consistent set. We define the conditions for consistency and maximality of a set, provide some examples of maximal consistent sets and attempt to deduce the steps for building up a maximal consistent set of probability distributions equivalent to Hilbert space. In particular, we demonstrate how the reconstruction procedure works for qutrits and observe how it reveals an elegant underlying symmetry among five SIC-POVMs and a complete set of mutually unbiased bases, known in finite affine geometry as the Hesse configuration.

  3. Enhancing titres of therapeutic viral vectors using the transgene repression in vector production (TRiP) system

    PubMed Central

    Maunder, H. E.; Wright, J.; Kolli, B. R.; Vieira, C. R.; Mkandawire, T. T.; Tatoris, S.; Kennedy, V.; Iqball, S.; Devarajan, G.; Ellis, S.; Lad, Y.; Clarkson, N. G.; Mitrophanous, K. A.; Farley, D. C.

    2017-01-01

    A key challenge in the field of therapeutic viral vector/vaccine manufacturing is maximizing production. For most vector platforms, the ‘benchmark' vector titres are achieved with inert reporter genes. However, expression of therapeutic transgenes can often adversely affect vector titres due to biological effects on cell metabolism and/or on the vector virion itself. Here, we exemplify the novel ‘Transgene Repression In vector Production' (TRiP) system for the production of both RNA- and DNA-based viral vectors. The TRiP system utilizes a translational block of one or more transgenes by employing the bacterial tryptophan RNA-binding attenuation protein (TRAP), which binds its target RNA sequence close to the transgene initiation codon. We report enhancement of titres of lentiviral vectors expressing Cyclo-oxygenase-2 by 600-fold, and adenoviral vectors expressing the pro-apoptotic gene Bax by >150,000-fold. The TRiP system is transgene-independent and will be a particularly useful platform in the clinical development of viral vectors expressing problematic transgenes. PMID:28345582

  4. On the Achievable Throughput Over TVWS Sensor Networks

    PubMed Central

    Caleffi, Marcello; Cacciapuoti, Angela Sara

    2016-01-01

    In this letter, we study the throughput achievable by an unlicensed sensor network operating over TV white space spectrum in presence of coexistence interference. Through the letter, we first analytically derive the achievable throughput as a function of the channel ordering. Then, we show that the problem of deriving the maximum expected throughput through exhaustive search is computationally unfeasible. Finally, we derive a computational-efficient algorithm characterized by polynomial-time complexity to compute the channel set maximizing the expected throughput and, stemming from this, we derive a closed-form expression of the maximum expected throughput. Numerical simulations validate the theoretical analysis. PMID:27043565

  5. Massage Therapy Education Online: Student Satisfaction and Achievement, Part I

    PubMed Central

    McQuillan, David James

    2010-01-01

    In recent years, providers of massage therapy education have, in growing numbers, started to use online technologies to support the learning processes of their students. Using a narrative review of the existing online learning literature, this paper aims to provide a solid pedagogical foundation for these early explorations. It identifies five key factors—instructional pedagogy, quality of instruction, interaction and communication, individual learner qualities, and the online interface—that contribute to student satisfaction and achievement in the online context. The relationships between those factors and the experience of the online learner are discussed with reference to maximization of student satisfaction and achievement. PMID:21589705

  6. Engineered therapeutic-releasing nanoporous anodic alumina-aluminum wires with extended release of therapeutics.

    PubMed

    Law, Cheryl Suwen; Santos, Abel; Kumeria, Tushar; Losic, Dusan

    2015-02-18

    In this study, we present a nanoengineered therapeutic-releasing system based on aluminum wires featuring nanoporous anodic alumina layers and chitosan coatings. Nanoporous anodic alumina layers are produced on the surface of aluminum wires by electrochemical anodization. These nanoporous layers with precisely engineered nanopore geometry are used as nanocontainers for bovine serum albumin molecules labeled with fluorescein isothiocyanate (BSA-FITC), which is selected as a model drug. The surface of these therapeutic-releasing implants is coated with a biocompatible and biodegradable polymer, chitosan, in order to achieve a sustained release of protein over extended periods of time. The performance of this therapeutic-releasing device is systematically assessed through a series of experiments under static and dynamic flow conditions. In these experiments, the effect of such parameters as the number of layers of chitosan coating and the temperature and pH of the eluting medium is established. The obtained results reveal that the proposed therapeutic-releasing system based on nanoporous aluminum wires can be engineered with sustained release performance for up to 6.5 weeks, which is a critical factor for medical treatments using sensitive therapeutics such as proteins and genes when a localized delivery is desired.

  7. [Nuclear transfer and therapeutic cloning].

    PubMed

    Xu, Xiao-Ming; Lei, An-Min; Hua, Jin-Lian; Dou, Zhong-Ying

    2005-03-01

    Nuclear transfer and therapeutic cloning have widespread and attractive prospects in animal agriculture and biomedical applications. We reviewed that the quality of oocytes and nuclear reprogramming of somatic donor cells were the main reasons of the common abnormalities in cloned animals and the low efficiency of cloning and showed the problems and outlets in therapeutic cloning, such as some basic problems in nuclear transfer affected clinical applications of therapeutic cloning. Study on isolation and culture of nuclear transfer embryonic stem (ntES) cells and specific differentiation of ntES cells into important functional cells should be emphasized and could enhance the efficiency. Adult stem cells could help to cure some great diseases, but could not replace therapeutic cloning. Ethics also impeded the development of therapeutic cloning. It is necessary to improve many techniques and reinforce the research of some basic theories, then somatic nuclear transfer and therapeutic cloning may apply to agriculture reproduction and benefit to human life better.

  8. Effectiveness of accommodation and constant resistance training on maximal strength and power in trained athletes.

    PubMed

    Ataee, Jalil; Koozehchian, Majid S; Kreider, Richard B; Zuo, Li

    2014-01-01

    Accommodation resistance is a training technique that may improve strength and power gains beyond those achieved by traditional free weights. In this method, chains are either added on a free-weight bar and combined with traditional plates or added to the bar as the entire load. Purpose. The aim of the current study was to compare the effectiveness of accommodation and constant resistance training methods during a four-week period on maximal strength and power in trained athletes. Methods. This study was comprised of 24 trained athletes, including 16 trained males [8 Wushu athletes (Kung-Fu) and 8 wrestlers, age: 20.5 ± 2.00 yrs. old]. Participants were initially tested on weight, body circumference, fat percent, upper and lower body maximal strength, determined by the 1-repetition maximum (1RM) test, which determines the greatest amount of weight a person can successfully lift, and upper and lower body power. Participants were equally randomized to either accommodation or constant resistance training groups. Both groups underwent resistance training for a four-week period that consisted of three sessions per week. Multivariate repeated-measures analyses of variance of the data were used to verify significant differences in strength and power between groups. The modified Bonferroni post hoc test was used to compare the obtained results in pre-, mid-, and post test. Results. In the accommodation resistance group, there was a significant difference in lower body maximal strength compared to the constant group (163.12 ± 18.82 kg in the accommodation group vs. 142.25 ± 20.04 kg in the constant group, P = 0.04). No significant differences were found in upper body power, lower body power, and upper body maximal strength between the two groups (P > 0.05). Conclusion. Although there was only a significant difference in lower body maximal strength between groups, accommodation resistance training may induce a physiological training response by improving the strength and

  9. Therapeutic use of nicergoline.

    PubMed

    Winblad, Bengt; Fioravanti, Mario; Dolezal, Tomas; Logina, Inara; Milanov, Ivan Gospodinov; Popescu, Dinu Cristian; Solomon, Alina

    2008-01-01

    The ergot alkaloid derivative nicergoline became clinically available about 35 years ago in the 1970s. Nicergoline has a broad spectrum of action: (i) as an alpha(1)-adrenoceptor antagonist, it induces vasodilation and increases arterial blood flow; (ii) it enhances cholinergic and catecholaminergic neurotransmitter function; (iii) it inhibits platelet aggregation; (iv) it promotes metabolic activity, resulting in increased utilization of oxygen and glucose; and (v) it has neurotrophic and antioxidant properties. Acting on several basic pathophysiological mechanisms, nicergoline has therapeutic potential in a number of disorders. This article provides an overview of the published clinical evidence relating to the efficacy and safety of nicergoline (30 mg twice daily) in the treatment of dementia (including Alzheimer's disease and vascular dementia) and vascular and balance disorders. For dementia of different aetiologies, the therapeutic benefit of nicergoline has been established, with up to 89% of patients showing improvements in cognition and behaviour. After as little as 2 months of treatment, symptom improvement is apparent compared with placebo, and most patients are still improved or stable after 12 months. Concomitant neurophysiological changes in the brain indicate (after only 4-8 weeks' treatment) improved vigilance and information processing. In patients with balance disorders, mean improvements of 44-78% in symptom severity and quality of life have been observed with nicergoline. Although clinical experience with nicergoline in vascular disorders is limited to relatively short-term, small-scale studies, it has been successfully used in rehabilitation therapy of patients with chronic ischaemic stroke. Open-label evaluations suggest that nicergoline may also be valuable in glaucoma, depression and peripheral arterio-pathy. Adverse events of nicergoline, if any, are related to the central nervous system, the metabolic system and the overall body. Most are

  10. Lifting Minority Achievement: Complex Answers. The Achievement Gap.

    ERIC Educational Resources Information Center

    Viadero, Debra; Johnston, Robert C.

    2000-01-01

    This fourth in a four-part series on why academic achievement gaps exist describes the Minority Achievement Committee scholars program at Shaker Heights High School in Cleveland, Ohio, a powerful antidote to the achievement gap between minority and white and Asian American students. It explains the need to break down stereotypes about academic…

  11. Achievement Motivation of Women: Effects of Achievement and Affiliation Arousal.

    ERIC Educational Resources Information Center

    Gama, Elizabeth Maria Pinheiro

    1985-01-01

    Assigned 139 Brazilian women to neutral, affiliation arousal, and achievement arousal conditions based on their levels of achievement (Ach) and affiliative (Aff) needs. Results of story analyses revealed that achievement arousal increased scores of high Ach subjects and that high Aff subjects obtained higher scores than low Aff subjects. (BL)

  12. Attitude Towards Physics and Additional Mathematics Achievement Towards Physics Achievement

    ERIC Educational Resources Information Center

    Veloo, Arsaythamby; Nor, Rahimah; Khalid, Rozalina

    2015-01-01

    The purpose of this research is to identify the difference in students' attitude towards Physics and Additional Mathematics achievement based on gender and relationship between attitudinal variables towards Physics and Additional Mathematics achievement with achievement in Physics. This research focused on six variables, which is attitude towards…

  13. The Impact of Reading Achievement on Overall Academic Achievement

    ERIC Educational Resources Information Center

    Churchwell, Dawn Earheart

    2009-01-01

    This study examined the relationship between reading achievement and achievement in other subject areas. The purpose of this study was to determine if there was a correlation between reading scores as measured by the Standardized Test for the Assessment of Reading (STAR) and academic achievement in language arts, math, science, and social studies…

  14. 'Smartening' anticancer therapeutic nanosystems using biomolecules.

    PubMed

    Núñez-Lozano, Rebeca; Cano, Manuel; Pimentel, Belén; de la Cueva-Méndez, Guillermo

    2015-12-01

    To be effective, anticancer agents must induce cell killing in a selective manner, something that is proving difficult to achieve. Drug delivery systems could help to solve problems associated with the lack of selectivity of classical chemotherapeutic agents. However, to realize this, such systems must overcome multiple physiological barriers. For instance, they must evade surveillance by the immune system, attach selectively to target cells, and gain access to their interior. Furthermore, there they must escape endosomal entrapment, and release their cargoes in a controlled manner, without affecting their functionality. Here we review recent efforts aiming at using biomolecules to confer these abilities to bare nanoparticles, to transform them into smart anticancer therapeutic nanosystems.

  15. Therapeutic cloning: The ethical limits

    SciTech Connect

    Whittaker, Peter A. . E-mail: p.whittaker@lancaster.ac.uk

    2005-09-01

    A brief outline of stem cells, stem cell therapy and therapeutic cloning is given. The position of therapeutic cloning with regard to other embryonic manipulations - IVF-based reproduction, embryonic stem formation from IVF embryos and reproductive cloning - is indicated. The main ethically challenging stages in therapeutic cloning are considered to be the nuclear transfer process including the source of eggs for this and the destruction of an embryo to provide stem cells for therapeutic use. The extremely polarised nature of the debate regarding the status of an early human embryo is noted, and some potential alternative strategies for preparing immunocompatible pluripotent stem cells are indicated.

  16. Clinical applications of therapeutic phlebotomy

    PubMed Central

    Kim, Kyung Hee; Oh, Ki Young

    2016-01-01

    Phlebotomy is the removal of blood from the body, and therapeutic phlebotomy is the preferred treatment for blood disorders in which the removal of red blood cells or serum iron is the most efficient method for managing the symptoms and complications. Therapeutic phlebotomy is currently indicated for the treatment of hemochromatosis, polycythemia vera, porphyria cutanea tarda, sickle cell disease, and nonalcoholic fatty liver disease with hyperferritinemia. This review discusses therapeutic phlebotomy and the related disorders and also offers guidelines for establishing a therapeutic phlebotomy program. PMID:27486346

  17. Plasmids encoding therapeutic agents

    DOEpatents

    Keener, William K.

    2007-08-07

    Plasmids encoding anti-HIV and anti-anthrax therapeutic agents are disclosed. Plasmid pWKK-500 encodes a fusion protein containing DP178 as a targeting moiety, the ricin A chain, an HIV protease cleavable linker, and a truncated ricin B chain. N-terminal extensions of the fusion protein include the maltose binding protein and a Factor Xa protease site. C-terminal extensions include a hydrophobic linker, an L domain motif peptide, a KDEL ER retention signal, another Factor Xa protease site, an out-of-frame buforin II coding sequence, the lacZ.alpha. peptide, and a polyhistidine tag. More than twenty derivatives of plasmid pWKK-500 are described. Plasmids pWKK-700 and pWKK-800 are similar to pWKK-500 wherein the DP178-encoding sequence is substituted by RANTES- and SDF-1-encoding sequences, respectively. Plasmid pWKK-900 is similar to pWKK-500 wherein the HIV protease cleavable linker is substituted by a lethal factor (LF) peptide-cleavable linker.

  18. Therapeutic antibody technology 97.

    PubMed

    Larrick, J W; Gavilondo, J

    1998-01-01

    Almost 200 antibody aficionados attended the Therapeutic Antibody Technology 97 meeting, held September 21-24, 1997 at the Holiday Inn, Union Square in the heart of San Francisco, CA. The meeting was sponsored by the Palo Alto Institute of Molecular Medicine and organized by James W. Larrick (PAIMM) and Dennis R. Burton (Scripps Research Institute). The meeting featured excellent discussions on many interesting talks and a number of poster presentations. It is likely that another meeting will be organized in 2 years, however in the meantime, an effort is underway to organize a 'Virtual Antibody Society' to be set up on the web server at Scripps Research Institute in La Jolla, CA (Questions and comments on this project can be sent to: Jwlarrick@aol.com or Burton@scripps.edu). Richard Lerner (Scripps) gave the keynote address on 'Catalytic Antibodies', describing recent work with Carlos Barbas on so-called reactive immunization to generate a high activity aldolase catalytic antibody. This antibody, soon to be described in an article in Science, is the first commercially available catalytic antibody.

  19. Leech Therapeutic Applications

    PubMed Central

    Abdualkader, A. M.; Ghawi, A. M.; Alaama, M.; Awang, M.; Merzouk, A.

    2013-01-01

    Hematophagous animals including leeches have been known to possess biologically active compounds in their secretions, especially in their saliva. The blood-sucking annelids, leeches have been used for therapeutic purposes since the beginning of civilization. Ancient Egyptian, Indian, Greek and Arab physicians used leeches for a wide range of diseases starting from the conventional use for bleeding to systemic ailments, such as skin diseases, nervous system abnormalities, urinary and reproductive system problems, inflammation, and dental problems. Recently, extensive researches on leech saliva unveiled the presence of a variety of bioactive peptides and proteins involving antithrombin (hirudin, bufrudin), antiplatelet (calin, saratin), factor Xa inhibitors (lefaxin), antibacterial (theromacin, theromyzin) and others. Consequently, leech has made a comeback as a new remedy for many chronic and life-threatening abnormalities, such as cardiovascular problems, cancer, metastasis, and infectious diseases. In the 20th century, leech therapy has established itself in plastic and microsurgery as a protective tool against venous congestion and served to salvage the replanted digits and flaps. Many clinics for plastic surgery all over the world started to use leeches for cosmetic purposes. Despite the efficacious properties of leech therapy, the safety, and complications of leeching are still controversial. PMID:24019559

  20. Phytonutrients as therapeutic agents.

    PubMed

    Gupta, Charu; Prakash, Dhan

    2014-09-01

    Nutrients present in various foods plays an important role in maintaining the normal functions of the human body. The major nutrients present in foods include carbohydrates, proteins, lipids, vitamins, and minerals. Besides these, there are some bioactive food components known as "phytonutrients" that play an important role in human health. They have tremendous impact on the health care system and may provide medical health benefits including the prevention and/or treatment of disease and various physiological disorders. Phytonutrients play a positive role by maintaining and modulating immune function to prevent specific diseases. Being natural products, they hold a great promise in clinical therapy as they possess no side effects that are usually associated with chemotherapy or radiotherapy. They are also comparatively cheap and thus significantly reduce health care cost. Phytonutrients are the plant nutrients with specific biological activities that support human health. Some of the important bioactive phytonutrients include polyphenols, terpenoids, resveratrol, flavonoids, isoflavonoids, carotenoids, limonoids, glucosinolates, phytoestrogens, phytosterols, anthocyanins, ω-3 fatty acids, and probiotics. They play specific pharmacological effects in human health such as anti-microbial, anti-oxidants, anti-inflammatory, antiallergic, anti-spasmodic, anti-cancer, anti-aging, hepatoprotective, hypolipidemic, neuroprotective, hypotensive, diabetes, osteoporosis, CNS stimulant, analgesic, protection from UVB-induced carcinogenesis, immuno-modulator, and carminative. This mini-review attempts to summarize the major important types of phytonutrients and their role in promoting human health and as therapeutic agents along with the current market trend and commercialization.

  1. LP-925219 maximizes urinary glucose excretion in mice by inhibiting both renal SGLT1 and SGLT2.

    PubMed

    Powell, David R; Smith, Melinda G; Doree, Deon D; Harris, Angela L; Xiong, Wendy W; Mseeh, Faika; Wilson, Alan; Gopinathan, Suma; Diaz, Damaris; Goodwin, Nicole C; Harrison, Bryce; Strobel, Eric; Rawlins, David B; Carson, Ken; Zambrowicz, Brian; Ding, Zhi-Ming

    2015-03-01

    Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of oral anti-diabetic agents that improve glycemic control by inhibiting SGLT2-mediated renal glucose reabsorption. Currently available agents increase urinary glucose excretion (UGE) to <50% of maximal values because they do not inhibit SGLT1, which reabsorbs >50% of filtered glucose when SGLT2 is completely inhibited. This led us to test whether LP-925219, a small molecule dual SGLT1/SGLT2 inhibitor, increases UGE to maximal values in wild-type (WT) mice. We first tested LP-925219 inhibition of glucose transport by HEK293 cells expressing SGLT1 or SGLT2, and then characterized LP-925219 pharmacokinetics. We found that LP-925219 was a potent inhibitor of mouse SGLT1 (IC50 = 22.6 nmol/L) and SGLT2 (IC50 = 0.5 nmol/L), and that a 10 mg/kg oral dose was bioavailable (87%) with a long half-life (7 h). We next delivered LP-925219 by oral gavage to WT, SGLT1 knockout (KO), SGLT2 KO, and SGLT1/SGLT2 double KO (DKO) mice and measured their 24-h UGE. We found that, in vehicle-treated mice, DKO UGE was maximal and SGLT2 KO, SGLT1 KO, and WT UGEs were 30%, 2%, and 0.2% of maximal, respectively; we also found that LP-925219 dosed at 60 mg/kg twice daily increased UGE of SGLT1 KO, SGLT2 KO, and WT mice to DKO UGE levels. These findings show that orally available dual SGLT1/SGLT2 inhibitors can maximize 24-h UGE in mammals, and suggest that such agents merit further evaluation for their potential, in diabetic patients, to achieve better glycemic control than is achieved using selective SGLT2 inhibitors.

  2. Left ventricular atrioventricular plane displacement is preserved with lifelong endurance training and is the main determinant of maximal cardiac output.

    PubMed

    Steding-Ehrenborg, Katarina; Boushel, Robert C; Calbet, José A; Åkeson, Per; Mortensen, Stefan P

    2015-12-01

    Age-related decline in cardiac function can be prevented or postponed by lifelong endurance training. However, effects of normal ageing as well as of lifelong endurance exercise on longitudinal and radial contribution to stroke volume are unknown. The aim of this study was to determine resting longitudinal and radial pumping in elderly athletes, sedentary elderly and young sedentary subjects. Furthermore, we aimed to investigate determinants of maximal cardiac output in elderly. Eight elderly athletes (63 ± 4 years), seven elderly sedentary (66 ± 4 years) and ten young sedentary subjects (29 ± 4 years) underwent cardiac magnetic resonance imaging. All subjects underwent maximal exercise testing and for elderly subjects maximal cardiac output during cycling was determined using a dye dilution technique. Longitudinal and radial contribution to stroke volume did not differ between groups (longitudinal left ventricle (LV) 52-65%, P = 0.12, right ventricle (RV) 77-87%, P = 0.16, radial 7.9-8.6%, P = 1.0). Left ventricular atrioventricular plane displacement (LVAVPD) was higher in elderly athletes and young sedentary compared with elderly sedentary subjects (14 ± 3, 15 ± 2 and 11 ± 1 mm, respectively, P < 0.05). There was no difference between groups for RVAVPD (P = 0.2). LVAVPD was an independent predictor of maximal cardiac output (R(2) = 0.61, P < 0.01, β = 0.78). Longitudinal and radial contributions to stroke volume did not differ between groups. However, how longitudinal pumping was achieved differed; elderly athletes and young sedentary subjects showed similar AVPD whereas this was significantly lower in elderly sedentary subjects. Elderly sedentary subjects achieved longitudinal pumping through increased short-axis area of the ventricle. Large AVPD was a determinant of maximal cardiac output and exercise capacity.

  3. Triggered Nanoparticles as Therapeutics

    PubMed Central

    Kim, Chang Soo; Duncan, Bradley; Creran, Brian; Rotello, Vincent M.

    2013-01-01

    Summary Drug delivery systems (DDSs) face several challenges including site-specific delivery, stability, and the programmed release of drugs. Engineered nanoparticle (NP) surfaces with responsive moieties can enhance the efficacy of DDSs for in vitro and in vivo systems. This triggering process can be achieved through both endogenous (biologically controlled release) and exogenous (external stimuli controlled release) activation. In this review, we will highlight recent examples of the use of triggered release strategies of engineered nanomaterials for in vitro and in vivo applications. PMID:24159362

  4. Protective, restorative, and therapeutic properties of recombinant human IL-1 in rodent models

    SciTech Connect

    Castelli, M.P.; Black, P.L.; Schneider, M.; Pennington, R.; Abe, F.; Talmadge, J.E.

    1988-06-01

    Human rIL-1 alpha and -1 beta are shown to increase significantly the CFU-culture activity in the spleen as well as at other sites after i.v. or i.p. administration. IL-1 can also significantly increase survival and can rescue a number of animals if administered either before or after lethal doses of cyclophosphamide or gamma-irradiation. The protective and reconstitutive activities of the rIL-1 are shown to correlate with increased CFU-culture frequency and total number, as well as increased cellularity in the bone marrow and peripheral blood, suggesting that this is one of their mechanisms of action. The sequence and timing of administration of human rIL-1 is critical for the protection or rescue of animals receiving DNA-damaging agents; maximal activity is achieved when IL-1 is given 20 h before insult or 48 h after alkylating agent administration. Minimal therapeutic activity is observed with IL-1 as a single agent for the treatment of metastatic disease compared with other biologic response modifiers including IFN-gamma.

  5. New therapeutic principles in dyslipidaemia: focus on LDL and Lp(a) lowering drugs

    PubMed Central

    Norata, Giuseppe Danilo; Ballantyne, Christie M.; Catapano, Alberico Luigi

    2013-01-01

    Dyslipidaemias play a key role in determining cardiovascular risk; the discovery of statins has contributed a very effective approach. However, many patients do not achieve, at the maximal tolerated dose, the recommended goals for low-density lipoprotein-cholesterol (LDL-C), non-high-density lipoprotein-cholesterol, and apolipoprotein B (apoB). Available agents combined with statins can provide additional LDL-C reduction, and agents in development will increase therapeutic options impacting also other atherogenic lipoprotein classes. In fact, genetic insights into mechanisms underlying regulation of LDL-C levels has expanded potential targets of drug therapy and led to the development of novel agents. Among them are modulators of apoB containing lipoproteins production and proprotein convertase subtilisin/kexin type-9 inhibitors. Alternative targets such as lipoprotein(a) also require attention; however, until we have a better understanding of these issues, further LDL-C lowering in high and very high-risk patients will represent the most sound clinical approach. PMID:23509227

  6. Increasing the Therapeutic Ratio of Stereotactic Ablative Radiotherapy by Individualized Isotoxic Dose Prescription.

    PubMed

    Zindler, Jaap D; Thomas, Charles R; Hahn, Stephen M; Hoffmann, Aswin L; Troost, Esther G C; Lambin, Philippe

    2016-02-01

    To obtain a favorable tradeoff between treatment benefits and morbidity ("therapeutic ratio"), radiotherapy (RT) dose is prescribed according to the tumor volume, with the goal of controlling the disease while respecting normal tissue tolerance levels. We propose a new paradigm for tumor dose prescription in stereotactic ablative radiotherapy (SABR) based on organ-at-risk (OAR) tolerance levels called isotoxic dose prescription (IDP), which is derived from experiences and limitations of conventionally fractionated radiotherapy. With IDP, the radiation dose is prescribed based on the predefined level of normal tissue complication probability of a nearby dose-limiting OAR at a prespecified dose-volume constraint. Simultaneously, the prescribed total tumor dose (TTD) is maximized to the technically highest achievable level in order to increase the local tumor control probability (TCP). IDP is especially relevant for tumors located at eloquent locations or for large tumors in which severe toxicity has been described. IDP will result in a lower RT dose or a treatment scheduled with more fractions if the OAR tolerance level is exceeded, and potential dose escalation occurs when the OAR tolerance level allows it and when it is expected to be beneficial (if TCP < 90%). For patients with small tumors at noneloquent sites, the current SABR dose prescription already results in high rates of local control at low toxicity rates. In this review, the concept of IDP is described in the context of SABR.

  7. AB047. Clinic therapeutic effect of sigmoid orthotopic neobladder after radical cystectomy

    PubMed Central

    Zhang, Jin; Li, Ranwei; Li, Shengwen

    2016-01-01

    Objective To investigate the clinic therapeutic effect of sigmoid orthotopic neobladder after radical cystectomy. Methods Sixteen patients with invasive bladder cancer (all males; age range from 53 to 75 years) were admitted and underwent radical cystectomy and sigmoid orthotopic neobladder. Results The 16 patients were hospitalized for 37 to 62 d, with an average of 51 d. All the 16 patients were followed up for a mean of 26 months (range from 5 months to 6 years). The serum creatinine and blood urea nitrogen levels were both in the normal range without acidosis in all the cases. No cases had unilateral ureteral urine reflux during cystography. Of the 16 patients 14 cases (87.5%) achieved continence during daytime; 6 cases (37.5%) were incontinent at night, but all of them could control urination by being woken up at night. The capacity of the neobladder was 245 to 380 mL with an average of 316 mL and the maximal pressure of the neobladder during filling was 28 to 57 cmH2O (1 cmH2O =0.098 kPa) with an average of 39 cmH2O. Conclusions As an operation the sigmoid orthotopic neobladder can be performed easily without serious postoperative complications and more reliable results. This operation may be generally applied in clinical practice.

  8. Intermittent Hypoxia in Childhood: The Harmful Consequences Versus Potential Benefits of Therapeutic Uses

    PubMed Central

    Serebrovskaya, Tatiana V.; Xi, Lei

    2015-01-01

    Intermittent hypoxia (IH) often occurs in early infancy in both preterm and term infants and especially at 36–44 weeks postmenstrual age. These episodes of IH could result from sleep-disordered breathing or may be temporally unrelated to apnea or bradycardia events. There are numerous reports indicating adverse effects of IH on development, behavior, academic achievement, and cognition in children with sleep apnea syndrome. It remains uncertain about the exact causative relationship between the neurocognitive and behavioral morbidities and IH and/or its associated sleep fragmentation. On the other hand, well-controlled and moderate IH conditioning/training has been used in sick children for treating their various forms of bronchial asthma, allergic dermatoses, autoimmune thyroiditis, cerebral palsy, and obesity. This review article provides an updated and impartial analysis on the currently available evidence in supporting either side of the seemingly contradictory scenarios. We wish to stimulate a comprehensive understanding of such a complex physiological phenomenon as intermittent hypoxia, which may be accompanied by other confounding factors (e.g., hypercapnia, polycythemia), in order to prevent or reduce its harmful consequences, while maximizing its potential utility as an effective therapeutic tool in pediatric patients. PMID:26042211

  9. Achievements in Stratospheric Ozone Protection

    EPA Pesticide Factsheets

    This report describes achievements in protecting the ozone layer, the benefits of these achievements, and strategies involved (e.g., using alternatives to ozone-depleting substances, phasing out harmful substances, and creating partnerships).

  10. Magnetic Microspheres for Therapeutical Applications

    NASA Technical Reports Server (NTRS)

    Mazuruk, K.; Ramachandran, N.; Curreri, Peter A. (Technical Monitor)

    2002-01-01

    Hyperthermia is a well known cancer therapy and consists of heating a tumor region to the elevated temperatures in the range of 40-45 C for an extended period of time (2-8 hours). This leads to thermal inactivation of cell regulatory and growth processes with resulting widespread necrosis, carbonization and coagulation. Moreover, heat boosts the tumor response to other treatments such as radiation, chemotherapy or immunotherapy. Of particular importance is careful control of generated heat in the treated region and keeping it localized. Higher heating, to about 56 C can lead to tissue thermo-ablation. With accurate temperature control, hyperthermia has the advantage of having minimal side effects. Several heating techniques are utilized for this purpose, such as whole body hyperthermia, radio-frequency (RF) hyperthermia, ultrasound technique, inductive microwave antenna hyperthermia, inductive needles (thermoseeds), and magnetic fluid hyperthermia (MFH).MFH offers many advantages as targeting capability by applying magnets. However, this technology still suffers significant inefficiencies due to lack of thermal control. This paper will provide a review of the topic and outline the ongoing work in this area. The main emphasis is in devising ways to overcome the technical difficulty in hyperthermia therapy of achieving a uniform therapeutic temperature over the required region of the body and holding it steady. The basic obstacle of the present heating methods are non-uniform thermal properties of the tissue. Our approach is to develop a novel class of magnetic fluids which have inherent thermoregulating properties. We have identified a few magnetic alloys which can serve as a suitable nano-particle material. The objective is to synthesize, characterize and evaluate the efficacy of TRMF for hyperthermia therapy.

  11. [Chemical constituents from the roots of Angelica polymorpha Maxim].

    PubMed

    Yang, Yu; Zhang, Yang; Ren, Feng-Xia; Yu, Neng-Jiang; Xu, Rui; Zhao, Yi-Min

    2013-05-01

    Angelica polymorpha Maxim. is a plant of the Angelica genus (Umbelliferae). The root and stem of this plant is a folk medicine known to have the actions of relieving rheumatism and cold and subsiding swelling and pains. To investigate the chemical constituents in the root of A. polymorpha Maxim., seven compounds were isolated from an 80% ethanol extract by column chromatography. Their structures were elucidated according to the spectroscopic analysis. Compound 1 is a new sesquiterpene, named as bisabolactone. Its absolute configuration was determined by 1D NOESY and CD analysis. The others were identified as 5-hydroxymethylfurfural (2), hycandinic acid ester 1 (3), ferulic acid (4), isooxypeucedanin (5), noreugenin (6) and cimifugin (7). Compound 2 and 3 were isolated from this genus for the first time and compound 4 was isolated from this plant for the first time.

  12. Maximally entangled mixed states for qubit-qutrit systems

    NASA Astrophysics Data System (ADS)

    Mendonça, Paulo E. M. F.; Marchiolli, Marcelo A.; Hedemann, Samuel R.

    2017-02-01

    We consider the problems of maximizing the entanglement negativity of X-form qubit-qutrit density matrices with (i) a fixed spectrum and (ii) a fixed purity. In the first case, the problem is solved in full generality whereas, in the latter, partial solutions are obtained by imposing extra spectral constraints such as rank deficiency and degeneracy, which enable a semidefinite programming treatment for the optimization problem at hand. Despite the technically motivated assumptions, we provide strong numerical evidence that threefold degenerate X states of purity P reach the highest entanglement negativity accessible to arbitrary qubit-qutrit density matrices of the same purity, hence characterizing a sparse family of likely qubit-qutrit maximally entangled mixed states.

  13. Exactly maximally convergent multipoint Padé approximants

    NASA Astrophysics Data System (ADS)

    Kovacheva, Ralitza K.

    2016-12-01

    Given a regular compact set E in the complex plane C, a unit measure µ supported by ∂E, a triangular point set β := {βn,kk=1nn=1∞, β ⊂ ∂E and a function f, holomorphic on E, let πn,m β ,f be the associated multipoint β- Padé approximant of order (n, m). We show that if the sequence πn,m β ,f , n ∈ Λ, m- fixed, converges exact maximally to f relatively to the measure µ, then the points βn,k are uniformly distributed on ∂E with respect to µ as n ∈ Λ. Furthermore, a result about the zeros behavior of the exact maximally convergent sequence Λ is provided, under the condition that Λ is "dense enough."

  14. High Intensity Interval Training For Maximizing Health Outcomes.

    PubMed

    Karlsen, Trine; Aamot, Inger-Lise; Haykowsky, Mark; Rognmo, Øivind

    2017-04-03

    Regular physical activity or exercise training are important actions to improve cardiorespiratory fitness and maintain health throughout life. There is solid evidence that exercise is an effective preventative strategy against at least 25 medical conditions, including cardiovascular disease, stroke, hypertension, colon and breast cancer, and type 2 diabetes. Traditionally, endurance exercise training (ET) to improve health related outcomes has consisted of low- to moderate ET intensity. However, a growing body of evidence suggests that higher exercise intensities may be superior to moderate intensity for maximizing health outcomes. The primary objective of this review is to discuss how aerobic high-intensity interval training (HIIT) as compared to moderate continuous training may maximize outcomes, and to provide practical advices for successful clinical and home-based HIIT.

  15. Likelihood maximization for list-mode emission tomographic image reconstruction.

    PubMed

    Byrne, C

    2001-10-01

    The maximum a posteriori (MAP) Bayesian iterative algorithm using priors that are gamma distributed, due to Lange, Bahn and Little, is extended to include parameter choices that fall outside the gamma distribution model. Special cases of the resulting iterative method include the expectation maximization maximum likelihood (EMML) method based on the Poisson model in emission tomography, as well as algorithms obtained by Parra and Barrett and by Huesman et al. that converge to maximum likelihood and maximum conditional likelihood estimates of radionuclide intensities for list-mode emission tomography. The approach taken here is optimization-theoretic and does not rely on the usual expectation maximization (EM) formalism. Block-iterative variants of the algorithms are presented. A self-contained, elementary proof of convergence of the algorithm is included.

  16. Momentary maximizing in concurrent schedules with a minimum interchangeover interval

    PubMed Central

    Todorov, João Claudio; Souza, Deisy G.; Bori, Carolina M.

    1993-01-01

    Eight pigeons were trained on concurrent variable-interval variable-interval schedules with a minimum interchangeover time programmed as a consequence of changeovers. In Experiment 1 the reinforcement schedules remained constant while the minimum interchangeover time varied from 0 to 200 s. Relative response rates and relative time deviated from relative reinforcement rates toward indifference with long minimum interchangeover times. In Experiment 2 different reinforcement ratios were scheduled in successive experimental conditions with the minimum interchangeover time constant at 0, 2, 10, or 120 s. The exponent of the generalized matching equation was close to 1.0 when the minimum interchangeover time was 0 s (the typical procedure for concurrent schedules without a changeover delay) and decreased as that duration was increased. The data support the momentary maximizing theory and contradict molar maximizing theories and the melioration theory. PMID:16812704

  17. Resistance maximization principle for defending networks against virus attack

    NASA Astrophysics Data System (ADS)

    Li, Angsheng; Zhang, Xiaohui; Pan, Yicheng

    2017-01-01

    We investigate the defending of networks against virus attack. We define the resistance of a network to be the maximum number of bits required to determine the code of the module that is accessible from random walk, from which random walk cannot escape. We show that for any network G, R(G) =H1(G) -H2(G) , where R(G) is the resistance of G, H1(G) and H2(G) are the one- and two-dimensional structural information of G, respectively, and that resistance maximization is the principle for defending networks against virus attack. By using the theory, we investigate the defending of real world networks and of the networks generated by the preferential attachment and the security models. We show that there exist networks that are defensible by a small number of controllers from cascading failure of any virus attack. Our theory demonstrates that resistance maximization is the principle for defending networks against virus attacks.

  18. Resting and maximal heart rates in ectothermic vertebrates.

    PubMed

    Lillywhite, H B; Zippel, K C; Farrell, A P

    1999-12-01

    Resting and maximal heart rates (HR) in ectothermic vertebrates are generally lower than those in endotherms and vary by more than an order of magnitude interspecifically. Variation of HR transcends phylogeny and is influenced by numerous factors including temperature, activity, gas exchange, intracardiac shunts, pH, posture, and reflexogenic regulation of blood pressure. The characteristic resting HR is rarely the intrinsic rate of the pacemaker, which is primarily modulated by cholinergic inhibition and adrenergic excitation in most species. Neuropeptides also appear to be involved in cardiac regulation, although their role is not well understood. The principal determinants of resting HR include temperature, metabolic rate and hemodynamic requirements. Maximal HRs generally do not exceed 120 b min-1, but notable exceptions include the heterothermic tuna and small reptiles having HRs in excess of 300 b min-1 at higher body temperatures. Temperature affects the intrinsic pacemaker rate as well as the relative influence of adrenergic and cholinergic modulation. It also influences the evolved capability to increase HR, with maximal cardiac responses matched to preferred body temperatures in some species. Additional factors either facilitate or limit the maximal level of HR, including: (1) characteristics of the pacemaker potential; (2) development of sarcoplasmic reticulum as a calcium store in excitation-contraction coupling; (3) low-resistance coupling of myocardial cells; (4) limitations of force development imposed by rate changes; (5) efficacy of sympathetic modulation; and (6) development of coronary circulation to enhance oxygen delivery to myocardium. In evolutionary terms, both hemodynamic and oxygen requirements appear to have been key selection pressures for rapid cardiac rates.

  19. Effect of sonic driving on maximal aerobic performance.

    PubMed

    Brilla, L.R.; Hatcher, Stefanie

    2000-07-01

    The study purpose was to evaluate antecedent binaural stimulation (ABS) on maximal aerobic physical performance. Twenty-two healthy, physically active subjects, 21-34 years, randomly received one of two preparations for each session: 15 min of quiet (BLANK) or percussive sonic driving at 200+ beats per minute (bpm) using a recorded compact disc (FSS, Mill Valley, CA) with headphones (ABS). Baseline HR, blood pressure (BP), and breathing frequency (f(br)) were obtained. During each condition, HR and f(br) were recorded at 3-min intervals. The graded maximal treadmill testing was administered immediately postpreparation session on separate days, with at least 48 h rest between sessions. There were significant differences in the antecedent period means between the two conditions, ABS (HR: 70.2 +/- 10.7 bpm; f(br): 18.5 +/- 3.3 br min(-1); BP: 134.5/87.9 +/- 13.6/9.2 mm Hg) and BLANK (HR: 64.6 +/- 7.9; f(br): 14.3 +/- 2.9; BP: 126.7/80.3 +/- 12.1/8.6). Differences were noted for each 3-min interval and pre- postantecedent period. The maximal graded exercise test (GXT) results showed that there was a small but significant (P < 0.05), increase in maximal VO(2) in the ABS (49.8 +/- 6.8 ml. kg(-1). min(-1)) vs. BLANK (46.7 +/- 8.7) conditions. Related to that finding was a slight increase (0.5 min) in time to exhaustion (P < 0.05). There were no significant differences in HR or RPE (P > 0.05). There may be a latency to ABS related to entrainment or imagery-enhanced warm-up. Am. J. Hum. Biol. 12:558-565, 2000. Copyright 2000 Wiley-Liss, Inc.

  20. [Research advance in rare and endemic plant Tetraena mongolica Maxim].

    PubMed

    Zhen, Jiang-Hong; Liu, Guo-Hou

    2008-02-01

    In this paper, the research advance in rare and endemic plant Tetraena mongolica Maxim. was summarized from the aspects of morphology, anatomy, palynology, cytology, seed-coat micro-morphology, embryology, physiology, biology, ecology, genetic diversity, chemical constituents, endangered causes, and conservation approaches, and the further research directions were prospected. It was considered that population viability, idioplasm conservation and artificial renewal, molecular biology of ecological adaptability, and assessment of habitat suitability should be the main aspects for the future study of T. mongolica.

  1. Project Scheduling to Maximize Positive Impacts of Reconstruction Operations

    DTIC Science & Technology

    2009-03-01

    require intervention — military or otherwise — by concerned states, and the frequency with which these interventions occur is increasing. To meet...this new op- erational challenge, the US military must adapt its planning procedures to account for Security, Stabilization, Transition, and...reconstruction activities in such a way as to maximize the positive impacts during the initial phase of SSTRO. Specifically, this research proposes to

  2. Mixed maximal and explosive strength training in recreational endurance runners.

    PubMed

    Taipale, Ritva S; Mikkola, Jussi; Salo, Tiina; Hokka, Laura; Vesterinen, Ville; Kraemer, William J; Nummela, Ari; Häkkinen, Keijo

    2014-03-01

    Supervised periodized mixed maximal and explosive strength training added to endurance training in recreational endurance runners was examined during an 8-week intervention preceded by an 8-week preparatory strength training period. Thirty-four subjects (21-45 years) were divided into experimental groups: men (M, n = 9), women (W, n = 9), and control groups: men (MC, n = 7), women (WC, n = 9). The experimental groups performed mixed maximal and explosive exercises, whereas control subjects performed circuit training with body weight. Endurance training included running at an intensity below lactate threshold. Strength, power, endurance performance characteristics, and hormones were monitored throughout the study. Significance was set at p ≤ 0.05. Increases were observed in both experimental groups that were more systematic than in the control groups in explosive strength (12 and 13% in men and women, respectively), muscle activation, maximal strength (6 and 13%), and peak running speed (14.9 ± 1.2 to 15.6 ± 1.2 and 12.9 ± 0.9 to 13.5 ± 0.8 km Ł h). The control groups showed significant improvements in maximal and explosive strength, but Speak increased only in MC. Submaximal running characteristics (blood lactate and heart rate) improved in all groups. Serum hormones fluctuated significantly in men (testosterone) and in women (thyroid stimulating hormone) but returned to baseline by the end of the study. Mixed strength training combined with endurance training may be more effective than circuit training in recreational endurance runners to benefit overall fitness that may be important for other adaptive processes and larger training loads associated with, e.g., marathon training.

  3. Planning for partnerships: Maximizing surge capacity resources through service learning.

    PubMed

    Adams, Lavonne M; Reams, Paula K; Canclini, Sharon B

    2015-01-01

    Infectious disease outbreaks and natural or human-caused disasters can strain the community's surge capacity through sudden demand on healthcare activities. Collaborative partnerships between communities and schools of nursing have the potential to maximize resource availability to meet community needs following a disaster. This article explores how communities can work with schools of nursing to enhance surge capacity through systems thinking, integrated planning, and cooperative efforts.

  4. Therapeutic Devices for Epilepsy

    PubMed Central

    Fisher, Robert S.

    2011-01-01

    Therapeutic devices provide new options for treating drug-resistant epilepsy. These devices act by a variety of mechanisms to modulate neuronal activity. Only vagus nerve stimulation, which continues to develop new technology, is approved for use in the United States. Deep brain stimulation (DBS) of anterior thalamus for partial epilepsy recently was approved in Europe and several other countries. Responsive neurostimulation, which delivers stimuli to one or two seizure foci in response to a detected seizure, recently completed a successful multicenter trial. Several other trials of brain stimulation are in planning or underway. Transcutaneous magnetic stimulation (TMS) may provide a noninvasive method to stimulate cortex. Controlled studies of TMS split on efficacy, and may depend on whether a seizure focus is near a possible region for stimulation. Seizure detection devices in the form of “shake” detectors via portable accelerometers can provide notification of an ongoing tonic-clonic seizure, or peace of mind in the absence of notification. Prediction of seizures from various aspects of EEG is in early stages. Prediction appears to be possible in a subpopulation of people with refractory seizures and a clinical trial of an implantable prediction device is underway. Cooling of neocortex or hippocampus reversibly can attenuate epileptiform EEG activity and seizures, but engineering problems remain in its implementation. Optogenetics is a new technique that can control excitability of specific populations of neurons with light. Inhibition of epileptiform activity has been demonstrated in hippocampal slices, but use in humans will require more work. In general, devices provide useful palliation for otherwise uncontrollable seizures, but with a different risk profile than with most drugs. Optimizing the place of devices in therapy for epilepsy will require further development and clinical experience. PMID:22367987

  5. Mitochondrial diseases: therapeutic approaches.

    PubMed

    DiMauro, Salvatore; Mancuso, Michelangelo

    2007-06-01

    Therapy of mitochondrial encephalomyopathies (defined restrictively as defects of the mitochondrial respiratory chain) is woefully inadequate, despite great progress in our understanding of the molecular bases of these disorders. In this review, we consider sequentially several different therapeutic approaches. Palliative therapy is dictated by good medical practice and includes anticonvulsant medication, control of endocrine dysfunction, and surgical procedures. Removal of noxious metabolites is centered on combating lactic acidosis, but extends to other metabolites. Attempts to bypass blocks in the respiratory chain by administration of electron acceptors have not been successful, but this may be amenable to genetic engineering. Administration of metabolites and cofactors is the mainstay of real-life therapy and is especially important in disorders due to primary deficiencies of specific compounds, such as carnitine or coenzyme Q10. There is increasing interest in the administration of reactive oxygen species scavengers both in primary mitochondrial diseases and in neurodegenerative diseases directly or indirectly related to mitochondrial dysfunction. Aerobic exercise and physical therapy prevent or correct deconditioning and improve exercise tolerance in patients with mitochondrial myopathies due to mitochondrial DNA (mtDNA) mutations. Gene therapy is a challenge because of polyplasmy and heteroplasmy, but interesting experimental approaches are being pursued and include, for example, decreasing the ratio of mutant to wild-type mitochondrial genomes (gene shifting), converting mutated mtDNA genes into normal nuclear DNA genes (allotopic expression), importing cognate genes from other species, or correcting mtDNA mutations with specific restriction endonucleases. Germline therapy raises ethical problems but is being considered for prevention of maternal transmission of mtDNA mutations. Preventive therapy through genetic counseling and prenatal diagnosis is

  6. The assessment of maximal respiratory mouth pressures in adults.

    PubMed

    Evans, John A; Whitelaw, William A

    2009-10-01

    Maximal inspiratory pressure (MIP) and maximal expiratory pressure (MEP) are simple, convenient, and noninvasive indices of respiratory muscle strength at the mouth, but standards are not clearly established. We review recent literature, update the 2002 American Thoracic Society/European Respiratory Society statement, and propose as the best choice using a flanged mouthpiece for reference values and lower limit of normal (LLN) values as a function of age for adults age up to about 70 years. Because male pressures are higher than female and MEP exceeds MIP, we present 4 linear regression reference equations as a function of age for adults age up to approximately 70 years: Male MIP=120-(0.41xage), and male MIP LLN=62-(0.15xage). Male MEP=174-(0.83xage), and male MEP LLN=117-(0.83xage). Female MIP=108-(0.61xage), and female MIP LLN=62-(0.50xage). Female MEP=131-(0.86xage), and female MEP LLN=95-(0.57xage). (Pressure in cm H2O and age in years.) We discuss normal values in older subjects, estimation of LLN values, and the relationship between vital capacity and respiratory muscle strength, and offer a guide to interpretation of maximal pressure measurements. The approach should allow direct implementation of MIP and MEP in a pulmonary function laboratory.

  7. Maximal anaerobic power: relationship to anthropometric characteristics during growth.

    PubMed

    Mercier, B; Mercier, J; Granier, P; Le Gallais, D; Préfaut, C

    1992-01-01

    The purpose of this study was to determine the effects of age in relation to anthropometric characteristics upon maximal anaerobic power of legs in sixty-nine young boys aged 11 to 19 years. Maximal anaerobic power (Wmax) was measured by the force-velocity test. Lean body mass (LBM) was determined from all four skin-fold thickness measurements, leg volume (LV) was estimated by anthropometric method, and anthropometric measurements were used to determine total muscular mass (TMM). Wmax increased significantly (F = 44.1, p less than 0.001) between 11 and 19 years and was correlated with LV (r = 0.84) and TMM (r = 0.88). It was most highly correlated with LBM (r = 0.94), which best explained the percentage of the total variance of Wmax (88%). Normalized Wmax (Wmax/LBM) also increased significantly between 11 and 19 years (F = 21.9, p less than 0.001). In conclusion, Wmax determined by the force-velocity test was closely related to anthropometric characteristics, especially LBM, during the growth period. Furthermore, even when corrected for lean body mass, maximal anaerobic power was always found to increase. This suggests that other undetermined factors, in addition to the amount of lean tissue mass, may explain the increase of Wmax during the force-velocity test.

  8. MADMX: a strategy for maximal dense motif extraction.

    PubMed

    Grossi, Roberto; Pietracaprina, Andrea; Pisanti, Nadia; Pucci, Geppino; Upfal, Eli; Vandin, Fabio

    2011-04-01

    We develop, analyze, and experiment with a new tool, called MADMX, which extracts frequent motifs from biological sequences. We introduce the notion of density to single out the "significant" motifs. The density is a simple and flexible measure for bounding the number of don't cares in a motif, defined as the fraction of solid (i.e., different from don't care) characters in the motif. A maximal dense motif has density above a certain threshold, and any further specialization of a don't care symbol in it or any extension of its boundaries decreases its number of occurrences in the input sequence. By extracting only maximal dense motifs, MADMX reduces the output size and improves performance, while enhancing the quality of the discoveries. The efficiency of our approach relies on a newly defined combining operation, dubbed fusion, which allows for the construction of maximal dense motifs in a bottom-up fashion, while avoiding the generation of nonmaximal ones. We provide experimental evidence of the efficiency and the quality of the motifs returned by MADMX.

  9. Column generation algorithms for exact modularity maximization in networks

    NASA Astrophysics Data System (ADS)

    Aloise, Daniel; Cafieri, Sonia; Caporossi, Gilles; Hansen, Pierre; Perron, Sylvain; Liberti, Leo

    2010-10-01

    Finding modules, or clusters, in networks currently attracts much attention in several domains. The most studied criterion for doing so, due to Newman and Girvan [Phys. Rev. E 69, 026113 (2004)]10.1103/PhysRevE.69.026113, is modularity maximization. Many heuristics have been proposed for maximizing modularity and yield rapidly near optimal solution or sometimes optimal ones but without a guarantee of optimality. There are few exact algorithms, prominent among which is a paper by Xu [Eur. Phys. J. B 60, 231 (2007)]10.1140/epjb/e2007-00331-0. Modularity maximization can also be expressed as a clique partitioning problem and the row generation algorithm of Grötschel and Wakabayashi [Math. Program. 45, 59 (1989)]10.1007/BF01589097 applied. We propose to extend both of these algorithms using the powerful column generation methods for linear and non linear integer programming. Performance of the four resulting algorithms is compared on problems from the literature. Instances with up to 512 entities are solved exactly. Moreover, the computing time of previously solved problems are reduced substantially.

  10. Random effects structure for confirmatory hypothesis testing: Keep it maximal

    PubMed Central

    Barr, Dale J.; Levy, Roger; Scheepers, Christoph; Tily, Harry J.

    2013-01-01

    Linear mixed-effects models (LMEMs) have become increasingly prominent in psycholinguistics and related areas. However, many researchers do not seem to appreciate how random effects structures affect the generalizability of an analysis. Here, we argue that researchers using LMEMs for confirmatory hypothesis testing should minimally adhere to the standards that have been in place for many decades. Through theoretical arguments and Monte Carlo simulation, we show that LMEMs generalize best when they include the maximal random effects structure justified by the design. The generalization performance of LMEMs including data-driven random effects structures strongly depends upon modeling criteria and sample size, yielding reasonable results on moderately-sized samples when conservative criteria are used, but with little or no power advantage over maximal models. Finally, random-intercepts-only LMEMs used on within-subjects and/or within-items data from populations where subjects and/or items vary in their sensitivity to experimental manipulations always generalize worse than separate F1 and F2 tests, and in many cases, even worse than F1 alone. Maximal LMEMs should be the ‘gold standard’ for confirmatory hypothesis testing in psycholinguistics and beyond. PMID:24403724

  11. The Evolution of Therapeutic Recreation.

    ERIC Educational Resources Information Center

    Riley, Bob; Skalko, Thomas K.

    1998-01-01

    Reviews elements that impact the delivery of therapeutic recreation services, emphasizing elements that are external to the discipline and influence practice and elements that are internal to the discipline and must be addressed if therapeutic recreation is to continue its evolution as a competitive health and human service discipline.…

  12. Toward Constructing the Therapeutic System.

    ERIC Educational Resources Information Center

    Andolfi, Maurizio; Angelo, Claudio

    1988-01-01

    Describes the therapist as an active participant in the construction of the therapeutic system, explaining how the therapist constructs complex relationships within the evolving therapeutic process. Reevaluates the importance of the individual in the family as an agent of change and as a mediator of triangular relational messages. (Author/NB)

  13. Therapeutic efficacy of nanomedicines for prostate cancer: An update

    PubMed Central

    2016-01-01

    Recent advances in cancer nanomedicine have attracted remarkable attention in medical sectors. Pharmacologic research on nanomedicines, including targeted cancer therapy, has increased dramatically in the past 5 years. The success stories of nanomedicines in the clinical field include the fabrication of nanomedicines that show maximum loading efficiency into carriers, maximal release kinetics, and minimum toxicity to healthy cells. Nanoparticle-mediated medicines have been developed to specifically target prostate cancer tissue by use of aptamers, antibody targeting, and sustained release of nanomedicines in a dose- and time-dependent manner. Nanomedicines have been developed for therapeutic application in combination with image-guided therapy in real time. The scope of one of these nanomedicines, Abraxane (paclitaxel), may be extended to prostate cancer therapeutic applications for better quality of patient life and longer survival. This review provides an update on the latest directions and developments in nanomedicines for prostate cancer. PMID:26966723

  14. Students’ Achievement Goals, Learning-Related Emotions and Academic Achievement

    PubMed Central

    Lüftenegger, Marko; Klug, Julia; Harrer, Katharina; Langer, Marie; Spiel, Christiane; Schober, Barbara

    2016-01-01

    In the present research, the recently proposed 3 × 2 model of achievement goals is tested and associations with achievement emotions and their joint influence on academic achievement are investigated. The study was conducted with 388 students using the 3 × 2 Achievement Goal Questionnaire including the six proposed goal constructs (task-approach, task-avoidance, self-approach, self-avoidance, other-approach, other-avoidance) and the enjoyment and boredom scales from the Achievement Emotion Questionnaire. Exam grades were used as an indicator of academic achievement. Findings from CFAs provided strong support for the proposed structure of the 3 × 2 achievement goal model. Self-based goals, other-based goals and task-approach goals predicted enjoyment. Task-approach goals negatively predicted boredom. Task-approach and other-approach predicted achievement. The indirect effects of achievement goals through emotion variables on achievement were assessed using bias-corrected bootstrapping. No mediation effects were found. Implications for educational practice are discussed. PMID:27199836

  15. Therapeutic applications of hydrogels in oral drug delivery

    PubMed Central

    Sharpe, Lindsey A; Daily, Adam M; Horava, Sarena D; Peppas, Nicholas A

    2015-01-01

    Introduction Oral delivery of therapeutics, particularly protein-based pharmaceutics, is of great interest for safe and controlled drug delivery for patients. Hydrogels offer excellent potential as oral therapeutic systems due to inherent biocompatibility, diversity of both natural and synthetic material options and tunable properties. In particular, stimuli-responsive hydrogels exploit physiological changes along the intestinal tract to achieve site-specific, controlled release of protein, peptide and chemotherapeutic molecules for both local and systemic treatment applications. Areas covered This review provides a wide perspective on the therapeutic use of hydrogels in oral delivery systems. General features and advantages of hydrogels are addressed, with more considerable focus on stimuli-responsive systems that respond to pH or enzymatic changes in the gastrointestinal environment to achieve controlled drug release. Specific examples of therapeutics are given. Last, in vitro and in vivo methods to evaluate hydrogel performance are discussed. Expert opinion Hydrogels are excellent candidates for oral drug delivery, due to the number of adaptable parameters that enable controlled delivery of diverse therapeutic molecules. However, further work is required to more accurately simulate physiological conditions and enhance performance, which is important to achieve improved bioavailability and increase commercial interest. PMID:24848309

  16. Therapeutic drug monitoring for antidepressant drug treatment.

    PubMed

    Ostad Haji, Elnaz; Hiemke, Christoph; Pfuhlmann, Bruno

    2012-01-01

    The aim of antidepressant drug treatment is to produce remission without causing adverse effects during the acute phase of the illness and to prevent relapses or recurrences during continuation or maintenance therapy. To achieve these goals, drug choice and dosage must be optimized for each patient individually. Therapeutic drug monitoring (TDM), which is based on the assumption that clinical effects correlate better with blood levels than doses, can be helpful. When using tricyclic antidepressant drugs TDM enhances safety and efficacy. For newer antidepressant drugs, however, it is a matter of debate to which extend TDM can have beneficial effects. For many antidepressants there exist carefully designed studies concerning the relationship between plasma concentration and clinical effects that allow the definition of recommended therapeutic ranges of the plasma concentration. In some drugs however, concentration-effect studies are lacking so far, but target ranges resulting from clinically relevant plasma concentrations or from pharmacokinetic studies could be provided. During the last years, knowledge on therapeutic references ranges in blood towards TDM guided treatment has markedly improved for new antidepressant drugs, and many specific indications have been defined for useful TDM. Recently published guidelines describe the best practice of TDM for neuropsychiatric drugs. The aim of this review is to summarize the current status of TDM for antidepressant drugs and discuss the literature with regard to response optimization, pharmacovigilance and economic benefits and with regard to needs for further research.

  17. Maximizing Health or Sufficient Capability in Economic Evaluation? A Methodological Experiment of Treatment for Drug Addiction.

    PubMed

    Goranitis, Ilias; Coast, Joanna; Day, Ed; Copello, Alex; Freemantle, Nick; Frew, Emma

    2016-11-17

    Conventional practice within the United Kingdom and beyond is to conduct economic evaluations with "health" as evaluative space and "health maximization" as the decision-making rule. However, there is increasing recognition that this evaluative framework may not always be appropriate, and this is particularly the case within public health and social care contexts. This article presents a methodological case study designed to explore the impact of changing the evaluative space within an economic evaluation from health to capability well-being and the decision-making rule from health maximization to the maximization of sufficient capability. Capability well-being is an evaluative space grounded on Amartya Sen's capability approach and assesses well-being based on individuals' ability to do and be the things they value in life. Sufficient capability is an egalitarian approach to decision making that aims to ensure everyone in society achieves a normatively sufficient level of capability well-being. The case study is treatment for drug addiction, and the cost-effectiveness of 2 psychological interventions relative to usual care is assessed using data from a pilot trial. Analyses are undertaken from a health care and a government perspective. For the purpose of the study, quality-adjusted life years (measured using the EQ-5D-5L) and years of full capability equivalent and years of sufficient capability equivalent (both measured using the ICECAP-A [ICEpop CAPability measure for Adults]) are estimated. The study concludes that different evaluative spaces and decision-making rules have the potential to offer opposing treatment recommendations. The implications for policy makers are discussed.

  18. Is peak VO2 a maximal index of children's aerobic fitness?

    PubMed

    Armstrong, N; Welsman, J; Winsley, R

    1996-07-01

    A levelling of oxygen uptake (VO2 plateau) at high exercise intensities is conventionally used as the criterion for establishing VO2max during progressive, incremental exercise testing. Only a minority of children, however, demonstrate a VO2 plateau during exercise to voluntary exhaustion. This study was therefore designed to investigate whether a VO2 plateau is required before peak VO2 can be considered a maximal index of children's aerobic fitness. Eighteen girls and 17 boys (age 9.9 +/- 0.4 yrs) carried out three treadmill tests to exhaustion one week apart. The first test comprised a discontinuous, incremental protocol to voluntary exhaustion. In test two each child warmed up and then ran to exhaustion at the same belt speed but on a gradient 2.5% greater than that which had produced an exhaustive effort on the first test. The third test was conducted similarly but the treadmill gradient was raised to 5% greater than that which had produced an exhaustive effort on the first test. Seven girls and 6 boys demonstrated a VO2 plateau (< or = 2 ml.kg-1.min-7) on the first test but no significant differences in either anthropometrical or peak physiological data were detected between those who demonstrated a plateau and those who did not. Mean peak VO2 values during tests two and three (supramaximal tests) did not increase significantly above that achieved on test one although indicators of an increased anaerobic contribution were significantly higher in both supramaximal tests. These findings indicate that peak VO2 in test one was a maximal value despite the absence of a VO2 plateau. The requirement of a VO2 plateau before peak VO2 can be regarded as a maximal index of young children's aerobic fitness is therefore untenable.

  19. The importance of maximal leg strength for female athletes when performing drop jumps.

    PubMed

    Barr, Matthew J; Nolte, Volker W

    2014-02-01

    A common suggestion is that a predetermined level of maximal leg strength is required before drop jump (DJ) training can begin. This study sought to examine the relationship between maximal squat strength (1 repetition maximum [RM]) and DJ performance in 15 female rugby players (n = 15). The subjects were tested for 1RM, countermovement jump, squat jump, and DJs from 0.24, 0.36, 0.48, 0.60, 0.72, and 0.84 m. Jump height (JH) was calculated for all jumps and relative peak eccentric force, relative peak concentric force, ground contact time (GCT), and reactive strength index were also calculated for DJs. Pearson correlations were used to examine the relationship between 1RM relative to body mass (BM) (1RM/BM) and JHs, reactive strength index, and GCT during DJs. The subjects were placed in a high strength (HS) or low strength (LS) group depending on whether or not their 1RM/BM was >1 or <1. The T-tests and 2-way analysis of variance (ANOVA) were used to compare the groups. A Fishers post hoc test was used for the ANOVA with significance set at p < 0.05. A large correlation between JH and 1RM/BM was shown at the 0.84-m dropping height (r = 0.56). A significant overall difference was found between the HS and LS groups for DJ JH with a post hoc analysis revealing a significant difference at the 0.84-m drop height (p = 0.029). It is likely beneficial for female athletes to achieve high levels of maximal leg strength if they are going to use high (>0.8-m) drop heights when performing DJs.

  20. Maximizing the probability of satisfying the clinical goals in radiation therapy treatment planning under setup uncertainty

    SciTech Connect

    Fredriksson, Albin Hårdemark, Björn; Forsgren, Anders

    2015-07-15

    Purpose: This paper introduces a method that maximizes the probability of satisfying the clinical goals in intensity-modulated radiation therapy treatments subject to setup uncertainty. Methods: The authors perform robust optimization in which the clinical goals are constrained to be satisfied whenever the setup error falls within an uncertainty set. The shape of the uncertainty set is included as a variable in the optimization. The goal of the optimization is to modify the shape of the uncertainty set in order to maximize the probability that the setup error will fall within the modified set. Because the constraints enforce the clinical goals to be satisfied under all setup errors within the uncertainty set, this is equivalent to maximizing the probability of satisfying the clinical goals. This type of robust optimization is studied with respect to photon and proton therapy applied to a prostate case and compared to robust optimization using an a priori defined uncertainty set. Results: Slight reductions of the uncertainty sets resulted in plans that satisfied a larger number of clinical goals than optimization with respect to a priori defined uncertainty sets, both within the reduced uncertainty sets and within the a priori, nonreduced, uncertainty sets. For the prostate case, the plans taking reduced uncertainty sets into account satisfied 1.4 (photons) and 1.5 (protons) times as many clinical goals over the scenarios as the method taking a priori uncertainty sets into account. Conclusions: Reducing the uncertainty sets enabled the optimization to find better solutions with respect to the errors within the reduced as well as the nonreduced uncertainty sets and thereby achieve higher probability of satisfying the clinical goals. This shows that asking for a little less in the optimization sometimes leads to better overall plan quality.

  1. Metrics for antibody therapeutics development.

    PubMed

    Reichert, Janice M

    2010-01-01

    A wide variety of full-size monoclonal antibodies (mAbs) and therapeutics derived from alternative antibody formats can be produced through genetic and biological engineering techniques. These molecules are now filling the preclinical and clinical pipelines of every major pharmaceutical company and many biotechnology firms. Metrics for the development of antibody therapeutics, including averages for the number of candidates entering clinical study and development phase lengths for mAbs approved in the United States, were derived from analysis of a dataset of over 600 therapeutic mAbs that entered clinical study sponsored, at least in part, by commercial firms. The results presented provide an overview of the field and context for the evaluation of on-going and prospective mAb development programs. The expansion of therapeutic antibody use through supplemental marketing approvals and the increase in the study of therapeutics derived from alternative antibody formats are discussed.

  2. Transdermal delivery of therapeutic agent

    NASA Technical Reports Server (NTRS)

    Kwiatkowski, Krzysztof C. (Inventor); Hayes, Ryan T. (Inventor); Magnuson, James W. (Inventor); Giletto, Anthony (Inventor)

    2008-01-01

    A device for the transdermal delivery of a therapeutic agent to a biological subject that includes a first electrode comprising a first array of electrically conductive microprojections for providing electrical communication through a skin portion of the subject to a second electrode comprising a second array of electrically conductive microprojections. Additionally, a reservoir for holding the therapeutic agent surrounding the first electrode and a pulse generator for providing an exponential decay pulse between the first and second electrodes may be provided. A method includes the steps of piercing a stratum corneum layer of skin with two arrays of conductive microprojections, encapsulating the therapeutic agent into biocompatible charged carriers, surrounding the conductive microprojections with the therapeutic agent, generating an exponential decay pulse between the two arrays of conductive microprojections to create a non-uniform electrical field and electrokinetically driving the therapeutic agent through the stratum corneum layer of skin.

  3. Bacteriophage Procurement for Therapeutic Purposes

    PubMed Central

    Weber-Dąbrowska, Beata; Jończyk-Matysiak, Ewa; Żaczek, Maciej; Łobocka, Małgorzata; Łusiak-Szelachowska, Marzanna; Górski, Andrzej

    2016-01-01

    Bacteriophages (phages), discovered 100 years ago, are able to infect and destroy only bacterial cells. In the current crisis of antibiotic efficacy, phage therapy is considered as a supplementary or even alternative therapeutic approach. Evolution of multidrug-resistant and pandrug-resistant bacterial strains poses a real threat, so it is extremely important to have the possibility to isolate new phages for therapeutic purposes. Our phage laboratory and therapy center has extensive experience with phage isolation, characterization, and therapeutic application. In this article we present current progress in bacteriophages isolation and use for therapeutic purposes, our experience in this field and its practical implications for phage therapy. We attempt to summarize the state of the art: properties of phages, the methods for their isolation, criteria of phage selection for therapeutic purposes and limitations of their use. Perspectives for the use of genetically engineered phages to specifically target bacterial virulence-associated genes are also briefly presented. PMID:27570518

  4. Nanoparticle-enabled, image-guided treatment planning of target specific RNAi therapeutics in an orthotopic prostate cancer model.

    PubMed

    Lin, Qiaoya; Jin, Cheng S; Huang, Huang; Ding, Lili; Zhang, Zhihong; Chen, Juan; Zheng, Gang

    2014-08-13

    The abilities to deliver siRNA to its intended action site and assess the delivery efficiency are challenges for current RNAi therapy, where effective siRNA delivery will join force with patient genetic profiling to achieve optimal treatment outcome. Imaging could become a critical enabler to maximize RNAi efficacy in the context of tracking siRNA delivery, rational dosimetry and treatment planning. Several imaging modalities have been used to visualize nanoparticle-based siRNA delivery but rarely did they guide treatment planning. We report a multimodal theranostic lipid-nanoparticle, HPPS(NIR)-chol-siRNA, which has a near-infrared (NIR) fluorescent core, enveloped by phospholipid monolayer, intercalated with siRNA payloads, and constrained by apoA-I mimetic peptides to give ultra-small particle size (<30 nm). Using fluorescence imaging, we demonstrated its cytosolic delivery capability for both NIR-core and dye-labeled siRNAs and its structural integrity in mice through intravenous administration, validating the usefulness of NIR-core as imaging surrogate for non-labeled therapeutic siRNAs. Next, we validated the targeting specificity of HPPS(NIR)-chol-siRNA to orthotopic tumor using sequential four-steps (in vivo, in situ, ex vivo and frozen-tissue) fluorescence imaging. The image co-registration of computed tomography and fluorescence molecular tomography enabled non-invasive assessment and treatment planning of siRNA delivery into the orthotopic tumor, achieving efficacious RNAi therapy.

  5. Comparison of EMG activity between maximal manual muscle testing and cybex maximal isometric testing of the quadriceps femoris.

    PubMed

    Lin, Hui-Ting; Hsu, Ar-Tyan; Chang, Jia-Hao; Chien, Chi-Sheng; Chang, Guan-Liang

    2008-02-01

    Two methods have been used to produce a maximal voluntary isometric contraction (MVIC) of the superficial quadriceps femoris muscles for normalization of electromyographic (EMG) data. The purposes of this study were to compare the myoelectic activity of MVIC of manual muscle testing (MMT) versus Cybex maximal isometric testing. Eighteen normal subjects were recruited. MMT and Cybex testing for MVIC of the dominant leg were performed. EMG activities of the vastus medialis, vastus lateralis and rectus femoris were recorded during MMT and Cybex trials. EMG amplitude and median frequency obtained from the two methods (MMT and Cybex testing) were used for statistical analysis of these three muscles. Statistically, the difference in the mean of the EMG signal amplitude and median frequency between MMT and Cybex testing were not significant. Considering cost and time, MMT for MVIC technique appears to be reliable and highly valuable.

  6. Athletic differences in the characteristics of the photoplethysmographic pulse shape: effect of maximal oxygen uptake and maximal muscular voluntary contraction.

    PubMed

    Wang, Anran; Yang, Lin; Liu, Chengyu; Cui, Jingxuan; Li, Yao; Yang, Xingxing; Zhang, Song; Zheng, Dingchang

    2015-01-01

    This study aimed to investigate the athletic differences in the characteristics of the photoplethysmographic (PPG) pulse shape. 304 athletes were enrolled and divided into three subgroups according to a typical sport classification in terms of the maximal oxygen uptake (MaxO2_low, MaxO2_middle and MaxO2_high groups) or the maximal muscular voluntary contraction (MMVC_low, MMVC_middle, and MMVC_high groups). Finger PPG pulses were digitally recorded and then normalized to derive the pulse area, pulse peak time T p , dicrotic notch time T n , and pulse reflection index (RI). The four parameters were finally compared between the three subgroups categorized by MaxO2 or by MMVC. In conclusion, it has been demonstrated by quantifying the characteristics of the PPG pulses in different athletes that MaxO2, but not MMVC, had significant effect on the arterial properties.

  7. Exubera. Inhale therapeutic systems.

    PubMed

    Bindra, Sanjit; Cefalu, William T

    2002-05-01

    Inhale, in colaboration with Pfizer and Aventis Pharma (formerly Hoechst Marion Roussel; HMR), is developing an insulin formulation utilizing its pulmonary delivery technology for macromolecules for the potential treatment of type I and II diabetes. By July 2001, the phase III program had been completed and the companies had begun to assemble data for MAA and NDA filings; however, it was already clear at this time that additional data might be required for filing. By December 2001, it had been decided that the NDA should include an increased level of controlled, long-term pulmonary safety data in diabetic patients and a major study was planned to be completed in 2002, with the NDA filed thereafter (during 2002). US-05997848 was issued to Inhale Therapeutic Systems in December 1999, and corresponds to WO-09524183, filed in February 1995. Equivalent applications have appeared to date in Australia, Brazil, Canada, China, Czech Republic, Europe, Finland, Hungary, Japan, Norway, New Zealand, Poland and South Africa. This family of applications is specific to pulmonary delivery of insulin. In February 1999, Lehman Brothers gave this inhaled insulin a 60% probability of reaching market, with a possible launch date of 2001. The analysts estimated peak sales at $3 billion in 2011. In May 2000, Aventis predicted that estimated peak sales would be in excess of $1 billion. In February 2000, Merrill Lynch expected product launch in 2002 and predicted that it would be a multibillion-dollar product. Analysts Merril Lynch predicted, in September and November 2000, that the product would be launched by 2002, with sales in that year of e75 million, rising to euro 500 million in 2004. In April 2001, Merrill Lynch predicted that filing for this drug would occur in 2001. Following the report of the potential delay in regulatory filing, issued in July 2001, Deutsche Banc Alex Brown predicted a filing would take place in the fourth quarter of 2002 and launch would take place in the first

  8. Stem cells as promising therapeutic options for neurological disorders.

    PubMed

    Yoo, Jongman; Kim, Han-Soo; Hwang, Dong-Youn

    2013-04-01

    Due to the limitations of pharmacological and other current therapeutic strategies, stem cell therapies have emerged as promising options for treating many incurable neurologic diseases. A variety of stem cells including pluripotent stem cells (i.e., embryonic stem cells and induced pluripotent stem cells) and multipotent adult stem cells (i.e., fetal brain tissue, neural stem cells, and mesenchymal stem cells from various sources) have been explored as therapeutic options for treating many neurologic diseases, and it is becoming obvious that each type of stem cell has pros and cons as a source for cell therapy. Wise selection of stem cells with regard to the nature and status of neurologic dysfunctions is required to achieve optimal therapeutic efficacy. To this aim, the stem cell-mediated therapeutic efforts on four major neurological diseases, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and stroke, will be introduced, and current problems and future directions will be discussed.

  9. Nanoparticle-Based Delivery of RNAi Therapeutics: Progress and Challenges

    PubMed Central

    Zhou, Jiehua; Shum, Ka-To; Burnett, John C.; Rossi, John J.

    2013-01-01

    RNA interference (RNAi) is an evolutionarily conserved, endogenous process for post-transcriptional regulation of gene expression. Although RNAi therapeutics have recently progressed through the pipeline toward clinical trials, the application of these as ideal, clinical therapeutics requires the development of safe and effective delivery systems. Inspired by the immense progress with nanotechnology in drug delivery, efforts have been dedicated to the development of nanoparticle-based RNAi delivery systems. For example, a precisely engineered, multifunctional nanocarrier with combined passive and active targeting capabilities may address the delivery challenges for the widespread use of RNAi as a therapy. Therefore, in this review, we introduce the major hurdles in achieving efficient RNAi delivery and discuss the current advances in applying nanotechnology-based delivery systems to overcome the delivery hurdles of RNAi therapeutics. In particular, some representative examples of nanoparticle-based delivery formulations for targeted RNAi therapeutics are highlighted. PMID:23667320

  10. Gas analyzer's drift leads to systematic error in maximal oxygen uptake and maximal respiratory exchange ratio determination

    PubMed Central

    Garcia-Tabar, Ibai; Eclache, Jean P.; Aramendi, José F.; Gorostiaga, Esteban M.

    2015-01-01

    The aim was to examine the drift in the measurements of fractional concentration of oxygen (FO2) and carbon dioxide (FCO2) of a Nafion-using metabolic cart during incremental maximal exercise in 18 young and 12 elderly males, and to propose a way in which the drift can be corrected. The drift was verified by comparing the pre-test calibration values with the immediate post-test verification values of the calibration gases. The system demonstrated an average downscale drift (P < 0.001) in FO2 and FCO2 of −0.18% and −0.05%, respectively. Compared with measured values, corrected average maximal oxygen uptakevalues were 5–6% lower (P < 0.001) whereas corrected maximal respiratory exchange ratio values were 8–9% higher (P < 0.001). The drift was not due to an electronic instability in the analyzers because it was reverted after 20 min of recovery from the end of the exercise. The drift may be related to an incomplete removal of water vapor from the expired gas during transit through the Nafion conducting tube. These data demonstrate the importance of checking FO2 and FCO2 values by regular pre-test calibrations and post-test verifications, and also the importance of correcting a possible shift immediately after exercise. PMID:26578980

  11. Gas analyzer's drift leads to systematic error in maximal oxygen uptake and maximal respiratory exchange ratio determination.

    PubMed

    Garcia-Tabar, Ibai; Eclache, Jean P; Aramendi, José F; Gorostiaga, Esteban M

    2015-01-01

    The aim was to examine the drift in the measurements of fractional concentration of oxygen (FO2) and carbon dioxide (FCO2) of a Nafion-using metabolic cart during incremental maximal exercise in 18 young and 12 elderly males, and to propose a way in which the drift can be corrected. The drift was verified by comparing the pre-test calibration values with the immediate post-test verification values of the calibration gases. The system demonstrated an average downscale drift (P < 0.001) in FO2 and FCO2 of -0.18% and -0.05%, respectively. Compared with measured values, corrected average maximal oxygen uptakevalues were 5-6% lower (P < 0.001) whereas corrected maximal respiratory exchange ratio values were 8-9% higher (P < 0.001). The drift was not due to an electronic instability in the analyzers because it was reverted after 20 min of recovery from the end of the exercise. The drift may be related to an incomplete removal of water vapor from the expired gas during transit through the Nafion conducting tube. These data demonstrate the importance of checking FO2 and FCO2 values by regular pre-test calibrations and post-test verifications, and also the importance of correcting a possible shift immediately after exercise.

  12. Maximizing the Impact of e-Therapy and Serious Gaming: Time for a Paradigm Shift.

    PubMed

    Fleming, Theresa M; de Beurs, Derek; Khazaal, Yasser; Gaggioli, Andrea; Riva, Giuseppe; Botella, Cristina; Baños, Rosa M; Aschieri, Filippo; Bavin, Lynda M; Kleiboer, Annet; Merry, Sally; Lau, Ho Ming; Riper, Heleen

    2016-01-01

    Internet interventions for mental health, including serious games, online programs, and apps, hold promise for increasing access to evidence-based treatments and prevention. Many such interventions have been shown to be effective and acceptable in trials; however, uptake and adherence outside of trials is seldom reported, and where it is, adherence at least, generally appears to be underwhelming. In response, an international Collaboration On Maximizing the impact of E-Therapy and Serious Gaming (COMETS) was formed. In this perspectives' paper, we call for a paradigm shift to increase the impact of internet interventions toward the ultimate goal of improved population mental health. We propose four pillars for change: (1) increased focus on user-centered approaches, including both user-centered design of programs and greater individualization within programs, with the latter perhaps utilizing increased modularization; (2) Increased emphasis on engagement utilizing processes such as gaming, gamification, telepresence, and persuasive technology; (3) Increased collaboration in program development, testing, and data sharing, across both sectors and regions, in order to achieve higher quality, more sustainable outcomes with greater reach; and (4) Rapid testing and implementation, including the measurement of reach, engagement, and effectiveness, and timely implementation. We suggest it is time for researchers, clinicians, developers, and end-users to collaborate on these aspects in order to maximize the impact of e-therapies and serious gaming.

  13. Comparative evaluation of multiresolution optimization strategies for multimodality image registration by maximization of mutual information.

    PubMed

    Maes, F; Vandermeulen, D; Suetens, P

    1999-12-01

    Maximization of mutual information of voxel intensities has been demonstrated to be a very powerful criterion for three-dimensional medical image registration, allowing robust and accurate fully automated affine registration of multimodal images in a variety of applications, without the need for segmentation or other preprocessing of the images. In this paper, we investigate the performance of various optimization methods and multiresolution strategies for maximization of mutual information, aiming at increasing registration speed when matching large high-resolution images. We show that mutual information is a continuous function of the affine registration parameters when appropriate interpolation is used and we derive analytic expressions of its derivatives that allow numerically exact evaluation of its gradient. Various multiresolution gradient- and non-gradient-based optimization strategies, such as Powell, simplex, steepest-descent, conjugate-gradient, quasi-Newton and Levenberg-Marquardt methods, are evaluated for registration of computed tomography (CT) and magnetic resonance images of the brain. Speed-ups of a factor of 3 on average compared to Powell's method at full resolution are achieved with similar precision and without a loss of robustness with the simplex, conjugate-gradient and Levenberg-Marquardt method using a two-level multiresolution scheme. Large data sets such as 256(2) x 128 MR and 512(2) x 48 CT images can be registered with subvoxel precision in <5 min CPU time on current workstations.

  14. Maximizing the Impact of e-Therapy and Serious Gaming: Time for a Paradigm Shift

    PubMed Central

    Fleming, Theresa M.; de Beurs, Derek; Khazaal, Yasser; Gaggioli, Andrea; Riva, Giuseppe; Botella, Cristina; Baños, Rosa M.; Aschieri, Filippo; Bavin, Lynda M.; Kleiboer, Annet; Merry, Sally; Lau, Ho Ming; Riper, Heleen

    2016-01-01

    Internet interventions for mental health, including serious games, online programs, and apps, hold promise for increasing access to evidence-based treatments and prevention. Many such interventions have been shown to be effective and acceptable in trials; however, uptake and adherence outside of trials is seldom reported, and where it is, adherence at least, generally appears to be underwhelming. In response, an international Collaboration On Maximizing the impact of E-Therapy and Serious Gaming (COMETS) was formed. In this perspectives’ paper, we call for a paradigm shift to increase the impact of internet interventions toward the ultimate goal of improved population mental health. We propose four pillars for change: (1) increased focus on user-centered approaches, including both user-centered design of programs and greater individualization within programs, with the latter perhaps utilizing increased modularization; (2) Increased emphasis on engagement utilizing processes such as gaming, gamification, telepresence, and persuasive technology; (3) Increased collaboration in program development, testing, and data sharing, across both sectors and regions, in order to achieve higher quality, more sustainable outcomes with greater reach; and (4) Rapid testing and implementation, including the measurement of reach, engagement, and effectiveness, and timely implementation. We suggest it is time for researchers, clinicians, developers, and end-users to collaborate on these aspects in order to maximize the impact of e-therapies and serious gaming. PMID:27148094

  15. MAXIMAL SPRINTING SPEED OF ELITE SOCCER PLAYERS DURING TRAINING AND MATCHES.

    PubMed

    Djaoui, Leo; Chamari, Karim; Owen, Adam; Dellal, Alexandre

    2016-09-23

    The aim of the present study was to compare 1) the maximal sprinting speed (MSS) attained by soccer players during matches (MSSmatch) according to their level of play (professional 1st French division vs. elite amateur 4th French division) and the playing positions; and 2) the MSS attained by professional soccer players during 14 different types of small-sided games (SSG, MSSSSG) and match-play. All players monitored through the study performed a 40-m sprint test to assess individual MSS (MSStest) and compare it to the training and match activity, with the calculation of the percentage of MSStest (%MSStest) reached. No differences were found according to the level of play, however positionally, wide players achieved a higher MSSmatch, %MSStest, and MSSSSG compared to central players (both defenders and midfielders) during matches and SSG. MSSmatch were higher than all MSSSSG, and MSSSSG were positively correlated with the area of the pitch (0.45, p<0.001), its length (0.53, p<0.001) and the number of players involved (0.38, p<0.001). The closer SSG was to match situation in term of rules, the higher the MSSSSG. Wide players reached higher MSS in match and SSG than central players, confirming the relevance of using SSG close to match situation to specifically prepare elite players to the maximal running speed demand of the match.

  16. Bioengineering and Coordination of Regulatory Networks and Intracellular Complexes to Maximize Hydrogen Production by Phototrophic Microorganisms

    SciTech Connect

    Tabita, F. Robert

    2013-07-30

    In this study, the Principal Investigator, F.R. Tabita has teemed up with J. C. Liao from UCLA. This project's main goal is to manipulate regulatory networks in phototrophic bacteria to affect and maximize the production of large amounts of hydrogen gas under conditions where wild-type organisms are constrained by inherent regulatory mechanisms from allowing this to occur. Unrestrained production of hydrogen has been achieved and this will allow for the potential utilization of waste materials as a feed stock to support hydrogen production. By further understanding the means by which regulatory networks interact, this study will seek to maximize the ability of currently available “unrestrained” organisms to produce hydrogen. The organisms to be utilized in this study, phototrophic microorganisms, in particular nonsulfur purple (NSP) bacteria, catalyze many significant processes including the assimilation of carbon dioxide into organic carbon, nitrogen fixation, sulfur oxidation, aromatic acid degradation, and hydrogen oxidation/evolution. Moreover, due to their great metabolic versatility, such organisms highly regulate these processes in the cell and since virtually all such capabilities are dispensable, excellent experimental systems to study aspects of molecular control and biochemistry/physiology are available.

  17. Role of Vertical Jumps and Anthropometric Variables in Maximal Kicking Ball Velocities in Elite Soccer Players

    PubMed Central

    Rodríguez-Lorenzo, Lois; Fernandez-del-Olmo, Miguel; Sanchez-Molina, José Andrés

    2016-01-01

    Abstract Kicking is one of the most important skills in soccer and the ability to achieve ma ximal kicking velocity with both legs leads to an advantage for the soccer player. This study examined the relationship be tween kicking ball velocity with both legs using anthropometric measurements and vertical jumps (a squat jump (SJ); a countermovement jump without (CMJ) and with the arm swing (CMJA) and a reactive jump (RJ)). Anthropome tric measurements did not correlate with kicking ball velocity. Vertical jumps correlated significantly with kicking ball velocity using the dominant leg only (r = .47, r = .58, r = .44, r = .51, for SJ, CMJ, CMJA and RJ, respectively) . Maximal kicking velocity with the dominant leg was significantly higher than with the non-dominant leg (t = 18.0 4, p < 0.001). Our results suggest that vertical jumps may be an optimal test to assess neuromuscular skills involved in kicking at maximal speed. Lack of the relationship between vertical jumps and kicking velocity with the non-dominant leg may reflect a difficulty to exhibit the neuromuscular skills during dominant leg kicking. PMID:28149419

  18. Motor unit firing rates of the gastrocnemii during maximal brief steady-state contractions in humans.

    PubMed

    Graham, Mitchell T; Rice, Charles L; Dalton, Brian H

    2016-02-01

    The human triceps surae (soleus, medial (MG) and lateral (LG) gastrocnemii) is complex and important for posture and gait. The soleus exhibits markedly lower motor unit firing rates (MUFRs; ∼16Hz) during maximal voluntary isometric contraction (MVC) than other limb muscles, but this information is unknown for the MG and LG. During multiple visits, subjects performed a series of 5-7, ∼7-s plantar flexor MVCs with tungsten microelectrodes inserted into the MG and LG. During a separate testing session, another group of subjects performed submaximal isometric contractions at 25%, 50%, and 75% MVC with inserted fine-wires in the MG, LG and soleus. Maximum steady-state MUFRs for MG and LG (∼23Hz) were not different, but faster than prior reports for the soleus. No differences between the three triceps surae components were detected for 25% or 50% MVC, but at 75% MVC, the MG MUFRs were 31% greater than soleus. The triceps surae exhibit similar torque modulation strategies at <75% MVC, but to achieve higher contraction intensities (>75% MVC) the gastrocnemii rely on faster rates to generate maximal torque than the soleus. Therefore, the MG and LG exhibit a larger range of MUFR capacities.

  19. Role of Vertical Jumps and Anthropometric Variables in Maximal Kicking Ball Velocities in Elite Soccer Players.

    PubMed

    Rodríguez-Lorenzo, Lois; Fernandez-Del-Olmo, Miguel; Sanchez-Molina, José Andrés; Martín-Acero, Rafael

    2016-12-01

    Kicking is one of the most important skills in soccer and the ability to achieve ma ximal kicking velocity with both legs leads to an advantage for the soccer player. This study examined the relationship be tween kicking ball velocity with both legs using anthropometric measurements and vertical jumps (a squat jump (SJ); a countermovement jump without (CMJ) and with the arm swing (CMJA) and a reactive jump (RJ)). Anthropome tric measurements did not correlate with kicking ball velocity. Vertical jumps correlated significantly with kicking ball velocity using the dominant leg only (r = .47, r = .58, r = .44, r = .51, for SJ, CMJ, CMJA and RJ, respectively) . Maximal kicking velocity with the dominant leg was significantly higher than with the non-dominant leg (t = 18.0 4, p < 0.001). Our results suggest that vertical jumps may be an optimal test to assess neuromuscular skills involved in kicking at maximal speed. Lack of the relationship between vertical jumps and kicking velocity with the non-dominant leg may reflect a difficulty to exhibit the neuromuscular skills during dominant leg kicking.

  20. Natural Products as Source of Therapeutics against Parasitic Diseases.

    PubMed

    Hertweck, Christian

    2015-12-01

    An end to suffering: Parasitic infections with protozoa and worms cause unimaginable misery, in particular in the tropics. Fortunately, natural products, such as the antimalarial artemisinin (1) and the anthelmintic avermectin (2) were discovered and developed into therapeutics. These major achievements now culminated in the 2015 Nobel Prize for Medicine.

  1. Optimal Halbach Permanent Magnet Designs for Maximally Pulling and Pushing Nanoparticles

    PubMed Central

    Sarwar, A.; Nemirovski, A.; Shapiro, B.

    2011-01-01

    Optimization methods are presented to design Halbach arrays to maximize the forces applied on magnetic nanoparticles at deep tissue locations. In magnetic drug targeting, where magnets are used to focus therapeutic nanoparticles to disease locations, the sharp fall off of magnetic fields and forces with distances from magnets has limited the depth of targeting. Creating stronger forces at depth by optimally designed Halbach arrays would allow treatment of a wider class of patients, e.g. patients with deeper tumors. The presented optimization methods are based on semi-definite quadratic programming, yield provably globally optimal Halbach designs in 2 and 3-dimensions, for maximal pull or push magnetic forces (stronger pull forces can collect nano-particles against blood forces in deeper vessels; push forces can be used to inject particles into precise locations, e.g. into the inner ear). These Halbach designs, here tested in simulations of Maxwell’s equations, significantly outperform benchmark magnets of the same size and strength. For example, a 3-dimensional 36 element 2000 cm3 volume optimal Halbach design yields a ×5 greater force at a 10 cm depth compared to a uniformly magnetized magnet of the same size and strength. The designed arrays should be feasible to construct, as they have a similar strength (≤ 1 Tesla), size (≤ 2000 cm3), and number of elements (≤ 36) as previously demonstrated arrays, and retain good performance for reasonable manufacturing errors (element magnetization direction errors ≤ 5°), thus yielding practical designs to improve magnetic drug targeting treatment depths. PMID:23335834

  2. Maximizing return on socioeconomic investment in phase II proof-of-concept trials.

    PubMed

    Chen, Cong; Beckman, Robert A

    2014-04-01

    Phase II proof-of-concept (POC) trials play a key role in oncology drug development, determining which therapeutic hypotheses will undergo definitive phase III testing according to predefined Go-No Go (GNG) criteria. The number of possible POC hypotheses likely far exceeds available public or private resources. We propose a design strategy for maximizing return on socioeconomic investment in phase II trials that obtains the greatest knowledge with the minimum patient exposure. We compare efficiency using the benefit-cost ratio, defined to be the risk-adjusted number of truly active drugs correctly identified for phase III development divided by the risk-adjusted total sample size in phase II and III development, for different POC trial sizes, powering schemes, and associated GNG criteria. It is most cost-effective to conduct small POC trials and set the corresponding GNG bars high, so that more POC trials can be conducted under socioeconomic constraints. If δ is the minimum treatment effect size of clinical interest in phase II, the study design with the highest benefit-cost ratio has approximately 5% type I error rate and approximately 20% type II error rate (80% power) for detecting an effect size of approximately 1.5δ. A Go decision to phase III is made when the observed effect size is close to δ. With the phenomenal expansion of our knowledge in molecular biology leading to an unprecedented number of new oncology drug targets, conducting more small POC trials and setting high GNG bars maximize the return on socioeconomic investment in phase II POC trials.

  3. Historical review: Cytokines as therapeutics and targets of therapeutics.

    PubMed

    Vilcek, Jan; Feldmann, Marc

    2004-04-01

    Cytokine research has spawned the introduction of new therapies that have revolutionized the treatment of many important diseases. These therapeutic advances have resulted from two very different strategies. The first therapeutic strategy embodies the administration of purified, recombinant cytokines. The second relies on the administration of therapeutics that inhibit the harmful effects of upregulated, endogenous cytokines. Examples of successful cytokine therapeutics include hematopoietic growth factors (colony stimulating factors) and interferons. Prime examples of cytokine antagonists that have profoundly altered the treatment of some inflammatory disorders are agents that inhibit the effects of tumor necrosis factor (TNF). In this article, we highlight some of the studies that have been responsible for the introduction of cytokine and anti-cytokine therapies, with emphasis on the development of interferons and anti-TNF agents.

  4. Nucleic acids as therapeutic agents.

    PubMed

    Alvarez-Salas, Luis M

    2008-01-01

    Therapeutic nucleic acids (TNAs) and its precursors are applied to treat several pathologies and infections. TNA-based therapy has different rationales and mechanisms and can be classified into three main groups: 1) Therapeutic nucleotides and nucleosides; 2) Therapeutic oligonucleotides; and 3) Therapeutic polynucleotides. This review will focus in those TNAs that have reached clinical trials with anticancer and antiviral protocols, the two most common applications of TNAs. Although therapeutic nucleotides and nucleosides that interfere with nucleic acid metabolism and DNA polymerization have been successfully used as anticancer and antiviral drugs, they often produce toxic secondary effects related to dosage and continuous use. The use of oligonucleotides such as ribozyme and antisense oligodeoxynucleotides (AS-ODNs) showed promise as therapeutic moieties but faced several issues such as nuclease sensitivity, off-target effects and efficient delivery. Nevertheless, immunostimulatory oligodeoxynucleotides and AS-ODNs represent the most successful group of therapeutic oligonucleotides in the clinic. A newer group of therapeutic oligonucleotides, the aptamers, is rapidly advancing towards early detection and treatment alternatives the have reached the commercial interest. Despite the very high in vitro efficiency of small interfering RNAs (siRNAs) they present issues with intracellular target accessibility, specificity and delivery. DNA vaccines showed great promise, but they resulted in very poor responses in the clinic and further development is uncertain. Despite their many issues, the exquisite specificity and versatility of therapeutic oligonucleotides attracts a great deal of research and resources that will certainly convert them in the TNA of choice for treating cancer and viral diseases in the near future.

  5. Therapeutic promise and principles: metabotropic glutamate receptors.

    PubMed

    Maiese, Kenneth; Chong, Zhao Zhong; Shang, Yan Chen; Hou, Jinling

    2008-01-01

    For a number of disease entities, oxidative stress becomes a significant factor in the etiology and progression of cell dysfunction and injury. Therapeutic strategies that can identify novel signal transduction pathways to ameliorate the toxic effects of oxidative stress may lead to new avenues of treatment for a spectrum of disorders that include diabetes, Alzheimer's disease, Parkinson's disease and immune system dysfunction. In this respect, metabotropic glutamate receptors (mGluRs) may offer exciting prospects for several disorders since these receptors can limit or prevent apoptotic cell injury as well as impact upon cellular development and function. Yet the role of mGluRs is complex in nature and may require specific mGluR modulation for a particular disease entity to maximize clinical efficacy and limit potential disability. Here we discuss the potential clinical translation of mGluRs and highlight the role of novel signal transduction pathways in the metabotropic glutamate system that may be vital for the clinical utility of mGluRs.

  6. Lifting speed preferences and their effects on the maximal lifting capacity

    PubMed Central

    LIN, Chiuhsiang Joe; CHENG, Chih-Feng

    2016-01-01

    The objectives of this study were to evaluate how lifting capacity and subjective preferences are affected by different lifting speeds. The maximum lifting capacity of lift was determined with three independent variables, lifting speed, lifting technique, and lifting height. Questionnaires were evaluated after the experiment by the participants for the lifting speed preferences. This study found that the lifting speed was a significant factor in the lifting capacity (p<0.001); and the lifting height (p<0.001) and the interaction of lifting speed and lifting height (p=0.005) affected the lifting capacity significantly. The maximal lifting capacity was achieved around the optimal speed that was neither too fast nor too slow. Moreover, the participants’ preferred lifting speeds were consistently close to the optimal lifting speed. The results showed that the common lifting practice guideline to lift slowly might make the worker unable to generate a large lifting capacity. PMID:27383532

  7. Maximizing beneficence and autonomy. Ethical support for the use of nonpharmacological methods for managing dental anxiety.

    PubMed

    Donate-Bartfield, Evelyn; Spellecy, Ryan; Shane, Nicholas J

    2010-01-01

    This article examines advantages associated with nonpharmacological behavioral management techniques and suggests that there are benefits to their use (such as achieving a more lasting solution to the problem of dental anxiety) that are not realized with medication-based interventions. Analyses that use Kantian and existential viewpoints for exploring the use of medication versus behavioral interventions for managing life problems yield parallel conclusions: there are advantages gained by using behavioral interventions that are not always associated with medication-based interventions. These analyses, taken together with an understanding of the psychology of dental anxiety management, suggest that using nonpharmacological techniques for the management of dental anxiety can maximize adherence to the ethical principles of beneficence and patient autonomy. The authors discuss the barriers that make nonpharmacological interventions for anxiety management difficult for dentists to routinely use, and suggest that additional training in these methods and increased collaboration with mental health professionals are needed for dentists.

  8. Lifting speed preferences and their effects on the maximal lifting capacity.

    PubMed

    Lin, Chiuhsiang Joe; Cheng, Chih-Feng

    2017-02-07

    The objectives of this study were to evaluate how lifting capacity and subjective preferences are affected by different lifting speeds. The maximum lifting capacity of lift was determined with three independent variables, lifting speed, lifting technique, and lifting height. Questionnaires were evaluated after the experiment by the participants for the lifting speed preferences. This study found that the lifting speed was a significant factor in the lifting capacity (p<0.001); and the lifting height (p<0.001) and the interaction of lifting speed and lifting height (p=0.005) affected the lifting capacity significantly. The maximal lifting capacity was achieved around the optimal speed that was neither too fast nor too slow. Moreover, the participants' preferred lifting speeds were consistently close to the optimal lifting speed. The results showed that the common lifting practice guideline to lift slowly might make the worker unable to generate a large lifting capacity.

  9. Power Maximization Control of Variable Speed Wind Generation System Using Permanent Magnet Synchronous Generator

    NASA Astrophysics Data System (ADS)

    Morimoto, Shigeo; Nakamura, Tomohiko; Takeda, Yoji

    This paper proposes the sensorless output power maximization control of the wind generation system. A permanent magnet synchronous generator (PMSG) is used as a variable speed generator in the proposed system. The generator torque is suitably controlled according to the generator speed and thus the power from a wind turbine settles down on the maximum power point by the proposed MPPT control method, where the information of wind velocity is not required. Moreover, the maximum available generated power is obtained by the optimum current vector control. The current vector of PMSG is optimally controlled according to the generator speed and the required torque in order to minimize the losses of PMSG considering the voltage and current constraints. The proposed wind power generation system can be achieved without mechanical sensors such as a wind velocity detector and a position sensor. Several experimental results show the effectiveness of the proposed control method.

  10. Correspondenceless 3D-2D registration based on expectation conditional maximization

    NASA Astrophysics Data System (ADS)

    Kang, X.; Taylor, R. H.; Armand, M.; Otake, Y.; Yau, W. P.; Cheung, P. Y. S.; Hu, Y.

    2011-03-01

    3D-2D registration is a fundamental task in image guided interventions. Due to the physics of the X-ray imaging, however, traditional point based methods meet new challenges, where the local point features are indistinguishable, creating difficulties in establishing correspondence between 2D image feature points and 3D model points. In this paper, we propose a novel method to accomplish 3D-2D registration without known correspondences. Given a set of 3D and 2D unmatched points, this is achieved by introducing correspondence probabilities that we model as a mixture model. By casting it into the expectation conditional maximization framework, without establishing one-to-one point correspondences, we can iteratively refine the registration parameters. The method has been tested on 100 real X-ray images. The experiments showed that the proposed method accurately estimated the rotations (< 1°) and in-plane (X-Y plane) translations (< 1 mm).

  11. Maximizing the Scientific Return and Legacy of the Hubble Space Telescope Mission

    NASA Astrophysics Data System (ADS)

    Wiseman, Jennifer J.

    2016-01-01

    The Hubble Space Telescope has pushed the forefront of astrophysics for over 25 years. Thanks to multiple upgrades over the years and innovative improvements in ground operations and observing techniques, the observatory is in excellent condition and is more scientifically powerful now than ever before. Yet with no more Space Shuttle servicing missions, it is critical at this juncture in the mission to maximize the near-term science return from the observatory, while simultaneously making sure we collect the most important data that only HST can obtain for Hubble's legacy archive and for preparation of future missions like JWST. I will discuss Hubble's greatest scientific achievements and, based on vigorous discussions with the astronomical community, the highest priority scientific goals for Hubble in its remaining years.

  12. Simple neural-like p systems for maximal independent set selection.

    PubMed

    Xu, Lei; Jeavons, Peter

    2013-06-01

    Membrane systems (P systems) are distributed computing models inspired by living cells where a collection of processors jointly achieves a computing task. The problem of maximal independent set (MIS) selection in a graph is to choose a set of nonadjacent nodes to which no further nodes can be added. In this letter, we design a class of simple neural-like P systems to solve the MIS selection problem efficiently in a distributed way. This new class of systems possesses two features that are attractive for both distributed computing and membrane computing: first, the individual processors do not need any information about the overall size of the graph; second, they communicate using only one-bit messages.

  13. Fair Scheduling and Throughput Maximization for IEEE 802.16 Mesh Mode Broadband Wireless Access Networks

    NASA Astrophysics Data System (ADS)

    Alam, Muhammad Mahbub; Hamid, Md. Abdul; Razzaque, Md. Abdur; Hong, Choong Seon

    Broadband wireless access networks are promising technology for providing better end user services. For such networks, designing a scheduling algorithm that fairly allocates the available bandwidth to the end users and maximizes the overall network throughput is a challenging task. In this paper, we develop a centralized fair scheduling algorithm for IEEE 802.16 mesh networks that exploits the spatio-temporal bandwidth reuse to further enhance the network throughput. The proposed mechanism reduces the length of a transmission round by increasing the number of non-contending links that can be scheduled simultaneously. We also propose a greedy algorithm that runs in polynomial time. Performance of the proposed algorithms is evaluated by extensive simulations. Results show that our algorithms achieve higher throughput than that of the existing ones and reduce the computational complexity.

  14. The Mechanics of Human Achievement.

    PubMed

    Duckworth, Angela L; Eichstaedt, Johannes C; Ungar, Lyle H

    2015-07-01

    Countless studies have addressed why some individuals achieve more than others. Nevertheless, the psychology of achievement lacks a unifying conceptual framework for synthesizing these empirical insights. We propose organizing achievement-related traits by two possible mechanisms of action: Traits that determine the rate at which an individual learns a skill are talent variables and can be distinguished conceptually from traits that determine the effort an individual puts forth. This approach takes inspiration from Newtonian mechanics: achievement is akin to distance traveled, effort to time, skill to speed, and talent to acceleration. A novel prediction from this model is that individual differences in effort (but not talent) influence achievement (but not skill) more substantially over longer (rather than shorter) time intervals. Conceptualizing skill as the multiplicative product of talent and effort, and achievement as the multiplicative product of skill and effort, advances similar, but less formal, propositions by several important earlier thinkers.

  15. The Mechanics of Human Achievement

    PubMed Central

    Duckworth, Angela L.; Eichstaedt, Johannes C.; Ungar, Lyle H.

    2015-01-01

    Countless studies have addressed why some individuals achieve more than others. Nevertheless, the psychology of achievement lacks a unifying conceptual framework for synthesizing these empirical insights. We propose organizing achievement-related traits by two possible mechanisms of action: Traits that determine the rate at which an individual learns a skill are talent variables and can be distinguished conceptually from traits that determine the effort an individual puts forth. This approach takes inspiration from Newtonian mechanics: achievement is akin to distance traveled, effort to time, skill to speed, and talent to acceleration. A novel prediction from this model is that individual differences in effort (but not talent) influence achievement (but not skill) more substantially over longer (rather than shorter) time intervals. Conceptualizing skill as the multiplicative product of talent and effort, and achievement as the multiplicative product of skill and effort, advances similar, but less formal, propositions by several important earlier thinkers. PMID:26236393

  16. [Therapeutic management of neurodermatitis atopica].

    PubMed

    Kägi, M K

    1998-08-01

    The therapy of atopic dermatitis remains a challenge. The success of any therapeutic concept is based on a broad and early diagnostic approach which allows to rule out relevant provocation factors and allergens. During remission periods the regular use of a topical basic therapy consisting of drug-free emolients is recommended. Topical corticosteroids as well as systemic or local antimicrobial therapy and antihistamines are essential during periods of acute exacerbations. Although during the last years a great number of new therapeutic approaches have been published, data of most of these therapeutic modalities are not sufficient to allow an unrestricted use in all patients with atopic dermatitis.

  17. Self-tuning bistable parametric feedback oscillator: Near-optimal amplitude maximization without model information

    NASA Astrophysics Data System (ADS)

    Braun, David J.; Sutas, Andrius; Vijayakumar, Sethu

    2017-01-01

    Theory predicts that parametrically excited oscillators, tuned to operate under resonant condition, are capable of large-amplitude oscillation useful in diverse applications, such as signal amplification, communication, and analog computation. However, due to amplitude saturation caused by nonlinearity, lack of robustness to model uncertainty, and limited sensitivity to parameter modulation, these oscillators require fine-tuning and strong modulation to generate robust large-amplitude oscillation. Here we present a principle of self-tuning parametric feedback excitation that alleviates the above-mentioned limitations. This is achieved using a minimalistic control implementation that performs (i) self-tuning (slow parameter adaptation) and (ii) feedback pumping (fast parameter modulation), without sophisticated signal processing past observations. The proposed approach provides near-optimal amplitude maximization without requiring model-based control computation, previously perceived inevitable to implement optimal control principles in practical application. Experimental implementation of the theory shows that the oscillator self-tunes itself near to the onset of dynamic bifurcation to achieve extreme sensitivity to small resonant parametric perturbations. As a result, it achieves large-amplitude oscillations by capitalizing on the effect of nonlinearity, despite substantial model uncertainties and strong unforeseen external perturbations. We envision the present finding to provide an effective and robust approach to parametric excitation when it comes to real-world application.

  18. Long maximal incremental tests accurately assess aerobic fitness in class II and III obese men.

    PubMed

    Lanzi, Stefano; Codecasa, Franco; Cornacchia, Mauro; Maestrini, Sabrina; Capodaglio, Paolo; Brunani, Amelia; Fanari, Paolo; Salvadori, Alberto; Malatesta, Davide

    2015-01-01

    This study aimed to compare two different maximal incremental tests with different time durations [a maximal incremental ramp test with a short time duration (8-12 min) (STest) and a maximal incremental test with a longer time duration (20-25 min) (LTest)] to investigate whether an LTest accurately assesses aerobic fitness in class II and III obese men. Twenty obese men (BMI≥35 kg.m-2) without secondary pathologies (mean±SE; 36.7±1.9 yr; 41.8±0.7 kg*m-2) completed an STest (warm-up: 40 W; increment: 20 W*min-1) and an LTest [warm-up: 20% of the peak power output (PPO) reached during the STest; increment: 10% PPO every 5 min until 70% PPO was reached or until the respiratory exchange ratio reached 1.0, followed by 15 W.min-1 until exhaustion] on a cycle-ergometer to assess the peak oxygen uptake [Formula: see text] and peak heart rate (HRpeak) of each test. There were no significant differences in [Formula: see text] (STest: 3.1±0.1 L*min-1; LTest: 3.0±0.1 L*min-1) and HRpeak (STest: 174±4 bpm; LTest: 173±4 bpm) between the two tests. Bland-Altman plot analyses showed good agreement and Pearson product-moment and intra-class correlation coefficients showed a strong correlation between [Formula: see text] (r=0.81 for both; p≤0.001) and HRpeak (r=0.95 for both; p≤0.001) during both tests. [Formula: see text] and HRpeak assessments were not compromised by test duration in class II and III obese men. Therefore, we suggest that the LTest is a feasible test that accurately assesses aerobic fitness and may allow for the exercise intensity prescription and individualization that will lead to improved therapeutic approaches in treating obesity and severe obesity.

  19. Metabolic heterogeneity in human calf muscle during maximal exercise

    SciTech Connect

    Vandenborne, K. Free Univ. of Brussels ); McCully, K.; Kakihira, H.; Prammer. M.; Bolinger, L.; Detre, J.A.; Walter, G.; Chance, B.; Leigh. J.S. ); De Meirleir, K. )

    1991-07-01

    Human skeletal muscle is composed of various muscle fiber types. The authors hypothesized that differences in metabolism between fiber types could be detected noninvasively with {sup 31}P nuclear magnetic resonance spectroscopy during maximal exercise. This assumes that during maximal exercise all fiber types are recruited and all vary in the amount of acidosis. The calf muscles of seven subjects were studied. Two different coils were applied: an 11-cm-diameter surface coil and a five-segment meander coil. The meander coil was used to localize the {sup 31}P signal to either the medial or the lateral gastrocnemius. Maximal exercise, consisting of rapid plantar flexions, resulted in an 83.7% {plus minus} 7.8% decrease of the phosphocreatine pool and an 8-fold increase of the inorganic phosphate (P{sub i}) pool. At rest the P{sub i} pool was observed as a single resonance (pH 7.0). Toward the end of the first minute of exercise, three subjects showed three distinct P{sub i} peaks. During the second minute of exercise the pH values stabilized. The same pattern was seen when the signal was collected from the medial or lateral gastrocnemius. In four subjects only two distinct P{sub i} peaks were observed. The P{sub i} peaks had differing relative areas in different subjects, but they were reproducible in each individual. This method allowed is to study the appearance and disappearance of the different P{sub i} peaks, together with the changes in pH. Because multiple P{sub i} peaks were seen in single muscles they most likely identify different muscle fiber types.

  20. Expectation maximization for hard X-ray count modulation profiles

    NASA Astrophysics Data System (ADS)

    Benvenuto, F.; Schwartz, R.; Piana, M.; Massone, A. M.

    2013-07-01

    Context. This paper is concerned with the image reconstruction problem when the measured data are solar hard X-ray modulation profiles obtained from the Reuven Ramaty High Energy Solar Spectroscopic Imager (RHESSI) instrument. Aims: Our goal is to demonstrate that a statistical iterative method classically applied to the image deconvolution problem is very effective when utilized to analyze count modulation profiles in solar hard X-ray imaging based on rotating modulation collimators. Methods: The algorithm described in this paper solves the maximum likelihood problem iteratively and encodes a positivity constraint into the iterative optimization scheme. The result is therefore a classical expectation maximization method this time applied not to an image deconvolution problem but to image reconstruction from count modulation profiles. The technical reason that makes our implementation particularly effective in this application is the use of a very reliable stopping rule which is able to regularize the solution providing, at the same time, a very satisfactory Cash-statistic (C-statistic). Results: The method is applied to both reproduce synthetic flaring configurations and reconstruct images from experimental data corresponding to three real events. In this second case, the performance of expectation maximization, when compared to Pixon image reconstruction, shows a comparable accuracy and a notably reduced computational burden; when compared to CLEAN, shows a better fidelity with respect to the measurements with a comparable computational effectiveness. Conclusions: If optimally stopped, expectation maximization represents a very reliable method for image reconstruction in the RHESSI context when count modulation profiles are used as input data.

  1. Comparison of maximal oxygen consumption with oral and nasal breathing.

    PubMed

    Morton, A R; King, K; Papalia, S; Goodman, C; Turley, K R; Wilmore, J H

    1995-09-01

    The major cause of exercise-induced asthma (EIA) is thought to be the drying and cooling of the airways during the 'conditioning' of the inspired air. Nasal breathing increases the respiratory system's ability to warm and humidity the inspired air compared to oral breathing and reduces the drying and cooling effects of the increased ventilation during exercise. This will reduce the severity of EIA provoked by a given intensity and duration of exercise. The purpose of the study was to determine the exercise intensity (%VO2 max) at which healthy subjects, free from respiratory disease, could perform while breathing through the nose-only and to compare this with mouth-only and mouth plus nose breathing. Twenty subjects (11 males and 9 females) ranging from 18-55 years acted as subjects in this study. They were all non-smokers and non-asthmatic. At the time of the study, all subjects were involved in regular physical activity and were classified, by a physician, as free from nasal polyps or other nasal obstruction. The percentage decrease in maximal ventilation with nose-only breathing compare to mouth and mouth plus nose breathing was three times the percentage decrease in maximal oxygen consumption. The pattern of nose-only breathing at maximal work showed a small reduction in tidal volume and large reduction in breathing frequency. Nasal breathing resulted in a reduction in FEO2 and an increase in FECO2. While breathing through the nose-only, all subjects could attain a work intensity great enough to produce an aerobic training effect (based on heart rate and percentage of VO2 max).

  2. Efficient Wideband Spectrum Sensing with Maximal Spectral Efficiency for LEO Mobile Satellite Systems.

    PubMed

    Li, Feilong; Li, Zhiqiang; Li, Guangxia; Dong, Feihong; Zhang, Wei

    2017-01-21

    The usable satellite spectrum is becoming scarce due to static spectrum allocation policies. Cognitive radio approaches have already demonstrated their potential towards spectral efficiency for providing more spectrum access opportunities to secondary user (SU) with sufficient protection to licensed primary user (PU). Hence, recent scientific literature has been focused on the tradeoff between spectrum reuse and PU protection within narrowband spectrum sensing (SS) in terrestrial wireless sensing networks. However, those narrowband SS techniques investigated in the context of terrestrial CR may not be applicable for detecting wideband satellite signals. In this paper, we mainly investigate the problem of joint designing sensing time and hard fusion scheme to maximize SU spectral efficiency in the scenario of low earth orbit (LEO) mobile satellite services based on wideband spectrum sensing. Compressed detection model is established to prove that there indeed exists one optimal sensing time achieving maximal spectral efficiency. Moreover, we propose novel wideband cooperative spectrum sensing (CSS) framework where each SU reporting duration can be utilized for its following SU sensing. The sensing performance benefits from the novel CSS framework because the equivalent sensing time is extended by making full use of reporting slot. Furthermore, in respect of time-varying channel, the spatiotemporal CSS (ST-CSS) is presented to attain space and time diversity gain simultaneously under hard decision fusion rule. Computer simulations show that the optimal sensing settings algorithm of joint optimization of sensing time, hard fusion rule and scheduling strategy achieves significant improvement in spectral efficiency. Additionally, the novel ST-CSS scheme performs much higher spectral efficiency than that of general CSS framework.

  3. Efficient Wideband Spectrum Sensing with Maximal Spectral Efficiency for LEO Mobile Satellite Systems

    PubMed Central

    Li, Feilong; Li, Zhiqiang; Li, Guangxia; Dong, Feihong; Zhang, Wei

    2017-01-01

    The usable satellite spectrum is becoming scarce due to static spectrum allocation policies. Cognitive radio approaches have already demonstrated their potential towards spectral efficiency for providing more spectrum access opportunities to secondary user (SU) with sufficient protection to licensed primary user (PU). Hence, recent scientific literature has been focused on the tradeoff between spectrum reuse and PU protection within narrowband spectrum sensing (SS) in terrestrial wireless sensing networks. However, those narrowband SS techniques investigated in the context of terrestrial CR may not be applicable for detecting wideband satellite signals. In this paper, we mainly investigate the problem of joint designing sensing time and hard fusion scheme to maximize SU spectral efficiency in the scenario of low earth orbit (LEO) mobile satellite services based on wideband spectrum sensing. Compressed detection model is established to prove that there indeed exists one optimal sensing time achieving maximal spectral efficiency. Moreover, we propose novel wideband cooperative spectrum sensing (CSS) framework where each SU reporting duration can be utilized for its following SU sensing. The sensing performance benefits from the novel CSS framework because the equivalent sensing time is extended by making full use of reporting slot. Furthermore, in respect of time-varying channel, the spatiotemporal CSS (ST-CSS) is presented to attain space and time diversity gain simultaneously under hard decision fusion rule. Computer simulations show that the optimal sensing settings algorithm of joint optimization of sensing time, hard fusion rule and scheduling strategy achieves significant improvement in spectral efficiency. Additionally, the novel ST-CSS scheme performs much higher spectral efficiency than that of general CSS framework. PMID:28117712

  4. Synthetic-aperture radar autofocus by maximizing sharpness.

    PubMed

    Fienup, J R

    2000-02-15

    To focus a synthetic-aperture radar image that is suffering from phase errors, a phase-error estimate is found that, when it is applied, maximizes the sharpness of the image. Closed-form expressions are derived for the gradients of a sharpness metric with respect to phase-error parameters, including both a point-by-point (nonparametric) phase function and coefficients of a polynomial expansion. Use of these expressions allows for a highly efficient gradient-search algorithm for high-order phase errors. The effectiveness of the algorithm is demonstrated with an example.

  5. Maximizing Team Performance: The Critical Role of the Nurse Leader.

    PubMed

    Manges, Kirstin; Scott-Cawiezell, Jill; Ward, Marcia M

    2017-01-01

    Facilitating team development is challenging, yet critical for ongoing improvement across healthcare settings. The purpose of this exemplary case study is to examine the role of nurse leaders in facilitating the development of a high-performing Change Team in implementing a patient safety initiative (TeamSTEPPs) using the Tuckman Model of Group Development as a guiding framework. The case study is the synthesis of 2.5 years of critical access hospital key informant interviews (n = 50). Critical juncture points related to team development and key nurse leader actions are analyzed, suggesting that nurse leaders are essential to maximize clinical teams' performance.

  6. A new solution for maximal clique problem based sticker model.

    PubMed

    Darehmiraki, Majid

    2009-02-01

    In this paper, we use stickers to construct a solution space of DNA for the maximal clique problem (MCP). Simultaneously, we also apply the DNA operation in the sticker-based model to develop a DNA algorithm. The results of the proposed algorithm show that the MCP is resolved with biological operations in the sticker-based model for the solution space of the sticker. Moreover, this work presents clear evidence of the ability of DNA computing to solve the NP-complete problem. The potential of DNA computing for the MCP is promising given the operational time complexity of O(nxk).

  7. Testing sequential quantum measurements: how can maximal knowledge be extracted?

    PubMed Central

    Nagali, Eleonora; Felicetti, Simone; de Assis, Pierre-Louis; D'Ambrosio, Vincenzo; Filip, Radim; Sciarrino, Fabio

    2012-01-01

    The extraction of information from a quantum system unavoidably implies a modification of the measured system itself. In this framework partial measurements can be carried out in order to extract only a portion of the information encoded in a quantum system, at the cost of inducing a limited amount of disturbance. Here we analyze experimentally the dynamics of sequential partial measurements carried out on a quantum system, focusing on the trade-off between the maximal information extractable and the disturbance. In particular we implement two sequential measurements observing that, by exploiting an adaptive strategy, is possible to find an optimal trade-off between the two quantities. PMID:22720131

  8. Method for maximizing shale oil recovery from an underground formation

    DOEpatents

    Sisemore, Clyde J.

    1980-01-01

    A method for maximizing shale oil recovery from an underground oil shale formation which has previously been processed by in situ retorting such that there is provided in the formation a column of substantially intact oil shale intervening between adjacent spent retorts, which method includes the steps of back filling the spent retorts with an aqueous slurry of spent shale. The slurry is permitted to harden into a cement-like substance which stabilizes the spent retorts. Shale oil is then recovered from the intervening column of intact oil shale by retorting the column in situ, the stabilized spent retorts providing support for the newly developed retorts.

  9. Maximizing the return on taxpayers' investments in fundamental biomedical research.

    PubMed

    Lorsch, Jon R

    2015-05-01

    The National Institute of General Medical Sciences (NIGMS) at the U.S. National Institutes of Health has an annual budget of more than $2.3 billion. The institute uses these funds to support fundamental biomedical research and training at universities, medical schools, and other institutions across the country. My job as director of NIGMS is to work to maximize the scientific returns on the taxpayers' investments. I describe how we are optimizing our investment strategies and funding mechanisms, and how, in the process, we hope to create a more efficient and sustainable biomedical research enterprise.

  10. Maximally exposed offsite individual location determination for NESHAPS compliance

    SciTech Connect

    Simpkins, A.A.

    2000-03-13

    The Environmental Protection Agency (EPA) requires the use of the computer program CAP88 for demonstrating compliance with the National Emission Standard for Hazardous Air Pollutants (NESHAPS.) One of the inputs required for CAP88 is the location of the maximally exposed individual (MEI) by sector and distance. Distances to the MEI have been determined for 15 different potential release locations at SRS. These locations were compared with previous work and differences were analyzed. Additionally, SREL Conference Center was included as a potential offsite location since in the future it may be used as a dormitory. Worst sectors were then determined based on the distances.

  11. Exact Distribution of the Maximal Height of p Vicious Walkers

    NASA Astrophysics Data System (ADS)

    Schehr, Grégory; Majumdar, Satya N.; Comtet, Alain; Randon-Furling, Julien

    2008-10-01

    Using path-integral techniques, we compute exactly the distribution of the maximal height Hp of p nonintersecting Brownian walkers over a unit time interval in one dimension, both for excursions p watermelons with a wall, and bridges p watermelons without a wall, for all integer p≥1. For large p, we show that ⟨Hp⟩˜2p (excursions) whereas ⟨Hp⟩˜p (bridges). Our exact results prove that previous numerical experiments only measured the preasymptotic behaviors and not the correct asymptotic ones. In addition, our method establishes a physical connection between vicious walkers and random matrix theory.

  12. Optimal Photon Blockade on the Maximal Atomic Coherence

    NASA Astrophysics Data System (ADS)

    Zhang, Yang; Zhang, Jun; Yu, Chang-shui

    2016-12-01

    There is generally no obvious evidence in any direct relation between photon blockade and atomic coherence. Here instead of only illustrating the photon statistics, we show an interesting relation between the steady-state photon blockade and the atomic coherence by designing a weakly driven cavity QED system with a two-level atom trapped. It is shown for the first time that the maximal atomic coherence has a perfect correspondence with the optimal photon blockade. The negative effects of the strong dissipations on photon statistics, atomic coherence and their correspondence are also addressed. The numerical simulation is also given to support all of our results.

  13. Maximizing biomass concentration in baker's yeast process by using a decoupled geometric controller for substrate and dissolved oxygen.

    PubMed

    Chopda, Viki R; Rathore, Anurag S; Gomes, James

    2015-11-01

    Biomass production by baker's yeast in a fed-batch reactor depends on the metabolic regime determined by the concentration of glucose and dissolved oxygen in the reactor. Achieving high biomass concentration in turn is dependent on the dynamic interaction between the glucose and dissolved oxygen concentration. Taking this into account, we present in this paper the implementation of a decoupled input-output linearizing controller (DIOLC) for maximizing biomass in a fed-batch yeast process. The decoupling is based on the inversion of 2×2 input-output matrix resulting from global linearization. The DIOLC was implemented online using a platform created in LabVIEW employing a TCP/IP protocol via the reactor's built-in electronic system. An improvement in biomass yield by 23% was obtained compared to that using a PID controller. The results demonstrate superior capability of the DIOLC and that the cumulative effect of smoother control action contributes to biomass maximization.

  14. How to Use Equipment Therapeutically.

    ERIC Educational Resources Information Center

    Bowne, Douglas

    1986-01-01

    Shares therapeutic and economic practices surrounding equipment used in New York's Higher Horizons adventure program of therapy for troubled youth. Encourages educators, therapists, and administrators to explore relationship between equipment selection, program goals, and clients. (NEC)

  15. Mesenchymal Stem Cells as Therapeutics

    PubMed Central

    Parekkadan, Biju; Milwid, Jack M.

    2013-01-01

    Mesenchymal stem cells (MSCs) are multipotent cells that are being clinically explored as a new therapeutic for treating a variety of immune-mediated diseases. First heralded as a regenerative therapy for skeletal tissue repair, MSCs have recently been shown to modulate endogenous tissue and immune cells. Preclinical studies of the mechanism of action suggest that the therapeutic effects afforded by MSC transplantation are short-lived and related to dynamic, paracrine interactions between MSCs and host cells. Therefore, representations of MSCs as drug-loaded particles may allow for pharmacokinetic models to predict the therapeutic activity of MSC transplants as a function of drug delivery mode. By integrating principles of MSC biology, therapy, and engineering, the field is armed to usher in the next generation of stem cell therapeutics. PMID:20415588

  16. Therapeutic Recreation and Adult Education.

    ERIC Educational Resources Information Center

    Jones, David

    1993-01-01

    Therapeutic recreation is a means of empowering individuals with disabilities through arts or sports. The field has developed differently in the United States and the United Kingdom; the former emphasizes professionalization and the latter the right to adult education. (SK)

  17. Inhalation delivery of protein therapeutics.

    PubMed

    Kane, Colleen; O'Neil, Karyn; Conk, Michelle; Picha, Kristen

    2013-04-01

    Inhaled therapeutics are used routinely to treat a variety of pulmonary diseases including asthma, COPD and cystic fibrosis. In addition, biological therapies represent the fastest growing segment of approved pharmaceuticals. However, despite the increased availability of biological therapies, nearly all inhaled therapeutics are small molecule drugs with only a single inhaled protein therapeutic approved. There remains a significant unmet need for therapeutics in pulmonary diseases, and biological therapies with potential to alter disease progression represent a significant opportunity to treat these challenging diseases. This review provides a background into efforts to develop inhaled biological therapies and highlights some of the associated challenges. In addition, we speculate on the ideal properties of a biologic therapy for inhaled delivery.

  18. RNAi therapeutics for CNS disorders.

    PubMed

    Boudreau, Ryan L; Davidson, Beverly L

    2010-06-18

    RNA interference (RNAi) is a process of sequence-specific gene silencing and serves as a powerful molecular tool to manipulate gene expression in vitro and in vivo. RNAi technologies have been applied to study gene function and validate drug targets. Researchers are investigating RNAi-based compounds as novel therapeutics to treat a variety of human diseases that are currently lacking sufficient treatment. To date, numerous studies support that RNAi therapeutics can improve disease phenotypes in various rodent models of human disease. Here, we focus on the development of RNAi-based therapies aimed at treating neurological disorders for which reduction of mutant or toxic gene expression may provide clinical benefit. We review RNAi-based gene-silencing strategies, proof-of-concept studies testing therapeutic RNAi for CNS disorders, and highlight the most recent research aimed at transitioning RNAi-based therapeutics toward clinical trials.

  19. Targeted Strategies for Henipavirus Therapeutics

    PubMed Central

    Bossart, Katharine N; Bingham, John; Middleton, Deborah

    2007-01-01

    Hendra and Nipah viruses are related emergent paramyxoviruses that infect and cause disease in animals and humans. Disease manifests as a generalized vasculitis affecting multiple organs, but is the most severe in the respiratory and central nervous systems. The high case fatality and person-to-person transmission associated with the most recent NiV outbreaks, and the recent re-emergence of HeV, emphasize the importance and necessity of effective therapeutics for these novel agents. In recent years henipavirus research has revealed a more complete understanding of pathogenesis and, as a consequence, viable approaches towards vaccines and therapeutics have emerged. All strategies target early steps in viral replication including receptor binding and membrane fusion. Animal models have been developed, some of which may prove more valuable than others for evaluating the efficacy of therapeutic agents and regimes. Assessments of protective host immunity and drug pharmacokinetics will be crucial to the further advancement of therapeutic compounds. PMID:19440455

  20. Therapeutic Vaccines for Chronic Infections

    NASA Astrophysics Data System (ADS)

    Autran, Brigitte; Carcelain, Guislaine; Combadiere, Béhazine; Debre, Patrice

    2004-07-01

    Therapeutic vaccines aim to prevent severe complications of a chronic infection by reinforcing host defenses when some immune control, albeit insufficient, can already be demonstrated and when a conventional antimicrobial therapy either is not available or has limited efficacy. We focus on the rationale and challenges behind this still controversial strategy and provide examples from three major chronic infectious diseases-human immunodeficiency virus, hepatitis B virus, and human papillomavirus-for which the efficacy of therapeutic vaccines is currently being evaluated.

  1. Graded Maximal Exercise Testing to Assess Mouse Cardio-Metabolic Phenotypes

    PubMed Central

    Petrosino, Jennifer M.; Heiss, Valerie J.; Maurya, Santosh K.; Kalyanasundaram, Anuradha; Periasamy, Muthu; LaFountain, Richard A.; Wilson, Jacob M.; Simonetti, Orlando P.; Ziouzenkova, Ouliana

    2016-01-01

    Functional assessments of cardiovascular fitness (CVF) are needed to establish animal models of dysfunction, test the effects of novel therapeutics, and establish the cardio-metabolic phenotype of mice. In humans, the graded maximal exercise test (GXT) is a standardized diagnostic for assessing CVF and mortality risk. These tests, which consist of concurrent staged increases in running speed and inclination, provide diagnostic cardio-metabolic parameters, such as, VO2max, anaerobic threshold, and metabolic crossover. Unlike the human-GXT, published mouse treadmill tests have set, not staged, increases in inclination as speed progress until exhaustion (PXT). Additionally, they often lack multiple cardio-metabolic parameters. Here, we developed a mouse-GXT with the intent of improving mouse-exercise testing sensitivity and developing translatable parameters to assess CVF in healthy and dysfunctional mice. The mouse-GXT, like the human-GXT, incorporated staged increases in inclination, speed, and intensity; and, was designed by considering imitations of the PXT and differences between human and mouse physiology. The mouse-GXT and PXTs were both tested in healthy mice (C57BL/6J, FVBN/J) to determine their ability to identify cardio-metabolic parameters (anaerobic threshold, VO2max, metabolic crossover) observed in human-GXTs. Next, theses assays were tested on established diet-induced (obese-C57BL/6J) and genetic (cardiac isoform Casq2-/-) models of cardiovascular dysfunction. Results showed that both tests reported VO2max and provided reproducible data about performance. Only the mouse-GXT reproducibly identified anaerobic threshold, metabolic crossover, and detected impaired CVF in dysfunctional models. Our findings demonstrated that the mouse-GXT is a sensitive, non-invasive, and cost-effective method for assessing CVF in mice. This new test can be used as a functional assessment to determine the cardio-metabolic phenotype of various animal models or the effects of

  2. EDUCATIONAL ACHIEVEMENT AND THE NAVAJO.

    ERIC Educational Resources Information Center

    HAAS, JOHN; MELVILLE, ROBERT

    A STUDY WAS DEVISED TO APPRAISE THE ACADEMIC ACHIEVEMENT OF NAVAJO STUDENTS LIVING IN DORMITORIES AWAY FROM THE INDIAN RESERVATION. THE FOLLOWING SEVEN FACTORS WERE CHOSEN TO BE INVESTIGATED AS BEING DIRECTLY RELATED TO ACHIEVEMENT--(1) INTELLIGENCE, (2) READING ABILITY, (3) ANXIETY, (4) SELF-CONCEPT, (5) MOTIVATION, (6) VERBAL DEVELOPMENT, (7)…

  3. Sociocultural Origins of Achievement Motivation

    ERIC Educational Resources Information Center

    Maehr, Martin L.

    1977-01-01

    Presents a theoretical review of work on sociocultural influences on achievement, focusing on a critical evaluation of the work of David McClellan. Offers an alternative conception of achievement motivation which stresses the role of contextual and situational factors in addition to personality factors. Available from: Transaction Periodicals…

  4. Raising Boys' Achievement in Schools.

    ERIC Educational Resources Information Center

    Bleach, Kevan, Ed.

    This book offers insights into the range of strategies and good practice being used to raise the achievement of boys. Case studies by school-based practitioners suggest ideas and measures to address the issue of achievement by boys. The contributions are: (1) "Why the Likely Lads Lag Behind" (Kevan Bleach); (2) "Helping Boys Do…

  5. Teaching the Low Level Achiever.

    ERIC Educational Resources Information Center

    Salomone, Ronald E., Ed.

    1986-01-01

    Intended for teachers of the English language arts, the articles in this issue offer suggestions and techniques for teaching the low level achiever. Titles and authors of the articles are as follows: (1) "A Point to Ponder" (Rachel Martin); (2) "Tracking: A Self-Fulfilling Prophecy of Failure for the Low Level Achiever" (James Christopher Davis);…

  6. Early Intervention and Student Achievement

    ERIC Educational Resources Information Center

    Hormes, Mridula T.

    2009-01-01

    The United States Department of Education has been rigorous in holding all states accountable with regard to student achievement. The No Child Left Behind Act of 2001 clearly laid out federal mandates for all schools to follow. K-12 leaders of public schools are very aware of the fact that results in terms of student achievement need to improve…

  7. Parental Involvement and Academic Achievement

    ERIC Educational Resources Information Center

    Goodwin, Sarah Christine

    2015-01-01

    This research study examined the correlation between student achievement and parent's perceptions of their involvement in their child's schooling. Parent participants completed the Parent Involvement Project Parent Questionnaire. Results slightly indicated parents of students with higher level of achievement perceived less demand or invitations…

  8. Asperger Syndrome and Academic Achievement.

    ERIC Educational Resources Information Center

    Griswold, Deborah E.; Barnhill, Gena P.; Myles, Brenda Smith; Hagiwara, Taku; Simpson, Richard L.

    2002-01-01

    A study focused on identifying the academic characteristics of 21 children and youth who have Asperger syndrome. Students had an extraordinary range of academic achievement scores, extending from significantly above average to far below grade level. Lowest achievement scores were shown for numerical operations, listening comprehension, and written…

  9. Perils of Standardized Achievement Testing

    ERIC Educational Resources Information Center

    Haladyna, Thomas M.

    2006-01-01

    This article argues that the validity of standardized achievement test-score interpretation and use is problematic; consequently, confidence and trust in such test scores may often be unwarranted. The problem is particularly severe in high-stakes situations. This essay provides a context for understanding standardized achievement testing, then…

  10. Stress Correlates and Academic Achievement.

    ERIC Educational Resources Information Center

    Bentley, Donna Anderson; And Others

    An ongoing concern for educators is the identification of factors that contribute to or are associated with academic achievement; one such group of variables that has received little attention are those involving stress. The relationship between perceived sources of stress and academic achievement was examined to determine if reactions to stress…

  11. School Size and Student Achievement

    ERIC Educational Resources Information Center

    Riggen, Vicki

    2013-01-01

    This study examined whether a relationship between high school size and student achievement exists in Illinois public high schools in reading and math, as measured by the Prairie State Achievement Exam (PSAE), which is administered to all Illinois 11th-grade students. This study also examined whether the factors of socioeconomic status, English…

  12. Do Brain Networks Evolve by Maximizing Their Information Flow Capacity?

    PubMed Central

    Antonopoulos, Chris G.; Srivastava, Shambhavi; Pinto, Sandro E. de S.; Baptista, Murilo S.

    2015-01-01

    We propose a working hypothesis supported by numerical simulations that brain networks evolve based on the principle of the maximization of their internal information flow capacity. We find that synchronous behavior and capacity of information flow of the evolved networks reproduce well the same behaviors observed in the brain dynamical networks of Caenorhabditis elegans and humans, networks of Hindmarsh-Rose neurons with graphs given by these brain networks. We make a strong case to verify our hypothesis by showing that the neural networks with the closest graph distance to the brain networks of Caenorhabditis elegans and humans are the Hindmarsh-Rose neural networks evolved with coupling strengths that maximize information flow capacity. Surprisingly, we find that global neural synchronization levels decrease during brain evolution, reflecting on an underlying global no Hebbian-like evolution process, which is driven by no Hebbian-like learning behaviors for some of the clusters during evolution, and Hebbian-like learning rules for clusters where neurons increase their synchronization. PMID:26317592

  13. Partial AUC maximization for essential gene prediction using genetic algorithms.

    PubMed

    Hwang, Kyu-Baek; Ha, Beom-Yong; Ju, Sanghun; Kim, Sangsoo

    2013-01-01

    Identifying genes indispensable for an organism's life and their characteristics is one of the central questions in current biological research, and hence it would be helpful to develop computational approaches towards the prediction of essential genes. The performance of a predictor is usually measured by the area under the receiver operating characteristic curve (AUC). We propose a novel method by implementing genetic algorithms to maximize the partial AUC that is restricted to a specific interval of lower false positive rate (FPR), the region relevant to follow-up experimental validation. Our predictor uses various features based on sequence information, protein-protein interaction network topology, and gene expression profiles. A feature selection wrapper was developed to alleviate the over-fitting problem and to weigh each feature's relevance to prediction. We evaluated our method using the proteome of budding yeast. Our implementation of genetic algorithms maximizing the partial AUC below 0.05 or 0.10 of FPR outperformed other popular classification methods.

  14. Maximizing the efficiency of a flexible propulsor using experimental optimization

    NASA Astrophysics Data System (ADS)

    Quinn, Daniel; Lauder, George; Smits, Alexander

    2014-11-01

    Experimental gradient-based optimization is used to maximize the propulsive efficiency of a heaving and pitching flexible panel. Optimum and near-optimum conditions are studied via direct force measurements and Particle Image Velocimetry (PIV). The net thrust and power are found to scale predictably with the frequency and amplitude of the leading edge, but the efficiency shows a complex multimodal response. Optimum pitch and heave motions are found to produce nearly twice the efficiencies of optimum heave-only motions. Efficiency is globally optimized when (1) the Strouhal number is within an optimal range that varies weakly with amplitude and boundary conditions; (2) the panel is actuated at a resonant frequency of the fluid-propulsor system; (3) heave amplitude is tuned such that trailing edge amplitude is maximized while flow along the body remains attached; and (4) the maximum pitch angle and phase lag are chosen so that the effective angle of attack is minimized. This work was supported by the Office of Naval Research under MURI Grant Number N00014-08-1-0642 (Program Director Dr. Bob Brizzolara), and the National Science Foundation under Grant DBI 1062052 (PI Lisa Fauci) and Grant EFRI-0938043 (PI George Lauder).

  15. Maximizing Information Diffusion in the Cyber-physical Integrated Network.

    PubMed

    Lu, Hongliang; Lv, Shaohe; Jiao, Xianlong; Wang, Xiaodong; Liu, Juan

    2015-11-11

    Nowadays, our living environment has been embedded with smart objects, such as smart sensors, smart watches and smart phones. They make cyberspace and physical space integrated by their abundant abilities of sensing, communication and computation, forming a cyber-physical integrated network. In order to maximize information diffusion in such a network, a group of objects are selected as the forwarding points. To optimize the selection, a minimum connected dominating set (CDS) strategy is adopted. However, existing approaches focus on minimizing the size of the CDS, neglecting an important factor: the weight of links. In this paper, we propose a distributed maximizing the probability of information diffusion (DMPID) algorithm in the cyber-physical integrated network. Unlike previous approaches that only consider the size of CDS selection, DMPID also considers the information spread probability that depends on the weight of links. To weaken the effects of excessively-weighted links, we also present an optimization strategy that can properly balance the two factors. The results of extensive simulation show that DMPID can nearly double the information diffusion probability, while keeping a reasonable size of selection with low overhead in different distributed networks.

  16. Maximizing Macromolecule Crystal Size for Neutron Diffraction Experiments

    NASA Technical Reports Server (NTRS)

    Judge, R. A.; Kephart, R.; Leardi, R.; Myles, D. A.; Snell, E. H.; vanderWoerd, M.; Curreri, Peter A. (Technical Monitor)

    2002-01-01

    A challenge in neutron diffraction experiments is growing large (greater than 1 cu mm) macromolecule crystals. In taking up this challenge we have used statistical experiment design techniques to quickly identify crystallization conditions under which the largest crystals grow. These techniques provide the maximum information for minimal experimental effort, allowing optimal screening of crystallization variables in a simple experimental matrix, using the minimum amount of sample. Analysis of the results quickly tells the investigator what conditions are the most important for the crystallization. These can then be used to maximize the crystallization results in terms of reducing crystal numbers and providing large crystals of suitable habit. We have used these techniques to grow large crystals of Glucose isomerase. Glucose isomerase is an industrial enzyme used extensively in the food industry for the conversion of glucose to fructose. The aim of this study is the elucidation of the enzymatic mechanism at the molecular level. The accurate determination of hydrogen positions, which is critical for this, is a requirement that neutron diffraction is uniquely suited for. Preliminary neutron diffraction experiments with these crystals conducted at the Institute Laue-Langevin (Grenoble, France) reveal diffraction to beyond 2.5 angstrom. Macromolecular crystal growth is a process involving many parameters, and statistical experimental design is naturally suited to this field. These techniques are sample independent and provide an experimental strategy to maximize crystal volume and habit for neutron diffraction studies.

  17. Maximizing switching current of superconductor nanowires via improved impedance matching

    NASA Astrophysics Data System (ADS)

    Zhang, Labao; Yan, Xiachao; Jia, Xiaoqing; Chen, Jian; Kang, Lin; Wu, Peiheng

    2017-02-01

    The temporary resistance triggered by phase slips will result in the switching of a superconductor nanowire to a permanent normal state, decreasing the switching current. In this letter, we propose an improved impedance matching circuit that releases the transition triggered by phase slips to the load resistor through the radio frequency (RF) port of a bias tee. The transportation properties with different load resistors indicate that the switching current decreases due to the reflection caused by impedance mismatching, and it is maximized by optimized impedance matching. Compared to the same setup without the impedance matching circuit, the switching current was increased from 8.0 μA to 12.2 μA in a niobium nitride nanowire after releasing the temporary transition triggered by phase slips. The leakage process with impedance matching outputs a voltage pulse, which enables the user to directly register the transition triggered by phase slips. The technique for maximizing the switching current has a potential practical application in superconductor devices, and the technique for counting phase slips may be applied to explore the behavior of phase slips.

  18. Maximal power outputs during the Wingate anaerobic test.

    PubMed

    Patton, J F; Murphy, M M; Frederick, F A

    1985-04-01

    The purpose of this study was to determine the resistance loads which elicit maximal values of power output (PO) during performance of the Wingate test (WT). Nineteen male subjects (mean age, 25.1 yrs; mean VO2 max, 3.52 l/min) performed multiple WTs in a random order at resistances ranging from 3.23 to 6.76 joules/pedal rev/kg BW. Tests were carried out on a Monark cycle ergometer modified to permit instantaneous application of resistance. Revolutions were determined by a computer interfaced frequency counter. The mean resistances eliciting the highest peak power (PP) and mean power (MP) outputs were 5.65 and 5.53 joules/pedal rev/kg BW, respectively (average of 5.59 joules/pedal rev/kg BW). Both PP and MP were significantly higher (15.5% and 13.0%, respectively) using a resistance load of 5.59 compared to the Wingate setting of 4.41 joules/pedal rev/kg BW. The test-retest reliability for PP and MP ranged between 0.91 and 0.93 at both resistance loads. Body weight and thigh volume did not significantly estimate the individual resistances eliciting maximal POs. The data suggest that resistance be assigned according to the subjects BW but consideration be given to increasing the resistance from that presently used in various laboratories.

  19. Maximal explosive power and aerobic exercise in humans.

    PubMed

    Capelli, C; di Prampero, P E

    1991-09-01

    The maximal explosive power (wmax), i.e. the mechanical power developed over short bursts (less than 5 s) of all-out cycling, or uphill running, in humans attains 12-17 W*kg-1 in non athletics subjects. Thus, in terms of O2 consumption wmax is about four times larger than the subjects VO2max. The peak instantaneous power during a vertical jump off both feet (w) in non athletic subjects is about 50-55 W kg-1 and attains 70-75 W*kg-1 in "power" athletes. Both wmax and w decrease when the all-out efforts is performed from a priming aerobic exercise: if the intensity of this last approaches VO2max, then wmax and w are reduced to about 75% the value attained from rest. Thus, in the course of high intensity efforts, an athlete can develop a still remarkable fraction of his maximal absolute power. The decrease mentioned above is proportional, and presumably causally related, to the decrease of the high energy phosphate concentration occurring in the muscle at the onset of the exercise, and maintained throughout the effort duration.

  20. Maximizing Photoluminescence Extraction in Silicon Photonic Crystal Slabs

    PubMed Central

    Mahdavi, Ali; Sarau, George; Xavier, Jolly; Paraïso, Taofiq K.; Christiansen, Silke; Vollmer, Frank

    2016-01-01

    Photonic crystal modes can be tailored for increasing light matter interactions and light extraction efficiencies. These PhC properties have been explored for improving the device performance of LEDs, solar cells and precision biosensors. Tuning the extended band structure of 2D PhC provides a means for increasing light extraction throughout a planar device. This requires careful design and fabrication of PhC with a desirable mode structure overlapping with the spectral region of emission. We show a method for predicting and maximizing light extraction from 2D photonic crystal slabs, exemplified by maximizing silicon photoluminescence (PL). Systematically varying the lattice constant and filling factor, we predict the increases in PL intensity from band structure calculations and confirm predictions in micro-PL experiments. With the near optimal design parameters of PhC, we demonstrate more than 500-fold increase in PL intensity, measured near band edge of silicon at room temperature, an enhancement by an order of magnitude more than what has been reported. PMID:27113674