Integrating Quality Improvement Education into the Nephrology Curricular Milestones Framework and the Clinical Learning Environment Review

PubMed Central

Prince, Lisa K.; Little, Dustin J.; Schexneider, Katherine I.

2017-01-01

The Accreditation Council for Graduate Medical Education requires that trainees show progressive milestone attainment in the practice–based learning and systems–based practice competencies. As part of the Clinical Learning Environment Review, sponsoring hospitals must educate trainees in health care quality improvement, provide them with specialty–specific quality data, and ensure trainee participation in quality improvement activities and committees. Subspecialty–specific quality improvement curricula in nephrology training programs have not been reported, although considerable curricular and assessment material exists for specialty residencies, including tools for assessing trainee and faculty competence. Nephrology–specific didactic material exists to assist nephrology fellows and faculty mentors in designing and implementing quality improvement projects. Nephrology is notable among internal medicine subspecialties for the emphasis placed on adherence to quality thresholds—specifically for chronic RRT shown by the Centers for Medicare and Medicaid Services Quality Incentive Program. We have developed a nephrology-specific curriculum that meets Accreditation Council for Graduate Medical Education and Clinical Learning Environment Review requirements, acknowledges regulatory quality improvement requirements, integrates with ongoing divisional quality improvement activities, and has improved clinical care and the training program. In addition to didactic training in quality improvement, we track trainee compliance with Kidney Disease Improving Global Outcomes CKD and ESRD quality indicators (emphasizing Quality Improvement Program indicators), and fellows collaborate on a yearly multidisciplinary quality improvement project. Over the past 6 years, each fellowship class has, on the basis of a successful quality improvement project, shown milestone achievement in Systems-Based Practice and Practice-Based Learning. Fellow quality improvement projects have improved nephrology clinical care within the institution and introduced new educational and assessment tools to the training program. All have been opportunities for quality improvement scholarship. The curriculum prepares fellows to apply quality improvement principals in independent clinical practice—while showing milestone advancement and divisional compliance with Clinical Learning Environment Review requirements. PMID:28174318

JT9D-70/59 Improved High Pressure Turbine Active Clearance Control System. [for specific fuel consumption improvement

NASA Technical Reports Server (NTRS)

Gaffin, W. O.

1979-01-01

The JT9D-70/59 high pressure turbine active clearance control system was modified to provide reduction of blade tip clearance when the system is activated during cruise operation. The modification increased the flow capacity and air impingement effectiveness of the cooling air manifold to augment turbine case shrinkage capability, and increased responsiveness of the airseal clearance to case shrinkage. The simulated altitude engine testing indicated a significant improvement in specific fuel consumption with the modified system. A 1000 cycle engine endurance test showed no unusual wear or performance deterioration effects on the engine or the clearance control system. Rig tests indicated that the air impingement and seal support configurations used in the engine tests are near optimum.

A site-specific PEGylated analog of exendin-4 with improved pharmacokinetics and pharmacodynamics in vivo.

PubMed

Gao, Mingming; Jin, Yuhao; Tong, Yue; Tian, Hong; Gao, Xiangdong; Yao, Wenbing

2012-11-01

Our aim was to improve the in vivo pharmacokinetics and pharmacodynamics of exendin-4 by using site-specific PEGylation. We designed the PEGylated peptide based on its structure and activity relationship and prepared the conjugate by two steps of chromatographic purification. After obtained the conjugate we confirmed its glucose-lowering activity in normal mice and determined its half-life in SD rats. Then we evaluated its anti-diabetic activity in a multiple low-dose Streptozocin (STZ)-induced diabetic mice model. With the process established in this study the product conjugate was obtained with a yield of over 60% and purity of above 99%. The conjugate maintained its original conformation after modification. In SD rats its half-life was prolonged to 27.12 ± 5.75 h which was 17.61-fold longer than that of the natural exendin-4 for which the half-life was only 1.54 ± 0.47 h. Its anti-diabetic activity was significantly improved in the diabetic mice. Compare with native exendin-4, the C-terminal site-specific PEGylated analog of exendin-4 obtained in this study has an improved pharmacokinetics and pharmacodynamics in vivo and could be regarded as a potential candidate for the future development of anti-diabetic drugs. © 2012 The Authors. JPP © 2012 Royal Pharmaceutical Society.

RNA Structure Design Improves Activity and Specificity of trans-Splicing-Triggered Cell Death in a Suicide Gene Therapy Approach.

PubMed

Poddar, Sushmita; Loh, Pei She; Ooi, Zi Hao; Osman, Farhana; Eul, Joachim; Patzel, Volker

2018-06-01

Spliceosome-mediated RNA trans-splicing enables correction or labeling of pre-mRNA, but therapeutic applications are hampered by issues related to the activity and target specificity of trans-splicing RNA (tsRNA). We employed computational RNA structure design to improve both on-target activity and specificity of tsRNA in a herpes simplex virus thymidine kinase/ganciclovir suicide gene therapy approach targeting alpha fetoprotein (AFP), a marker of hepatocellular carcinoma (HCC) or human papillomavirus type 16 (HPV-16) pre-mRNA. While unstructured, mismatched target binding domains significantly improved 3' exon replacement (3'ER), 5' exon replacement (5'ER) correlated with the thermodynamic stability of the tsRNA 3' end. Alternative on-target trans-splicing was found to be a prevalent event. The specificity of trans-splicing with the intended target splice site was improved 10-fold by designing tsRNA that harbors secondary target binding domains shielding alternative on-target and blinding off-target splicing events. Such rationally designed suicide RNAs efficiently triggered death of HPV-16-transduced or hepatoblastoma-derived human tissue culture cells without evidence for off-target cell killing. Highest cell death activities were observed with novel dual-targeting tsRNAs programmed for trans-splicing toward AFP and a second HCC pre-mRNA biomarker. Our observations suggest trans-splicing represents a promising approach to suicide gene therapy. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Exceptional oxygen reduction reaction activity and durability of platinum–nickel nanowires through synthesis and post-treatment optimization

DOE PAGES

Alia, Shaun M.; Ngo, Chilan; Shulda, Sarah; ...

2017-04-11

For the first time, extended nanostructured catalysts are demonstrated with both high specific activity (>6000 μA cm Pt –2 at 0.9 V) and high surface areas (>90 m 2 g Pt –1). Platinum–nickel (Pt—Ni) nanowires, synthesized by galvanic displacement, have previously produced surface areas in excess of 90 m 2 g Pt –1, a significant breakthrough in and of itself for extended surface catalysts. Unfortunately, these materials were limited in terms of their specific activity and durability upon exposure to relevant electrochemical test conditions. Through a series of optimized postsynthesis steps, significant improvements were made to the activity (3-fold increasemore » in specific activity), durability (21% mass activity loss reduced to 3%), and Ni leaching (reduced from 7 to 0.3%) of the Pt—Ni nanowires. Finally, these materials show more than a 10-fold improvement in mass activity compared to that of traditional carbon-supported Pt nanoparticle catalysts and offer significant promise as a new class of electrocatalysts in fuel cell applications.« less

Exceptional oxygen reduction reaction activity and durability of platinum–nickel nanowires through synthesis and post-treatment optimization

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alia, Shaun M.; Ngo, Chilan; Shulda, Sarah

For the first time, extended nanostructured catalysts are demonstrated with both high specific activity (>6000 μA cm Pt –2 at 0.9 V) and high surface areas (>90 m 2 g Pt –1). Platinum–nickel (Pt—Ni) nanowires, synthesized by galvanic displacement, have previously produced surface areas in excess of 90 m 2 g Pt –1, a significant breakthrough in and of itself for extended surface catalysts. Unfortunately, these materials were limited in terms of their specific activity and durability upon exposure to relevant electrochemical test conditions. Through a series of optimized postsynthesis steps, significant improvements were made to the activity (3-fold increasemore » in specific activity), durability (21% mass activity loss reduced to 3%), and Ni leaching (reduced from 7 to 0.3%) of the Pt—Ni nanowires. Finally, these materials show more than a 10-fold improvement in mass activity compared to that of traditional carbon-supported Pt nanoparticle catalysts and offer significant promise as a new class of electrocatalysts in fuel cell applications.« less

Improving Teacher Feedback during Active Learning: Effects of a Professional Development Program

ERIC Educational Resources Information Center

Van den Bergh, Linda; Ros, Anje; Beijaard, Douwe

2014-01-01

This study focuses on improving teacher feedback during active learning. Changing teachers' behavior sustainably, however, is very difficult. Several conditions should be taken into account, and programs should build on teachers' cognitions and practices. Effects of a specifically designed professional development program on 16 elementary…

Active Learning Improves Student Performance in a Respiratory Physiology Lab

ERIC Educational Resources Information Center

Wolf, Alex M.; Liachovitzky, Carlos; Abdullahi, Abass S.

2015-01-01

This study assessed the effectiveness of the introduction of active learning exercises into the anatomy and physiology curriculum in a community college setting. Specifically, the incorporation of a spirometry-based respiratory physiology lab resulted in improved student performance in two concepts (respiratory volumes and the hallmarks of…

Assessment of Teaching Competence for Improvement of Instruction.

ERIC Educational Resources Information Center

National IOTA Program, Tempe, AZ.

This report provides a general overview of the Instrument for the Observation of Teaching Activities (IOTA) program for assessing and improving teacher competence. IOTA is an analytic, objective, and specific means of assessing teaching activities. The normal three-step progression of groups through the introductory and training stages of the…

Multiple domains of social support are associated with diabetes self-management among Veterans.

PubMed

Gray, Kristen E; Hoerster, Katherine D; Reiber, Gayle E; Bastian, Lori A; Nelson, Karin M

2018-01-01

Objectives To examine, among Veterans, relationships of general social support and diabetes-specific social support for physical activity and healthy eating with diabetes self-management behaviors. Methods Patients from VA Puget Sound, Seattle completed a cross-sectional survey in 2012-2013 ( N = 717). We measured (a) general social support and (b) diabetes-specific social support for healthy eating and physical activity with domains reflecting support person participation, encouragement, and sharing ideas. Among 189 self-reporting diabetes patients, we fit linear and modified Poisson regression models estimating associations of social support with diabetes self-management behaviors: adherence to general and diabetes-specific diets and blood glucose monitoring (days/week); physical activity (< vs. ≥150 min/week); and smoking status (smoker/non-smoker). Results General social support was not associated with diabetes self-management. For diabetes-specific social support, higher healthy eating support scores across all domains were associated with better adherence to general and diabetes-specific diets. Higher physical activity support scores were positively associated with ≥150 min/week of physical activity only for the participation domain. Discussion Diabetes-specific social support was a stronger and more consistent correlate of improved self-management than general social support, particularly for lifestyle behaviors. Incorporating family/friends into Veterans' diabetes self-management routines may lead to better self-management and improvements in disease control and outcomes.

ISO Technical Specification for the Ionosphere -IRI Recent Activities

NASA Astrophysics Data System (ADS)

Bilitza, Dieter; Reinisch, Bodo; Tamara, Gulyaeva

ISO Technical Specification TS 16457 recommends the International Reference Ionosphere (IRI) for the specification of ionospheric densities and temperatures. We review the latest develop-ments towards improving the IRI model and the newest version of the model IRI-2010. IRI-2010 includes several important improvements and additions. This presentation introduces these changes and discusses their benefits. The changes affect primarily the density profiles in the bottomside ionosphere and the density and height of the F2 peak, the point of highest density in the ionosphere. An important new addition to the model is the inclusion of auroral boundaries and their movement with magnetic activity. We will also discuss the status of other ongoing IRI activities and some of the recent applications of the IRI model. The homepage for the IRI project is at http://IRI.gsfc.nasa.gov/.

Physiotherapy treatment of the diabetic shoulder: a longitudinal study following patients with diabetes and shoulder pain using a pre-post treatment design.

PubMed

Kyhlbäck, Maria; Schröder Winter, Helena; Thierfelder, Tomas; Söderlund, Anne

2014-01-01

The aim of this study was to describe and evaluate a physiotherapy program targeted to reduce pain intensity and improve the daily functioning of diabetics with shoulder problems. It was hypothesized that patients receiving specific physiotherapy treatment improved more frequently and rapidly than diabetic patients followed up without specific physiotherapeutic intervention. A pre-post treatment design was completed for a group of 10 subjects. The treatment protocol, also applied during the daily activities of the subjects, was aiming at reducing pain intensity and shoulder stiffness and improving impaired functioning in daily activities by muscle relaxation, light-load exercise and enhancing proper shoulder co-ordination. The group analysis showed significant decrease of pain intensity level as well as improved shoulder functioning and sustained level of subject self-efficacy beliefs throughout the study period. The results suggest that it is possible to relieve shoulder pain intensity and improve daily activities of patients with diabetes-related shoulder problems by employing a physiotherapy program focusing on muscle relaxation, light-load exercise and on the enhancement of proper shoulder co-ordination in daily activities. A physiotherapy program can be effective in reducing pain and improving shoulder function in diabetics with shoulder problems. The treatment should focus on muscle relaxation, light-load exercise and on the enhancement of proper shoulder co-ordination in daily activities.

Activities and impairments in the early stage of rehabilitation after Colles' fracture.

PubMed

Dekkers, Merete; Søballe, Kjeld

2004-06-03

The purpose of this study was to investigate problems in performing activities after Colles' fracture, and to correlate activity limitations with impairments in the early stage of rehabilitation. Assessments were performed 1 and 5 weeks after removing plaster casts. A client-specific instrument, The Canadian Occupational Performance Measure, and a disease-specific dichotomous scale of 10 activities of daily living were used. Range of motion, grip strength, pain and dexterity were also assessed according to standardized methods. Thirty-three women, aged 51-87 years, with Colles' fracture treated with closed reduction and a plaster cast participated. Highly significant statistical and clinical improvements were found in the capacity, number and performance of activities. Problems were mainly classified as self-care activities at 1 week, and as productivity activities at 5 weeks, while problems in leisure activities were practically the same. However, one-third of the patients were not able to perform all basic activities of daily living at 5 weeks. Improvements in pain frequency, range of motion, grip strength and dexterity did not correlate very well with improvements in performance or the patients' satisfaction with the performance of their activities. The importance of assessing both impairments and activities in patients with Colles' fracture must be stressed.

Semirational Directed Evolution of Loop Regions in Aspergillus japonicus β-Fructofuranosidase for Improved Fructooligosaccharide Production

PubMed Central

Trollope, K. M.; Görgens, J. F.

2015-01-01

The Aspergillus japonicus β-fructofuranosidase catalyzes the industrially important biotransformation of sucrose to fructooligosaccharides. Operating at high substrate loading and temperatures between 50 and 60°C, the enzyme activity is negatively influenced by glucose product inhibition and thermal instability. To address these limitations, the solvent-exposed loop regions of the β-fructofuranosidase were engineered using a combined crystal structure- and evolutionary-guided approach. This semirational approach yielded a functionally enriched first-round library of 36 single-amino-acid-substitution variants with 58% retaining activity, and of these, 71% displayed improved activities compared to the parent. The substitutions yielding the five most improved variants subsequently were exhaustively combined and evaluated. A four-substitution combination variant was identified as the most improved and reduced the time to completion of an efficient industrial-like reaction by 22%. Characterization of the top five combination variants by isothermal denaturation assays indicated that these variants displayed improved thermostability, with the most thermostable variant displaying a 5.7°C increased melting temperature. The variants displayed uniquely altered, concentration-dependent substrate and product binding as determined by differential scanning fluorimetry. The altered catalytic activity was evidenced by increased specific activities of all five variants, with the most improved variant doubling that of the parent. Variant homology modeling and computational analyses were used to rationalize the effects of amino acid changes lacking direct interaction with substrates. Data indicated that targeting substitutions to loop regions resulted in improved enzyme thermostability, specific activity, and relief from product inhibition. PMID:26253664

Battery designs with high capacity anode materials and cathode materials

DOEpatents

Masarapu, Charan; Anguchamy, Yogesh Kumar; Han, Yongbong; Deng, Haixia; Kumar, Sujeet; Lopez, Herman A.

2017-10-03

Improved high energy capacity designs for lithium ion batteries are described that take advantage of the properties of high specific capacity anode active compositions and high specific capacity cathode active compositions. In particular, specific electrode designs provide for achieving very high energy densities. Furthermore, the complex behavior of the active materials is used advantageously in a radical electrode balancing design that significantly reduced wasted electrode capacity in either electrode when cycling under realistic conditions of moderate to high discharge rates and/or over a reduced depth of discharge.

Opening wedge and anatomic-specific plates in foot and ankle applications.

PubMed

Kluesner, Andrew J; Morris, Jason B

2011-08-01

As surgeons continually push to improve techniques and outcomes, anatomic-specific and procedure-specific fixation options are becoming increasingly available. The unique size, shape, and function of the foot provide an ideal framework for the use of anatomic-specific plates. These distinctive plate characteristics range from anatomic contouring and screw placements to incorporated step-offs and wedges. By optimizing support, compression, and stabilization, patients may return to weight bearing and activity sooner, improving outcomes. This article discusses anatomic-specific plates and their use in forefoot and rearfoot surgical procedures. Copyright © 2011 Elsevier Inc. All rights reserved.

Specific balance training included in an endurance-resistance exercise program improves postural balance in elderly patients undergoing haemodialysis.

PubMed

Frih, Bechir; Mkacher, Wajdi; Jaafar, Hamdi; Frih, Ameur; Ben Salah, Zohra; El May, Mezry; Hammami, Mohamed

2018-04-01

The purpose of this study was to evaluate the effects of 6 months of specific balance training included in endurance-resistance program on postural balance in haemodialysis (HD) patients. Forty-nine male patients undergoing HD were randomly assigned to an intervention group (balance training included in an endurance-resistance training, n = 26) or a control group (resistance-endurance training only, n = 23). Postural control was assessed using six clinical tests; Timed Up and Go test, Tinetti Mobility Test, Berg Balance Scale, Unipodal Stance test, Mini-Balance Evaluation Systems Test and Activities Balance Confidence scale. All balance measures increased significantly after the period of rehabilitation training in the intervention group. Only the Timed Up and Go, Berg Balance Scale, Mini-Balance Evaluation Systems Test and Activities Balance Confidence scores were improved in the control group. The ranges of change in these tests were greater in the balance training group. In HD patients, specific balance training included in a usual endurance-resistance training program improves static and dynamic balance better than endurance-resistance training only. Implications for rehabilitation Rehabilitation using exercise in haemodialysis patients improved global mobility and functional abilities. Specific balance training included in usual endurance resistance training program could lead to improved static and dynamic balance.

Continuous directed evolution of aminoacyl-tRNA synthetases

PubMed Central

Bryson, David I.; Fan, Chenguang; Guo, Li-Tao; Miller, Corwin; Söll, Dieter; Liu, David R.

2017-01-01

Directed evolution of orthogonal aminoacyl-tRNA synthetases (AARSs) enables site-specific installation of non-canonical amino acids (ncAAs) into proteins. Traditional evolution techniques typically produce AARSs with greatly reduced activity and selectivity compared to their wild-type counterparts. We designed phage-assisted continuous evolution (PACE) selections to rapidly produce highly active and selective orthogonal AARSs through hundreds of generations of evolution. PACE of a chimeric Methanosarcina spp. pyrrolysyl-tRNA synthetase (PylRS) improved its enzymatic efficiency (kcat/KMtRNA) 45-fold compared to the parent enzyme. Transplantation of the evolved mutations into other PylRS-derived synthetases improved yields of proteins containing non-canonical residues up to 9.7-fold. Simultaneous positive and negative selection PACE over 48 h greatly improved the selectivity of a promiscuous Methanocaldococcus jannaschii tyrosyl-tRNA synthetase variant for site-specific incorporation of p-iodo-L-phenylalanine. These findings offer new AARSs that increase the utility of orthogonal translation systems and establish the capability of PACE to efficiently evolve orthogonal AARSs with high activity and amino acid specificity. PMID:29035361

Bridging the gap between finance and clinical operations with activity-based cost management.

PubMed

Storfjell, J L; Jessup, S

1996-12-01

Activity-based cost management (ABCM) is an exciting management tool that links financial information with operations. By determining the costs of specific activities and processes, nurse managers accurately determine true costs of services more accurately than traditional cost accounting methods, and then can target processes for improvement and monitor them for change and improvement. The authors describe the ABCM process applied to nursing management situations.

Modeling task-specific neuronal ensembles improves decoding of grasp

NASA Astrophysics Data System (ADS)

Smith, Ryan J.; Soares, Alcimar B.; Rouse, Adam G.; Schieber, Marc H.; Thakor, Nitish V.

2018-06-01

Objective. Dexterous movement involves the activation and coordination of networks of neuronal populations across multiple cortical regions. Attempts to model firing of individual neurons commonly treat the firing rate as directly modulating with motor behavior. However, motor behavior may additionally be associated with modulations in the activity and functional connectivity of neurons in a broader ensemble. Accounting for variations in neural ensemble connectivity may provide additional information about the behavior being performed. Approach. In this study, we examined neural ensemble activity in primary motor cortex (M1) and premotor cortex (PM) of two male rhesus monkeys during performance of a center-out reach, grasp and manipulate task. We constructed point process encoding models of neuronal firing that incorporated task-specific variations in the baseline firing rate as well as variations in functional connectivity with the neural ensemble. Models were evaluated both in terms of their encoding capabilities and their ability to properly classify the grasp being performed. Main results. Task-specific ensemble models correctly predicted the performed grasp with over 95% accuracy and were shown to outperform models of neuronal activity that assume only a variable baseline firing rate. Task-specific ensemble models exhibited superior decoding performance in 82% of units in both monkeys (p  <  0.01). Inclusion of ensemble activity also broadly improved the ability of models to describe observed spiking. Encoding performance of task-specific ensemble models, measured by spike timing predictability, improved upon baseline models in 62% of units. Significance. These results suggest that additional discriminative information about motor behavior found in the variations in functional connectivity of neuronal ensembles located in motor-related cortical regions is relevant to decode complex tasks such as grasping objects, and may serve the basis for more reliable and accurate neural prosthesis.

Immunological markers of frequently recurrent genital herpes simplex virus and their response to hypnotherapy: a pilot study.

PubMed

Fox, P A; Henderson, D C; Barton, S E; Champion, A J; Rollin, M S; Catalan, J; McCormack, S M; Gruzelier, J

1999-11-01

Patients were recruited for hypnotherapy from a clinic for patients with frequently recurrent genital herpes simplex virus (rgHSV). Psychological and immunological parameters were measured 6 weeks prior to hypnotherapy and 6 weeks afterwards, during which time each patient kept a diary of symptoms of rgHSV. Following hypnotherapy there was a significant overall reduction in the number of reported episodes of rgHSV, accompanied by an increase in the numbers of CD3 and CD8 lymphocytes, which may represent a non specific effect of hypnosis. The improvers showed significant rises in natural killer (NK) cell counts, HSV specific lymphokine activated killer (LAK) activity, and reduced levels of anxiety when compared to non-improvers. NK cell numbers and HSV specific LAK activity may therefore be important in the reduction in rgHSV following hypnotherapy.

Crew interface specifications development for inflight maintenance and stowage functions

NASA Technical Reports Server (NTRS)

Carl, J. G.

1974-01-01

Findings and data products developed during crew specification study for inflight maintenance and stowage functions are reported. From this information base, a family of data concepts to support crew inflight troubleshooting and corrective maintenance activities was developed and specified. Recommendations are made for the improvement of inflight maintenance planning, preparations and operations in future space flight programs through the establishment of an inflight maintenance organization and specific suggestions for techniques to improve the management of the inflight maintenance function.

Substrate-specific modifications on magnetic iron oxide nanoparticles as an artificial peroxidase for improving sensitivity in glucose detection.

PubMed

Liu, Yanping; Yu, Faquan

2011-04-08

Magnetic iron oxide nanoparticles (MION) were recently found to act as a peroxidase with intrinsic advantages over natural counterparts. Their limited affinity toward catalysis substrates, however, dramatically reduces their utility. In this paper, some effective groups were screened out and conjugated on MION as substrate-specific modifications for improving MION's affinity to substrates and hence utility. Nanoparticles of four different superficial structures were synthesized and characterized by TEM, size, zeta potential and SQUID, and assayed for peroxidase activity. Glucose detection was selected as an application model system to evaluate the bonus thereof. Catalysis was found to follow Michaelis-Menten kinetics. Sulfhydryl groups incorporated on MION (SH-MION) notably improve the affinity toward a substrate (hydrogen peroxide) and so do amino groups (NH₂-MION) toward another substrate, proved by variation in the determined kinetic parameters. A synergistically positive effect was observed and an apparently elevated detection sensitivity and a significantly lowered detection limit of glucose were achieved when integrated with both sulfhydryl and amino groups (SH-NH₂-MION). Our findings suggest that substrate-specific surface modifications are a straightforward and robust strategy to improve MION peroxidase-like activity. The high activity extends magnetic nanoparticles to wide applications other than glucose detection.

Evolution of Bacillus thuringiensis Cry toxins insecticidal activity.

PubMed

Bravo, Alejandra; Gómez, Isabel; Porta, Helena; García-Gómez, Blanca Ines; Rodriguez-Almazan, Claudia; Pardo, Liliana; Soberón, Mario

2013-01-01

Insecticidal Cry proteins produced by Bacillus thuringiensis are use worldwide in transgenic crops for efficient pest control. Among the family of Cry toxins, the three domain Cry family is the better characterized regarding their natural evolution leading to a large number of Cry proteins with similar structure, mode of action but different insect specificity. Also, this group is the better characterized regarding the study of their mode of action and the molecular basis of insect specificity. In this review we discuss how Cry toxins have evolved insect specificity in nature and analyse several cases of improvement of Cry toxin action by genetic engineering, some of these examples are currently used in transgenic crops. We believe that the success in the improvement of insecticidal activity by genetic evolution of Cry toxins will depend on the knowledge of the rate-limiting steps of Cry toxicity in different insect pests, the mapping of the specificity binding regions in the Cry toxins, as well as the improvement of mutagenesis strategies and selection procedures. © 2012 The Authors. Microbial Biotechnology © 2012 Society for Applied Microbiology and Blackwell Publishing Ltd.

Tuning Liposome Membrane Permeability by Competitive Peptide Dimerization and Partitioning-Folding Interactions Regulated by Proteolytic Activity

NASA Astrophysics Data System (ADS)

Lim, Seng Koon; Sandén, Camilla; Selegård, Robert; Liedberg, Bo; Aili, Daniel

2016-02-01

Membrane active peptides are of large interest for development of drug delivery vehicles and therapeutics for treatment of multiple drug resistant infections. Lack of specificity can be detrimental and finding routes to tune specificity and activity of membrane active peptides is vital for improving their therapeutic efficacy and minimize harmful side effects. We describe a de novo designed membrane active peptide that partition into lipid membranes only when specifically and covalently anchored to the membrane, resulting in pore-formation. Dimerization with a complementary peptide efficiently inhibits formation of pores. The effect can be regulated by proteolytic digestion of the inhibitory peptide by the matrix metalloproteinase MMP-7, an enzyme upregulated in many malignant tumors. This system thus provides a precise and specific route for tuning the permeability of lipid membranes and a novel strategy for development of recognition based membrane active peptides and indirect enzymatically controlled release of liposomal cargo.

Context Matters: Systematic Observation of Place-Based Physical Activity

ERIC Educational Resources Information Center

McKenzie, Thomas L.

2016-01-01

Physical activity is place-based, and being able to assess the number of people and their characteristics in specific locations is important both for public health surveillance and for practitioners in their design of physical activity spaces and programs. Although physical activity measurement has improved recently, many investigators avoid or…

INDIRECT MEASUREMENT OF BIOLOGICAL ACTIVITY TO MONITOR NATURAL ATTENUATION

EPA Science Inventory

The remediation of ground water contamination by natural attenuation, specifically biodegradation, requires continual monitoring. This research is aimed at improving methods for evaluating the long-term performance of Monitored Natural Attenuation (MNA), specifically changes in ...

Feasibility of High-Repetition, Task-Specific Training for Individuals With Upper-Extremity Paresis

PubMed Central

Waddell, Kimberly J.; Birkenmeier, Rebecca L.; Moore, Jennifer L.; Hornby, T. George

2014-01-01

OBJECTIVE. We investigated the feasibility of delivering an individualized, progressive, high-repetition upper-extremity (UE) task-specific training protocol for people with stroke in the inpatient rehabilitation setting. METHOD. Fifteen patients with UE paresis participated in this study. Task-specific UE training was scheduled for 60 min/day, 4 days/wk, during occupational therapy for the duration of a participant’s inpatient stay. During each session, participants were challenged to complete ≥300 repetitions of various tasks. RESULTS. Participants averaged 289 repetitions/session, spending 47 of 60 min in active training. Participants improved on impairment and activity level outcome measures. CONCLUSION. People with stroke in an inpatient setting can achieve hundreds of repetitions of task-specific training in 1-hr sessions. As expected, all participants improved on functional outcome measures. Future studies are needed to determine whether this high-repetition training program results in better outcomes than current UE interventions. PMID:25005508

Improved specificity of TALE-based genome editing using an expanded RVD repertoire.

PubMed

Miller, Jeffrey C; Zhang, Lei; Xia, Danny F; Campo, John J; Ankoudinova, Irina V; Guschin, Dmitry Y; Babiarz, Joshua E; Meng, Xiangdong; Hinkley, Sarah J; Lam, Stephen C; Paschon, David E; Vincent, Anna I; Dulay, Gladys P; Barlow, Kyle A; Shivak, David A; Leung, Elo; Kim, Jinwon D; Amora, Rainier; Urnov, Fyodor D; Gregory, Philip D; Rebar, Edward J

2015-05-01

Transcription activator-like effector (TALE) proteins have gained broad appeal as a platform for targeted DNA recognition, largely owing to their simple rules for design. These rules relate the base specified by a single TALE repeat to the identity of two key residues (the repeat variable diresidue, or RVD) and enable design for new sequence targets via modular shuffling of these units. A key limitation of these rules is that their simplicity precludes options for improving designs that are insufficiently active or specific. Here we address this limitation by developing an expanded set of RVDs and applying them to improve the performance of previously described TALEs. As an extreme example, total conversion of a TALE nuclease to new RVDs substantially reduced off-target cleavage in cellular studies. By providing new RVDs and design strategies, these studies establish options for developing improved TALEs for broader application across medicine and biotechnology.

Improving CRISPR-Cas specificity with chemical modifications in single-guide RNAs.

PubMed

Ryan, Daniel E; Taussig, David; Steinfeld, Israel; Phadnis, Smruti M; Lunstad, Benjamin D; Singh, Madhurima; Vuong, Xuan; Okochi, Kenji D; McCaffrey, Ryan; Olesiak, Magdalena; Roy, Subhadeep; Yung, Chong Wing; Curry, Bo; Sampson, Jeffrey R; Bruhn, Laurakay; Dellinger, Douglas J

2018-01-25

CRISPR systems have emerged as transformative tools for altering genomes in living cells with unprecedented ease, inspiring keen interest in increasing their specificity for perfectly matched targets. We have developed a novel approach for improving specificity by incorporating chemical modifications in guide RNAs (gRNAs) at specific sites in their DNA recognition sequence ('guide sequence') and systematically evaluating their on-target and off-target activities in biochemical DNA cleavage assays and cell-based assays. Our results show that a chemical modification (2'-O-methyl-3'-phosphonoacetate, or 'MP') incorporated at select sites in the ribose-phosphate backbone of gRNAs can dramatically reduce off-target cleavage activities while maintaining high on-target performance, as demonstrated in clinically relevant genes. These findings reveal a unique method for enhancing specificity by chemically modifying the guide sequence in gRNAs. Our approach introduces a versatile tool for augmenting the performance of CRISPR systems for research, industrial and therapeutic applications. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

Improving CRISPR–Cas specificity with chemical modifications in single-guide RNAs

PubMed Central

Ryan, Daniel E; Taussig, David; Steinfeld, Israel; Phadnis, Smruti M; Lunstad, Benjamin D; Singh, Madhurima; Vuong, Xuan; Okochi, Kenji D; McCaffrey, Ryan; Olesiak, Magdalena; Roy, Subhadeep; Yung, Chong Wing; Curry, Bo; Sampson, Jeffrey R; Dellinger, Douglas J

2018-01-01

Abstract CRISPR systems have emerged as transformative tools for altering genomes in living cells with unprecedented ease, inspiring keen interest in increasing their specificity for perfectly matched targets. We have developed a novel approach for improving specificity by incorporating chemical modifications in guide RNAs (gRNAs) at specific sites in their DNA recognition sequence (‘guide sequence’) and systematically evaluating their on-target and off-target activities in biochemical DNA cleavage assays and cell-based assays. Our results show that a chemical modification (2′-O-methyl-3′-phosphonoacetate, or ‘MP’) incorporated at select sites in the ribose-phosphate backbone of gRNAs can dramatically reduce off-target cleavage activities while maintaining high on-target performance, as demonstrated in clinically relevant genes. These findings reveal a unique method for enhancing specificity by chemically modifying the guide sequence in gRNAs. Our approach introduces a versatile tool for augmenting the performance of CRISPR systems for research, industrial and therapeutic applications. PMID:29216382

Specific character of sustainable innovative development of transport construction in self-regulation conditions

NASA Astrophysics Data System (ADS)

Gumba, Khuta; Belyaeva, Svetlana

2017-10-01

The providing of sustainable development is impossible without activating the innovative activity of backbone economical sectors, in particular of transport construction. The system of self-regulation of activities is a specific feature of the transport industry development. The authors carried out the correlation analysis of innovative activity of construction enterprises, which proved the necessity of improving the normative and technical documents. The authors proposed and calculated the index of the legislation stability in the industry. The article suggests recommendations on the activation of innovative development in construction industry basing on the results of the modeling.

The effect of ankle-foot orthoses on self-reported balance confidence in persons with chronic poststroke hemiplegia.

PubMed

Zissimopoulos, Angelika; Fatone, Stefania; Gard, Steven

2014-04-01

One intervention often used to address physical impairments post stroke is an ankle-foot orthosis. Ankle-foot orthoses may improve walking speed, stride length, and gait pattern. However, effects on balance, crucial for safe ambulation, are thus far inconclusive. One aspect of balance shown to contribute to functional ability is self-efficacy. Self-efficacy, defined as the belief in one's ability to succeed in particular situations, has been shown to be more strongly associated with activity and participation (as defined by the International Classification of Functioning, Disability, and Health) than physical performance measures of gait or balance. We investigated whether self-efficacy, or balance confidence when referred to in the context of balance capabilities, is improved with ankle-foot orthosis use. Repeated measures study design. Balance confidence was measured using the Activities-specific Balance Confidence Scale in 15 persons with chronic poststroke hemiplegia, with and without their regular ankle-foot orthosis. Activities-specific Balance Confidence Scale scores were significantly higher (p ≤ 0.01) for the ankle-foot orthosis condition compared to no ankle-foot orthosis. One mechanism by which ankle-foot orthosis use may influence balance is improved balance confidence. Future work should explore the specific mechanisms underlying this improvement in self-efficacy. Clinical relevance Self-efficacy may be an important factor to consider when evaluating functioning post stroke. Rehabilitative interventions that improve balance confidence may help restore participation and overall functioning in pathological populations, particularly in the fall-prone poststroke population. Study results provide evidence for improvements in balance confidence with ankle-foot orthosis use.

Life review based on remembering specific positive events in active aging.

PubMed

Latorre, José M; Serrano, Juan P; Ricarte, Jorge; Bonete, Beatriz; Ros, Laura; Sitges, Esther

2015-02-01

The aim of this study is to evaluate the effectiveness of life review (LR) based on specific positive events in non-depressed older adults taking part in an active aging program. Fifty-five older adults were randomly assigned to an experimental group or an active control (AC) group. A six-session individual training of LR based on specific positive events was carried out with the experimental group. The AC group undertook a "media workshop" of six sessions focused on learning journalistic techniques. Pre-test and post-test measures included life satisfaction, depressive symptoms, experiencing the environment as rewarding, and autobiographical memory (AM) scales. LR intervention decreased depressive symptomatology, improved life satisfaction, and increased specific memories. The findings suggest that practice in AM for specific events is an effective component of LR that could be a useful tool in enhancing emotional well-being in active aging programs, thus reducing depressive symptoms. © The Author(s) 2014.

Engineering Neprilysin Activity and Specificity to Create a Novel Therapeutic for Alzheimer’s Disease

PubMed Central

Webster, Carl I.; Burrell, Matthew; Olsson, Lise-Lotte; Fowler, Susan B.; Digby, Sarah; Sandercock, Alan; Snijder, Arjan; Tebbe, Jan; Haupts, Ulrich; Grudzinska, Joanna; Jermutus, Lutz; Andersson, Christin

2014-01-01

Neprilysin is a transmembrane zinc metallopeptidase that degrades a wide range of peptide substrates. It has received attention as a potential therapy for Alzheimer’s disease due to its ability to degrade the peptide amyloid beta. However, its broad range of peptide substrates has the potential to limit its therapeutic use due to degradation of additional peptides substrates that tightly regulate many physiological processes. We sought to generate a soluble version of the ectodomain of neprilysin with improved activity and specificity towards amyloid beta as a potential therapeutic for Alzheimer’s disease. Extensive amino acid substitutions were performed at positions surrounding the active site and inner surface of the enzyme and variants screened for activity on amyloid beta 1–40, 1–42 and a variety of other physiologically relevant peptides. We identified several mutations that modulated and improved both enzyme selectivity and intrinsic activity. Neprilysin variant G399V/G714K displayed an approximately 20-fold improved activity on amyloid beta 1–40 and up to a 3,200-fold reduction in activity on other peptides. Along with the altered peptide substrate specificity, the mutant enzyme produced a markedly altered series of amyloid beta cleavage products compared to the wild-type enzyme. Crystallisation of the mutant enzyme revealed that the amino acid substitutions result in alteration of the shape and size of the pocket containing the active site compared to the wild-type enzyme. The mutant enzyme offers the potential for the more efficient degradation of amyloid beta in vivo as a therapeutic for the treatment of Alzheimer’s disease. PMID:25089527

Improving practice with integration of patient directed activity during inpatient rehabilitation.

PubMed

Trammell, Molly; Kapoor, Priyanka; Swank, Chad; Driver, Simon

2017-01-01

Early initiation of rehabilitation following stroke promotes better long-term outcomes than delayed onset, emphasizing the importance of inpatient therapy. However, literature indicates that following stroke individuals in inpatient rehabilitation spend the majority of their day in their bedroom and inactive. Consequently, since amount of functional activity is posited to relate to outcomes, the current rehabilitation model needs to be challenged with innovative solutions to maximize recovery. In an attempt to promote greater activity and higher doses of therapy during inpatient rehabilitation, we implemented the "Patient Directed Activity Program" to facilitate specific movement and improve outcomes for patients post stroke. Our interdisciplinary activity program was conceptualized on a theoretical model for stroke recovery and principles of experience-dependent neural plasticity. The "Patient Directed Activity Program" includes distinct activity stations designed to increase repetition, stimulation, attention, and activity of the affected upper extremities, lower extremities, and trunk. Each task-specific activity was easily graded to achieve moderate- to high-intensity. The activity program prescribed individuals up to three additional 30-minute bouts of activities daily that were to be completed independently, and in addition to standard of care. Clinical application: After implementing this program in our facility for one year as a quality improvement project, the intervention has been delivered as an Institutional Review Board approved randomized controlled trial (Clinical Trial #NCT02446197). Challenges with people and facilities have been overcome, resulting in a feasible program that can be delivered in an inpatient setting. High satisfaction has been reported by patients and clinicians.

Changes in Locomotor Muscle Activity After Treadmill Training in Subjects With Incomplete Spinal Cord Injury

PubMed Central

Gorassini, Monica A.; Norton, Jonathan A.; Nevett-Duchcherer, Jennifer; Roy, Francois D.; Yang, Jaynie F.

2009-01-01

Intensive treadmill training after incomplete spinal cord injury can improve functional walking abilities. To determine the changes in muscle activation patterns that are associated with improvements in walking, we measured the electromyography (EMG) of leg muscles in 17 individuals with incomplete spinal cord injury during similar walking conditions both before and after training. Specific differences were observed between subjects that eventually gained functional improvements in overground walking (responders), compared with subjects where treadmill training was ineffective (nonresponders). Although both groups developed a more regular and less clonic EMG pattern on the treadmill, it was only the tibialis anterior and hamstring muscles in the responders that displayed increases in EMG activation. Likewise, only the responders demonstrated decreases in burst duration and cocontraction of proximal (hamstrings and quadriceps) muscle activity. Surprisingly, the proximal muscle activity in the responders, unlike nonresponders, was three- to fourfold greater than that in uninjured control subjects walking at similar speeds and level of body weight support, suggesting that the ability to modify muscle activation patterns after injury may predict the ability of subjects to further compensate in response to motor training. In summary, increases in the amount and decreases in the duration of EMG activity of specific muscles are associated with functional recovery of walking skills after treadmill training in subjects that are able to modify muscle activity patterns following incomplete spinal cord injury. PMID:19073799

Oxidation of platinum nickel nanowires to improve durability of oxygen-reducing electrocatalysts

DOE PAGES

Alia, Shaun M.; Pylypenko, Svitlana; Dameron, Arrelaine; ...

2016-01-12

In this study, the impact of heat treating platinum-coated nickel (Pt-Ni) nanowires in oxygen is examined to determine the effect on oxygen reduction (ORR) activity and durability. Pt-Ni nanowires exhibit promising ORR mass activities (3 times greater than Pt nanoparticles, 1.5 times greater than U.S. Department of Energy target) both before and after potential cycling for all but the highest annealing temperatures explored. The annealing of Pt-Ni nanowires in oxygen with increasing temperature is found to reduce surface area and ORR activity in comparison to the untreated material, but also reduces activity losses following durability testing. Following potential cycling, unannealedmore » Pt-Ni nanowires show significant losses in surface area (23%) and specific activity (18%) while Pt-Ni nanowires annealed at 200°C show modest increases in surface area (2%) and specific activity (6%) after potential cycling. Increasing annealing temperatures also show a clear trend of decreasing Ni dissolution rates. While oxygen annealing has shown the ability to improve durability of Pt-Ni nanowires, significant Ni dissolution was observed in all samples and suggests oxide passivation while showing promise for improved durability, when employed by itself is insufficient to prevent all contamination concerns involving Ni dissolution.« less

Improvement of activity-related knee joint discomfort following supplementation of specific collagen peptides.

PubMed

Zdzieblik, Denise; Oesser, Steffen; Gollhofer, Albert; König, Daniel

2017-06-01

The aim of the study was to evaluate the use of specific collagen peptides in reducing pain in athletes with functional knee problems during sport. Athletic subjects (n = 139) with functional knee pain ingested 5 g of bioactive collagen peptides (BCP) or a placebo per day for 12 weeks. The primary outcome of the study was a change in pain intensity during activity, which was evaluated by the participants and the attending physicians using a visual analogue scale (VAS). As secondary endpoints, pain intensity under resting conditions, the range of motion of the knee joint, and the use of additional therapeutic options were assessed. The results revealed a statistically significant improvement in activity-related pain intensity in the verum group compared with placebo. (ΔVAS BCP = 19.5 ± 2.4; ΔVAS Placebo = 13.9 ± 2.1; p = 0.046). The results were confirmed by the physician's assessment. (ΔVAS BCP = 16.7 ± 1.8; ΔVAS Placebo = 12.2 ± 1.8; p = 0.021). Pain under resting conditions was also improved, but no significance compared with placebo was detected (ΔVAS BCP = 10.2 ± 18.4; ΔVAS Placebo = 7.4 ± 15.2; p = 0.209). Due to the high joint mobility at baseline, no significant changes of this parameter could be detected. The use of additional treatment options was significantly reduced after BCP intake. The study demonstrated that the supplementation of specific collagen peptides in young adults with functional knee problems led to a statistically significant improvement of activity-related joint pain.

Screening and Development of New Inhibitors of FtsZ from M. Tuberculosis

PubMed Central

Mathew, Bini; Ross, Larry; Connelly, Michele C.; Lofton, Hava; Rajagopalan, Malini; Guy, R. Kiplin; Reynolds, Robert C.

2016-01-01

A variety of commercial analogs and a newer series of Sulindac derivatives were screened for inhibition of M. tuberculosis (Mtb) in vitro and specifically as inhibitors of the essential mycobacterial tubulin homolog, FtsZ. Due to the ease of preparing diverse analogs and a favorable in vivo pharmacokinetic and toxicity profile of a representative analog, the Sulindac scaffold may be useful for further development against Mtb with respect to in vitro bacterial growth inhibition and selective activity for Mtb FtsZ versus mammalian tubulin. Further discovery efforts will require separating reported mammalian cell activity from both antibacterial activity and inhibition of Mtb FtsZ. Modeling studies suggest that these analogs bind in a specific region of the Mtb FtsZ polymer that differs from human tubulin and, in combination with a pharmacophore model presented herein, future hybrid analogs of the reported active molecules that more efficiently bind in this pocket may improve antibacterial activity while improving other drug characteristics. PMID:27768711

Food Safety Instruction Improves Knowledge and Behavior Risk and Protection Factors for Foodborne Illnesses in Pregnant Populations.

PubMed

Kendall, Patricia; Scharff, Robert; Baker, Susan; LeJeune, Jeffrey; Sofos, John; Medeiros, Lydia

2017-08-01

Objective This study compared knowledge and food-handling behavior after pathogen-specific (experimental treatment) versus basic food safety instruction (active control) presented during nutrition education classes for low-income English- and Spanish-language pregnant women. Methods Subjects (n = 550) were randomly assigned to treatment groups in two different locations in the United States. Food safety instruction was part of an 8-lesson curriculum. Food safety knowledge and behavior were measured pre/post intervention. Descriptive data were analyzed by Chi-Square or ANOVA; changes after intervention were analyzed by regression analysis. Results Knowledge improved after intervention in the pathogen-specific treatment group compared to active control, especially among Spanish-language women. Behavior change after intervention for the pathogen-specific treatment group improved for thermometer usage, refrigeration and consumption of foods at high risk for safety; however, all other improvements in behavior were accounted for by intervention regardless of treatment group. As expected, higher pre-instruction behavioral competency limited potential gain in behavior post-instruction due to a ceiling effect. This effect was more dominant among English-language women. Improvements were also linked to formal education completed, a partner at home, and other children in the home. Conclusions for Practice This study demonstrated that pathogen-specific food safety instruction leads to enhance knowledge and food handling behaviors that may improve the public health of pregnant women and their unborn children, especially among Spanish-language women. More importantly, food safety instruction, even at the most basic level, benefited pregnant women's food safety knowledge and food-handling behavior after intervention.

Physical activity, sedentary behaviour and sleep in COPD guidelines: A systematic review.

PubMed

Lewthwaite, Hayley; Effing, Tanja W; Olds, Timothy; Williams, Marie T

2017-08-01

Physical activity, sedentary and sleep behaviours have strong associations with health. This systematic review aimed to identify how clinical practice guidelines (CPGs) for the management of chronic obstructive pulmonary disease (COPD) report specific recommendations and strategies for these movement behaviours. A systematic search of databases (Medline, Scopus, CiNAHL, EMbase, Clinical Guideline), reference lists and websites identified current versions of CPGs published since 2005. Specific recommendations and strategies concerning physical activity, sedentary behaviour and sleep were extracted verbatim. The proportions of CPGs providing specific recommendations and strategies were reported. From 2370 citations identified, 35 CPGs were eligible for inclusion. Of these, 21 (60%) provided specific recommendations for physical activity, while none provided specific recommendations for sedentary behaviour or sleep. The most commonly suggested strategies to improve movement behaviours were encouragement from a healthcare provider (physical activity n = 20; sedentary behaviour n = 2) and referral for a diagnostic sleep study (sleep n = 4). Since optimal physical activity, sedentary behaviour and sleep durations and patterns are likely to be associated with mitigating the effects of COPD, as well as with general health and well-being, there is a need for further COPD-specific research, consensus and incorporation of recommendations and strategies into CPGs.

Rational design to improve thermostability and specific activity of the truncated Fibrobacter succinogenes 1,3-1,4-β-D-glucanase.

PubMed

Huang, Jian-Wen; Cheng, Ya-Shan; Ko, Tzu-Ping; Lin, Cheng-Yen; Lai, Hui-Lin; Chen, Chun-Chi; Ma, Yanhe; Zheng, Yingying; Huang, Chun-Hsiang; Zou, Peijian; Liu, Je-Ruei; Guo, Rey-Ting

2012-04-01

1,3-1,4-β-D-Glucanase has been widely used as a feed additive to help non-ruminant animals digest plant fibers, with potential in increasing nutrition turnover rate and reducing sanitary problems. Engineering of enzymes for better thermostability is of great importance because it not only can broaden their industrial applications, but also facilitate exploring the mechanism of enzyme stability from structural point of view. To obtain enzyme with higher thermostability and specific activity, structure-based rational design was carried out in this study. Eleven mutants of Fibrobacter succinogenes 1,3-1,4-β-D-glucanase were constructed in attempt to improve the enzyme properties. In particular, the crude proteins expressed in Pichia pastoris were examined firstly to ensure that the protein productions meet the need for industrial fermentation. The crude protein of V18Y mutant showed a 2 °C increment of Tm and W203Y showed ∼30% increment of the specific activity. To further investigate the structure-function relationship, some mutants were expressed and purified from P. pastoris and Escherichia coli. Notably, the specific activity of purified W203Y which was expressed in E. coli was 63% higher than the wild-type protein. The double mutant V18Y/W203Y showed the same increments of Tm and specific activity as the single mutants did. When expressed and purified from E. coli, V18Y/W203Y showed similar pattern of thermostability increment and 75% higher specific activity. Furthermore, the apo-form and substrate complex structures of V18Y/W203Y were solved by X-ray crystallography. Analyzing protein structure of V18Y/W203Y helps elucidate how the mutations could enhance the protein stability and enzyme activity.

Electrolytes with Improved Safety Characteristics for High Voltage, High Specific Energy Li-ion Cells

NASA Technical Reports Server (NTRS)

Smart, M. C.; Krause, F. C.; Hwang, C.; West, W. C.; Soler, J.; Whitcanack, L. W.; Prakash, G. K. S.; Ratnakumar, B. V.

2012-01-01

(1) NASA is actively pursuing the development of advanced electrochemical energy storage and conversion devices for future lunar and Mars missions; (2) The Exploration Technology Development Program, Energy Storage Project is sponsoring the development of advanced Li-ion batteries and PEM fuel cell and regenerative fuel cell systems for the Altair Lunar Lander, Extravehicular Activities (EVA), and rovers and as the primary energy storage system for Lunar Surface Systems; (3) At JPL, in collaboration with NASA-GRC, NASA-JSC and industry, we are actively developing advanced Li-ion batteries with improved specific energy, energy density and safety. One effort is focused upon developing Li-ion battery electrolyte with enhanced safety characteristics (i.e., low flammability); and (4) A number of commercial applications also require Li-ion batteries with enhanced safety, especially for automotive applications.

Targeted transfection increases siRNA uptake and gene silencing of primary endothelial cells in vitro--a quantitative study.

PubMed

Asgeirsdóttir, Sigridur A; Talman, Eduard G; de Graaf, Inge A; Kamps, Jan A A M; Satchell, Simon C; Mathieson, Peter W; Ruiters, Marcel H J; Molema, Grietje

2010-01-25

Applications of small-interfering RNA (siRNA) call for specific and efficient delivery of siRNA into particular cell types. We developed a novel, non-viral targeting system to deliver siRNA specifically into inflammation-activated endothelial cells. This was achieved by conjugating the cationic amphiphilic lipid SAINT to antibodies recognizing the inflammatory cell adhesion molecule E-selectin. These anti-E-selectin-SAINT lipoplexes (SAINTarg) maintained antigen recognition capacity of the parental antibody in vitro, and ex vivo in human kidney tissue slices subjected to inflammatory conditions. Regular SAINT mediated transfection resulted in efficient gene silencing in human microvascular endothelial cells (HMEC-1) and conditionally immortalized glomerular endothelial cells (ciGEnC). However, primary human umbilical vein endothelial cells (HUVEC) transfected poorly, a phenomenon that we could quantitatively correlate with a cell-type specific capacity to facilitate siRNA uptake. Importantly, SAINTarg increased siRNA uptake and transfection specificity for activated endothelial cells. Transfection with SAINTarg delivered significantly more siRNA into activated HUVEC, compared to transfection with non-targeted SAINT. The enhanced uptake of siRNA was corroborated by improved silencing of both gene- and protein expression of VE-cadherin in activated HUVEC, indicating that SAINTarg delivered functionally active siRNA into endothelial cells. The obtained results demonstrate a successful design of a small nucleotide carrier system with improved and specific siRNA delivery into otherwise difficult-to-transfect primary endothelial cells, which in addition reduced considerably the amount of siRNA needed for gene silencing. Copyright 2009 Elsevier B.V. All rights reserved.

Improving specific activity and thermostability of Escherichia coli phytase by structure-based rational design.

PubMed

Wu, Tzu-Hui; Chen, Chun-Chi; Cheng, Ya-Shan; Ko, Tzu-Ping; Lin, Cheng-Yen; Lai, Hui-Lin; Huang, Ting-Yung; Liu, Je-Ruei; Guo, Rey-Ting

2014-04-10

Escherichia coli phytase (EcAppA) which hydrolyzes phytate has been widely applied in the feed industry, but the need to improve the enzyme activity and thermostability remains. Here, we conduct rational design with two strategies to enhance the EcAppA performance. First, residues near the substrate binding pocket of EcAppA were modified according to the consensus sequence of two highly active Citrobacter phytases. One out of the eleven mutants, V89T, exhibited 17.5% increase in catalytic activity, which might be a result of stabilized protein folding. Second, the EcAppA glycosylation pattern was modified in accordance with the Citrobacter phytases. An N-glycosylation motif near the substrate binding site was disrupted to remove spatial hindrance for phytate entry and product departure. The de-glycosylated mutants showed 9.6% increase in specific activity. On the other hand, the EcAppA mutants that adopt N-glycosylation motifs from CbAppA showed improved thermostability that three mutants carrying single N-glycosylation motif exhibited 5.6-9.5% residual activity after treatment at 80°C (1.8% for wild type). Furthermore, the mutant carrying all three glycosylation motifs exhibited 27% residual activity. In conclusion, a successful rational design was performed to obtain several useful EcAppA mutants with better properties for further applications. Copyright © 2014 Elsevier B.V. All rights reserved.

A training paradigm to enhance motor recovery in contused rats: effects of staircase training.

PubMed

Singh, Anita; Murray, Marion; Houle, John D

2011-01-01

Ambulating on stairs is an important aspect of daily activities for many individuals with incomplete spinal cord injury (SCI), and little is known about the effect of training for this specific task. The goal of this study was to determine whether staircase ascent training enhances motor recovery in animals with contusion injury. Rats received a midthoracic contusion lesion of moderate severity and were randomly divided into 2 groups, with one group receiving staircase ascent training for up to 8 weeks and the other receiving no training. To assess the direct effect of training, a task-specific staircase climbing test was performed. Open field test (BBB) and gait analysis (CatWalk) assessed overground recovery, and a grid test was used to assess improvement in sensorimotor tasks. Changes in muscle mass of the forelimb and hindlimb muscles were also measured, and the extent of spared white matter was determined for lesion verification and anatomical correlations. Staircase training improved the task-specific performance of ascent. Gait parameters, including base of support, stride length, regularity index (RI), and step sequence, also improved. Overground locomotion and the grid test, both showed a trend of improved performance. Finally, hindlimb muscle mass was maintained with training. Staircase ascent training after incomplete SCI has beneficial effects on task-specific as well as nonspecific motor and sensorimotor activities.

Toll-Like Receptor 7 Agonist GS-9620 Induces HIV Expression and HIV-Specific Immunity in Cells from HIV-Infected Individuals on Suppressive Antiretroviral Therapy.

PubMed

Tsai, Angela; Irrinki, Alivelu; Kaur, Jasmine; Cihlar, Tomas; Kukolj, George; Sloan, Derek D; Murry, Jeffrey P

2017-04-15

Antiretroviral therapy can suppress HIV replication to undetectable levels but does not eliminate latent HIV, thus necessitating lifelong therapy. Recent efforts to target this persistent reservoir have focused on inducing the expression of latent HIV so that infected cells may be recognized and eliminated by the immune system. Toll-like receptor (TLR) activation stimulates antiviral immunity and has been shown to induce HIV from latently infected cells. Activation of TLR7 leads to the production of several stimulatory cytokines, including type I interferons (IFNs). In this study, we show that the selective TLR7 agonist GS-9620 induced HIV in peripheral blood mononuclear cells (PBMCs) from HIV-infected individuals on suppressive antiretroviral therapy. GS-9620 increased extracellular HIV RNA 1.5- to 2-fold through a mechanism that required type I IFN signaling. GS-9620 also activated HIV-specific T cells and enhanced antibody-mediated clearance of HIV-infected cells. Activation by GS-9620 in combination with HIV peptide stimulation increased CD8 T cell degranulation, production of intracellular cytokines, and cytolytic activity. T cell activation was again dependent on type I IFNs produced by plasmacytoid dendritic cells. GS-9620 induced phagocytic cell maturation and improved effector-mediated killing of HIV-infected CD4 T cells by the HIV envelope-specific broadly neutralizing antibody PGT121. Collectively, these data show that GS-9620 can activate HIV production and improve the effector functions that target latently infected cells. GS-9620 may effectively complement orthogonal therapies designed to stimulate antiviral immunity, such as therapeutic vaccines or broadly neutralizing antibodies. Clinical studies are under way to determine if GS-9620 can target HIV reservoirs. IMPORTANCE Though antiretroviral therapies effectively suppress viral replication, they do not eliminate integrated proviral DNA. This stable intermediate of viral infection is persistently maintained in reservoirs of latently infected cells. Consequently, lifelong therapy is required to maintain viral suppression. Ultimately, new therapies that specifically target and eliminate the latent HIV reservoir are needed. Toll-like receptor agonists are potent enhancers of innate antiviral immunity that can also improve the adaptive immune response. Here, we show that a highly selective TLR7 agonist, GS-9620, activated HIV from peripheral blood mononuclear cells isolated from HIV-infected individuals with suppressed infection. GS-9620 also improved immune effector functions that specifically targeted HIV-infected cells. Previously published studies on the compound in other chronic viral infections show that it can effectively induce immune activation at safe and tolerable clinical doses. Together, the results of these studies suggest that GS-9620 may be useful for treating HIV-infected individuals on suppressive antiretroviral therapy. Copyright © 2017 Tsai et al.

Toll-Like Receptor 7 Agonist GS-9620 Induces HIV Expression and HIV-Specific Immunity in Cells from HIV-Infected Individuals on Suppressive Antiretroviral Therapy

PubMed Central

Tsai, Angela; Irrinki, Alivelu; Kaur, Jasmine; Cihlar, Tomas; Kukolj, George

2017-01-01

ABSTRACT Antiretroviral therapy can suppress HIV replication to undetectable levels but does not eliminate latent HIV, thus necessitating lifelong therapy. Recent efforts to target this persistent reservoir have focused on inducing the expression of latent HIV so that infected cells may be recognized and eliminated by the immune system. Toll-like receptor (TLR) activation stimulates antiviral immunity and has been shown to induce HIV from latently infected cells. Activation of TLR7 leads to the production of several stimulatory cytokines, including type I interferons (IFNs). In this study, we show that the selective TLR7 agonist GS-9620 induced HIV in peripheral blood mononuclear cells (PBMCs) from HIV-infected individuals on suppressive antiretroviral therapy. GS-9620 increased extracellular HIV RNA 1.5- to 2-fold through a mechanism that required type I IFN signaling. GS-9620 also activated HIV-specific T cells and enhanced antibody-mediated clearance of HIV-infected cells. Activation by GS-9620 in combination with HIV peptide stimulation increased CD8 T cell degranulation, production of intracellular cytokines, and cytolytic activity. T cell activation was again dependent on type I IFNs produced by plasmacytoid dendritic cells. GS-9620 induced phagocytic cell maturation and improved effector-mediated killing of HIV-infected CD4 T cells by the HIV envelope-specific broadly neutralizing antibody PGT121. Collectively, these data show that GS-9620 can activate HIV production and improve the effector functions that target latently infected cells. GS-9620 may effectively complement orthogonal therapies designed to stimulate antiviral immunity, such as therapeutic vaccines or broadly neutralizing antibodies. Clinical studies are under way to determine if GS-9620 can target HIV reservoirs. IMPORTANCE Though antiretroviral therapies effectively suppress viral replication, they do not eliminate integrated proviral DNA. This stable intermediate of viral infection is persistently maintained in reservoirs of latently infected cells. Consequently, lifelong therapy is required to maintain viral suppression. Ultimately, new therapies that specifically target and eliminate the latent HIV reservoir are needed. Toll-like receptor agonists are potent enhancers of innate antiviral immunity that can also improve the adaptive immune response. Here, we show that a highly selective TLR7 agonist, GS-9620, activated HIV from peripheral blood mononuclear cells isolated from HIV-infected individuals with suppressed infection. GS-9620 also improved immune effector functions that specifically targeted HIV-infected cells. Previously published studies on the compound in other chronic viral infections show that it can effectively induce immune activation at safe and tolerable clinical doses. Together, the results of these studies suggest that GS-9620 may be useful for treating HIV-infected individuals on suppressive antiretroviral therapy. PMID:28179531

24 CFR 570.202 - Eligible rehabilitation and preservation activities.

Code of Federal Regulations, 2012 CFR

2012-04-01

... replacement of heating and cooling equipment, including the use of solar energy equipment; (5) Improvements to... objectives; (4) Improvements to increase the efficient use of energy in structures through such means as... counseling, energy auditing, preparation of work specifications, loan processing, inspections, and other...

24 CFR 570.202 - Eligible rehabilitation and preservation activities.

Code of Federal Regulations, 2014 CFR

2014-04-01

... replacement of heating and cooling equipment, including the use of solar energy equipment; (5) Improvements to... objectives; (4) Improvements to increase the efficient use of energy in structures through such means as... counseling, energy auditing, preparation of work specifications, loan processing, inspections, and other...

24 CFR 570.202 - Eligible rehabilitation and preservation activities.

Code of Federal Regulations, 2013 CFR

2013-04-01

... replacement of heating and cooling equipment, including the use of solar energy equipment; (5) Improvements to... objectives; (4) Improvements to increase the efficient use of energy in structures through such means as... counseling, energy auditing, preparation of work specifications, loan processing, inspections, and other...

24 CFR 570.202 - Eligible rehabilitation and preservation activities.

Code of Federal Regulations, 2011 CFR

2011-04-01

... replacement of heating and cooling equipment, including the use of solar energy equipment; (5) Improvements to... objectives; (4) Improvements to increase the efficient use of energy in structures through such means as... counseling, energy auditing, preparation of work specifications, loan processing, inspections, and other...

A Review of New and Developing Technology to Significantly Improve Mars Sample-Return Missions

NASA Technical Reports Server (NTRS)

Carsey, F.; Brophy, J.; Gilmore, M.; Rodgers, D.; Wilcox, B.

2000-01-01

A JPL development activity was initiated in FY 1999 for the purpose of examining and evaluating technologies that could materially improve future (i.e., beyond the 2005 launch) Mars sample return missions. The scope of the technology review was comprehensive and end-to-end; the goal was to improve mass, cost, risk, and scientific return. A specific objective was to assess approaches to sample return with only one Earth launch. While the objective of the study was specifically for sample-return, in-situ missions can also benefit from using many of the technologies examined.

A Review of New and Developing Technology to Significantly Improve Mars Sample-Return Missions

NASA Astrophysics Data System (ADS)

Carsey, F.; Brophy, J.; Gilmore, M.; Rodgers, D.; Wilcox, B.

2000-07-01

A JPL development activity was initiated in FY 1999 for the purpose of examining and evaluating technologies that could materially improve future (i.e., beyond the 2005 launch) Mars sample return missions. The scope of the technology review was comprehensive and end-to-end; the goal was to improve mass, cost, risk, and scientific return. A specific objective was to assess approaches to sample return with only one Earth launch. While the objective of the study was specifically for sample-return, in-situ missions can also benefit from using many of the technologies examined.

Investigating Commercial Cellulase Performances Toward Specific Biomass Recalcitrance Factors Using Reference Substrates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ju, Xiaohui; Bowden, Mark E.; Engelhard, Mark H.

Three commercial cellulase preparations, Novozymes Cellic® Ctec2, Dupont Accellerase® 1500, and DSM Cytolase CL, were evaluated for their hydrolytic activity using a set of reference biomass substrates with controlled substrate characteristics. It was found that lignin remains a significant recalcitrance factor to all the preparations, although different enzyme preparations respond to the inhibitory effect of lignin differently. Also, different types of biomass lignin can inhibit cellulose enzymes in different manners. Enhancing enzyme activity toward biomass fiber swelling is an area significantly contributing to potential improvement in cellulose performance. While the degree of polymerization of cellulose in the reference substrates didmore » not present a major recalcitrance factor to Novozymes Cellic® Ctec2, cellulose crystallite has been shown to have a significant lower reactivity toward all enzyme mixtures. The presence of polysaccharide monooxygenases (PMOs) in Novozymes Ctec2 appears to enhance enzyme activity toward decrystallization of cellulose. This study demonstrated that reference substrates with controlled chemical and physical characteristics of structural features can be applied as an effective and practical strategy to identify cellulosic enzyme activities toward specific biomass recalcitrance factor(s) and provide specific targets for enzyme improvement.« less

Investigating commercial cellulase performances toward specific biomass recalcitrance factors using reference substrates.

PubMed

Ju, Xiaohui; Bowden, Mark; Engelhard, Mark; Zhang, Xiao

2014-05-01

Three commercial cellulase preparations, Novozymes Cellic(®) Ctec2, Dupont Accellerase(®) 1500, and DSM Cytolase CL, were evaluated for their hydrolytic activity using a set of reference biomass substrates with controlled substrate characteristics. It was found that lignin remains a significant recalcitrance factor to all the preparations, although different enzyme preparations respond to the inhibitory effect of lignin differently. Also, different types of biomass lignin can inhibit cellulase enzymes in different manners. Enhancing enzyme activity toward biomass fiber swelling is an area significantly contributing to potential improvement in cellulase performance. While the degree of polymerization of cellulose in the reference substrates did not present a major recalcitrance factor to Novozymes Cellic(®) Ctec2, cellulose crystallite has been shown to have a significant lower reactivity toward all enzyme mixtures. The presence of polysaccharide monooxygenases (PMOs) in Novozymes Ctec2 appears to enhance enzyme activity toward decrystallization of cellulose. This study demonstrated that reference substrates with controlled chemical and physical characteristics of structural features can be applied as an effective and practical strategy to identify cellulosic enzyme activities toward specific biomass recalcitrance factor(s) and provide specific targets for enzyme improvement.

Exergaming in older adults: A scoping review and implementation potential for patients with heart failure

PubMed Central

Verheijden Klompstra, Leonie; Jaarsma, Tiny; Strömberg, Anna

2013-01-01

Background: Physical activity can improve exercise capacity, quality of life and reduce mortality and hospitalization in patients with heart failure (HF). Adherence to exercise recommendations in patients with HF is low. The use of exercise games (exergames) might be a way to encourage patients with HF to exercise especially those who may be reluctant to more traditional forms of exercise. No studies have been conducted on patients with HF and exergames. Aim: This scoping review focuses on the feasibility and influence of exergames on physical activity in older adults, aiming to target certain characteristics that are important for patients with HF to become more physically active. Methods: A literature search was undertaken in August 2012 in the databases PsychInfo, PUBMED, Scopus, Web of Science and CINAHL. Included studies evaluated the influence of exergaming on physical activity in older adults. Articles were excluded if they focused on rehabilitation of specific limbs, improving specific tasks or describing no intervention. Fifty articles were found, 11 were included in the analysis. Results: Exergaming was described as safe and feasible, and resulted in more energy expenditure compared to rest. Participants experienced improved balance and reported improved cognitive function after exergaming. Participants enjoyed playing the exergames, their depressive symptoms decreased, and they reported improved quality of life and empowerment. Exergames made them feel more connected with their family members, especially their grandchildren. Conclusion: Although this research field is small and under development, exergaming might be promising in order to enhance physical activity in patients with HF. However, further testing is needed. PMID:24198306

Exergaming in older adults: a scoping review and implementation potential for patients with heart failure.

PubMed

Verheijden Klompstra, Leonie; Jaarsma, Tiny; Strömberg, Anna

2014-10-01

Physical activity can improve exercise capacity, quality of life and reduce mortality and hospitalization in patients with heart failure (HF). Adherence to exercise recommendations in patients with HF is low. The use of exercise games (exergames) might be a way to encourage patients with HF to exercise especially those who may be reluctant to more traditional forms of exercise. No studies have been conducted on patients with HF and exergames. This scoping review focuses on the feasibility and influence of exergames on physical activity in older adults, aiming to target certain characteristics that are important for patients with HF to become more physically active. A literature search was undertaken in August 2012 in the databases PsychInfo, PUBMED, Scopus, Web of Science and CINAHL. Included studies evaluated the influence of exergaming on physical activity in older adults. Articles were excluded if they focused on rehabilitation of specific limbs, improving specific tasks or describing no intervention. Fifty articles were found, 11 were included in the analysis. Exergaming was described as safe and feasible, and resulted in more energy expenditure compared to rest. Participants experienced improved balance and reported improved cognitive function after exergaming. Participants enjoyed playing the exergames, their depressive symptoms decreased, and they reported improved quality of life and empowerment. Exergames made them feel more connected with their family members, especially their grandchildren. Although this research field is small and under development, exergaming might be promising in order to enhance physical activity in patients with HF. However, further testing is needed. © The European Society of Cardiology 2013.

Manipulating motor performance and memory through real-time fMRI neurofeedback.

PubMed

Scharnowski, Frank; Veit, Ralf; Zopf, Regine; Studer, Petra; Bock, Simon; Diedrichsen, Jörn; Goebel, Rainer; Mathiak, Klaus; Birbaumer, Niels; Weiskopf, Nikolaus

2015-05-01

Task performance depends on ongoing brain activity which can be influenced by attention, arousal, or motivation. However, such modulating factors of cognitive efficiency are unspecific, can be difficult to control, and are not suitable to facilitate neural processing in a regionally specific manner. Here, we non-pharmacologically manipulated regionally specific brain activity using technically sophisticated real-time fMRI neurofeedback. This was accomplished by training participants to simultaneously control ongoing brain activity in circumscribed motor and memory-related brain areas, namely the supplementary motor area and the parahippocampal cortex. We found that learned voluntary control over these functionally distinct brain areas caused functionally specific behavioral effects, i.e. shortening of motor reaction times and specific interference with memory encoding. The neurofeedback approach goes beyond improving cognitive efficiency by unspecific psychological factors such as attention, arousal, or motivation. It allows for directly manipulating sustained activity of task-relevant brain regions in order to yield specific behavioral or cognitive effects. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Manipulating motor performance and memory through real-time fMRI neurofeedback

PubMed Central

Scharnowski, Frank; Veit, Ralf; Zopf, Regine; Studer, Petra; Bock, Simon; Diedrichsen, Jörn; Goebel, Rainer; Mathiak, Klaus; Birbaumer, Niels; Weiskopf, Nikolaus

2015-01-01

Task performance depends on ongoing brain activity which can be influenced by attention, arousal, or motivation. However, such modulating factors of cognitive efficiency are unspecific, can be difficult to control, and are not suitable to facilitate neural processing in a regionally specific manner. Here, we non-pharmacologically manipulated regionally specific brain activity using technically sophisticated real-time fMRI neurofeedback. This was accomplished by training participants to simultaneously control ongoing brain activity in circumscribed motor and memory-related brain areas, namely the supplementary motor area and the parahippocampal cortex. We found that learned voluntary control over these functionally distinct brain areas caused functionally specific behavioral effects, i.e. shortening of motor reaction times and specific interference with memory encoding. The neurofeedback approach goes beyond improving cognitive efficiency by unspecific psychological factors such as attention, arousal, or motivation. It allows for directly manipulating sustained activity of task-relevant brain regions in order to yield specific behavioral or cognitive effects. PMID:25796342

48 CFR 1602.170-14 - FEHB-specific medical loss ratio threshold calculation.

Code of Federal Regulations, 2011 CFR

2011-10-01

... issuer's expenditures for activities that improve health care quality, to total premium revenue determined by OPM, as defined by the Department of Health and Human Services. (b) The FEHB-specific MLR will... OFFICE OF PERSONNEL MANAGEMENT FEDERAL EMPLOYEES HEALTH BENEFITS ACQUISITION REGULATION GENERAL...

Improved specificity of hippocampal memory trace labeling.

PubMed

Cazzulino, Alejandro S; Martinez, Randy; Tomm, Nicole K; Denny, Christine A

2016-06-01

Recent studies have focused on the identification and manipulation of memory traces in rodent models. The two main mouse models utilized are either a CreER(T2) /loxP tamoxifen (TAM)- or a tetracycline transactivator/tetracycline-response element doxycycline-inducible system. These systems, however, could be improved to label a more specific population of activated neurons corresponding to behavior. Here, we sought to identify an improved selective estrogen receptor (ER) modulator (SERM) in which we could label an individual memory trace in ArcCreER(T2) mice. We found that 4-hydroxytamoxifen (4-OHT) is a selective SERM in the ArcCreER(T2) × Rosa26-CAG-stop(flox) -channelrhodospin (ChR2)-enhanced yellow fluorescent protein (eYFP) mice. The half-life of 4-OHT is shorter than TAM, allowing for more specificity of memory trace labeling. Furthermore, 4-OHT allowed for context-specific labeling in the dentate gyrus and CA3. In summary, we believe that 4-OHT improves the specificity of memory trace labeling and will allow for refined memory trace studies in the future. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.

The effect of active video games on cognitive functioning in clinical and non-clinical populations: A meta-analysis of randomized controlled trials.

PubMed

Stanmore, Emma; Stubbs, Brendon; Vancampfort, Davy; de Bruin, Eling D; Firth, Joseph

2017-07-01

Physically-active video games ('exergames') have recently gained popularity for leisure and entertainment purposes. Using exergames to combine physical activity and cognitively-demanding tasks may offer a novel strategy to improve cognitive functioning. Therefore, this systematic review and meta-analysis was performed to establish effects of exergames on overall cognition and specific cognitive domains in clinical and non-clinical populations. We identified 17 eligible RCTs with cognitive outcome data for 926 participants. Random-effects meta-analyses found exergames significantly improved global cognition (g=0.436, 95% CI=0.18-0.69, p=0.001). Significant effects still existed when excluding waitlist-only controlled studies, and when comparing to physical activity interventions. Furthermore, benefits of exergames where observed for both healthy older adults and clinical populations with conditions associated with neurocognitive impairments (all p<0.05). Domain-specific analyses found exergames improved executive functions, attentional processing and visuospatial skills. The findings present the first meta-analytic evidence for effects of exergames on cognition. Future research must establish which patient/treatment factors influence efficacy of exergames, and explore neurobiological mechanisms of action. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

Gingerol activates noxious cold ion channel TRPA1 in gastrointestinal tract.

PubMed

Yang, Meng-Qi; Ye, Lin-Lan; Liu, Xiao-Ling; Qi, Xiao-Ming; Lv, Jia-Di; Wang, Gang; Farhan, Ulah-Khan; Waqas, Nawaz; Chen, Ding-Ding; Han, Lei; Zhou, Xiao-Hui

2016-06-01

TRPA1 channels are non-selective cation channels that could be activated by plant-derived pungent products, including gingerol, a main active constituent of ginger. Ginger could improve the digestive function; however whether ginger improves the digestive function through activating TRPA1 receptor in gastrointestinal tract has not been investigated. In the present study, gingerol was used to stimulate cell lines (RIN14B or STC-1) while depletion of extracellular calcium. TRPA1 inhibitor (rethenium red) and TRPA1 gene silencing via TRPA1-specific siRNA were also used for mechanistic studies. The intracellular calcium and secretion of serotonin or cholecystokinin were measured by fura-2/AM and ELISA. Stimulation of those cells with gingerol increased intracellular calcium levels and the serotonin or cholecystokinin secretion. The gingerol-induced intracellular calcium increase and secretion (serotonin or cholecystokinin) release were completely blocked by ruthenium red, EGTA, and TRPA1-specific siRNA. In summary, our results suggested that gingerol derived from ginger might improve the digestive function through secretion releasing from endocrine cells of the gut by inducing TRPA1-mediated calcium influx. Copyright © 2016 China Pharmaceutical University. Published by Elsevier B.V. All rights reserved.

Are HIV/AIDS Prevention Interventions for Heterosexually Active Men in the United States Gender-Specific?

PubMed Central

Fullilove, Robert E.; Peacock, Dean

2009-01-01

Although gender-specific theories are often deployed in interventions to reduce women's HIV risks, the same is often not true for interventions among men. Theories of masculinity are not guiding most US research on the risky sexual behavior of heterosexual men or on what can be done to intervene. We first assess the extent to which evidence-based HIV-prevention interventions among heterosexually active men in the United States draw upon relevant theories of masculinity. Next, we introduce a useful framework within masculinity and gender studies that can be applied to HIV-prevention interventions with heterosexually active men. Finally, we make suggestions to improve the gender specificity of HIV-prevention interventions for heterosexually active men in the United States. PMID:19372506

Implementing a user-driven online quality improvement toolkit for cancer care.

PubMed

Luck, Jeff; York, Laura S; Bowman, Candice; Gale, Randall C; Smith, Nina; Asch, Steven M

2015-05-01

Peer-to-peer collaboration within integrated health systems requires a mechanism for sharing quality improvement lessons. The Veterans Health Administration (VA) developed online compendia of tools linked to specific cancer quality indicators. We evaluated awareness and use of the toolkits, variation across facilities, impact of social marketing, and factors influencing toolkit use. A diffusion of innovations conceptual framework guided the collection of user activity data from the Toolkit Series SharePoint site and an online survey of potential Lung Cancer Care Toolkit users. The VA Toolkit Series site had 5,088 unique visitors in its first 22 months; 5% of users accounted for 40% of page views. Social marketing communications were correlated with site usage. Of survey respondents (n = 355), 54% had visited the site, of whom 24% downloaded at least one tool. Respondents' awareness of the lung cancer quality performance of their facility, and facility participation in quality improvement collaboratives, were positively associated with Toolkit Series site use. Facility-level lung cancer tool implementation varied widely across tool types. The VA Toolkit Series achieved widespread use and a high degree of user engagement, although use varied widely across facilities. The most active users were aware of and active in cancer care quality improvement. Toolkit use seemed to be reinforced by other quality improvement activities. A combination of user-driven tool creation and centralized toolkit development seemed to be effective for leveraging health information technology to spread disease-specific quality improvement tools within an integrated health care system. Copyright © 2015 by American Society of Clinical Oncology.

34 CFR 606.7 - What definitions apply?

Code of Federal Regulations, 2012 CFR

2012-07-01

... implementation plan designed to meet one or more objectives. An activity is a part of a project and has its own... or improved programs and services, beyond those regularly budgeted, specifically designed to improve... expended by an institution of higher education for instruction, research, public service, academic support...

34 CFR 606.7 - What definitions apply?

Code of Federal Regulations, 2013 CFR

2013-07-01

... implementation plan designed to meet one or more objectives. An activity is a part of a project and has its own... or improved programs and services, beyond those regularly budgeted, specifically designed to improve... expended by an institution of higher education for instruction, research, public service, academic support...

34 CFR 606.7 - What definitions apply?

Code of Federal Regulations, 2014 CFR

2014-07-01

... implementation plan designed to meet one or more objectives. An activity is a part of a project and has its own... or improved programs and services, beyond those regularly budgeted, specifically designed to improve... expended by an institution of higher education for instruction, research, public service, academic support...

34 CFR 606.7 - What definitions apply?

Code of Federal Regulations, 2011 CFR

2011-07-01

... implementation plan designed to meet one or more objectives. An activity is a part of a project and has its own... or improved programs and services, beyond those regularly budgeted, specifically designed to improve... expended by an institution of higher education for instruction, research, public service, academic support...

34 CFR 606.7 - What definitions apply?

Code of Federal Regulations, 2010 CFR

2010-07-01

... implementation plan designed to meet one or more objectives. An activity is a part of a project and has its own... or improved programs and services, beyond those regularly budgeted, specifically designed to improve... expended by an institution of higher education for instruction, research, public service, academic support...

A Bottom-Up Proteomic Approach to Identify Substrate Specificity of Outer-Membrane Protease OmpT.

PubMed

Wood, Sarah E; Sinsinbar, Gaurav; Gudlur, Sushanth; Nallani, Madhavan; Huang, Che-Fan; Liedberg, Bo; Mrksich, Milan

2017-12-22

Identifying peptide substrates that are efficiently cleaved by proteases gives insights into substrate recognition and specificity, guides development of inhibitors, and improves assay sensitivity. Peptide arrays and SAMDI mass spectrometry were used to identify a tetrapeptide substrate exhibiting high activity for the bacterial outer-membrane protease (OmpT). Analysis of protease activity for the preferred residues at the cleavage site (P1, P1') and nearest-neighbor positions (P2, P2') and their positional interdependence revealed FRRV as the optimal peptide with the highest OmpT activity. Substituting FRRV into a fragment of LL37, a natural substrate of OmpT, led to a greater than 400-fold improvement in OmpT catalytic efficiency, with a k cat /K m value of 6.1×10 6  L mol -1  s -1 . Wild-type and mutant OmpT displayed significant differences in their substrate specificities, demonstrating that even modest mutants may not be suitable substitutes for the native enzyme. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Improvement of L(+)-Lactic Acid Production of Rhizopus Oryzae by Low-Energy Ions and Analysis of Its Mechanism

NASA Astrophysics Data System (ADS)

Ge, Chunmei; Yang, Yingge; Fan, Yonghong; Li, Wen; Pan, Renrui; Zheng, Zhiming; Yu, Zengliang

2008-02-01

The wild type strain Rhizopus oryzae PW352 was mutated by means of nitrogen ion implantation (15 keV, 7.8 × 1014 ~ 2.08 × 1015 ions/cm2) to find an industrial strain with a higher L(+)-lactic acid yield, and two mutants RE3303 and RF9052 were isolated. In order to discuss the mechanism primarily, Lactate Dehydrogenase of Rhizopus oryzae was studied. While the two mutants produced L(+)-lactic acid by 75% more than the wild strain did, their specific activity of Lactate Dehydrogenase was found to be higher than that in the wild strain. The optimum temperature of Lactate Dehydrogenase in Rhizopus oryzae RF9052 was higher. Compared to the wild strain, the Michaelis constant (Km) value of Lactate Dehydrogenase in the mutants was changed. All these changes show that L(+)-lactic acid production has a correlation with the specific activity of Lactate Dehydrogenase. The low-energy ions, implanted into the strain, may improve the specific activity of Lactate Dehydrogenase by influencing its gene structure and protein structure.

The national strategic plan for federal aquaculture research, specific goal #4: Improve production efficiency and well-being

USDA-ARS?s Scientific Manuscript database

The 2014-2019 National Strategic Plan for Federal Aquaculture Research identifies a series of specific goals that identify research priorities for Federal agency and interagency research programs. Collectively, these priorities define research activities with the broad outcome of supporting aquacul...

Sports Potentials for Physical Fitness.

ERIC Educational Resources Information Center

Clarke, H. Harrison, Ed.

1978-01-01

This report, one of a series on research into specific physical activities and their efficacy in improving and maintaining physical fitness, examines sport participation and the potential it has for developing muscular strength, muscular endurance, and circulatory-respiratory endurance. The activities consist primarily of the following twelve…

76 FR 35454 - Agency Information Collection Activities: Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2011-06-17

..., selective and targeted prevention activities and services; and (4) to collect performance and outcome data... other Federal partners to use in working with States and Territories to improve their behavioral health... seventeen goals were population specific (pregnant [[Page 35456

ROS-activated anticancer prodrugs: a new strategy for tumor-specific damage

PubMed Central

Peng, Xiaohua; Gandhi, Varsha

2013-01-01

Targeting tumor cells is an important strategy to improve the selectivity of cancer therapies. With the advanced studies in cancer biology, we know that cancer cells are usually under increased oxidative stress. The high level of reactive oxygen species in cancer cells has been exploited for developing novel therapeutic strategies to preferentially kill cancer cells. Our group, amongst others, have used boronic acids/esters as triggers for developing ROS-activated anticancer prodrugs that target cancer cells. The selectivity was achieved by combining a specific reaction between boronates and H2O2 with the efficient masking of drug toxicity in the prodrug via boronates. Prodrugs activated via ferrocene-mediated oxidation have also been developed to improve the selectivity of anticancer drugs. We describe how the strategies of ROS-activation can be used for further development of new ROS-targeting prodrugs, eventually leading to novel approaches and/or combined technology for more efficient and selective treatment of cancers. PMID:22900465

An experimental study on PEO polymer electrolyte based all-solid-state supercapacitor

NASA Astrophysics Data System (ADS)

Yijing, Yin

Supercapacitors are one of the most important electrochemical energy storage and conversion devices, however low ionic conductivity of solid state polymer electrolytes and the poor accessibility of the ions to the active sites in the porous electrode will cause low performance for all-solid-state supercapacitors and will limit their application. The objective of the dissertation is to improve the performance of all-solid-state supercapactor by improving electrolyte conductivity and solving accessibility problem of the ions to the active sites. The low ionic conductivity (10-8 S/cm) of poly(ethylene oxide) (PEO) limits its application as an electrolyte. Since PEO is a semicrystal polymer and the ion conduction take place mainly in the amorphous regions of the PEO/Lithium salt complex, improvements in the percentage of amorphous phase in PEO or increasing the charge carrier concentration and mobility could increase the ionic conductivity of PEO electrolyte. Hot pressing along with the additions of different lithium salts, inorganic fillers and plasticizers were applied to improve the ionic conductivity of PEO polymer electrolytes. Four electrode methods were used to evaluate the conductivity of PEO based polymer electrolytes. Results show that adding certain lithium salts, inorganic fillers, and plasticizers could improve the ionic conductivity of PEO electrolytes up 10-4 S/cm. Further hot pressing treatment could improve the ionic conductivity of PEO electrolytes up to 10-3 S/cm. The conductivity improvement after hot pressing treatment is elucidated as that the spherulite crystal phase is convert into the fringed micelle crystal phase or the amorphous phase of PEO electrolytes. PEO electrolytes were added into active carbon as a binder and an ion conductor, so as to provide electrodes with not only ion conduction, but also the accessibility of ion to the active sites of electrodes. The NaI/I 2 mediator was added to improve the conductivity of PEO electrolyte and provide pseudocapacitance for all-solid-state supercapacitors. Impedance, cyclic voltammetry, and gavalnostatic charge/discharge measurements were conducted to evaluate the electrochemical performance of PEO polymer electrolytes based all-solid-state supercapacitors. Results demonstrate that the conductivity of PEO electrolyte could be improved to 0.1 S/cm with a mediator concentration of 50wt%. A high conductivity in the PEO electrolyte with mediator is an indication of a high electron exchange rate between the mediator and mediator. The high electron exchange rates at mediator carbon interface and between mediator and mediator are essential in order to obtain a high response rate and high power. This automatically solves the accessibility problem. With the addition of NaI/I2 mediator, the specific capacitance increased more than 30 folds, specific power increased almost 20 folds, and specific energy increased around 10 folds. Further addition of filler to the electrodes along with the mediator could double the specific capacitor and specific power of the all-solid-state supercapacitor. The stability of the corresponded supercapacitor is good within 2000 cycles.

Evaluating Community Engagement in an Academic Medical Center

PubMed Central

Shone, Laura P.; Dozier, Ann M.; Newton, Gail L.; Green, Theresa; Bennett, Nancy M.

2014-01-01

From the perspective of academic medical centers (AMCs), community engagement is a collaborative process of working toward mutually defined goals to improve the community’s health, and involves partnerships between AMCs, individuals, and entities representing the surrounding community. AMCs increasingly recognize the importance of community engagement, and recent programs such as Prevention Research Centers and Clinical and Translational Science Awards have highlighted community engagement activities. However, there is no standard or accepted metric for evaluating AMCs’ performance and impact of community engagement activities. In this article, the authors present a framework for evaluating AMCs’ community engagement activities. The framework includes broad goals and specific activities within each goal, wherein goals and activities are evaluated using a health services research framework consisting of structure, process, and outcome criteria. To illustrate how to use this community engagement evaluation framework, the authors present specific community engagement goals and activities of the University of Rochester Medical Center to (1) improve the health of the community served by the AMC; (2) increase the AMC’s capacity for community engagement; and (3) increase generalizable knowledge and practices in community engagement and public health. Using a structure-process-outcomes framework, a multidisciplinary team should regularly evaluate an AMC’s community engagement program with the purpose of measurably improving the performance of the AMC and the health of its surrounding community. PMID:24556768

Synthesis of Platinum-nickel Nanowires and Optimization for Oxygen Reduction Performance.

PubMed

Alia, Shaun M; Pivovar, Bryan S

2018-04-27

Platinum-nickel (Pt-Ni) nanowires were developed as fuel cell electrocatalysts, and were optimized for the performance and durability in the oxygen reduction reaction. Spontaneous galvanic displacement was used to deposit Pt layers onto Ni nanowire substrates. The synthesis approach produced catalysts with high specific activities and high Pt surface areas. Hydrogen annealing improved Pt and Ni mixing and specific activity. Acid leaching was used to preferentially remove Ni near the nanowire surface, and oxygen annealing was used to stabilize near-surface Ni, improving durability and minimizing Ni dissolution. These protocols detail the optimization of each post-synthesis processing step, including hydrogen annealing to 250 °C, exposure to 0.1 M nitric acid, and oxygen annealing to 175 °C. Through these steps, Pt-Ni nanowires produced increased activities more than an order of magnitude than Pt nanoparticles, while offering significant durability improvements. The presented protocols are based on Pt-Ni systems in the development of fuel cell catalysts. These techniques have also been used for a variety of metal combinations, and can be applied to develop catalysts for a number of electrochemical processes.

Topical ivermectin improves allergic skin inflammation.

PubMed

Ventre, E; Rozières, A; Lenief, V; Albert, F; Rossio, P; Laoubi, L; Dombrowicz, D; Staels, B; Ulmann, L; Julia, V; Vial, E; Jomard, A; Hacini-Rachinel, F; Nicolas, J-F; Vocanson, M

2017-08-01

Ivermectin (IVM) is widely used in both human and veterinary medicine to treat parasitic infections. Recent reports have suggested that IVM could also have anti-inflammatory properties. Here, we investigated the activity of IVM in a murine model of atopic dermatitis (AD) induced by repeated exposure to the allergen Dermatophagoides farinae, and in standard cellular immunological assays. Our results show that topical IVM improved allergic skin inflammation by reducing the priming and activation of allergen-specific T cells, as well as the production of inflammatory cytokines. While IVM had no major impact on the functions of dendritic cells in vivo and in vitro, IVM impaired T-cell activation, proliferation, and cytokine production following polyclonal and antigen-specific stimulation. Altogether, our results show that IVM is endowed with topical anti-inflammatory properties that could have important applications for the treatment of T-cell-mediated skin inflammatory diseases. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Resistance-training exercises with different stability requirements: time course of task specificity.

PubMed

Saeterbakken, Atle Hole; Andersen, Vidar; Behm, David G; Krohn-Hansen, Espen Krogseth; Smaamo, Mats; Fimland, Marius Steiro

2016-12-01

The aim of the study was to assess the task-specificity (greater improvements in trained compared to non-trained tasks), transferability and time-course adaptations of resistance-training programs with varying instability requirements. Thirty-six resistance-trained men were randomized to train chest press 2 days week -1 for 10 week (6 repetitions × 4 series) using a Swiss ball, Smith machine or dumbbells. A six-repetition maximum-strength test with the aforementioned exercises and traditional barbell chest press were performed by all participants at the first, 7th, 14th and final training session in addition to electromyographic activities of the prime movers measured during isometric bench press. The groups training with the unstable Swiss-ball and dumbbells, but not the stable Smith-machine, demonstrated task-specificity, which became apparent in the early phase and remained throughout the study. The improvements in the trained exercise tended to increase more with instability (dumbbells vs. Smith machine, p = 0.061). The group training with Smith machine had similar improvements in the non-trained exercises. Greater improvements were observed in the early phase of the strength-training program (first-7th session) for all groups in all three exercises, but most notably for the unstable exercises. No differences were observed between the groups or testing times for EMG activity. These findings suggest that among resistance-trained individuals, the concept of task-specificity could be most relevant in resistance training with greater stability requirements, particularly due to rapid strength improvements for unstable resistance exercises.

A focused exercise regimen improves clinical measures of balance in patients with peripheral neuropathy.

PubMed

Richardson, J K; Sandman, D; Vela, S

2001-02-01

To determine the effect of a specific exercise regimen on clinical measures of postural stability and confidence in a population with peripheral neuropathy (PN). Prospective, controlled, single blind study. Outpatient clinic of a university hospital. Twenty subjects with diabetes mellitus and electrodiagnostically confirmed PN. Ten subjects underwent a 3-week intervention exercise regimen designed to increase rapidly available distal strength and balance. The other 10 subjects performed a control exercise regimen. Unipedal stance time, functional reach, tandem stance time, and score on the activities-specific balance and confidence (ABC) scale. The intervention subjects, but not the control subjects, showed significant improvement in all 3 clinical measures of balance and nonsignificant improvement on the ABC scale. A brief, specific exercise regimen improved clinical measures of balance in patients with diabetic PN. Further studies are needed to determine if this result translates into a lower fall frequency in this high-risk population.

Dietary Animal Plasma Proteins Improve the Intestinal Immune Response in Senescent Mice.

PubMed

Miró, Lluïsa; Garcia-Just, Alba; Amat, Concepció; Polo, Javier; Moretó, Miquel; Pérez-Bosque, Anna

2017-12-11

Increased life expectancy has promoted research on healthy aging. Aging is accompanied by increased non-specific immune activation (inflammaging) which favors the appearance of several disorders. Here, we study whether dietary supplementation with spray-dried animal plasma (SDP), which has been shown to reduce the activation of gut-associated lymphoid tissue (GALT) in rodents challenged by S. aureus enterotoxin B (SEB), and can also prevent the effects of aging on immune system homeostasis. We first characterized GALT in a mouse model of accelerated senescence (SAMP8) at different ages (compared to mice resistant to accelerated senescence; SAMR1). Second, we analyzed the SDP effects on GALT response to an SEB challenge in SAMP8 mice. In GALT characterization, aging increased the cell number and the percentage of activated Th lymphocytes in mesenteric lymph nodes and Peyer's patches (all, p < 0.05), as well as the expression of IL-6 and TNF-α in intestinal mucosa (both, p < 0.05). With respect to GALT response to the SEB challenge, young mice showed increased expression of intestinal IL-6 and TNF-α, as well as lymphocyte recruitment and activation (all, p < 0.05). However, the immune response of senescent mice to the SEB challenge was weak, since SEB did not change cell recruitment or the percentage of activated Th lymphocytes. Mice supplemented with SDP showed improved capacity to respond to the SEB challenge, similar to the response of the young mice. These results indicate that senescent mice have an impaired mucosal immune response characterized by unspecific GALT activation and a weak specific immune response. SDP supplementation reduces non-specific basal immune activation, allowing for the generation of specific responses.

Methods of increasing the performance of radionuclide generators used in nuclear medicine: daughter nuclide build-up optimisation, elution-purification-concentration integration, and effective control of radionuclidic purity.

PubMed

Le, Van So; Do, Zoe Phuc-Hien; Le, Minh Khoi; Le, Vicki; Le, Natalie Nha-Truc

2014-06-10

Methods of increasing the performance of radionuclide generators used in nuclear medicine radiotherapy and SPECT/PET imaging were developed and detailed for 99Mo/99mTc and 68Ge/68Ga radionuclide generators as the cases. Optimisation methods of the daughter nuclide build-up versus stand-by time and/or specific activity using mean progress functions were developed for increasing the performance of radionuclide generators. As a result of this optimisation, the separation of the daughter nuclide from its parent one should be performed at a defined optimal time to avoid the deterioration in specific activity of the daughter nuclide and wasting stand-by time of the generator, while the daughter nuclide yield is maintained to a reasonably high extent. A new characteristic parameter of the formation-decay kinetics of parent/daughter nuclide system was found and effectively used in the practice of the generator production and utilisation. A method of "early elution schedule" was also developed for increasing the daughter nuclide production yield and specific radioactivity, thus saving the cost of the generator and improving the quality of the daughter radionuclide solution. These newly developed optimisation methods in combination with an integrated elution-purification-concentration system of radionuclide generators recently developed is the most suitable way to operate the generator effectively on the basis of economic use and improvement of purposely suitable quality and specific activity of the produced daughter radionuclides. All these features benefit the economic use of the generator, the improved quality of labelling/scan, and the lowered cost of nuclear medicine procedure. Besides, a new method of quality control protocol set-up for post-delivery test of radionuclidic purity has been developed based on the relationship between gamma ray spectrometric detection limit, required limit of impure radionuclide activity and its measurement certainty with respect to optimising decay/measurement time and product sample activity used for QC quality control. The optimisation ensures a certainty of measurement of the specific impure radionuclide and avoids wasting the useful amount of valuable purified/concentrated daughter nuclide product. This process is important for the spectrometric measurement of very low activity of impure radionuclide contamination in the radioisotope products of much higher activity used in medical imaging and targeted radiotherapy.

Physical activity, sedentary behaviour and sleep in COPD guidelines: A systematic review

PubMed Central

Effing, Tanja W; Olds, Timothy; Williams, Marie T

2017-01-01

Objectives: Physical activity, sedentary and sleep behaviours have strong associations with health. This systematic review aimed to identify how clinical practice guidelines (CPGs) for the management of chronic obstructive pulmonary disease (COPD) report specific recommendations and strategies for these movement behaviours. Methods: A systematic search of databases (Medline, Scopus, CiNAHL, EMbase, Clinical Guideline), reference lists and websites identified current versions of CPGs published since 2005. Specific recommendations and strategies concerning physical activity, sedentary behaviour and sleep were extracted verbatim. The proportions of CPGs providing specific recommendations and strategies were reported. Results: From 2370 citations identified, 35 CPGs were eligible for inclusion. Of these, 21 (60%) provided specific recommendations for physical activity, while none provided specific recommendations for sedentary behaviour or sleep. The most commonly suggested strategies to improve movement behaviours were encouragement from a healthcare provider (physical activity n = 20; sedentary behaviour n = 2) and referral for a diagnostic sleep study (sleep n = 4). Conclusion: Since optimal physical activity, sedentary behaviour and sleep durations and patterns are likely to be associated with mitigating the effects of COPD, as well as with general health and well-being, there is a need for further COPD-specific research, consensus and incorporation of recommendations and strategies into CPGs. PMID:28774202

Neural network-based QSAR and insecticide discovery: spinetoram

NASA Astrophysics Data System (ADS)

Sparks, Thomas C.; Crouse, Gary D.; Dripps, James E.; Anzeveno, Peter; Martynow, Jacek; DeAmicis, Carl V.; Gifford, James

2008-06-01

Improvements in the efficacy and spectrum of the spinosyns, novel fermentation derived insecticide, has long been a goal within Dow AgroSciences. As large and complex fermentation products identifying specific modifications to the spinosyns likely to result in improved activity was a difficult process, since most modifications decreased the activity. A variety of approaches were investigated to identify new synthetic directions for the spinosyn chemistry including several explorations of the quantitative structure activity relationships (QSAR) of spinosyns, which initially were unsuccessful. However, application of artificial neural networks (ANN) to the spinosyn QSAR problem identified new directions for improved activity in the chemistry, which subsequent synthesis and testing confirmed. The ANN-based analogs coupled with other information on substitution effects resulting from spinosyn structure activity relationships lead to the discovery of spinetoram (XDE-175). Launched in late 2007, spinetoram provides both improved efficacy and an expanded spectrum while maintaining the exceptional environmental and toxicological profile already established for the spinosyn chemistry.

Functional Assessment and Intervention by Nursing Assistants in Hospice and Palliative Care Inpatient Care Settings: A Quality Improvement Pilot Study.

PubMed

Mueller, Karen; Hamilton, Gillian; Rodden, Betheny; DeHeer, Hendrick D

2016-03-01

This study assessed the impact of a nursing assistant-led functional intervention in an urban hospice. Thirty-three patients participated. A physical therapist trained 4 nursing assistants to assess 4 basic functional activities at admission and discharge and to provide daily activity training to intervention group participants. Control group participants were assessed at admission and discharge and received the usual standard of care. Both groups improved. The intervention group participants demonstrated significant improvement in the Timed up and Go test as well as their self-reported ability to achieve goals on the Patient-Specific Functional Scale. Control group participants made significant improvements in the ability to move from supine to sit in bed. These findings suggest that nursing assistants can provide activity-based assessment and intervention leading to improved function among patients in hospice. © The Author(s) 2014.

Trichostatin A specifically improves the aberrant expression of transcription factor genes in embryos produced by somatic cell nuclear transfer

PubMed Central

Inoue, Kimiko; Oikawa, Mami; Kamimura, Satoshi; Ogonuki, Narumi; Nakamura, Toshinobu; Nakano, Toru; Abe, Kuniya; Ogura, Atsuo

2015-01-01

Although mammalian cloning by somatic cell nuclear transfer (SCNT) has been established in various species, the low developmental efficiency has hampered its practical applications. Treatment of SCNT-derived embryos with histone deacetylase (HDAC) inhibitors can improve their development, but the underlying mechanism is still unclear. To address this question, we analysed gene expression profiles of SCNT-derived 2-cell mouse embryos treated with trichostatin A (TSA), a potent HDAC inhibitor that is best used for mouse cloning. Unexpectedly, TSA had no effect on the numbers of aberrantly expressed genes or the overall gene expression pattern in the embryos. However, in-depth investigation by gene ontology and functional analyses revealed that TSA treatment specifically improved the expression of a small subset of genes encoding transcription factors and their regulatory factors, suggesting their positive involvement in de novo RNA synthesis. Indeed, introduction of one of such transcription factors, Spi-C, into the embryos at least partially mimicked the TSA-induced improvement in embryonic development by activating gene networks associated with transcriptional regulation. Thus, the effects of TSA treatment on embryonic gene expression did not seem to be stochastic, but more specific than expected, targeting genes that direct development and trigger zygotic genome activation at the 2-cell stage. PMID:25974394

Engineering Isoprene Synthase Expression and Activity in Cyanobacteria.

PubMed

Chaves, Julie E; Rueda-Romero, Paloma; Kirst, Henning; Melis, Anastasios

2017-12-15

Efforts to heterologously produce quantities of isoprene hydrocarbons (C 5 H 8 ) renewably from CO 2 and H 2 O through the photosynthesis of cyanobacteria face barriers, including low levels of recombinant enzyme accumulation compounded by their slow innate catalytic activity. The present work sought to alleviate the "expression level" barrier upon placing the isoprene synthase (IspS) enzyme in different fusion configurations with the cpcB protein, the highly expressed β-subunit of phycocyanin. Different cpcB*IspS fusion constructs were made, distinguished by the absence or presence of linker amino acids between the two proteins. Composition of linker amino acids was variable with lengths of 7, 10, 16, and 65 amino acids designed to test for optimal activity of the IspS through spatial positioning between the cpcB and IspS. Results showed that fusion constructs with the highly expressed cpcB gene, as the leader sequence, improved transgene expression in the range of 61 to 275-fold over what was measured with the unfused IspS control. However, the specific activity of the IspS enzyme was attenuated in all fusion transformants, possibly because of allosteric effects exerted by the leader cpcB fusion protein. This inhibition varied depending on the nature of the linker amino acids between the cpcB and IspS proteins. In terms of isoprene production, the results further showed a trade-off between specific activity and transgenic enzyme accumulation. For example, the cpcB*L7*IspS strain showed only about 10% the isoprene synthase specific-activity of the unfused cpcB-IspS control, but it accumulated 254-fold more IspS enzyme. The latter more than countered the slower specific activity and made the cpcB*L7*IspS transformant the best isoprene producing strain in this work. Isoprene to biomass yield ratios improved from 0.2 mg g -1 in the unfused cpcB-IspS control to 5.4 mg g -1 in the cpcB*L7*IspS strain, a 27-fold improvement.

Synthesis, Activity and Structural Analysis of Novel α-Hydroxytropolone Inhibitors of Human Immunodeficiency Virus Reverse Transcriptase-Associated Ribonuclease H

PubMed Central

Chung, Suhman; Himmel, Daniel M.; Jiang, Jian-Kang; Wojtak, Krzysztof; Bauman, Joseph D.; Rausch, Jason W.; Wilson, Jennifer A.; Beutler, John A.; Thomas, Craig J.; Arnold, Eddy; Le Grice, Stuart F.J.

2011-01-01

The α-hydroxytroplone, manicol (5,7-dihydroxy-2-isopropenyl-9-methyl-1,2,3,4-tetrahydro-benzocyclohepten-6-one) potently and specifically inhibits ribonuclease H (RNase H) activity of human immunodeficiency virus reverse transcriptase (HIV RT) in vitro. However, manicol was ineffective in reducing virus replication in culture. Ongoing efforts to improve the potency and specificity over the lead compound led us to synthesize 14 manicol derivatives that retain the divalent metal-chelating α-hydroxytropolone pharmacophore. These efforts were augmented by a high resolution structure of p66/p51 HIV-1 RT containing the nonnucleoside reverse transcriptase inhibitor (NNRTI), TMC278 and manicol in the DNA polymerase and RNase H active sites, respectively. We demonstrate here that several modified α-hydroxytropolones exhibit antiviral activity at non-cytotoxic concentrations. Inclusion of RNase H active site mutants indicated that manicol analogs can occupy an additional site in or around the DNA polymerase catalytic center. Collectively, our studies will promote future structure-based design of improved α-hydroxytropolones to complement the NRTI and NNRTI currently in clinical use. PMID:21568335

Improving the Physical Activity and Outdoor Play Environment of Family Child Care Homes in Nebraska Through Go Nutrition and Physical Activity Self-Assessment for Child Care.

PubMed

Dinkel, Danae; Dev, Dipti; Guo, Yage; Hulse, Emily; Rida, Zainab; Sedani, Ami; Coyle, Brian

2018-05-09

The purpose of this study was to determine if the Go Nutrition and Physical Activity Self-Assessment in Child Care (Go NAP SACC) intervention was effective in improving best practices in the areas of infant and child physical activity and outdoor play and learning in family child care homes (FCCHs) in Nebraska. FCCHs (n = 201) participated in a pre-post evaluation using the Infant and Child Physical Activity and Outdoor Play and Learning assessments from the Go NAP SACC validated measure to assess compliance with best practices. At post, FCCHs demonstrated significant differences in 85% of the Infant and Child Physical Activity items (17 of 20) and 80% of the Outdoor Play and Learning items (12 of 15). Significant differences in best practices between urban and rural FCCH providers were also found. Go NAP SACC appears to be an effective intervention in Nebraska as, after participation in the initiative, providers were improving child care physical activity best practices. Additional research is needed to objectively determine if these changes resulted in objective improvements in children's physical activity levels. Further, efforts are needed to develop and/or identify geographic-specific resources for continued improvement.

Improving activity recognition using temporal coherence.

PubMed

Ataya, Abbas; Jallon, Pierre; Bianchi, Pascal; Doron, Maeva

2013-01-01

Assessment of daily physical activity using data from wearable sensors has recently become a prominent research area in the biomedical engineering field and a substantial application for pattern recognition. In this paper, we present an accelerometer-based activity recognition scheme on the basis of a hierarchical structured classifier. A first step consists of distinguishing static activities from dynamic ones in order to extract relevant features for each activity type. Next, a separate classifier is applied to detect more specific activities of the same type. On top of our activity recognition system, we introduce a novel approach to take into account the temporal coherence of activities. Inter-activity transition information is modeled by a directed graph Markov chain. Confidence measures in activity classes are then evaluated from conventional classifier's outputs and coupled with the graph to reinforce activity estimation. Accurate results and significant improvement of activity detection are obtained when applying our system for the recognition of 9 activities for 48 subjects.

Para-nitrobenzyl esterases with enhanced activity in aqueous and nonaqueous media

DOEpatents

Arnold, Frances H.; Moore, Jeffrey C.

1998-01-01

A method for isolating and identifying modified para-nitrobenzyl esterases which exhibit improved stability and/or esterase hydrolysis activity toward selected substrates and under selected reaction conditions relative to the unmodified para-nitrobenzyl esterase. The method involves preparing a library of modified para-nitrobenzyl esterase nucleic acid segments (genes) which have nucleotide sequences that differ from the nucleic acid segment which encodes for unmodified para-nitrobenzyl esterase. The library of modified para-nitrobenzyl nucleic acid segments is expressed to provide a plurality of modified enzymes. The clones expressing modified enzymes are then screened to identify which enzymes have improved esterase activity by measuring the ability of the enzymes to hydrolyze the selected substrate under the selected reaction conditions. Specific modified para-nitrobenzyl esterases are disclosed which have improved stability and/or ester hydrolysis activity in aqueous or aqueous-organic media relative to the stability and/or ester hydrolysis activity of unmodified naturally occurring para-nitrobenzyl esterase.

Para-nitrobenzyl esterases with enhanced activity in aqueous and nonaqueous media

DOEpatents

Arnold, Frances H.; Moore, Jeffrey C.

1999-01-01

A method for isolating and identifying modified para-nitrobenzyl esterases which exhibit improved stability and/or esterase hydrolysis activity toward selected substrates and under selected reaction conditions relative to the unmodified para-nitrobenzyl esterase. The method involves preparing a library of modified para-nitrobenzyl esterase nucleic acid segments (genes) which have nucleotide sequences that differ from the nucleic acid segment which encodes for unmodified para-nitrobenzyl esterase. The library of modified para-nitrobenzyl nucleic acid segments is expressed to provide a plurality of modified enzymes. The clones expressing modified enzymes are then screened to identify which enzymes have improved esterase activity by measuring the ability of the enzymes to hydrolyze the selected substrate under the selected reaction conditions. Specific modified para-nitrobenzyl esterases are disclosed which have improved stability and/or ester hydrolysis activity in aqueous or aqueous-organic media relative to the stability and/or ester hydrolysis activity of unmodified naturally occurring para-nitrobenzyl esterase.

The rational design of a novel potent analogue of the 5’-AMP-activated protein kinase inhibitor compound C with improved selectivity and cellular activity

PubMed Central

Machrouhi, Fouzia; Ouhamou, Nouara; Laderoute, Keith; Calaoagan, Joy; Bukhtiyarova, Marina; Ehrlich, Paula J.; Klon, Anthony E.

2010-01-01

We have designed and synthesized analogues of compound C, a non-specific inhibitor of 5’-AMP-activated protein kinase (AMPK), using a computational fragment-based drug design (FBDD) approach. Synthesizing only twenty-seven analogues yielded a compound that was equipotent to compound C in the inhibition of the human AMPK (hAMPK) α2 subunit in the heterotrimeric complex in vitro, exhibited significantly improved selectivity against a subset of relevant kinases, and demonstrated enhanced cellular inhibition of AMPK. PMID:20932747

A calibration protocol for population-specific accelerometer cut-points in children.

PubMed

Mackintosh, Kelly A; Fairclough, Stuart J; Stratton, Gareth; Ridgers, Nicola D

2012-01-01

To test a field-based protocol using intermittent activities representative of children's physical activity behaviours, to generate behaviourally valid, population-specific accelerometer cut-points for sedentary behaviour, moderate, and vigorous physical activity. Twenty-eight children (46% boys) aged 10-11 years wore a hip-mounted uniaxial GT1M ActiGraph and engaged in 6 activities representative of children's play. A validated direct observation protocol was used as the criterion measure of physical activity. Receiver Operating Characteristics (ROC) curve analyses were conducted with four semi-structured activities to determine the accelerometer cut-points. To examine classification differences, cut-points were cross-validated with free-play and DVD viewing activities. Cut-points of ≤ 372, >2160 and >4806 counts • min(-1) representing sedentary, moderate and vigorous intensity thresholds, respectively, provided the optimal balance between the related needs for sensitivity (accurately detecting activity) and specificity (limiting misclassification of the activity). Cross-validation data demonstrated that these values yielded the best overall kappa scores (0.97; 0.71; 0.62), and a high classification agreement (98.6%; 89.0%; 87.2%), respectively. Specificity values of 96-97% showed that the developed cut-points accurately detected physical activity, and sensitivity values (89-99%) indicated that minutes of activity were seldom incorrectly classified as inactivity. The development of an inexpensive and replicable field-based protocol to generate behaviourally valid and population-specific accelerometer cut-points may improve the classification of physical activity levels in children, which could enhance subsequent intervention and observational studies.

Influence of gold nanoparticles of varying size in improving the lipase activity within cationic reverse micelles.

PubMed

Maiti, Subhabrata; Das, Dibyendu; Shome, Anshupriya; Das, Prasanta Kumar

2010-02-08

Herein, we report the effect of gold nanoparticles (GNPs) in enhancing lipase activity in reverse micelles of cetyltrimethylammonium bromide (CTAB)/water/isooctane/n-hexanol. The size and concentration of the nanoparticles were varied and their specific roles were assessed in detail. An overall enhancement of activity was observed in the GNP-doped CTAB reverse micelles. The improvement in activity becomes more prominent with increasing concentration and size of the GNPs (0-52 microM and ca. 3-30 nm, respectively). The observed highest lipase activity (k(2)=1070+/-12 cm(3) g(-1) s(-1)) in GNP-doped CTAB reverse micelles ([GNP]: 52 microm, ca. 20 nm) is 2.5-fold higher than in CTAB reverse micelles without GNPs. Improvement in the lipase activity is only specific to the GNP-doped reverse micellar media, whereas GNP deactivates and structurally deforms the enzyme in aqueous media. The reason for this activation is probably due to the formation of larger-sized reverse micelles in which the GNP acts as a polar core and the surfactants aggregate around the nanoparticle ('GNP pool') instead of only water. Lipase at the augmented interface of the GNP-doped reverse micelle showed improved activity because of enhancement in both the substrate and enzyme concentrations and increased flexibility in the lipase conformation. The extent of the activation is greater in the case of the larger-sized GNPs. A correlation has been established between the activity of lipase and its secondary structure by using circular dichroism and FTIR spectroscopic analysis. The generalized influence of GNP is verified in the reverse micelles of another surfactant, namely, cetyltripropylammonium bromide (CTPAB). TEM, dynamic light scattering (DLS), and UV/Vis spectroscopic analysis were utilized to characterize the GNPs and the organized aggregates. For the first time, CTAB-based reverse micelles have been found to be an excellent host for lipase simply by doping with appropriately sized GNPs.

Aptamer-based liposomes improve specific drug loading and release.

PubMed

Plourde, Kevin; Derbali, Rabeb Mouna; Desrosiers, Arnaud; Dubath, Céline; Vallée-Bélisle, Alexis; Leblond, Jeanne

2017-04-10

Aptamer technology has shown much promise in cancer therapeutics for its targeting abilities. However, its potential to improve drug loading and release from nanocarriers has not been thoroughly explored. In this study, we employed drug-binding aptamers to actively load drugs into liposomes. We designed a series of DNA aptamer sequences specific to doxorubicin, displaying multiple binding sites and various binding affinities. The binding ability of aptamers was preserved when incorporated into cationic liposomes, binding up to 15equivalents of doxorubicin per aptamer, therefore drawing the drug into liposomes. Optimization of the charge and drug/aptamer ratios resulted in ≥80% encapsulation efficiency of doxorubicin, ten times higher than classical passively-encapsulating liposomal formulations and similar to a pH-gradient active loading strategy. In addition, kinetic release profiles and cytotoxicity assay on HeLa cells demonstrated that the release and therapeutic efficacy of liposomal doxorubicin could be controlled by the aptamer's structure. Our results suggest that the aptamer exhibiting a specific intermediate affinity is the best suited to achieve high drug loading while maintaining efficient drug release and therapeutic activity. This strategy was successfully applied to tobramycin, a hydrophilic drug suffering from low encapsulation into liposomes, where its loading was improved six-fold using aptamers. Overall, we demonstrate that aptamers could act, in addition to their targeting properties, as multifunctional excipients for liposomal formulations. Copyright © 2017 Elsevier B.V. All rights reserved.

Improving Comprehension through Repetition...Repetition...Repetition. Working Paper No. 276.

ERIC Educational Resources Information Center

White, Sandra; Witte, Pauline

Because teachers are asking for specific suggestions to help students apply comprehension skills and read content material, a mechanism that assists students in acquiring and applying specific comprehension skills as they read content texts is being investigated. The mechanism is called marginal gloss because learning activities are placed in the…

Profile of software engineering within the National Aeronautics and Space Administration (NASA)

NASA Technical Reports Server (NTRS)

Sinclair, Craig C.; Jeletic, Kellyann F.

1994-01-01

This paper presents findings of baselining activities being performed to characterize software practices within the National Aeronautics and Space Administration. It describes how such baseline findings might be used to focus software process improvement activities. Finally, based on the findings to date, it presents specific recommendations in focusing future NASA software process improvement efforts. The findings presented in this paper are based on data gathered and analyzed to date. As such, the quantitative data presented in this paper are preliminary in nature.

Effects of Pretests on Children's Numerical Magnitude Representations

ERIC Educational Resources Information Center

Fazio, Lisa K.; Gumbel, Lauren; Robert S. Siegler

2011-01-01

In this experiment, the authors sought to further examine the effects of pretests on later learning. Specifically, they were interested in if activating a correct mental representation on the pretest would improve later learning and if activating an incorrect representation would impair learning. Kindergarteners and preschoolers were split into…

Requirement Specifications for a Design and Verification Unit.

ERIC Educational Resources Information Center

Pelton, Warren G.; And Others

A research and development activity to introduce new and improved education and training technology into Bureau of Medicine and Surgery training is recommended. The activity, called a design and verification unit, would be administered by the Education and Training Sciences Department. Initial research and development are centered on the…

Combating HER2-overexpressing breast cancer through induction of calreticulin exposure by Tras-Permut CrossMab

PubMed Central

Zhang, Fan; Zhang, Jie; Liu, Moyan; Zhao, Lichao; LingHu, RuiXia; Feng, Fan; Gao, Xudong; Jiao, Shunchang; Zhao, Lei; Hu, Yi; Yang, Junlan

2015-01-01

Although trastuzumab has succeeded in breast cancer treatment, acquired resistance is one of the prime obstacles for breast cancer therapies. There is an urgent need to develop novel HER2 antibodies against trastuzumab resistance. Here, we first rational designed avidity-imporved trastuzumab and pertuzumab variants, and explored the correlation between the binding avidity improvement and their antitumor activities. After characterization of a pertuzumab variant L56TY with potent antitumor activities, a bispecific immunoglobulin G-like CrossMab (Tras-Permut CrossMab) was generated from trastuzumab and binding avidity-improved pertuzumab variant L56TY. Although, the antitumor efficacy of trastuzumab was not enhanced by improving its binding avidity, binding avidity improvement could significantly increase the anti-proliferative and antibody-dependent cellular cytotoxicity (ADCC) activities of pertuzumab. Further studies showed that Tras-Permut CrossMab exhibited exceptional high efficiency to inhibit the progression of trastuzumab-resistant breast cancer. Notably, we found that calreticulin (CRT) exposure induced by Tras-Permut CrossMab was essential for induction of tumor-specific T cell immunity against tumor recurrence. These data indicated that simultaneous blockade of HER2 protein by Tras-Permut CrossMab could trigger CRT exposure and subsequently induce potent tumor-specific T cell immunity, suggesting it could be a promising therapeutic strategy against trastuzumab resistance. PMID:25949918

Fossils, Facies and Geologic Time: Active Learning Yields More Expert-Like Thinking in a Large Class for Senior Science Students

NASA Astrophysics Data System (ADS)

Sutherland, S.; Jones, F. M.

2012-12-01

Teaching and assessing concepts involving the relationships between deep time and the Earth System can be challenging. This is especially true in elective courses for senior general science students who should be starting to think more like experts, but lack background knowledge in geology. By comparing student activities and work, both before and after introducing active learning strategies, we show that increased maturity of thinking about geological time was achieved in the science elective "Earth and Life through Time" taken by 150 upper level general science students. Student demographics were very similar in 2010 and 2011 allowing comparison of data from a consistent end of term survey, classroom observations, and test or exercise questions used in both years. Students identified the workload as greater in 2011, yet they also gave the course a stronger overall rating of excellence. Also, students in 2011 felt assessments and homework were more appropriate and expressed a nearly unanimous preference for group versus solo class work. More objective indicators of improvement include item analysis on test questions which shows increased difficulty and discrimination without compromising overall scores. The wide variety of changes introduced in 2011 do make it difficult to rigorously ascribe specific causes for improvement in how students think about geologic time. However the shift towards more sophisticated thinking involving skills rather than recall can be demonstrated by comparing geological interpretations produced by students in early and improved versions of exercises. For example, labs have always involved basic identification of rocks and fossils. Now, the new in-class group-based activities enable students to use data to establish the relative history of a geologic section, including environments, ages of known materials, and time spans of materials missing at unconformities. In addition to activities, specific exam questions and corresponding results from both versions of the course also reveal improvements. In order to help educators improve teaching and assessment of geologic time in similar settings, we will offer some details about course modifications and activities. First, learning goals were adjusted to emphasize skills geologists use when interpreting the geological record, rather than focusing on specific knowledge such dates, time spans and rock or fossil names. Then, one third of the lectures were replaced with 50-minute guided group activities, higher level clicker-based questioning strategies were introduced, labs were restructured to include follow up in-class group activities, structured reading and homework exercises were added, and formative and evaluative assessments were diversified. In conclusion, we will show that introducing active learning strategies has helped meet the challenges of increasing the sophistication of students' thinking about geologic time, at the same time as increasing their satisfaction. The specific strategies should be transferrable to any course in which senior general science students learn to use the rock and fossil record to experience the ways in which geoscientists integrate geology and paleontology to interpret the Earth System's evolution.

Terminal Duplex Stability and Nucleotide Identity Differentially Control siRNA Loading and Activity in RNA Interference

PubMed Central

Angart, Phillip A.; Carlson, Rebecca J.; Adu-Berchie, Kwasi

2016-01-01

Efficient short interfering RNA (siRNA)-mediated gene silencing requires selection of a sequence that is complementary to the intended target and possesses sequence and structural features that encourage favorable functional interactions with the RNA interference (RNAi) pathway proteins. In this study, we investigated how terminal sequence and structural characteristics of siRNAs contribute to siRNA strand loading and silencing activity and how these characteristics ultimately result in a functionally asymmetric duplex in cultured HeLa cells. Our results reiterate that the most important characteristic in determining siRNA activity is the 5′ terminal nucleotide identity. Our findings further suggest that siRNA loading is controlled principally by the hybridization stability of the 5′ terminus (Nucleotides: 1–2) of each siRNA strand, independent of the opposing terminus. Postloading, RNA-induced silencing complex (RISC)–specific activity was found to be improved by lower hybridization stability in the 5′ terminus (Nucleotides: 3–4) of the loaded siRNA strand and greater hybridization stability toward the 3′ terminus (Nucleotides: 17–18). Concomitantly, specific recognition of the 5′ terminal nucleotide sequence by human Argonaute 2 (Ago2) improves RISC half-life. These findings indicate that careful selection of siRNA sequences can maximize both the loading and the specific activity of the intended guide strand. PMID:27399870

Brain-Behavior Mechanisms for the Transfer of Neuromuscular Training Adaptions to Simulated Sport: Initial Findings from the Train the Brain Project.

PubMed

Grooms, Dustin R; Kiefer, Adam W; Riley, Michael A; Ellis, Jonathan D; Thomas, Staci; Kitchen, Katie; DiCesare, Christopher; Bonnette, Scott; Gadd, Brooke; Barber Foss, Kim D; Yuan, Weihong; Silva, Paula; Galloway, Ryan; Diekfuss, Jed; Leach, James; Berz, Kate; Myer, Gregory D

2018-03-27

A limiting factor for reducing anterior cruciate ligament (ACL) injury risk is ensuring that the movement adaptions made during the prevention program transfer to sport-specific activity. Virtual reality provides a mechanism to assess transferability and neuroimaging provides a means to assay the neural processes allowing for such skill transfer. To determine the neural mechanisms for injury risk reducing biomechanics transfer to sport after ACL injury prevention training. Cohort study Setting: Research laboratory Participants: Four healthy high school soccer athletes. Participants completed augmented neuromuscular training utilizing real-time visual feedback. An unloaded knee extension task and a loaded leg-press task was completed with neuroimaging before and after training. A virtual reality soccer specific landing task was also competed following training to assess transfer of movement mechanics. Landing mechanics during the virtual reality soccer task and blood oxygen level dependent signal change during neuroimaging. Increased motor planning, sensory and visual region activity during unloaded knee extension and decreased motor cortex activity during loaded leg-press were highly correlated with improvements in landing mechanics (decreased hip adduction and knee rotation). Changes in brain activity may underlie adaptation and transfer of injury risk reducing movement mechanics to sport activity. Clinicians may be able to target these specific brain processes with adjunctive therapy to facilitate intervention improvements transferring to sport.

Veterinary student attitudes toward curriculum integration at James Cook University.

PubMed

Cavalieri, John

2009-01-01

The aim of this study was to investigate the attitudes of veterinary science students to activities designed to promote curriculum integration. Students (N = 33) in their second year of a five-year veterinary degree were surveyed in regard to their attitudes to activities that aimed to promote integration. Imaging, veterinary practice practicals, and a field trip to a cattle property were classified as the three most valuable learning activities that were designed to promote integration. Veterinary practice practicals, case studies, and palpable anatomy were regarded by students as helping them to learn information presented in other teaching sessions. They also appeared to enhance student motivation, and students indicated that the activities assisted them with their preparation for and performance at examinations. Attitudes to whether the learning exercises helped improve a range of skills and specific knowledge varied, with 39-88% of students agreeing that specific skills and knowledge were enhanced to a large or very large extent by the learning activities. The results indicate that learning activities designed to promote curriculum integration helped improve motivation, reinforced learning, created links between foundational knowledge and its application, and assisted with the development of skills that are related to what students will do in their future careers.

Motor Skill Development in Italian Pre-School Children Induced by Structured Activities in a Specific Playground.

PubMed

Tortella, Patrizia; Haga, Monika; Loras, Håvard; Sigmundsson, Hermundur; Fumagalli, Guido

2016-01-01

This study examined the effects and specificity of structured and unstructured activities played at the playground Primo Sport 0246 in Northern Italy on motor skill competence in five years old children. The playground was specifically designed to promote gross motor skills in preschool children; in this study 71 children from local kindergartens came to the park once a week for ten consecutive weeks and were exposed to 30 minutes of free play and 30 minutes of structured activities. Before and after the ten visits, each child completed nine tests to assess levels of motor skills, three for fine-motor skills and six for gross-motor skills. As control, motor skills were also assessed on 39 children from different kindergartens who did not come to the park. The results show that the experimental group who practiced gross-motor activities in the playground for 1 hour a week for 10 weeks improved significantly in 4 out of the 6 gross motor tasks and in none of the fine motor tasks. The data indicate that limited transfer occurred between tasks referring to different domains of motor competences while suggesting cross feeding for improvement of gross-motor skills between different exercises when domains related to physical fitness and strength of specific muscle groups are involved. These results are relevant to the issue of condition(s) appropriate for maintaining and developing motor skills in this age group as well as for the planning, organization and implementation of play and physical activities in kindergartens.

Motor Skill Development in Italian Pre-School Children Induced by Structured Activities in a Specific Playground

PubMed Central

Tortella, Patrizia; Haga, Monika; Loras, Håvard

2016-01-01

This study examined the effects and specificity of structured and unstructured activities played at the playground Primo Sport 0246 in Northern Italy on motor skill competence in five years old children. The playground was specifically designed to promote gross motor skills in preschool children; in this study 71 children from local kindergartens came to the park once a week for ten consecutive weeks and were exposed to 30 minutes of free play and 30 minutes of structured activities. Before and after the ten visits, each child completed nine tests to assess levels of motor skills, three for fine-motor skills and six for gross-motor skills. As control, motor skills were also assessed on 39 children from different kindergartens who did not come to the park. The results show that the experimental group who practiced gross-motor activities in the playground for 1 hour a week for 10 weeks improved significantly in 4 out of the 6 gross motor tasks and in none of the fine motor tasks. The data indicate that limited transfer occurred between tasks referring to different domains of motor competences while suggesting cross feeding for improvement of gross-motor skills between different exercises when domains related to physical fitness and strength of specific muscle groups are involved. These results are relevant to the issue of condition(s) appropriate for maintaining and developing motor skills in this age group as well as for the planning, organization and implementation of play and physical activities in kindergartens. PMID:27462985

Traditional Indigenous Games promoting physical activity and cultural connectedness in primary schools--cluster randomised control trial.

PubMed

Kiran, Asha; Knights, Janice

2010-08-01

This study investigated the effectiveness of Traditional Indigenous Games (TIG) to improve physical activity and cultural connectedness among primary school students in the community renewal areas of Townsville in North Queensland. A cluster randomised control trial was conducted in four primary schools in 2007. Baseline and post implementation surveys were conducted in two intervention and two control schools and the results were compared. TIG delivered in primary schools every week over period of three months did not contribute to any statistically significant improvement in intervention and control groups in physical activity levels or cultural connectedness. Further research specifically in terms of intensity and duration of TIG may inform whether physical activity may be improved. Enhancing the Indigenous cultural features of the existing TIG kit might positively influence Indigenous cultural connectedness.

Use of the impedance threshold device improves survival rate and neurological outcome in a swine model of asphyxial cardiac arrest*.

PubMed

Pantazopoulos, Ioannis N; Xanthos, Theodoros T; Vlachos, Ioannis; Troupis, Georgios; Kotsiomitis, Evangelos; Johnson, Elisabeth; Papalois, Apostolos; Skandalakis, Panagiotis

2012-03-01

To assess whether intermittent impedance of inspiratory gas exchange improves hemodynamic parameters, 48-hr survival, and neurologic outcome in a swine model of asphyxial cardiac arrest treated with active compression-decompression cardiopulmonary resuscitation. Prospective, randomized, double-blind study. Laboratory investigation. Thirty healthy Landrace/Large-White piglets of both sexes, aged 10 to 15 wks, whose average weight was 19 ± 2 kg. At approximately 7 mins following endotracheal tube clamping, ventricular fibrillation was induced and remained untreated for another 8 mins. Before initiation of cardiopulmonary resuscitation, animals were randomly assigned to either receive active compression-decompression cardiopulmonary resuscitation plus a sham impedance threshold device (control group, n = 15), or active compression-decompression cardiopulmonary resuscitation plus an active impedance threshold device (experimental group, n = 15). Electrical defibrillation was attempted every 2 mins until return of spontaneous circulation or asystole. Return of spontaneous circulation was observed in six (40%) animals treated with the sham valve and 14 (93.3%) animals treated with the active valve (p = .005, odds ratio 21.0, 95% confidence interval 2.16-204.6). Neuron-specific enolase and S-100 levels increased in the ensuing 4 hrs post resuscitation in both groups, but they were significantly elevated in animals treated with the sham valve (p < .01). At 48 hrs, neurologic alertness score was significantly better in animals treated with the active valve (79.1 ± 18.7 vs. 50 ± 10, p < .05) and was strongly negatively correlated with 1- and 4-hr postresuscitation neuron-specific enolase (r = -.86, p < .001 and r = -.87, p < .001, respectively) and S-100 (r = -.77, p < .001 and r = -0.8, p = .001) values. In this model of asphyxial cardiac arrest, intermittent airway occlusion with the impedance threshold device during the decompression phase of active compression-decompression cardiopulmonary resuscitation significantly improved hemodynamic parameters, 24- and 48-hr survival, and neurologic outcome evaluated both with clinical and biochemical parameters (neuron-specific enolase, S-100).

The Role of Christian Educational Institutions in Improving Economic Self-Reliance

ERIC Educational Resources Information Center

Nwosu, Constance C.

2012-01-01

This article argues that Christian educational institutions in Africa can play a major role in improving economic self-reliance within the continent, if those who establish Christian universities there take time to plan the programs and activities in those institutions. Specifically, it argues that with proper planning of quality education--the…

42 CFR 495.316 - State monitoring and reporting regarding activities required to receive an incentive payment.

Code of Federal Regulations, 2013 CFR

2013-10-01

... quality measures data; and (v) A description and quantitative data on how its incentive payment program... conditions to use for quality improvement, reduction of disparities, research or outreach. (B) Capability to... specific conditions to use for quality improvement, reduction of disparities, research, or outreach. (B...

42 CFR 495.316 - State monitoring and reporting regarding activities required to receive an incentive payment.

Code of Federal Regulations, 2014 CFR

2014-10-01

... quality measures data; and (v) A description and quantitative data on how its incentive payment program... conditions to use for quality improvement, reduction of disparities, research or outreach. (B) Capability to... specific conditions to use for quality improvement, reduction of disparities, research, or outreach. (B...

42 CFR 495.316 - State monitoring and reporting regarding activities required to receive an incentive payment.

Code of Federal Regulations, 2012 CFR

2012-10-01

... quality measures data; and (v) A description and quantitative data on how its incentive payment program... conditions to use for quality improvement, reduction of disparities, research or outreach. (B) Capability to... specific conditions to use for quality improvement, reduction of disparities, research, or outreach. (B...

Teaching Audience Adaptation Using Connected Presentations and Teamwork

ERIC Educational Resources Information Center

Opt, Susan K.

2017-01-01

Courses: Introduction to Communication, Public Speaking, Persuasion, Business Communication. Objective: This activity increases students' understanding of audience adaptation and improves their ability to adapt presentations to specific audiences.

Computational Modeling and Neuroimaging Techniques for Targeting during Deep Brain Stimulation

PubMed Central

Sweet, Jennifer A.; Pace, Jonathan; Girgis, Fady; Miller, Jonathan P.

2016-01-01

Accurate surgical localization of the varied targets for deep brain stimulation (DBS) is a process undergoing constant evolution, with increasingly sophisticated techniques to allow for highly precise targeting. However, despite the fastidious placement of electrodes into specific structures within the brain, there is increasing evidence to suggest that the clinical effects of DBS are likely due to the activation of widespread neuronal networks directly and indirectly influenced by the stimulation of a given target. Selective activation of these complex and inter-connected pathways may further improve the outcomes of currently treated diseases by targeting specific fiber tracts responsible for a particular symptom in a patient-specific manner. Moreover, the delivery of such focused stimulation may aid in the discovery of new targets for electrical stimulation to treat additional neurological, psychiatric, and even cognitive disorders. As such, advancements in surgical targeting, computational modeling, engineering designs, and neuroimaging techniques play a critical role in this process. This article reviews the progress of these applications, discussing the importance of target localization for DBS, and the role of computational modeling and novel neuroimaging in improving our understanding of the pathophysiology of diseases, and thus paving the way for improved selective target localization using DBS. PMID:27445709

Improved specific energy Ni-H2 cell

NASA Astrophysics Data System (ADS)

Miller, L.

1985-07-01

Design optimization activities which have evolved and validated the necessary technology to produce Ni-H2 battery cells exhibiting a specific energy of 75-80 Whr/Kg (energy density approximately 73 Whr/L are summarized. Final design validation is currently underway with the production of battery cells for qualification and life testing. The INTELSAT type Ni-H2 battery cell design has been chosen for expository purposes. However, it should be recognized portions of the improved technology could be applied to the Air Force type Ni-H2 battery cell design with equal benefit.

Improved Specific Energy Ni-h2 Cell

NASA Technical Reports Server (NTRS)

Miller, L.

1985-01-01

Design optimization activities which have evolved and validated the necessary technology to produce Ni-H2 battery cells exhibiting a specific energy of 75-80 Whr/Kg (energy density approximately 73 Whr/L are summarized. Final design validation is currently underway with the production of battery cells for qualification and life testing. The INTELSAT type Ni-H2 battery cell design has been chosen for expository purposes. However, it should be recognized portions of the improved technology could be applied to the Air Force type Ni-H2 battery cell design with equal benefit.

Soluble Milk Protein Supplementation with Moderate Physical Activity Improves Locomotion Function in Aging Rats.

PubMed

Lafoux, Aude; Baudry, Charlotte; Bonhomme, Cécile; Le Ruyet, Pascale; Huchet, Corinne

2016-01-01

Aging is associated with a loss of muscle mass and functional capacity. Present study was designed to compare the impact of specific dairy proteins on muscular function with or without a low-intensity physical activity program on a treadmill in an aged rat model. We investigated the effects of nutritional supplementation, five days a week over a 2-month period with a slow digestible protein, casein or fast digestible proteins, whey or soluble milk protein, on strength and locomotor parameters in sedentary or active aged Wistar RjHan rats (17-19 months of age). An extensive gait analysis was performed before and after protein supplementation. After two months of protein administration and activity program, muscle force was evaluated using a grip test, spontaneous activity using an open-field and muscular mass by specific muscle sampling. When aged rats were supplemented with proteins without exercise, only minor effects of different diets on muscle mass and locomotion were observed: higher muscle mass in the casein group and improvement of stride frequencies with soluble milk protein. By contrast, supplementation with soluble milk protein just after physical activity was more effective at improving overall skeletal muscle function in old rats compared to casein. For active old rats supplemented with soluble milk protein, an increase in locomotor activity in the open field and an enhancement of static and dynamic gait parameters compared to active groups supplemented with casein or whey were observed without any differences in muscle mass and forelimb strength. These results suggest that consumption of soluble milk protein as a bolus immediately after a low intensity physical activity may be a suitable nutritional intervention to prevent decline in locomotion in aged rats and strengthen the interest to analyze the longitudinal aspect of locomotion in aged rodents.

Soluble Milk Protein Supplementation with Moderate Physical Activity Improves Locomotion Function in Aging Rats

PubMed Central

Lafoux, Aude; Baudry, Charlotte; Bonhomme, Cécile; Le Ruyet, Pascale; Huchet, Corinne

2016-01-01

Aging is associated with a loss of muscle mass and functional capacity. Present study was designed to compare the impact of specific dairy proteins on muscular function with or without a low-intensity physical activity program on a treadmill in an aged rat model. We investigated the effects of nutritional supplementation, five days a week over a 2-month period with a slow digestible protein, casein or fast digestible proteins, whey or soluble milk protein, on strength and locomotor parameters in sedentary or active aged Wistar RjHan rats (17–19 months of age). An extensive gait analysis was performed before and after protein supplementation. After two months of protein administration and activity program, muscle force was evaluated using a grip test, spontaneous activity using an open-field and muscular mass by specific muscle sampling. When aged rats were supplemented with proteins without exercise, only minor effects of different diets on muscle mass and locomotion were observed: higher muscle mass in the casein group and improvement of stride frequencies with soluble milk protein. By contrast, supplementation with soluble milk protein just after physical activity was more effective at improving overall skeletal muscle function in old rats compared to casein. For active old rats supplemented with soluble milk protein, an increase in locomotor activity in the open field and an enhancement of static and dynamic gait parameters compared to active groups supplemented with casein or whey were observed without any differences in muscle mass and forelimb strength. These results suggest that consumption of soluble milk protein as a bolus immediately after a low intensity physical activity may be a suitable nutritional intervention to prevent decline in locomotion in aged rats and strengthen the interest to analyze the longitudinal aspect of locomotion in aged rodents. PMID:27973615

Do enhanced states exist? Boosting cognitive capacities through an action video-game.

PubMed

Kozhevnikov, Maria; Li, Yahui; Wong, Sabrina; Obana, Takashi; Amihai, Ido

2018-04-01

This research reports the existence of enhanced cognitive states in which dramatic temporary improvements in temporal and spatial aspects of attention were exhibited by participants who played (but not by those who merely observed) action video-games meeting certain criteria. Specifically, Experiments 1 and 2 demonstrate that the attentional improvements were exhibited only by participants whose skills matched the difficulty level of the video game. Experiment 2 showed that arousal (as reflected by the reduction in parasympathetic activity and increase in sympathetic activity) is a critical physiological condition for enhanced cognitive states and corresponding attentional enhancements. Experiment 3 showed that the cognitive enhancements were transient, and were no longer observed after 30 min of rest following video-gaming. Moreover, the results suggest that the enhancements were specific to tasks requiring visual-spatial focused attention, but not distribution of spatial attention as has been reported to improve significantly and durably as a result of long-term video-game playing. Overall, the results suggest that the observed enhancements cannot be simply due to the activity of video-gaming per se, but might rather represent an enhanced cognitive state resulting from specific conditions (heightened arousal in combination with active engagement and optimal challenge), resonant with what has been described in previous phenomenological literature as "flow" (Csikszentmihalyi, 1975) or "peak experiences" (Maslov, 1962). The findings provide empirical evidence for the existence of the enhanced cognitive states and suggest possibilities for consciously accessing latent resources of our brain to temporarily boost our cognitive capacities upon demand. Copyright © 2018 Elsevier B.V. All rights reserved.

Improving physical activity in arthritis clinical trial (IMPAACT): study design, rationale, recruitment, and baseline data.

PubMed

Chang, Rowland W; Semanik, Pamela A; Lee, Jungwha; Feinglass, Joseph; Ehrlich-Jones, Linda; Dunlop, Dorothy D

2014-11-01

Over 21 million Americans report an arthritis-attributable activity limitation. Knee osteoarthritis (OA) and rheumatoid arthritis (RA) are two of the most common/disabling forms of arthritis. Various forms of physical activity (PA) can improve a variety of health outcomes and reduce health care costs, but the proportion of the US population engaging in the recommended amount of PA is low and even lower among those with arthritis. The Improving Motivation for Physical Activity in Arthritis Clinical Trial (IMPAACT) is a randomized clinical trial that studied the effects of a lifestyle PA promotion intervention on pain and physical function outcomes. The IMPAACT intervention was based on a chronic care/disease management model in which allied health professionals promote patient self-management activities outside of traditional physician office encounters. The program was a motivational interviewing-based, individualized counseling and referral intervention, directed by a comprehensive assessment of individual patient barriers and strengths related to PA performance. The specific aims of IMPAACT were to test the efficacy of the IMPAACT intervention for persons with arthritis (N=185 persons with RA and 155 persons with knee OA) in improving arthritis-specific and generic self-reported pain and Physical Function outcomes, observed measures of function, and objectively measured and self-reported PA levels. Details of the stratified-randomized study design, subject recruitment, and data collection are described. The results from IMPAACT will generate empiric evidence pertaining to increasing PA levels in persons with arthritis and result in widely applicable strategies for health behavior change. Copyright © 2014 Elsevier Inc. All rights reserved.

Bioinspired Nanocomplex for Spatiotemporal Imaging of Sequential mRNA Expression in Differentiating Neural Stem Cells

PubMed Central

2015-01-01

Messenger RNA plays a pivotal role in regulating cellular activities. The expression dynamics of specific mRNA contains substantial information on the intracellular milieu. Unlike the imaging of stationary mRNAs, real-time intracellular imaging of the dynamics of mRNA expression is of great value for investigating mRNA biology and exploring specific cellular cascades. In addition to advanced imaging methods, timely extracellular stimulation is another key factor in regulating the mRNA expression repertoire. The integration of effective stimulation and imaging into a single robust system would significantly improve stimulation efficiency and imaging accuracy, producing fewer unwanted artifacts. In this study, we developed a multifunctional nanocomplex to enable self-activating and spatiotemporal imaging of the dynamics of mRNA sequential expression during the neural stem cell differentiation process. This nanocomplex showed improved enzymatic stability, fast recognition kinetics, and high specificity. With a mechanism regulated by endogenous cell machinery, this nanocomplex realized the successive stimulating motif release and the dynamic imaging of chronological mRNA expression during neural stem cell differentiation without the use of transgenetic manipulation. The dynamic imaging montage of mRNA expression ultimately facilitated genetic heterogeneity analysis. In vivo lateral ventricle injection of this nanocomplex enabled endogenous neural stem cell activation and labeling at their specific differentiation stages. This nanocomplex is highly amenable as an alternative tool to explore the dynamics of intricate mRNA activities in various physiological and pathological conditions. PMID:25494492

Bioinspired nanocomplex for spatiotemporal imaging of sequential mRNA expression in differentiating neural stem cells.

PubMed

Wang, Zhe; Zhang, Ruili; Wang, Zhongliang; Wang, He-Fang; Wang, Yu; Zhao, Jun; Wang, Fu; Li, Weitao; Niu, Gang; Kiesewetter, Dale O; Chen, Xiaoyuan

2014-12-23

Messenger RNA plays a pivotal role in regulating cellular activities. The expression dynamics of specific mRNA contains substantial information on the intracellular milieu. Unlike the imaging of stationary mRNAs, real-time intracellular imaging of the dynamics of mRNA expression is of great value for investigating mRNA biology and exploring specific cellular cascades. In addition to advanced imaging methods, timely extracellular stimulation is another key factor in regulating the mRNA expression repertoire. The integration of effective stimulation and imaging into a single robust system would significantly improve stimulation efficiency and imaging accuracy, producing fewer unwanted artifacts. In this study, we developed a multifunctional nanocomplex to enable self-activating and spatiotemporal imaging of the dynamics of mRNA sequential expression during the neural stem cell differentiation process. This nanocomplex showed improved enzymatic stability, fast recognition kinetics, and high specificity. With a mechanism regulated by endogenous cell machinery, this nanocomplex realized the successive stimulating motif release and the dynamic imaging of chronological mRNA expression during neural stem cell differentiation without the use of transgenetic manipulation. The dynamic imaging montage of mRNA expression ultimately facilitated genetic heterogeneity analysis. In vivo lateral ventricle injection of this nanocomplex enabled endogenous neural stem cell activation and labeling at their specific differentiation stages. This nanocomplex is highly amenable as an alternative tool to explore the dynamics of intricate mRNA activities in various physiological and pathological conditions.

Increasing Specificity of Correlate Research: Exploring Correlates of Children’s Lunchtime and After-School Physical Activity

PubMed Central

Stanley, Rebecca M.; Ridley, Kate; Olds, Timothy S.; Dollman, James

2014-01-01

Background The lunchtime and after-school contexts are critical windows in a school day for children to be physically active. While numerous studies have investigated correlates of children’s habitual physical activity, few have explored correlates of physical activity occurring at lunchtime and after-school from a social-ecological perspective. Exploring correlates that influence physical activity occurring in specific contexts can potentially improve the prediction and understanding of physical activity. Using a context-specific approach, this study investigated correlates of children’s lunchtime and after-school physical activity. Methods Cross-sectional data were collected from 423 South Australian children aged 10.0–13.9 years (200 boys; 223 girls) attending 10 different schools. Lunchtime and after-school physical activity was assessed using accelerometers. Correlates were assessed using purposely developed context-specific questionnaires. Correlated Component Regression analysis was conducted to derive correlates of context-specific physical activity and determine the variance explained by prediction equations. Results The model of boys’ lunchtime physical activity contained 6 correlates and explained 25% of the variance. For girls, the model explained 17% variance from 9 correlates. Enjoyment of walking during lunchtime was the strongest correlate for both boys and girls. Boys’ and girls’ after-school physical activity models explained 20% variance from 14 correlates and 7% variance from the single item correlate, “I do an organised sport or activity after-school because it gets you fit”, respectively. Conclusions Increasing specificity of correlate research has enabled the identification of unique features of, and a more in-depth interpretation of, lunchtime and after-school physical activity behaviour and is a potential strategy for advancing the physical activity correlate research field. The findings of this study could be used to inform and tailor gender-specific public health messages and interventions for promoting lunchtime and after-school physical activity in children. PMID:24809440

Surgical education to improve the quality of patient care: the role of practice-based learning and improvement.

PubMed

Sachdeva, Ajit K

2007-11-01

Health care is going through immense change, and concerns regarding the quality of patient care and patient safety continue to be expressed in many national forums. A variety of stakeholders are demanding greater accountability from the health care profession. Education is key to supporting surgeons' efforts to provide high-quality patient care during these challenging times. Educational programs for surgeons should be founded on principles of continuous professional development (CPD) and practice-based learning and improvement (PBLI). CPD focuses on the specific needs of individual surgeons and involves lifelong learning throughout a surgeon's career. It needs to form the basis of PBLI efforts. PBLI involves a cycle of four steps--identifying areas for improvement, engaging in learning, applying new knowledge and skills to practice, and checking for improvement. Ongoing involvement in PBLI activities to address specific learning needs should positively impact a surgeon's practice and improve outcomes of surgical care.

A Systematic Review of the Effects of Exercise and Physical Activity on Non-Specific Chronic Low Back Pain

PubMed Central

Gordon, Rebecca; Bloxham, Saul

2016-01-01

Back pain is a major health issue in Western countries and 60%–80% of adults are likely to experience low back pain. This paper explores the impact of back pain on society and the role of physical activity for treatment of non-specific low back pain. A review of the literature was carried out using the databases SPORTDiscuss, Medline and Google Scholar. A general exercise programme that combines muscular strength, flexibility and aerobic fitness is beneficial for rehabilitation of non-specific chronic low back pain. Increasing core muscular strength can assist in supporting the lumbar spine. Improving the flexibility of the muscle-tendons and ligaments in the back increases the range of motion and assists with the patient’s functional movement. Aerobic exercise increases the blood flow and nutrients to the soft tissues in the back, improving the healing process and reducing stiffness that can result in back pain. PMID:27417610

What Makes Patient Navigation Most Effective: Defining Useful Tasks and Networks.

PubMed

Gunn, Christine; Battaglia, Tracy A; Parker, Victoria A; Clark, Jack A; Paskett, Electra D; Calhoun, Elizabeth; Snyder, Frederick R; Bergling, Emily; Freund, Karen M

2017-01-01

Given the momentum in adopting patient navigation into cancer care, there is a need to understand the contribution of specific navigator activities to improved clinical outcomes. A mixed-methods study combined direct observations of patient navigators within the Patient Navigation Research Program and outcome data from the trial. We correlated the frequency of navigator tasks with the outcome of rate of diagnostic resolution within 365 days among patients who received the intervention relative to controls. A focused content analysis examined those tasks with the strongest correlations between navigator tasks and patient outcomes. Navigating directly with specific patients (r = 0.679), working with clinical providers to facilitate patient care (r = 0.643), and performing tasks not directly related to their diagnostic evaluation for patients were positively associated with more timely diagnosis (r = 0.714). Using medical records for non-navigation tasks had a negative association (r = -0.643). Content analysis revealed service provision directed at specific patients improved care while systems-focused activities did not.

Using TENS for pain control: the state of the evidence

PubMed Central

Vance, Carol GT; Dailey, Dana L; Rakel, Barbara A; Sluka, Kathleen A

2014-01-01

Summary Transcutaneous electrical nerve stimulation (TENS) is a nonpharmacological intervention that activates a complex neuronal network to reduce pain by activating descending inhibitory systems in the central nervous system to reduce hyperalgesia. The evidence for TENS efficacy is conflicting and requires not only description but also critique. Population-specific systemic reviews and meta-analyses are emerging, indicating both HF and LF TENS being shown to provide analgesia, specifically when applied at a strong, nonpainful intensity. The purpose of this article is to provide a critical review of the latest basic science and clinical evidence for TENS. Additional research is necessary to determine if TENS has effects specific to mechanical stimuli and/or beyond reduction of pain and will improve activity levels, function and quality of life. PMID:24953072

Barriers to physical activity among working mothers.

PubMed

Dombrowski, Jill J

2011-04-01

Working mothers experience several barriers to physical activity. If these barriers can be identified by occupational health nurses and they can partner with working mothers to reduce these perceived barriers, the health of these workers can be improved and chronic disease risk prevented. The purpose of this study was to measure the effect of self-regulatory efficacy on physical activity among working mothers and to describe specific barriers to physical activity. The Barriers Specific Self-Efficacy Scale (BARSE) and the Kaiser Physical Activity Survey (KPAS) were used to measure the variables. Self-regulatory efficacy was found to be a strong predictor of physical activity in a diverse sample of working mothers who did not meet current recommendations for physical activity. Occupational health nurses can use these findings to design programs for groups and for counseling individuals. Copyright 2011, SLACK Incorporated.

Improved capacitance characteristics of electrospun ACFs by pore size control and vanadium catalyst.

PubMed

Im, Ji Sun; Woo, Sang-Wook; Jung, Min-Jung; Lee, Young-Seak

2008-11-01

Nano-sized carbon fibers were prepared by using electrospinning, and their electrochemical properties were investigated as a possible electrode material for use as an electric double-layer capacitor (EDLC). To improve the electrode capacitance of EDLC, we implemented a three-step optimization. First, metal catalyst was introduced into the carbon fibers due to the excellent conductivity of metal. Vanadium pentoxide was used because it could be converted to vanadium for improved conductivity as the pore structure develops during the carbonization step. Vanadium catalyst was well dispersed in the carbon fibers, improving the capacitance of the electrode. Second, pore-size development was manipulated to obtain small mesopore sizes ranging from 2 to 5 nm. Through chemical activation, carbon fibers with controlled pore sizes were prepared with a high specific surface and pore volume, and their pore structure was investigated by using a BET apparatus. Finally, polyacrylonitrile was used as a carbon precursor to enrich for nitrogen content in the final product because nitrogen is known to improve electrode capacitance. Ultimately, the electrospun activated carbon fibers containing vanadium show improved functionality in charge/discharge, cyclic voltammetry, and specific capacitance compared with other samples because of an optimal combination of vanadium, nitrogen, and fixed pore structures.

[Studies on the structure-activity relationship of retinoids--Hansch analysis and 3D-OSAR studies on specific ligands of retinoid x receptor].

PubMed

Huang, N; Chu, F; Guo, Z

1998-06-01

Retinoids (Vitamin A, its metabolites and synthetic analogues) play important roles in a variety of biological processes, including cellular differentiation, proliferation and apoptosis. The many diverse actions of retinoids attribute to the ability of regulating transcription of different target genes through activation of multiple retinoid nuclear receptors (RAR of RXR). So, retinoids with selective binding ability to specific receptor may not only have improved therapeutic indices, but may also be invaluable for elucidating the molecular mechanism of retinoidal transcriptional activation. Based on the two dimensional and three dimensional quantitative structure-activity relationships of specific ligands of RXR, we carried out mimesis of environment of ligands interacting with their receptor and, to some extent, mapping the topological and physico-chemical characteristics of receptor. The knowledge of the QSAR study will offer detailed molecular information for design, synthesis and biological evaluation in drug research and development.

Aqueous lithium air batteries

DOEpatents

Visco, Steven J.; Nimon, Yevgeniy S.; De Jonghe, Lutgard C.; Petrov, Alexei; Goncharenko, Nikolay

2017-05-23

Aqueous Li/Air secondary battery cells are configurable to achieve high energy density and prolonged cycle life. The cells include a protected a lithium metal or alloy anode and an aqueous catholyte in a cathode compartment. The aqueous catholyte comprises an evaporative-loss resistant and/or polyprotic active compound or active agent that partakes in the discharge reaction and effectuates cathode capacity for discharge in the acidic region. This leads to improved performance including one or more of increased specific energy, improved stability on open circuit, and prolonged cycle life, as well as various methods, including a method of operating an aqueous Li/Air cell to simultaneously achieve improved energy density and prolonged cycle life.

Does the latissimus dorsi tendon transfer for massive rotator cuff tears remain active postoperatively and restore active external rotation?

PubMed

Henseler, Jan Ferdinand; Nagels, Jochem; Nelissen, Rob G H H; de Groot, Jurriaan H

2014-04-01

The purpose of this study is to evaluate the muscle activity with surface electromyography (EMG) and the clinical outcome of the latissimus dorsi transfer. It remains unclear whether the clinical results of the latissimus dorsi transfer for massive posterosuperior rotator cuff tears are achieved either by active muscle contractions or by a passive tenodesis effect of the transfer. Eight patients were evaluated preoperatively and at 1 year (SD, 0.1) after the latissimus dorsi transfer. Clinical evaluation of outcomes included active range of motion, Constant score, and visual analog scale (VAS) for pain and activities of daily living (ADL). Muscle activity was recorded with EMG during directional isometric abduction and adduction tasks. The external rotation in adduction improved from 23° to 51° (P = .03). The external rotation in abduction improved from 10° to 70° (P = .02). The mean Constant score improved from 39 to 62 postoperatively (P = .01). The VAS for pain at rest improved from 3.3 preoperatively to 0.1 (P = .02). The VAS for ADL improved from 4.9 to 2.3 (P = .05). The transferred latissimus dorsi remained active in all cases, as reflected by increased latissimus dorsi EMG activity during abduction tasks. In addition, the latissimus dorsi EMG activity shifted from preoperative antagonistic co-activation in adduction to synergistic activation in abduction. The latissimus dorsi has synergistic muscle activity after transfer. Apart from a tenodesis effect, directional muscle activity seems relevant for improved clinical outcome and pain relief. A specific gain was observed for external rotation in elevated arm positions, a motion essential for ADL tasks. Copyright © 2014 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Mosby, Inc. All rights reserved.

RTEMS CENTRE- RTEMS Improvement

NASA Astrophysics Data System (ADS)

Silva, Helder; Constantino, Alexandre; Freitas, Daniel; Coutinho, Manuel; Faustino, Sergio; Sousa, Jose; Dias, Luis; Zulianello, Marco

2010-08-01

During the last two years, EDISOFT's RTEMS CENTRE team [1], jointly with the European Space Agency and with the support of the worldwide RTEMS community [2], have been developing an activity to facilitate the qualification of the real-time operating system RTEMS (Real-Time Operating System for Multiprocessor Systems). This paper intends to give a high level visibility of the progress and the results obtained in the RTEMS Improvement [3] activity. The primary objective [4] of the project is to improve the RTEMS product, its documentation and to facilitate the qualification of RTEMS for future space missions, taking into consideration the specific operational requirements. The sections below provide a brief overview of the RTEMS operating system and the activities performed in the RTEMS Improvement project, which includes the selection of API managers to be qualified, the tailoring process, the requirements analysis, the reverse engineering and design of the RTEMS, the quality assurance process, the ISVV activities, the test campaign, the results obtained, the criticality analysis and the facilitation of qualification process.

Ultra-high-throughput screening method for the directed evolution of glucose oxidase.

PubMed

Ostafe, Raluca; Prodanovic, Radivoje; Nazor, Jovana; Fischer, Rainer

2014-03-20

Glucose oxidase (GOx) is used in many industrial processes that could benefit from improved versions of the enzyme. Some improvements like higher activity under physiological conditions and thermal stability could be useful for GOx applications in biosensors and biofuel cells. Directed evolution is one of the currently available methods to engineer improved GOx variants. Here, we describe an ultra-high-throughput screening system for sorting the best enzyme variants generated by directed evolution that incorporates several methodological refinements: flow cytometry, in vitro compartmentalization, yeast surface display, fluorescent labeling of the expressed enzyme, delivery of glucose substrate to the reaction mixture through the oil phase, and covalent labeling of the cells with fluorescein-tyramide. The method enables quantitative screening of gene libraries to identify clones with improved activity and it also allows cells to be selected based not only on the overall activity but also on the specific activity of the enzyme. Copyright © 2014 Elsevier Ltd. All rights reserved.

Overview of Development and Formulation of ¹⁷⁷Lu-DOTA-TATE for PRRT.

PubMed

Breeman, Wouter A P; Chan, Ho Sze; de Zanger, Rory M S; Konijnenberg, Mark K; de Blois, Erik

2016-01-01

Peptide receptor radionuclide therapy (PRRT) using radiolabeled somatostatin analogs has become an established procedure for the treatment of patients suffering from inoperable neuroendocrine cancers over-expressing somatostatin receptors. Success of PRRT depends on the availability of the radiolabeled peptide with adequately high specific activity, so that required therapeutic efficacy can be achieved without saturating the limited number of receptors available on the target lesions. Specific activity of the radionuclide and the radiolabeled somatostatin analog are therefore an important parameters. Although these analogs have been investigated and improved, and successfully applied for PRRT for more than 15 years, there are still many possibilities for further improvements that fully exploit PRRT with 177Lu-DOTA-TATE. The here summarized data presented herein on increased knowledge of the components of 177Lu-DOTA-TATE (especially the purity of 177Lu and specific activity of 177Lu) and the reaction kinetics during labeling 177Lu-DOTA-TATE clearly show that the peptide dose and dose in GBq can be varied. Here we present an overview of the development, formulation and optimisation of 177Lu-DOTA-TATE, mainly addressing radiochemical parameters.

Summary of International Guidelines for Physical Activity Following Pregnancy

PubMed Central

Evenson, Kelly R.; Mottola, Michelle F.; Owe, Katrine M.; Rousham, Emily K.; Brown, Wendy J.

2014-01-01

Postpartum physical activity can improve mood, maintain cardiorespiratory fitness, improve weight control, promote weight loss, and reduce depression and anxiety. This review summarizes current guidelines for postpartum physical activity worldwide. PubMed (MedLINE) was searched for country-specific government and clinical guidelines on physical activity following pregnancy through the year 2013. Only the most recent guideline was included in the review. An abstraction form facilitated extraction of key details and helped to summarize results. Six guidelines were identified from five countries (Australia, Canada, Norway, United Kingdom, United States). All guidelines were embedded within pregnancy-related physical activity recommendations. All provided physical activity advice related to breastfeeding and three remarked about physical activity following Caesarean delivery. Recommended physical activities mentioned in the guidelines included aerobic (3/6), pelvic floor exercise (3/6), strengthening (2/6), stretching (2/6), and walking (2/6). None of the guidelines discussed sedentary behavior. The guidelines that were identified lacked specificity for physical activity. Greater clarity in guidelines would be more useful to both practitioners and the women they serve. Postpartum physical activity guidelines have the potential to assist women to initiate or resume physical activity following childbirth, so that they can transition to meeting recommended levels of physical activity. Health care providers have a critical role in encouraging women to be active at this time, and the availability of more explicit guidelines may assist them to routinely include physical activity advice in their postpartum care. PMID:25112589

Patients with Revision Modern Megaprostheses of the Distal Femur Have Improved Disease-Specific and Health-Related Outcomes Compared to Those with Primary Replacements.

PubMed

Heyberger, Clémence; Auberger, Guillaume; Babinet, Antoine; Anract, Philippe; Biau, David J

2017-12-21

We asked whether there would be any difference between primary and revision modern cemented fixed hinge megaprosthesis of the distal femur in function and activity-related outcomes following treatment of a bone tumor. An identical custom-made fixed hinge cemented megaprosthesis with a hydroxyapatite collar was used in all cases. The main outcomes were joint-specific function, disease-specific activity, and health-related quality of life. Implant survival was also evaluated. Patients in the revision group performed slightly better than patients in the primary group on disease-specific (Toronto Extremity Salvage Score, p  = 0.033; Musculoskeletal Tumor Society, p  = 0.072) and health-related outcomes (Short Form 36 [SF-36] physical component, p  = 0.085; SF-36 mental component, p  = 0.069) but not on joint-specific outcomes (Knee Society Score, p  = 0.94). The cumulative probabilities of revision for any reason were 14.5% (7-25%) at 5 years with no statistically significant difference between primary and revision procedures ( p  = 0.77). In conclusion, patients undergoing a revision have similar joint-specific functional outcome but improved disease-specific and health-related outcomes. Implant survival are similar between groups. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

The Role of Exergaming in Improving Physical Activity: A Review

PubMed Central

Sween, Jennifer; Wallington, Sherrie Flynnt; Sheppard, Vanessa; Taylor, Teletia; Llanos, Adana A.; Adams-Campbell, Lucile Lauren

2013-01-01

Background The high prevalence of obesity in America can be attributed to inadequate energy expenditure as a result of high levels of physical inactivity. This review presents an overview of the current literature on physical activity, specifically through active videogame systems (exergaming) and how these systems can help to increase physical activity levels. Methods The search strategy for this review was to identify previous studies which investigated energy expenditure levels using a single active video game or a combination of active videogames. Results Based on data from 27 studies, a strong correlation exists between exergaming and increased energy expenditure (up to 300% above resting levels). The majority of active videogames tested were found to achieve physical activity levels of moderate intensity, which meet American College of Sports Medicine guidelines for health and fitness. Conclusions Exergaming is a new and exciting strategy to potentially improve physical activity levels and reduce obesity among Americans. PMID:25078529

Measuring Physical Activity in Outdoor Community Recreational Environments: Implications for Research, Policy, and Practice.

PubMed

Aytur, Semra A; Jones, Sydney A; Stransky, Michelle; Evenson, Kelly R

2015-01-01

Chronic diseases such as cardiovascular disease (CVD) are major contributors to escalating health care costs in the USA. Physical activity is an important protective factor against CVD, and the National Prevention Strategy recognizes active living (defined as a way of life that integrates physical activity into everyday routines) as a priority for improving the nation's health. This paper focuses on developing more inclusive measures of physical activity in outdoor community recreational environments, specifically parks and trails, to enhance their usability for at-risk populations such as persons with mobility limitations. We develop an integrated conceptual framework for measuring physical activity in outdoor community recreational environments, describe examples of evidence-based tools for measuring physical activity in these settings, and discuss strategies to improve measurement of physical activity for persons with mobility limitations. Addressing these measurement issues is critically important to making progress towards national CVD goals pertaining to active community environments.

Synthesis of Platinum-nickel Nanowires and Optimization for Oxygen Reduction Performance

DOE PAGES

Alia, Shaun M.; Pivovar, Bryan S.

2018-01-01

Platinum-nickel (Pt-Ni) nanowires were developed as fuel cell electrocatalysts, and were optimized for the performance and durability in the oxygen reduction reaction. Spontaneous galvanic displacement was used to deposit Pt layers onto Ni nanowire substrates. The synthesis approach produced catalysts with high specific activities and high Pt surface areas. Hydrogen annealing improved Pt and Ni mixing and specific activity. Acid leaching was used to preferentially remove Ni near the nanowire surface, and oxygen annealing was used to stabilize near-surface Ni, improving durability and minimizing Ni dissolution. These protocols detail the optimization of each post-synthesis processing step, including hydrogen annealing tomore » 250 degrees C, exposure to 0.1 M nitric acid, and oxygen annealing to 175 degrees C. Through these steps, Pt-Ni nanowires produced increased activities more than an order of magnitude than Pt nanoparticles, while offering significant durability improvements. The presented protocols are based on Pt-Ni systems in the development of fuel cell catalysts. Furthermore, these techniques have also been used for a variety of metal combinations, and can be applied to develop catalysts for a number of electrochemical processes.« less

Synthesis of Platinum-nickel Nanowires and Optimization for Oxygen Reduction Performance

DOE Office of Scientific and Technical Information (OSTI.GOV)

Alia, Shaun M.; Pivovar, Bryan S.

Platinum-nickel (Pt-Ni) nanowires were developed as fuel cell electrocatalysts, and were optimized for the performance and durability in the oxygen reduction reaction. Spontaneous galvanic displacement was used to deposit Pt layers onto Ni nanowire substrates. The synthesis approach produced catalysts with high specific activities and high Pt surface areas. Hydrogen annealing improved Pt and Ni mixing and specific activity. Acid leaching was used to preferentially remove Ni near the nanowire surface, and oxygen annealing was used to stabilize near-surface Ni, improving durability and minimizing Ni dissolution. These protocols detail the optimization of each post-synthesis processing step, including hydrogen annealing tomore » 250 degrees C, exposure to 0.1 M nitric acid, and oxygen annealing to 175 degrees C. Through these steps, Pt-Ni nanowires produced increased activities more than an order of magnitude than Pt nanoparticles, while offering significant durability improvements. The presented protocols are based on Pt-Ni systems in the development of fuel cell catalysts. Furthermore, these techniques have also been used for a variety of metal combinations, and can be applied to develop catalysts for a number of electrochemical processes.« less

Mutagenesis of solvent-exposed amino acids in Photinus pyralis luciferase improves thermostability and pH-tolerance

PubMed Central

Law, G. H. Erica; Gandelman, Olga A.; Tisi, Laurence C.; Lowe, Christopher R.; Murray, James A. H.

2006-01-01

Firefly luciferase catalyses a two-step reaction, using ATP-Mg2+, firefly luciferin and molecular oxygen as substrates, leading to the efficient emission of yellow–green light. We report the identification of novel luciferase mutants which combine improved pH-tolerance and thermostability and that retain the specific activity of the wild-type enzyme. These were identified by the mutagenesis of solvent-exposed non-conserved hydrophobic amino acids to hydrophilic residues in Photinus pyralis firefly luciferase followed by in vivo activity screening. Mutants F14R, L35Q, V182K, I232K and F465R were found to be the preferred substitutions at the respective positions. The effects of these amino acid replacements are additive, since combination of the five substitutions produced an enzyme with greatly improved pH-tolerance and stability up to 45 °C. All mutants, including the mutant with all five substitutions, showed neither a decrease in specific activity relative to the recombinant wild-type enzyme, nor any substantial differences in kinetic constants. It is envisaged that the combined mutant will be superior to wild-type luciferase for many in vitro and in vivo applications. PMID:16551268

Cognitive Motor Coordination Training Improves Mental Rotation Performance in Primary School-Aged Children

ERIC Educational Resources Information Center

Pietsch, Stefanie; Böttcher, Caroline; Jansen, Petra

2017-01-01

The long-term physical activity in specific sport activities can change the quality of mental rotation performance. This study investigates the influence of "Life Kinetik"--a motion program with tasks of cognition and motor coordination--on mental rotation performance of 44 primary school-aged children. While the experimental group…

Participation in Sports-Related Extracurricular Activities: A Strategy That Enhances School Engagement

ERIC Educational Resources Information Center

St-Amand, Jerome; Girard, Stéphanie; Hiroux, Marie-Hélène; Smith, Jonathan

2017-01-01

This article outlines a strategy that we, as high school teachers, used in the academic year 2012-2013 to improve a student's school engagement. Extracurricular activities such as sports have proven useful (among other strategies) to counter school disengagement, specifically in enhancing positive social relations among the teachers and students…

Global variations in the level of cancer-related research activity and correlation to cancer-specific mortality: Proposal for a global curriculum.

PubMed

Are, C; Caniglia, A; Malik, Mohammed; Smith, L; Cummings, Charmaine; Lecoq, Carine; Berman, R; Audisio, R; Wyld, L

2018-01-01

The aim of this study was to analyze global variations in the level of cancer-related research activity and correlate this with cancer-specific mortality. The SCOPUS database was explored to obtain data relating to the number of cancer-related publications per country. Cancer-specific mortality rates were obtained from the World Health Organization. Global variations in the level of scholarly activity were analyzed and correlated with variations in cancer-specific mortality. Data for 142 countries were obtained and significant variations in the level of research activity was noted. The level of research activity increased with rising socio-economic status. The United States was the most prolific country with 222,300 publications followed by Japan and Germany. Several countries in different regions of the world had a low level of research activity. An inverse relationship between the level of research activity and cancer-specific mortality was noted. This relationship persisted even in countries with a low level of research activity. The socioeconomic status of a nation and geographic location (continent) had a mixed influence with an overall apparent correlation with cancer-related research activity. This study demonstrates significant global variation in the level of cancer-related research activity and a correlation with cancer-specific mortality. The presence of a minimum set of standards for research literacy, as proposed by the European Society of Surgical Oncology and the Society of Surgical Oncology may contribute to enhanced research activity and improve outcomes for cancer patients worldwide. Copyright © 2017 Society of Surgical Oncology, European Society of Surgical Oncology. Published by Elsevier Ltd.. All rights reserved.

Intein-mediated site-specific synthesis of tumor-targeting protein delivery system: Turning PEG dilemma into prodrug-like feature

PubMed Central

Chen, Yingzhi; Zhang, Meng; Jin, Hongyue; Tang, Yisi; Wang, Huiyuan; Xu, Qin; Li, Yaping; Li, Feng; Huang, Yongzhuo

2017-01-01

Poor tumor-targeted and cytoplasmic delivery is a bottleneck for protein toxin-based cancer therapy. Ideally, a protein toxin drug should remain stealthy in circulation for prolonged half-life and reduced side toxicity, but turn activated at tumor. PEGylation is a solution to achieve the first goal, but creates a hurdle for the second because PEG rejects interaction between the drugs and tumor cells therein. Such PEG dilemma is an unsolved problem in protein delivery. Herein proposed is a concept of turning PEG dilemma into prodrug-like feature. A site-selectively PEGylated, gelatinase-triggered cell-penetrating trichosanthin protein delivery system is developed with three specific aims. The first is to develop an intein-based ligation method for achieving site-specific modification of protein toxins. The second is to develop a prodrug feature that renders protein toxins remaining stealthy in blood for reduced side toxicity and improved EPR effect. The third is to develop a gelatinase activatable cell-penetration strategy for enhanced tumor targeting and cytoplasmic delivery. Of note, site-specific modification is a big challenge in protein drug research, especially for such a complicated, multifunctional protein delivery system. We successfully develop a protocol for constructing a macromolecular prodrug system with intein-mediated ligation synthesis. With an on-column process of purification and intein-mediated cleavage, the site-specific PEGylation then can be readily achieved by conjugation with the activated C-terminus, thus constructing a PEG-capped, cell-penetrating trichosanthin system with a gelatinase-cleavable linker that enables tumor-specific activation of cytoplasmic delivery. It provides a promising method to address the PEG dilemma for enhanced protein drug delivery, and importantly, a facile protocol for site-specific modification of such a class of protein drugs for improving their druggability and industrial translation. PMID:27914267

Prior automatic posture and activity identification improves physical activity energy expenditure prediction from hip-worn triaxial accelerometry.

PubMed

Garnotel, M; Bastian, T; Romero-Ugalde, H M; Maire, A; Dugas, J; Zahariev, A; Doron, M; Jallon, P; Charpentier, G; Franc, S; Blanc, S; Bonnet, S; Simon, C

2018-03-01

Accelerometry is increasingly used to quantify physical activity (PA) and related energy expenditure (EE). Linear regression models designed to derive PAEE from accelerometry-counts have shown their limits, mostly due to the lack of consideration of the nature of activities performed. Here we tested whether a model coupling an automatic activity/posture recognition (AAR) algorithm with an activity-specific count-based model, developed in 61 subjects in laboratory conditions, improved PAEE and total EE (TEE) predictions from a hip-worn triaxial-accelerometer (ActigraphGT3X+) in free-living conditions. Data from two independent subject groups of varying body mass index and age were considered: 20 subjects engaged in a 3-h urban-circuit, with activity-by-activity reference PAEE from combined heart-rate and accelerometry monitoring (Actiheart); and 56 subjects involved in a 14-day trial, with PAEE and TEE measured using the doubly-labeled water method. PAEE was estimated from accelerometry using the activity-specific model coupled to the AAR algorithm (AAR model), a simple linear model (SLM), and equations provided by the companion-software of used activity-devices (Freedson and Actiheart models). AAR-model predictions were in closer agreement with selected references than those from other count-based models, both for PAEE during the urban-circuit (RMSE = 6.19 vs 7.90 for SLM and 9.62 kJ/min for Freedson) and for EE over the 14-day trial, reaching Actiheart performances in the latter (PAEE: RMSE = 0.93 vs. 1.53 for SLM, 1.43 for Freedson, 0.91 MJ/day for Actiheart; TEE: RMSE = 1.05 vs. 1.57 for SLM, 1.70 for Freedson, 0.95 MJ/day for Actiheart). Overall, the AAR model resulted in a 43% increase of daily PAEE variance explained by accelerometry predictions. NEW & NOTEWORTHY Although triaxial accelerometry is widely used in free-living conditions to assess the impact of physical activity energy expenditure (PAEE) on health, its precision and accuracy are often debated. Here we developed and validated an activity-specific model which, coupled with an automatic activity-recognition algorithm, improved the variance explained by the predictions from accelerometry counts by 43% of daily PAEE compared with models relying on a simple relationship between accelerometry counts and EE.

AHA Scientific Statement Population Approaches to Improve Diet, Physical Activity, and Smoking Habits A Scientific Statement From the American Heart Association

PubMed Central

Mozaffarian, Dariush; Afshin, Ashkan; Benowitz, Neal L.; Bittner, Vera; Daniels, Stephen R.; Franch, Harold A.; Jacobs, David R.; Kraus, William E.; Kris-Etherton, Penny M.; Krummel, Debra A.; Popkin, Barry M.; Whitsel, Laurie P.; Zakai, Neil A.

2013-01-01

Background Poor lifestyle, including suboptimal diet, physical inactivity, and tobacco use are leading causes of preventable diseases globally. Although even modest population shifts in risk substantially alter health outcomes, the optimal population-level approaches to improve lifestyle are not well established. Methods and Results For this American Heart Association Scientific Statement, the writing group systematically reviewed and graded the current scientific evidence for effective population approaches to improve dietary habits, increase physical activity, and reduce tobacco use. Strategies were considered in 6 broad domains: (1) media and education campaigns; (2) labeling and consumer information; (3) taxation, subsidies, and other economic incentives; (4) school and workplace approaches; (5) local environmental changes; and (6) direct restrictions and mandates. The writing group also reviewed the potential contributions of healthcare systems and surveillance systems to behavior change efforts. Several specific population interventions that achieved a Class I or IIa recommendation with grade A or B evidence were identified, providing a set of specific evidence-based strategies that deserve close attention and prioritization for wider implementation. Effective interventions included specific approaches in all 6 domains evaluated for improving diet, increasing activity, and reducing tobacco use. The writing group also identified several specific interventions in each of these domains for which current evidence was less robust, as well as other inconsistencies and evidence gaps, informing the need for further rigorous and interdisciplinary approaches to evaluate population programs and policies. Conclusions This systematic review identified and graded the evidence for a range of population-based strategies to promote lifestyle change. The findings provide a framework for policy makers, advocacy groups, researchers, clinicians, communities, and other stakeholders to understand and implement the most effective approaches. New strategic initiatives and partnerships are needed to translate this evidence into action. PMID:22907934

Kinetic modeling of benzodiazepine receptor binding with PET and high specific activity [(11)C]Iomazenil in healthy human subjects.

PubMed

Bremner, J D; Horti, A; Staib, L H; Zea-Ponce, Y; Soufer, R; Charney, D S; Baldwin, R

2000-01-01

Quantitation of the PET benzodiazepine receptor antagonist, [(11)C]Iomazenil, using low specific activity radioligand was recently described. The purpose of this study was to quantitate benzodiazepine receptor binding in human subjects using PET and high specific activity [(11)C]Iomazenil. Six healthy human subjects underwent PET imaging following a bolus injection of high specific activity (>100 Ci/mmol) [(11)C]iomazenil. Arterial samples were collected at multiple time points after injection for measurement of unmetabolized total and nonprotein-bound parent compound in plasma. Time activity curves of radioligand concentration in brain and plasma were analyzed using two and three compartment model. Kinetic rate constants of transfer of radioligand between plasma, nonspecifically bound brain tissue, and specifically bound brain tissue compartments were fitted to the model. Values for fitted kinetic rate constants were used in the calculation of measures of benzodiazepine receptor binding, including binding potential (the ratio of receptor density to affinity), and product of BP and the fraction of free nonprotein-bound parent compound (V(3)'). Use of the three compartment model improved the goodness of fit in comparison to the two compartment model. Values for kinetic rate constants and measures of benzodiazepine receptor binding, including BP and V(3)', were similar to results obtained with the SPECT radioligand [(123)I]iomazenil, and a prior report with low specific activity [(11)C]Iomazenil. Kinetic modeling using the three compartment model with PET and high specific activity [(11)C]Iomazenil provides a reliable measure of benzodiazepine receptor binding. Synapse 35:68-77, 2000. Published 2000 Wiley-Liss, Inc.

Cyclophilin A as a potential genetic adjuvant to improve HIV-1 Gag DNA vaccine immunogenicity by eliciting broad and long-term Gag-specific cellular immunity in mice.

PubMed

Hou, Jue; Zhang, Qicheng; Liu, Zheng; Wang, Shuhui; Li, Dan; Liu, Chang; Liu, Ying; Shao, Yiming

2016-01-01

Previous research has shown that host Cyclophilin A (CyPA) can promote dendritic cell maturation and the subsequent innate immune response when incorporated into an HIV-1 Gag protein to circumvent the resistance of dendritic cells to HIV-1 infection. This led us to hypothesize that CyPA may improve HIV-1 Gag-specific vaccine immunogenicity via binding with Gag antigen. The adjuvant effect of CyPA was evaluated using a DNA vaccine with single or dual expression cassettes. Mouse studies indicated that CyPA specifically and markedly promoted HIV-1 Gag-specific cellular immunity but not an HIV-1 Env-specific cellular response. The Gag/CyPA dual expression cassettes stimulated a greater Gag-specific cellular immune response, than Gag immunization alone. Furthermore, CyPA induced a broad Gag-specific T cell response and strong cellular immunity that lasted up to 5 months. In addition, CyPA skewed to cellular rather than humoral immunity. To investigate the mechanisms of the adjuvant effect, site-directed mutagenesis in CyPA, including active site residues H54Q and F60A resulted in mutants that were co-expressed with Gag in dual cassettes. The immune response to this vaccine was analyzed in vivo. Interestingly, the wild type CyPA markedly increased Gag cellular immunity, but the H54Q and F60A mutants drastically reduced CyPA adjuvant activation. Therefore, we suggest that the adjuvant effect of CyPA was based on Gag-CyPA-specific interactions. Herein, we report that Cyclophilin A can augment HIV-1 Gag-specific cellular immunity as a genetic adjuvant in multiplex DNA immunization strategies, and that activity of this adjuvant is specific, broad, long-term, and based on Gag-CyPA interaction.

How children use drawing to regulate their emotions.

PubMed

Drake, Jennifer E; Winner, Ellen

2013-01-01

We examined two ways in which drawing may function to elevate mood in children-venting (expressing negative feelings) and distraction (expressing something unrelated to the negative feelings). We examined the effectiveness of drawing as an emotion regulator when drawing is used to vent versus distract (Study 1) and tested whether the effects found are specific to the activity of creating one's own drawing or generalisable to a drawing activity in which children had to copy another's drawing (Study 2). To induce a negative mood, we asked children to think of a disappointing event. Mood was assessed before and after the assigned activity. In both studies, mood improved significantly more in the distract than in the vent or copy condition. Study 1 demonstrates that drawing improves mood in children via distraction and not via venting. Study 2 demonstrates that this effect is specific to a drawing task in which an image is freely constructed. When a copying task is used, the effect disappears.

Advanced generation anti-prostate specific membrane antigen designer T cells for prostate cancer immunotherapy.

PubMed

Ma, Qiangzhong; Gomes, Erica M; Lo, Agnes Shuk-Yee; Junghans, Richard P

2014-02-01

Adoptive immunotherapy by infusion of designer T cells (dTc) engineered with chimeric antigen receptors (CARs) for tumoricidal activity represents a potentially highly specific modality for the treatment of cancer. In this study, 2nd generation (gen) anti-prostate specific membrane antigen (PSMA) dTc were developed for improving the efficacy of previously developed 1st gen dTc for prostate cancer immunotherapy. The 1st gen dTc are modified with chimeric immunoglobulin-T cell receptor (IgTCR) while the 2nd gen dTc are engineered with an immunoglobulin-CD28-T cell receptor (IgCD28TCR), which incorporates a CD28 costimulatory signal for optimal T cell activation. A 2nd gen anti-PSMA IgCD28TCR CAR was constructed by inserting the CD28 signal domain into the 1st gen CAR. 1st and 2nd gen anti-PSMA dTc were created by transducing human T cells with anti-PSMA CARs and their antitumor efficacy was compared for specific activation on PSMA-expressing tumor contact, cytotoxicity against PSMA-expressing tumor cells in vitro, and suppression of tumor growth in an animal model. The 2nd gen dTc can be optimally activated to secrete larger amounts of cytokines such as IL2 and IFNγ than 1st gen and to proliferate more vigorously on PSMA-expressing tumor contact. More importantly, the 2nd gen dTc preserve the PSMA-specific cytotoxicity in vitro and suppress tumor growth in animal models with significant higher potency. Our results demonstrate that 2nd gen anti-PSMA designer T cells exhibit superior antitumor functions versus 1st gen, providing a rationale for advancing this improved agent toward clinical application in prostate cancer immunotherapy. © 2013 Wiley Periodicals, Inc.

Recyclable Thermoresponsive Polymer-β-Glucosidase Conjugate with Intact Hydrolysis Activity.

PubMed

Mukherjee, Ishita; Sinha, Sushant K; Datta, Supratim; De, Priyadarsi

2018-06-11

β-Glucosidase (BG) catalyzes the hydrolysis of cellobiose to glucose and is a rate-limiting enzyme in the conversion of lignocellulosic biomass to sugars toward biofuels. Since the cost of enzyme is a major contributor to biofuel economics, we report the bioconjugation of a temperature-responsive polymer with the highly active thermophilic β-glucosidase (B8CYA8) from Halothermothrix orenii toward improving enzyme recyclability. The bioconjugate, with a lower critical solution temperature (LCST) of 33 °C withstands high temperatures up to 70 °C. Though the secondary structure of the enzyme in the conjugate is slightly distorted with a higher percentage of β-sheet like structure, the stability and specific activity of B8CYA8 in the conjugate remains unaltered up to 30 °C and retains more than 70% specific activity of the unmodified enzyme at 70 °C. The conjugate can be reused for β-glucosidic bond cleavage of cellobiose for at least four cycles without any significant loss in specific activity.

Dietary supplementation with a specific combination of high protein, leucine, and fish oil improves muscle function and daily activity in tumour-bearing cachectic mice

PubMed Central

van Norren, K; Kegler, D; Argilés, J M; Luiking, Y; Gorselink, M; Laviano, A; Arts, K; Faber, J; Jansen, H; van der Beek, E M; van Helvoort, A

2009-01-01

Cancer cachexia is characterised by metabolic alterations leading to loss of adipose tissue and lean body mass and directly compromises physical performance and the quality of life of cancer patients. In a murine cancer cachectic model, the effects of dietary supplementation with a specific combination of high protein, leucine and fish oil on weight loss, muscle function and physical activity were investigated. Male CD2F1 mice, 6–7 weeks old, were divided into body weight-matched groups: (1) control, (2) tumour-bearing, and (3) tumour-bearing receiving experimental diets. Tumours were induced by s.c. inoculation with murine colon adenocarcinoma (C26) cells. Food intake, body mass, tumour size and 24 h-activity were monitored. Then, 20 days after tumour/vehicle inoculation, the animals were killed and muscle function was tested ex vivo. Tumour-bearing mice showed reduced carcass, muscle and fat mass compared with controls. EDL muscle performance and total daily activity were impaired in the tumour-bearing mice. Addition of single nutrients resulted in no or modest effects. However, supplementation of the diet with the all-in combination of high protein, leucine and fish oil significantly reduced loss of carcass, muscle and fat mass (loss in mass 45, 52 and 65% of TB-con, respectively (P<0.02)) and improved muscle performance (loss of max force reduced to 55–64% of TB-con (P<0.05)). Moreover, total daily activity normalised after intervention with the specific nutritional combination (50% of the reduction in activity of TB-con (P<0.05)). In conclusion, a nutritional combination of high protein, leucine and fish oil reduced cachectic symptoms and improved functional performance in cancer cachectic mice. Comparison of the nutritional combination with its individual modules revealed additive effects of the single components provided. PMID:19259092

Methods for Optimizing CRISPR-Cas9 Genome Editing Specificity

PubMed Central

Tycko, Josh; Myer, Vic E.; Hsu, Patrick D.

2016-01-01

Summary Advances in the development of delivery, repair, and specificity strategies for the CRISPR-Cas9 genome engineering toolbox are helping researchers understand gene function with unprecedented precision and sensitivity. CRISPR-Cas9 also holds enormous therapeutic potential for the treatment of genetic disorders by directly correcting disease-causing mutations. Although the Cas9 protein has been shown to bind and cleave DNA at off-target sites, the field of Cas9 specificity is rapidly progressing with marked improvements in guide RNA selection, protein and guide engineering, novel enzymes, and off-target detection methods. We review important challenges and breakthroughs in the field as a comprehensive practical guide to interested users of genome editing technologies, highlighting key tools and strategies for optimizing specificity. The genome editing community should now strive to standardize such methods for measuring and reporting off-target activity, while keeping in mind that the goal for specificity should be continued improvement and vigilance. PMID:27494557

MOBE-ChIP: Probing Cell Type-Specific Binding Through Large-Scale Chromatin Immunoprecipitation.

PubMed

Wang, Shenqi; Lau, On Sun

2018-01-01

In multicellular organisms, the initiation and maintenance of specific cell types often require the activity of cell type-specific transcriptional regulators. Understanding their roles in gene regulation is crucial but probing their DNA targets in vivo, especially in a genome-wide manner, remains a technical challenge with their limited expression. To improve the sensitivity of chromatin immunoprecipitation (ChIP) for detecting the cell type-specific signals, we have developed the Maximized Objects for Better Enrichment (MOBE)-ChIP, where ChIP is performed at a substantially larger experimental scale and under low background conditions. Here, we describe the procedure in the study of transcription factors in the model plant Arabidopsis. However, with some modifications, the technique should also be implemented in other systems. Besides cell type-specific studies, MOBE-ChIP can also be used as a general strategy to improve ChIP signals.

Safety performance functions for intersections : final report, December 2009.

DOT National Transportation Integrated Search

2009-12-01

Road safety management activities include screening the network for sites with a potential for safety improvement (Network : Screening), diagnosing safety problems at specific sites, and evaluating the safety effectiveness of implemented : countermea...

Irritable Bowel Syndrome in Children

MedlinePlus

... and adjust the activity of the GI tract. Probiotics Probiotics are live microorganisms, usually bacteria, that are similar ... in the GI tract. Studies have found that probiotics, specifically Bifidobacteria and certain probiotic combinations, improve symptoms ...

Advanced Light Source Activity Report 2002

DOE Office of Scientific and Technical Information (OSTI.GOV)

Duque, Theresa; Greiner, Annette; Moxon, Elizabeth

2003-06-12

This annual report of the Advanced Light Source details science highlights and facility improvements during the year. It also offers information on events sponsored by the facility, technical specifications, and staff and publication information.

75 FR 43168 - Agency Information Collection Activities: Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2010-07-23

... the Medicare Prescription Drug, Improvement, and Modernization Act of 2003 (MMA). Specifically, the MMA under Sec. 1860D-4 (Information to Facilitate Enrollment) requires CMS to conduct consumer...

Impeding Xist expression from the active X chromosome improves mouse somatic cell nuclear transfer.

PubMed

Inoue, Kimiko; Kohda, Takashi; Sugimoto, Michihiko; Sado, Takashi; Ogonuki, Narumi; Matoba, Shogo; Shiura, Hirosuke; Ikeda, Rieko; Mochida, Keiji; Fujii, Takashi; Sawai, Ken; Otte, Arie P; Tian, X Cindy; Yang, Xiangzhong; Ishino, Fumitoshi; Abe, Kuniya; Ogura, Atsuo

2010-10-22

Cloning mammals by means of somatic cell nuclear transfer (SCNT) is highly inefficient because of erroneous reprogramming of the donor genome. Reprogramming errors appear to arise randomly, but the nature of nonrandom, SCNT-specific errors remains elusive. We found that Xist, a noncoding RNA that inactivates one of the two X chromosomes in females, was ectopically expressed from the active X (Xa) chromosome in cloned mouse embryos of both sexes. Deletion of Xist on Xa showed normal global gene expression and resulted in about an eight- to ninefold increase in cloning efficiency. We also identified an Xist-independent mechanism that specifically down-regulated a subset of X-linked genes through somatic-type repressive histone blocks. Thus, we have identified nonrandom reprogramming errors in mouse cloning that can be altered to improve the efficiency of SCNT methods.

[Do you mean benchmarking?].

PubMed

Bonnet, F; Solignac, S; Marty, J

2008-03-01

The purpose of benchmarking is to settle improvement processes by comparing the activities to quality standards. The proposed methodology is illustrated by benchmark business cases performed inside medical plants on some items like nosocomial diseases or organization of surgery facilities. Moreover, the authors have built a specific graphic tool, enhanced with balance score numbers and mappings, so that the comparison between different anesthesia-reanimation services, which are willing to start an improvement program, is easy and relevant. This ready-made application is even more accurate as far as detailed tariffs of activities are implemented.

Are treatment effects of neurofeedback training in children with ADHD related to the successful regulation of brain activity? A review on the learning of regulation of brain activity and a contribution to the discussion on specificity

PubMed Central

Zuberer, Agnieszka; Brandeis, Daniel; Drechsler, Renate

2015-01-01

While issues of efficacy and specificity are crucial for the future of neurofeedback training, there may be alternative designs and control analyses to circumvent the methodological and ethical problems associated with double-blind placebo studies. Surprisingly, most NF studies do not report the most immediate result of their NF training, i.e., whether or not children with ADHD gain control over their brain activity during the training sessions. For the investigation of specificity, however, it seems essential to analyze the learning and adaptation processes that take place in the course of the training and to relate improvements in self-regulated brain activity across training sessions to behavioral, neuropsychological and electrophysiological outcomes. To this aim, a review of studies on neurofeedback training with ADHD patients which include the analysis of learning across training sessions or relate training performance to outcome is presented. Methods on how to evaluate and quantify learning of EEG regulation over time are discussed. “Non-learning” has been reported in a small number of ADHD-studies, but has not been a focus of general methodological discussion so far. For this reason, selected results from the brain-computer interface (BCI) research on the so-called “brain-computer illiteracy”, the inability to gain control over one’s brain activity, are also included. It is concluded that in the discussion on specificity, more attention should be devoted to the analysis of EEG regulation performance in the course of the training and its impact on clinical outcome. It is necessary to improve the knowledge on characteristic cross-session and within-session learning trajectories in ADHD and to provide the best conditions for learning. PMID:25870550

Beclomethasone Dipropionate Nasal Aerosol in Patients with Perennial Allergic Rhinitis (BALANCE) study: 6-month results.

PubMed

Bukstein, Donald; Parikh, Ruchir; Eid, Sherrine; Ferro, Thomas; Morello, Jean-Pierre

2016-01-01

Perennial allergic rhinitis (PAR) exerts significant quality-of-life and economic burdens on society. Beclomethasone dipropionate (BDP) nasal aerosol is the first nonaqueous, hydrofluoroalkane-propelled intranasal corticosteroid approved for patients in the United States to treat PAR and seasonal allergic rhinitis. To evaluate real-world effectiveness of BDP nasal aerosol from the patient's perspective by using a postmarketing observational registry. Patients (N = 824) from 43 U.S. study sites completed monthly patient-reported outcome instruments, including the Rhinitis Control Assessment Test (primary outcome variable), Treatment Satisfaction Questionnaire for Medication, Work Productivity and Activity Impairment Questionnaire plus Classroom Impairment Questions: Allergy-Specific, Pittsburgh Sleep Quality Index, and Mini Rhinoconjunctivitis Quality of Life Questionnaire for 6 months. The primary outcome assessment (Rhinitis Control Assessment Test score) (N = 527) indicated significant symptomatic improvement over baseline beginning at month 1 (p < 0.001), with >78.8% of respondents who achieved clinically meaningful improvement over 6 months. Secondary outcome measures Mini Rhinoconjunctivitis Quality of Life Questionnaire (p < 0.001), Pittsburgh Sleep Quality Index (p < 0.001), and Treatment Satisfaction Questionnaire for Medication-9 scales of effectiveness (p < 0.001), global satisfaction (p = 0.001), and patient-rated convenience (p = 0.03), significantly increased from baseline to month 6. Five of seven measurements of the Work Productivity and Activity Impairment Questionnaire plus Classroom Impairment Questions: Allergy-Specific, with the exception of work time missed and class time missed, were significantly (p < 0.001) improved in patients treated with BDP compared with baseline. Treatment with nonaqueous BDP nasal aerosol in a real-world setting significantly improved PAR symptoms and measures of quality of life, work, and school-related activities, and is associated with high patient satisfaction, reduced productivity loss and activity impairment, and improvement in sleep quality.

Evaluation of the neuroactive steroid ganaxolone on social and repetitive behaviors in the BTBR mouse model of autism

PubMed Central

Kazdoba, Tatiana M.; Hagerman, Randi J.; Zolkowska, Dorota; Rogawski, Michael A.; Crawley, Jacqueline N.

2015-01-01

Rationale Abnormalities in excitatory/inhibitory neurotransmission are hypothesized to contribute to autism spectrum disorder (ASD) etiology. BTBR, an inbred mouse strain, displays social deficits and repetitive self-grooming, offering face validity to ASD diagnostic symptoms. Reduced GABAergic neurotransmission in BTBR suggests that GABAA receptor positive allosteric modulators (PAMs) could improve ASD-relevant BTBR phenotypes. The neuroactive steroid ganaxolone acts as a PAM, displaying anticonvulsant properties in rodent epilepsy models and an anxiolytic-like profile in the elevated plus-maze. Objectives We evaluated ganaxolone in BTBR and C57BL/6J mice in standardized assays for sociability and repetitive behaviors. Open field and anxiety-related behaviors were tested as internal controls and for comparison with the existing neuroactive steroid literature. Results Ganaxolone improved aspects of social approach and reciprocal social interactions in BTBR, with no effect on repetitive self-grooming, and no detrimental effects in C57BL/6J. Ganaxolone increased overall exploratory activity in BTBR and C57BL/6J in the open field, social approach, and elevated plus-maze, introducing a confound for the interpretation of social improvements. Allopregnanolone and diazepam similarly increased total entries in the elevated plus-maze, indicating that behavioral activation may be a general property of GABAA receptor PAMs in these strains. Conclusions Ganaxolone shows promise for improving sociability. In addition, ganaxolone, as well as other GABAA receptor PAMs, enhanced overall BTBR activity. The translational implications of specific sociability improvements and non-specific behavioral activation by ganaxolone in the BTBR model remains to be determined. Future studies to explore whether PAMs provide a novel profile with unique benefits for ASD treatment will be worthwhile. PMID:26525567

Roles of s3 site residues of nattokinase on its activity and substrate specificity.

PubMed

Wu, Shuming; Feng, Chi; Zhong, Jin; Huan, Liandong

2007-09-01

Nattokinase (Subtilisin NAT, NK) is a bacterial serine protease with high fibrinolytic activity. To probe their roles on protease activity and substrate specificity, three residues of S3 site (Gly(100), Ser(101) and Leu(126)) were mutated by site-directed mutagenesis. Kinetics parameters of 20 mutants were measured using tetrapeptides as substrates, and their fibrinolytic activities were determined by fibrin plate method. Results of mutation analysis showed that Gly(100) and Ser(101) had reverse steric and electrostatic effects. Residues with bulky or positively charged side chains at position 100 decreased the substrate binding and catalytic activity drastically, while residues with the same characters at position 101 could obviously enhance protease and fibrinolytic activity of NK. Mutation of Leu(126) might impair the structure of the active cleft and drastically decreased the activity of NK. Kinetics studies of the mutants showed that S3 residues were crucial to keep protease activity while they moderately affected substrate specificity of NK. The present study provided some original insight into the P3-S3 interaction in NK and other subtilisins, as well as showed successful protein engineering cases to improve NK as a potential therapeutic agent.

Directed evolution of an endoinulinase from Talaromyces purpureogenus toward efficient production of inulooligosaccharides.

PubMed

Afriat-Jurnou, Livnat; Cohen, Rami; Paluy, Irina; Ben-Adiva, Ran; Yadid, Itamar

2018-02-01

Inulinases are fructofuranosyl hydrolases that target the β-2,1 linkage of inulin and hydrolyze it into fructose, glucose and inulooligosaccharides (IOS), the latter are of growing interest as dietary fibers. Inulinases from various microorganisms have been purified, characterized and produced for industrial applications. However, there remains a need for inulinases with increased catalytic activity and better production yields to improve the hydrolysis process and fulfill the growing industrial demands for specific fibers. In this study, we used directed enzyme evolution to increase the yield and activity of an endoinulinase enzyme originated from the filamentous fungus Talaromyces purpureogenus (Penicillium purpureogenum ATCC4713). Our directed evolution approach yielded variants showing up to fivefold improvements in soluble enzyme production compared to the starting point which enabled high-yield production of highly purified recombinant enzyme. The distribution of the enzymatic reaction products demonstrated that after 24 h of incubation, the main product (57%) had a degree of polymerization of 3 (DP3). To the best of our knowledge, this is the first application of directed enzyme evolution to improve inulooligosaccharide production. The approach enabled the screening of large genetic libraries within short time frames and facilitated screening for improved enzymatic activities and properties, such as substrate specificity, product range, thermostability and pH optimum. © 2018 American Institute of Chemical Engineers Biotechnol. Prog., 2018. © 2018 American Institute of Chemical Engineers.

Para-nitrobenzyl esterases with enhanced activity in aqueous and nonaqueous media

DOEpatents

Arnold, F.H.; Moore, J.C.

1999-05-25

A method is disclosed for isolating and identifying modified para-nitrobenzyl esterases which exhibit improved stability and/or esterase hydrolysis activity toward selected substrates and under selected reaction conditions relative to the unmodified para-nitrobenzyl esterase. The method involves preparing a library of modified para-nitrobenzyl esterase nucleic acid segments (genes) which have nucleotide sequences that differ from the nucleic acid segment which encodes for unmodified para-nitrobenzyl esterase. The library of modified para-nitrobenzyl nucleic acid segments is expressed to provide a plurality of modified enzymes. The clones expressing modified enzymes are then screened to identify which enzymes have improved esterase activity by measuring the ability of the enzymes to hydrolyze the selected substrate under the selected reaction conditions. Specific modified para-nitrobenzyl esterases are disclosed which have improved stability and/or ester hydrolysis activity in aqueous or aqueous-organic media relative to the stability and/or ester hydrolysis activity of unmodified naturally occurring para-nitrobenzyl esterase. 43 figs.

Para-nitrobenzyl esterases with enhanced activity in aqueous and nonaqueous media

DOEpatents

Arnold, F.H.; Moore, J.C.

1998-04-21

A method is disclosed for isolating and identifying modified para-nitrobenzyl esterases. These enzymes exhibit improved stability and/or esterase hydrolysis activity toward selected substrates and under selected reaction conditions relative to the unmodified para-nitrobenzyl esterase. The method involves preparing a library of modified para-nitrobenzyl esterase nucleic acid segments (genes) which have nucleotide sequences that differ from the nucleic acid segment which encodes for unmodified para-nitrobenzyl esterase. The library of modified para-nitrobenzyl nucleic acid segments is expressed to provide a plurality of modified enzymes. The clones expressing modified enzymes are then screened to identify which enzymes have improved esterase activity by measuring the ability of the enzymes to hydrolyze the selected substrate under the selected reaction conditions. Specific modified para-nitrobenzyl esterases are disclosed which have improved stability and/or ester hydrolysis activity in aqueous or aqueous-organic media relative to the stability and/or ester hydrolysis activity of unmodified naturally occurring para-nitrobenzyl esterase. 43 figs.

Implicit sequence-specific motor learning after sub-cortical stroke is associated with increased prefrontal brain activations: An fMRI study

PubMed Central

Meehan, Sean K.; Randhawa, Bubblepreet; Wessel, Brenda; Boyd, Lara A.

2010-01-01

Implicit motor learning is preserved after stroke, but how the brain compensates for damage to facilitate learning is unclear. We used a random effects analysis to determine how stroke alters patterns of brain activity during implicit sequence-specific motor learning as compared to general improvements in motor control. Nine healthy participants and 9 individuals with chronic, right focal sub-cortical stroke performed a continuous joystick-based tracking task during an initial fMRI session, over 5 days of practice, and a retention test during a separate fMRI session. Sequence-specific implicit motor learning was differentiated from general improvements in motor control by comparing tracking performance on a novel, repeated tracking sequences during early practice and again at the retention test. Both groups demonstrated implicit sequence-specific motor learning at the retention test, yet substantial differences were apparent. At retention, healthy control participants demonstrated increased BOLD response in left dorsal premotor cortex (BA 6) but decreased BOLD response left dorsolateral prefrontal cortex (DLPFC; BA 9) during repeated sequence tracking. In contrast, at retention individuals with stroke did not show this reduction in DLPFC during repeated tracking. Instead implicit sequence-specific motor learning and general improvements in motor control were associated with increased BOLD response in the left middle frontal gyrus BA 8, regardless of sequence type after stroke. These data emphasize the potential importance of a prefrontal-based attentional network for implicit motor learning after stroke. The present study is the first to highlight the importance of the prefrontal cortex for implicit sequence-specific motor learning after stroke. PMID:20725908

Near infrared light-mediated photoactivation of cytotoxic Re(i) complexes by using lanthanide-doped upconversion nanoparticles.

PubMed

Hu, Ming; Zhao, Jixian; Ai, Xiangzhao; Budanovic, Maja; Mu, Jing; Webster, Richard D; Cao, Qian; Mao, Zongwan; Xing, Bengang

2016-09-13

Platinum-based chemotherapy, although it has been well proven to be effective in the battle against cancer, suffers from limited specificity, severe side effects and drug resistance. The development of new alternatives with potent anticancer effects and improved specificity is therefore urgently needed. Recently, there are some new chemotherapy reagents based on photoactive Re(i) complexes which have been reported as promising alternatives to improve specificity mainly attributed to the spatial and temporal activation process by light irradiation. However, most of them respond to short-wavelength light (e.g. UV, blue or green light), which may cause unwanted photo damage to cells. Herein, we demonstrate a system for near-infrared (NIR) light controlled activation of Re(i) complex cytotoxicity by integration of photoactivatable Re(i) complexes and lanthanide-doped upconversion nanoparticles (UCNPs). Upon NIR irradiation at 980 nm, the Re(i) complex can be locally activated by upconverted UV light emitted from UCNPs and subsequently leads to enhanced cell lethality. Cytotoxicity studies showed effective inactivation of both drug susceptible human ovarian carcinoma A2780 cells and cisplatin resistant subline A2780cis cells by our UCNP based system with NIR irradiation, and there was minimum light toxicity observed in the whole process, suggesting that such a system could provide a promising strategy to control localized activation of Re(i) complexes and therefore minimize potential side effects.

Language Diversity & Practice in Higher Education: Can Discipline-Specific Language Instruction Improve Economics Learning Outcomes?

ERIC Educational Resources Information Center

Nguyen, Trien; Trimarchi, Angela; Williams, Julia

2012-01-01

In the field of second language acquisition, discipline-specific language instruction is becoming widely known as Content and Language Integrated Learning. This method includes any activity that involves teaching a subject in a second language for the purpose of teaching both the subject content and the language. Research has shown that this two…

Improving Diagnosis of Sepsis After Burn Injury Using a Portable Sepsis Alert System

DTIC Science & Technology

2016-10-01

application listed milestones/target dates for important activities or phases of the project, identify these dates and show actual completion dates or the... activities ; 2) specific objectives; 3) significant results or key outcomes, including major findings, developments, or conclusions (both positive and...progresses to completion, the emphasis in reporting in this section should shift from reporting activities to reporting accomplishments. Task 1. Test the

Soil acidity amelioration in a no-till system in west Tennessee USA differs by cover crop type and nitrogen application rate

USDA-ARS?s Scientific Manuscript database

Conservation soil management practices may influence the soil acidity. Surface application of lime may be required in no-till systems to ameliorate soil acidity and to improve crop yields. The application of lime may also increase microbial activity on soil. Specifically, the microbial activity of s...

Second generation engineering of transketolase for polar aromatic aldehyde substrates.

PubMed

Payongsri, Panwajee; Steadman, David; Hailes, Helen C; Dalby, Paul A

2015-04-01

Transketolase has significant industrial potential for the asymmetric synthesis of carboncarbon bonds with new chiral centres. Variants evolved on propanal were found previously with nascent activity on polar aromatic aldehydes 3-formylbenzoic acid (3-FBA), 4-formylbenzoic acid (4-FBA), and 3-hydroxybenzaldehyde (3-HBA), suggesting a potential novel route to analogues of chloramphenicol. Here we evolved improved transketolase activities towards aromatic aldehydes, by saturation mutagenesis of two active-site residues (R358 and S385), predicted to interact with the aromatic substituents. S385 variants selectively controlled the aromatic substrate preference, with up to 13-fold enhanced activities, and KM values comparable to those of natural substrates with wild-type transketolase. S385E even completely removed the substrate inhibition for 3-FBA, observed in all previous variants. The mechanisms of catalytic improvement were both mutation type and substrate dependent. S385E improved 3-FBA activity via kcat, but reduced 4-FBA activity via KM. Conversely, S385Y/T improved 3-FBA activity via KM and 4-FBA activity via kcat. This suggested that both substrate proximity and active-site orientation are very sensitive to mutation. Comparison of all variant activities on each substrate indicated different binding modes for the three aromatic substrates, supported by computational docking. This highlights a potential divergence in the evolution of different substrate specificities, with implications for enzyme engineering. Copyright © 2015 Elsevier Inc. All rights reserved.

Brain-Computer Interface with Inhibitory Neurons Reveals Subtype-Specific Strategies.

PubMed

Mitani, Akinori; Dong, Mingyuan; Komiyama, Takaki

2018-01-08

Brain-computer interfaces have seen an increase in popularity due to their potential for direct neuroprosthetic applications for amputees and disabled individuals. Supporting this promise, animals-including humans-can learn even arbitrary mapping between the activity of cortical neurons and movement of prosthetic devices [1-4]. However, the performance of neuroprosthetic device control has been nowhere near that of limb control in healthy individuals, presenting a dire need to improve the performance. One potential limitation is the fact that previous work has not distinguished diverse cell types in the neocortex, even though different cell types possess distinct functions in cortical computations [5-7] and likely distinct capacities to control brain-computer interfaces. Here, we made a first step in addressing this issue by tracking the plastic changes of three major types of cortical inhibitory neurons (INs) during a neuron-pair operant conditioning task using two-photon imaging of IN subtypes expressing GCaMP6f. Mice were rewarded when the activity of the positive target neuron (N+) exceeded that of the negative target neuron (N-) beyond a set threshold. Mice improved performance with all subtypes, but the strategies were subtype specific. When parvalbumin (PV)-expressing INs were targeted, the activity of N- decreased. However, targeting of somatostatin (SOM)- and vasoactive intestinal peptide (VIP)-expressing INs led to an increase of the N+ activity. These results demonstrate that INs can be individually modulated in a subtype-specific manner and highlight the versatility of neural circuits in adapting to new demands by using cell-type-specific strategies. Copyright © 2017 Elsevier Ltd. All rights reserved.

Cloning, expression and mutation of a triazophos hydrolase gene from Burkholderia sp. SZL-1.

PubMed

Zhang, Hao; Li, Qiang; Guo, Su-Hui; Cheng, Ming-Gen; Zhao, Meng-Jun; Hong, Qing; Huang, Xing

2016-06-01

Triazophos is a broad-spectrum and highly effective insecticide, and the residues of triazophos have been frequently detected in the environment. A triazophos-degrading bacterium, Burkholderia sp. SZL-1, was isolated from a long-term triazophos-polluted soil. Strain SZL-1 could hydrolyze triazophos to 1-phenyl-3-hydroxy-1,2,4-triazole, which was further utilized as the carbon sources for growth. The triazophos hydrolase gene trhA, cloned from strain SZL-1, was expressed and homogenously purified using Ni-nitrilotriacetic acid affinity chromatography. TrhA is 55 kDa and displays maximum activity at 25°C, pH 8.0. This enzyme still has nearly 60% activity at the range of 15°C-50°C for 30 min. TrhA was mutated by sequential error prone PCR and screened for improved activity for triazophos degradation. One purified variant protein (Val89-Gly89) named TrhA-M1 showed up to 3-fold improvement in specific activity against triazophos, and the specificity constants of Kcat and Kcat/Km for TrhA-M1 were improved up to 2.3- and 8.28-fold, respectively, compared to the wild-type enzyme. The results in this paper provided potential material for the contaminated soil remediation and hydrolase genetic structure research. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Neglected Children: Suggestions for Early Childhood Educators.

ERIC Educational Resources Information Center

Peterson, Karen L.; Roscoe, Bruce

1983-01-01

Discusses enhancing the development and improving the quality of life of neglected children through acquiring a special understanding and style of interacting with them and by using activities designed specifically to meet their developmental needs. (RH)

The effect of single-task and dual-task balance exercise programs on balance performance in adults with osteoporosis: a randomized controlled preliminary trial.

PubMed

Konak, H E; Kibar, S; Ergin, E S

2016-11-01

Osteoporosis is a serious disease characterized by muscle weakness in the lower extremities, shortened length of trunk, and increased dorsal kyphosis leading to poor balance performance. Although balance impairment increases in adults with osteoporosis, falls and fall-related injuries have been shown to occur mainly during the dual-task performance. Several studies have shown that dual-task performance was improved with specific repetitive dual-task exercises. The aims of this study were to compare the effect of single- and dual-task balance exercise programs on static balance, dynamic balance, and activity-specific balance confidence in adults with osteoporosis and to assess the effectiveness of dual-task balance training on gait speed under dual-task conditions. Older adults (N = 42) (age range, 45-88 years) with osteoporosis were randomly assigned into two groups. Single-task balance training group was given single-task balance exercises for 4 weeks, whereas dual-task balance training group received dual-task balance exercises. Participants received 45-min individualized training session, three times a week. Static balance was evaluated by one-leg stance (OLS) and a kinesthetic ability trainer (KAT) device. Dynamic balance was measured by the Berg Balance Scale (BBS), Time Up and Go (TUG) test, and gait speed. Self-confidence was assessed with the Activities-specific Balance Confidence (ABC-6) scale. Assessments were performed at baseline and after the 4-week program. At the end of the treatment periods, KAT score, BBS score, time in OLS and TUG, gait speeds under single- and dual-task conditions, and ABC-6 scale scores improved significantly in all patients (p < 0.05). However, BBS and gait speeds under single- and dual-task conditions showed significantly greater improvement in the dual-task balance training group than in the single-task balance training group (p < 0.05). ABC-6 scale scores improved more in the single-task balance training group than in the dual-task balance training group (p < 0.05). A 4-week single- and dual-task balance exercise programs are effective in improving static balance, dynamic balance, and balance confidence during daily activities in older adults with osteoporosis. However, single- and dual-task gait speeds showed greater improvement following the application of a specific type of dual-task exercise programs. 24102014-2.

Process-Improvement Cost Model for the Emergency Department.

PubMed

Dyas, Sheila R; Greenfield, Eric; Messimer, Sherri; Thotakura, Swati; Gholston, Sampson; Doughty, Tracy; Hays, Mary; Ivey, Richard; Spalding, Joseph; Phillips, Robin

2015-01-01

The objective of this report is to present a simplified, activity-based costing approach for hospital emergency departments (EDs) to use with Lean Six Sigma cost-benefit analyses. The cost model complexity is reduced by removing diagnostic and condition-specific costs, thereby revealing the underlying process activities' cost inefficiencies. Examples are provided for evaluating the cost savings from reducing discharge delays and the cost impact of keeping patients in the ED (boarding) after the decision to admit has been made. The process-improvement cost model provides a needed tool in selecting, prioritizing, and validating Lean process-improvement projects in the ED and other areas of patient care that involve multiple dissimilar diagnoses.

Specific muscle EMG biofeedback for hand dystonia.

PubMed

Deepak, K K; Behari, M

1999-12-01

Currently available therapies have only limited success in patients having hand dystonia (writer's cramp). We employed specific muscle EMG biofeedback (audio feedback of the EMG from proximal large muscles of the limb that show abnormally high activity during writing) in 10 of 13 consecutive patients (age, 19-62 years; all males) with a duration of illness from 6 months to 8 years. In three patients, biofeedback was not applicable due to lack of abnormal EMG values. Nine patients showed dystonic posture during writing and had hypertrophy of one or more large muscles of the dominant hand. The remaining four patients showed either involvement of small muscles or muscle wasting. Ten patients were given four or more sessions of EMG audio biofeedback from the proximal large limb muscles, which showed maximum EMG activity. They also practiced writing daily with the relaxed limb for 5 to 10 min. Nine patients showed improvement from 37 to 93% in handwriting, alleviation of discomfort, and pain (assessed on a visual analogue scale). One patient did not show any improvement. Thus EMG biofeedback improved the clinical and electromyographic picture in those patients with hand dystonia who showed EMG overactivity of proximal limb muscles during writing. This specific type of EMG biofeedback appears to be a promising tool for hand dystonia and might also be applied to other types of dystonias.

Chapter One in Ohio: Education Consolidation and Improvement Act. 21st Annual Evaluation Report, Fiscal 1986.

ERIC Educational Resources Information Center

Young, Eileen, Ed.

Recent activities provided in Ohio through Chapter 1 of the Education Consolidation and Improvement Act and its predecessor, Title I of the Elementary and Secondary Education Act are summarized in this annual report. Specific information contained in the report includes statistics for fiscal 1986 (the 1985-86 school year and the summer that…

Improving Learning through Interventions of Student-Generated Questions and Concept Maps

ERIC Educational Resources Information Center

Berry, Jack W.; Chew, Stephen L.

2008-01-01

Using the principles of the scholarship of teaching and learning, we evaluated 2 learning strategies to determine if they could improve student exam performance in general psychology. After the second of 3 exams, we gave students the option of participating in a specific learning activity and assessed its impact using the third exam. In Study 1,…

Potential application of algicidal bacteria for improved lipid recovery with specific algae.

PubMed

Lenneman, Eric M; Wang, Ping; Barney, Brett M

2014-05-01

The utility of specific strains of natural algicidal bacteria isolated from shallow wetland sediments was evaluated against several strains of algae with potential immediate or future commercial value. Two strains of bacteria, Pseudomonas pseudoalcaligenes AD6 and Aeromonas hydrophila AD9, were identified and demonstrated to have algicidal activity against the microalgae Neochloris oleoabundans and Dunaliella tertiolecta. These bacteria were further evaluated for the potential to improve lipid extraction using a mild solvent extraction approach. Aeromonas hydrophila AD9 showed a nearly 12-fold increase in lipid extraction with D. tertiolecta, while both bacteria showed a sixfold improvement in lipid extraction with N. oleoabundans. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

Definition of improvement in juvenile idiopathic arthritis using the juvenile arthritis disease activity score.

PubMed

Horneff, Gerd; Becker, Ingrid

2014-07-01

The aim of this study was to define improvement thresholds for the Juvenile Arthritis Disease Activity Score (JADAS). Physicians' and parents' judgements on treatment efficacy, the ACR paediatric response measure (PedACR) and JADAS were extracted from BIKER. Patients were categorized by baseline classes in the 10-joint JADAS (JADAS10) as low (5 to <15), moderate (15 to <25) and high (25 to ≤40). Cut-offs for defining improvement following treatment with biologics or MTX were chosen by calculating the interquartile ranges (IQRs) of the judgement groups and considering the accuracy, sensitivity and specificity of the resulting model. Differences in the change of JADAS10 by JIA category were also analysed by analysis of variance (ANOVA). Sensitivity, specificity and accuracy were calculated. A total of 1315 treatment courses were analysed. The ANOVA of the JIA categories showed no significant differences of the mean JADAS10 in all baseline classes and IQRs also showed good overall limits. Therefore all JIA categories were combined for a collective cut-off. Analysis by baseline class revealed clear cut-off points. Improvement could be defined by the minimal decrease in the JADAS10 in baseline class low by 4 (41%), moderate by 10 (53%) and high by 17 (57%). The model shows values for accuracy from 75.6 to 85.5% and comparable values for sensitivity and specificity. Improvement after 3 months can be defined efficiently by the decrease of the JADAS10, depending on the baseline JADAS10 score, which specifies low, moderate or high disease activity. Our model demonstrates clear cut-off values. The JADAS10 may be used in addition to ACR criteria in clinical trials. Also, since the JADAS10 can easily be calculated at each patient visit, it also can be used for clinical decisions. © The Author 2014. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Enhancing motor performance improvement by personalizing non-invasive cortical stimulation with concurrent functional near-infrared spectroscopy and multi-modal motor measurements

NASA Astrophysics Data System (ADS)

Khan, Bilal; Hodics, Timea; Hervey, Nathan; Kondraske, George; Stowe, Ann; Alexandrakis, George

2015-03-01

Transcranial direct current stimulation (tDCS) is a non-invasive cortical stimulation technique that can facilitate task specific plasticity that can improve motor performance. Current tDCS interventions uniformly apply a chosen electrode montage to a subject population without personalizing electrode placement for optimal motor gains. We propose a novel perturbation tDCS (ptDCS) paradigm for determining a personalized electrode montage in which tDCS intervention yields maximal motor performance improvements during stimulation. PtDCS was applied to ten healthy adults and five stroke patients with upper hemiparesis as they performed an isometric wrist flexion task with their non-dominant arm. Simultaneous recordings of torque applied to a stationary handle, muscle activity by electromyography (EMG), and cortical activity by functional near-infrared spectroscopy (fNIRS) during ptDCS helped interpret how cortical activity perturbations by any given electrode montage related to changes in muscle activity and task performance quantified by a Reaction Time (RT) X Error product. PtDCS enabled quantifying the effect on task performance of 20 different electrode pair montages placed over the sensorimotor cortex. Interestingly, the electrode montage maximizing performance in all healthy adults did not match any of the ones being explored in current literature as a means of improving the motor performance of stroke patients. Furthermore, the optimal montage was found to be different in each stroke patient and the resulting motor gains were very significant during stimulation. This study supports the notion that task-specific ptDCS optimization can lend itself to personalizing the rehabilitation of patients with brain injury.

Site-Specific, Covalent Immobilization of Dehalogenase ST2570 Catalyzed by Formylglycine-Generating Enzymes and Its Application in Batch and Semi-Continuous Flow Reactors.

PubMed

Jian, Hui; Wang, Yingwu; Bai, Yan; Li, Rong; Gao, Renjun

2016-07-11

Formylglycine-generating enzymes can selectively recognize and oxidize cysteine residues within the sulfatase sub motif at the terminus of proteins to form aldehyde-bearing formylglycine (FGly) residues, and are normally used in protein labeling. In this study, an aldehyde tag was introduced to proteins using formylglycine-generating enzymes encoded by a reconstructed set of the pET28a plasmid system for enzyme immobilization. The haloacid dehalogenase ST2570 from Sulfolobus tokodaii was used as a model enzyme. The C-terminal aldehyde-tagged ST2570 (ST2570CQ) exhibited significant enzymological properties, such as new free aldehyde groups, a high level of protein expression and improved enzyme activity. SBA-15 has widely been used as an immobilization support for its large surface and excellent thermal and chemical stability. It was functionalized with amino groups by aminopropyltriethoxysilane. The C-terminal aldehyde-tagged ST2570 was immobilized to SBA-15 by covalent binding. The site-specific immobilization of ST2570 avoided the chemical denaturation that occurs in general covalent immobilization and resulted in better fastening compared to physical adsorption. The site-specific immobilized ST2570 showed 3-fold higher thermal stability, 1.2-fold higher catalytic ability and improved operational stability than free ST2570. The site-specific immobilized ST2570 retained 60% of its original activity after seven cycles of batch operation, and it was superior to the ST2570 immobilized to SBA-15 by physical adsorption, which loses 40% of its original activity when used for the second time. It is remarkable that the site-specific immobilized ST2570 still retained 100% of its original activity after 10 cycles of reuse in the semi-continuous flow reactor. Overall, these results provide support for the industrial-scale production and application of site-specific, covalently immobilized ST2570.

Unsupervised machine-learning method for improving the performance of ambulatory fall-detection systems

PubMed Central

2012-01-01

Background Falls can cause trauma, disability and death among older people. Ambulatory accelerometer devices are currently capable of detecting falls in a controlled environment. However, research suggests that most current approaches can tend to have insufficient sensitivity and specificity in non-laboratory environments, in part because impacts can be experienced as part of ordinary daily living activities. Method We used a waist-worn wireless tri-axial accelerometer combined with digital signal processing, clustering and neural network classifiers. The method includes the application of Discrete Wavelet Transform, Regrouping Particle Swarm Optimization, Gaussian Distribution of Clustered Knowledge and an ensemble of classifiers including a multilayer perceptron and Augmented Radial Basis Function (ARBF) neural networks. Results Preliminary testing with 8 healthy individuals in a home environment yields 98.6% sensitivity to falls and 99.6% specificity for routine Activities of Daily Living (ADL) data. Single ARB and MLP classifiers were compared with a combined classifier. The combined classifier offers the greatest sensitivity, with a slight reduction in specificity for routine ADL and an increased specificity for exercise activities. In preliminary tests, the approach achieves 100% sensitivity on in-group falls, 97.65% on out-group falls, 99.33% specificity on routine ADL, and 96.59% specificity on exercise ADL. Conclusion The pre-processing and feature-extraction steps appear to simplify the signal while successfully extracting the essential features that are required to characterize a fall. The results suggest this combination of classifiers can perform better than MLP alone. Preliminary testing suggests these methods may be useful for researchers who are attempting to improve the performance of ambulatory fall-detection systems. PMID:22336100

Improving reading comprehension in reading and listening settings: the effect of two training programmes focusing on metacognition and working memory.

PubMed

Carretti, Barbara; Caldarola, Nadia; Tencati, Chiara; Cornoldi, Cesare

2014-06-01

Metacognition and working memory (WM) have been found associated with success in reading comprehension, but no studies have examined their combined effect on the training of reading comprehension. Another open question concerns the role of listening comprehension: In particular, it is not clear whether training to improve reading comprehension must necessarily be based on processing written material or whether, as suggested in a recent study by Clarke et al. (2010, Psychol. Sci., 21, 1106), a programme based on verbal language could also be effective. The study examined the feasibility of improving text comprehension in school children by comparing the efficacy of two training programmes, both involving metacognition and WM, but one based on listening comprehension, the other on reading comprehension. The study involved a sample of 159 pupils attending eight classes in the fourth and fifth grades (age range 9-11 years). The listening and reading programmes focused on the same abilities/processes strictly related to text comprehension, and particularly metacognitive knowledge and control, WM (per se and in terms of integrating information in a text). The training programmes were implemented by school teachers as part of the class's normal school activities, under the supervision of experts. Their efficacy was compared with the results obtained in an active control group that completed standard text comprehension activities. Our results showed that both the training programmes focusing on specific text comprehension skills were effective in improving the children's achievement, but training in reading comprehension generated greater gains than the listening comprehension programme. Our study suggests that activities focusing specifically on metacognition and WM could foster text comprehension, but the potential benefit is influenced by the training modality, that is, the Reading group obtained greater and longer-lasting improvements than the Active control or Listening groups. © 2013 The British Psychological Society.

Effects of CO{sub 2} activation on electrochemical performance of microporous carbons derived from poly(vinylidene fluoride)

DOE Office of Scientific and Technical Information (OSTI.GOV)

Lee, Seul-Yi; Park, Soo-Jin, E-mail: sjpark@inha.ac.kr

In this work, we have prepared microporous carbons (MPCs) derived from poly(vinylidene fluoride) (PVDF), and the physical activation of MPCs using CO{sub 2} gas is subsequently carried out with various activation temperatures to investigate the electrochemical performance. PVDF is successfully converted into MPCs with a high specific surface area and well-developed micropores. After CO{sub 2} activation, the specific surface areas of MPCs (CA-MPCs) are enhanced by 12% compared with non-activated MPCs. With increasing activation temperature, the micropore size distributions of A-MPCs also become narrower and shift to larger pore size. It is also confirmed that the CO{sub 2} activation hadmore » developed the micropores and introduced the oxygen-containing groups to MPCs′ surfaces. From the results, the specific capacitances of the electrodes in electric double layer capacitors (EDLCs) based on CA-MPCs are distinctly improved through CO{sub 2} activation. The highest specific capacitance of the A-MPCs activated at 700 °C is about 125 F/g, an enhancement of 74% in comparison with NA-MPCs, at a discharge current of 2 A/g in a 6 M KOH electrolyte solution. We also found that micropore size of 0.67 nm has a specific impact on the capacitance behaviors, besides the specific surface area of the electrode samples. - Graphical abstract: The A-MPC samples with high specific surface area (ranging from 1030 to 1082 m{sup 2}/g), corresponding to micropore sizes of 0.67 and 0.72 nm, and with the amount of oxygen-containing groups ranging from 3.2% to 4.4% have been evaluated as electrodes for EDLC applications. . Display Omitted - Highlights: • Microporous carbons (MPCs) were synthesized without activation process. • Next, we carried out the CO{sub 2} activation of MPCs with activation temperatures. • It had developed the micropores and introduced the O-functional groups to MPCs. • The highest specific capacitance: 125 F/g, an increase of 74% compared to MPCs.« less

Adoptive immunotherapy for the treatment of glioblastoma: progress and possibilities.

PubMed

Kuramitsu, Shunichiro; Yamamichi, Akane; Ohka, Fumiharu; Motomura, Kazuya; Hara, Masahito; Natsume, Atsushi

2016-12-01

Patients with glioblastoma have a very poor prognosis. Adoptive cellular therapy (ACT) is defined as the collection of circulating or tumor-infiltrating lymphocytes, their selection, modification, expansion and activation, and their re-administration to patients in order to induce antitumor activity. Although various ACTs have been attempted, most failed to improve the outcome. Immune checkpoint blockade antibodies and T cell engineering with tumor-specific chimeric antigen receptors suggest the emergence of a new era of immunotherapy. Here, we summarize approaches with ACTs using genetically modified T cells, which have been improved by enhancing their antitumor activity, and discuss strategies to develop these therapies. The mechanisms by which gliomas modulate and evade the immune system are also discussed.

Task-specific Dystonias

PubMed Central

Torres-Russotto, Diego; Perlmutter, Joel S.

2009-01-01

Task-specific dystonias are primary focal dystonias characterized by excessive muscle contractions producing abnormal postures during selective motor activities that often involve highly skilled, repetitive movements. Historically these peculiar postures were considered psychogenic but have now been classified as forms of dystonia. Writer’s cramp is the most commonly identified task-specific dystonia and has features typical of this group of disorders. Symptoms may begin with lack of dexterity during performance of a specific motor task with increasingly abnormal posturing of the involved body part as motor activity continues. Initially, the dystonia may manifest only during the performance of the inciting task, but as the condition progresses it may also occur during other activities or even at rest. Neurological exam is usually unremarkable except for the dystonia-related abnormalities. Although the precise pathophysiology remains unclear, increasing evidence suggests reduced inhibition at different levels of the sensorimotor system. Symptomatic treatment options include oral medications, botulinum toxin injections, neurosurgical procedures, and adaptive strategies. Prognosis may vary depending upon body part involved and specific type of task affected. Further research may reveal new insights into the etiology, pathophysiology, natural history, and improved treatment of these conditions. PMID:18990127

An EEG Finger-Print of fMRI deep regional activation.

PubMed

Meir-Hasson, Yehudit; Kinreich, Sivan; Podlipsky, Ilana; Hendler, Talma; Intrator, Nathan

2014-11-15

This work introduces a general framework for producing an EEG Finger-Print (EFP) which can be used to predict specific brain activity as measured by fMRI at a given deep region. This new approach allows for improved EEG spatial resolution based on simultaneous fMRI activity measurements. Advanced signal processing and machine learning methods were applied on EEG data acquired simultaneously with fMRI during relaxation training guided by on-line continuous feedback on changing alpha/theta EEG measure. We focused on demonstrating improved EEG prediction of activation in sub-cortical regions such as the amygdala. Our analysis shows that a ridge regression model that is based on time/frequency representation of EEG data from a single electrode, can predict the amygdala related activity significantly better than a traditional theta/alpha activity sampled from the best electrode and about 1/3 of the times, significantly better than a linear combination of frequencies with a pre-defined delay. The far-reaching goal of our approach is to be able to reduce the need for fMRI scanning for probing specific sub-cortical regions such as the amygdala as the basis for brain-training procedures. On the other hand, activity in those regions can be characterized with higher temporal resolution than is obtained by fMRI alone thus revealing additional information about their processing mode. Copyright © 2013 Elsevier Inc. All rights reserved.

Activation of structural carbon fibres for potential applications in multifunctional structural supercapacitors.

PubMed

Qian, Hui; Diao, Hele; Shirshova, Natasha; Greenhalgh, Emile S; Steinke, Joachim G H; Shaffer, Milo S P; Bismarck, Alexander

2013-04-01

The feasibility of modifying conventional structural carbon fibres via activation has been studied to create fibres, which can be used simultaneously as electrode and reinforcement in structural composite supercapacitors. Both physical and chemical activation, including using steam, carbon dioxide, acid and potassium hydroxide, were conducted and the resulting fibre properties compared. It was proven that the chemical activation using potassium hydroxide is an effective method to prepare activated structural carbon fibres that possess both good electrochemical and mechanical properties. The optimal activation conditions, such as the loading of activating agent and the burn-off of carbon fibres, was identified and delivered a 100-fold increase in specific surface area and 50-fold improvement in specific electrochemical capacitance without any degradation of the fibre mechanical properties. The activation process was successfully scaled-up, showing good uniformity and reproducibility. These activated structural carbon fibres are promising candidates as reinforcement/electrodes for multifunctional structural energy storage devices. Copyright © 2012 Elsevier Inc. All rights reserved.

An evaluation of perinatal mental health interventions: An integrative literature review.

PubMed

Lavender, Theressa J; Ebert, Lyn; Jones, Donovan

2016-10-01

National statistics related specifically to the mental health of women in the perinatal period is poorly acknowledged in Australia. Maternal deaths related to mental health in the perinatal period can be attributed to a lack of appropriate treatment and/or support. A barrier to women's help-seeking behaviors is the lack of discrete, perinatal specific interventions where women can self-assess and access support. This review examines original research evaluating perinatal mental health interventions used by women to improve mental health. An integrative literature review was undertaken. A comprehensive search strategy using 5 electronic databases resulted in the retrieval of 1898 articles. Use of an inclusion and exclusion criteria and Critical Appraisal Skills Program tools resulted in 4 original research papers. Thematic analysis identified universal themes. Cognitive Behavioral Therapy, Behavioral Activation and Mindfulness-based interventions, specifically adapted to meet the needs of women in the perinatal period, demonstrate an overall improvement in mental health. Women involved in the interventions experienced both improvements in symptoms of anxiety and depression as well as secondary benefits from participating in the research. To improve perinatal mental health outcomes, innovative modes of providing effective perinatal mental health interventions that address the unique needs of women in the perinatal period are needed. Future development of perinatal mental health interventions require adaptions of Cognitive Behavioral Therapy, Behavioral Activation and/or Mindfulness-based methods to address mental health outcomes for women in the perinatal period. Copyright © 2016 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

Improved composite targets for small scale 64Cu production comparing Au- and Pt-foils as 64Ni backing

NASA Astrophysics Data System (ADS)

Walther, M.; Preusche, S.; Fuechtner, F.; Pietzsch, H. J.; Steinbach, J.

2012-12-01

Advantages of a stacked assembly of target support components for 64Cu production via 64Ni(p,n)64Cu reaction were reported recently. The present work shows the applicability of these composite targets for beam currents up to 22 μA. Gold and platinum foils were evaluated as 64Ni backing. The effective specific activity (ESA) and specific activity (SA) were determined by TETA titration at room temperature and at 80 °C and compared with additional copper quantification results via ICP-MS and stripping voltammetric trace analysis (VA).

Recent Sikorsky R and D progress

NASA Technical Reports Server (NTRS)

1988-01-01

The recent activities and progress in four specific areas of Sikorsky's research and development program are summarized. Since the beginning of the S-76 design in 1974, Sikorsky has been aggressively developing the technology for using composite materials in helicopter design. Four specific topics are covered: advanced cockpit/controller efforts, fly-by-wire controls on RSRA/X-Wing, vibration control via higher harmonic control, and main rotor aerodynamic improvements.

Effects of balance-specific exercises on balance, physical activity and quality of life in adults with multiple sclerosis: a pilot investigation.

PubMed

Kasser, Susan L; Jacobs, Jesse V; Ford, Marley; Tourville, Timothy W

2015-01-01

To evaluate the efficacy of functional balance exercises on balance impairment, physical activity and quality of life (QOL) in adults with multiple sclerosis (MS). A multiple-baseline time-series design with an uncontrolled intervention. Ten subjects with MS completed assessments twice before and once after a 10-week balance intervention. ANOVA were used to evaluate the effects of testing session on the Brief-BESTest, instrumented stance and gait recordings by inertial motion sensors, lower-limb strength recorded by force transducers, accelerometry-based activity, the 12-item MS Walking Scale (MSWS-12), the Multiple Sclerosis Quality of Life-54 (MSQOL-54) questionnaire, the Modified Fatigue Impact scale (MFIS) and the Activity-specific Balance Confidence (ABC) scale. The intervention associated with significantly improved scores on the MSQOL-54 mental component, MFIS, MSWS-12 and Brief-BESTest. Sway amplitude significantly decreased and jerk significantly increased during instrumented standing on foam with eyes closed. Instrumented gait recordings of sagittal trunk range of motion also significantly decreased. ABC scores, strength measures and activity measures were not significantly changed. Ten weeks of functional balance exercises provided a feasible intervention for individuals with MS that improved components of balance, mental well-being and perceived fatigue impact and ambulation disability. A future randomized, controlled clinical trial should confirm these preliminary findings. Implications for Rehabilitation A balance-specific exercise program is both safe and feasible for individuals with mild-to-moderate MS. Comprehensive exercise interventions that are conceptually driven and employ well-designed progressive exercise across multiple contexts of balance control can facilitate improvements in balance impairments associated with MS. Functional balance exercises can positively impact clinical and objective measures of balance control and favorably influence perceptions of ambulation disability and fatigue as well as perceived quality of life in people with MS.

Effects of a kindergarten-based, family-involved intervention on motor performance ability in 3- to 6-year-old children: the ToyBox-study.

PubMed

Birnbaum, Julia; Geyer, Christine; Kirchberg, Franca; Manios, Yannis; Koletzko, Berthold

2017-02-01

This study targeted to examine the effect of the ToyBox-intervention, a kindergarten-based, family-involved intervention, aiming to improve preschooler's energy-related behaviours (e.g., physical activity) on motor performance ability. Physical activity sessions, classroom activities, environmental changes and tools for parents were the components of the 1-year intervention. The intervention and control were cluster-randomised, and children's anthropometry and two motor test items (jumping from side to side, JSS and standing long jump, SLJ) were assessed. A total of 1293 (4.6 ± 0.69 years; 52% boys) from 45 kindergartens in Germany were included (intervention, n = 863; control, n = 430). The effect was assessed using generalised estimating equation. The intervention group showed a better improvement in JSS (Estimate 2.19 jumps, P = 0.01) and tended to improve better in SLJ (Estimate 2.73 cm, P = 0.08). The intervention was more effective in boys with respect to SLJ (P of interaction effect = 0.01). Children aged <4.5 years did not show a significant benefit while older children improved (JSS, Estimate 3.38 jumps, P = 0.004; SLJ, Estimate 4.18 cm, P = 0.04). Children with low socio-economic status improved in JSS (Estimate 5.98 jumps, P = 0.0001). The ToyBox-intervention offers an effective strategy to improve specific components of motor performance ability in early childhood. Future programmes should consider additional strategies specifically targeting girls and younger aged children. BMI: body mass index; SES: socio-economic status; JSS: jumping from side to side; SLJ: standing long jump; SD: standard deviation; GEE: generalised estimating equation.

Motivational "spill-over" during weight control: increased self-determination and exercise intrinsic motivation predict eating self-regulation.

PubMed

Mata, Jutta; Silva, Marlene N; Vieira, Paulo N; Carraça, Eliana V; Andrade, Ana M; Coutinho, Sílvia R; Sardinha, Luis B; Teixeira, Pedro J

2009-11-01

Successful weight management relies on at least two health behaviors, eating and exercise. However, little is known about their interaction on a motivational and behavioral level. Based on the Hierarchical Model of Motivation the authors examined whether exercise-specific motivation can transfer to eating regulation during a lifestyle weight control program. The authors further investigated whether general, treatment-related, and exercise motivation underlie the relation between increased exercise and improved eating regulation. Overweight/obese women participated in a 1-year randomized controlled trial (N = 239). The intervention focused on promoting physical activity and internal motivation for exercise and weight loss, following Self-Determination Theory. The control group received general health education. General and exercise specific self-determination, eating self-regulation variables, and physical activity behavior. General self-determination and more autonomous exercise motivation predicted eating self-regulation over 12 months. Additionally, general and exercise self-determination fully mediated the relation between physical activity and eating self-regulation. Increased general self-determination and exercise motivation seem to facilitate improvements in eating self-regulation during weight control in women. These motivational mechanisms also underlie the relationship between improvements in exercise behavior and eating regulation. PsycINFO Database Record (c) 2009 APA, all rights reserved.

Nutrition and physical activity randomized control trial in child care centers improves knowledge, policies, and children’s body mass index

PubMed Central

2014-01-01

Background To address the public health crisis of overweight and obese preschool-age children, the Nutrition And Physical Activity Self Assessment for Child Care (NAP SACC) intervention was delivered by nurse child care health consultants with the objective of improving child care provider and parent nutrition and physical activity knowledge, center-level nutrition and physical activity policies and practices, and children’s body mass index (BMI). Methods A seven-month randomized control trial was conducted in 17 licensed child care centers serving predominantly low income families in California, Connecticut, and North Carolina, including 137 child care providers and 552 families with racially and ethnically diverse children three to five years old. The NAP SACC intervention included educational workshops for child care providers and parents on nutrition and physical activity and consultation visits provided by trained nurse child care health consultants. Demographic characteristics and pre - and post-workshop knowledge surveys were completed by providers and parents. Blinded research assistants reviewed each center’s written health and safety policies, observed nutrition and physical activity practices, and measured randomly selected children’s nutritional intake, physical activity, and height and weight pre- and post-intervention. Results Hierarchical linear models and multiple regression models assessed individual- and center-level changes in knowledge, policies, practices and age- and sex-specific standardized body mass index (zBMI), controlling for state, parent education, and poverty level. Results showed significant increases in providers’ and parents’ knowledge of nutrition and physical activity, center-level improvements in policies, and child-level changes in children’s zBMI based on 209 children in the intervention and control centers at both pre- and post-intervention time points. Conclusions The NAP SACC intervention, as delivered by trained child health professionals such as child care health consultants, increases provider knowledge, improves center policies, and lowers BMI for children in child care centers. More health professionals specifically trained in a nutrition and physical activity intervention in child care are needed to help reverse the obesity epidemic. Trial registration National Clinical Trials Number NCT01921842 PMID:24580983

Nutrition and physical activity randomized control trial in child care centers improves knowledge, policies, and children's body mass index.

PubMed

Alkon, Abbey; Crowley, Angela A; Neelon, Sara E Benjamin; Hill, Sherika; Pan, Yi; Nguyen, Viet; Rose, Roberta; Savage, Eric; Forestieri, Nina; Shipman, Linda; Kotch, Jonathan B

2014-03-01

To address the public health crisis of overweight and obese preschool-age children, the Nutrition And Physical Activity Self Assessment for Child Care (NAP SACC) intervention was delivered by nurse child care health consultants with the objective of improving child care provider and parent nutrition and physical activity knowledge, center-level nutrition and physical activity policies and practices, and children's body mass index (BMI). A seven-month randomized control trial was conducted in 17 licensed child care centers serving predominantly low income families in California, Connecticut, and North Carolina, including 137 child care providers and 552 families with racially and ethnically diverse children three to five years old. The NAP SACC intervention included educational workshops for child care providers and parents on nutrition and physical activity and consultation visits provided by trained nurse child care health consultants. Demographic characteristics and pre - and post-workshop knowledge surveys were completed by providers and parents. Blinded research assistants reviewed each center's written health and safety policies, observed nutrition and physical activity practices, and measured randomly selected children's nutritional intake, physical activity, and height and weight pre- and post-intervention. Hierarchical linear models and multiple regression models assessed individual- and center-level changes in knowledge, policies, practices and age- and sex-specific standardized body mass index (zBMI), controlling for state, parent education, and poverty level. Results showed significant increases in providers' and parents' knowledge of nutrition and physical activity, center-level improvements in policies, and child-level changes in children's zBMI based on 209 children in the intervention and control centers at both pre- and post-intervention time points. The NAP SACC intervention, as delivered by trained child health professionals such as child care health consultants, increases provider knowledge, improves center policies, and lowers BMI for children in child care centers. More health professionals specifically trained in a nutrition and physical activity intervention in child care are needed to help reverse the obesity epidemic. National Clinical Trials Number NCT01921842.

Frontolimbic Neural Circuit Changes in Emotional Processing and Inhibitory Control Associated With Clinical Improvement Following Transference-Focused Psychotherapy in Borderline Personality Disorder

PubMed Central

Perez, David L.; Vago, David R.; Pan, Hong; Root, James; Tuescher, Oliver; Fuchs, Benjamin H.; Leung, Lorene; Epstein, Jane; Cain, Nicole M.; Clarkin, John F.; Lenzenweger, Mark F.; Kernberg, Otto F.; Levy, Kenneth N.; Silbersweig, David A.; Stern, Emily

2015-01-01

Aim Borderline personality disorder (BPD) is characterized by self-regulation deficits, including impulsivity and affective lability. Transference-Focused Psychotherapy (TFP) is an evidence-based treatment proven to reduce symptoms across multiple cognitive-emotional domains in BPD. This pilot study aims to investigate neural activation associated with, and predictive of, clinical improvement in emotional and behavioral regulation in BPD following TFP. Methods BPD subjects (N=10) were scanned pre- and post-TFP treatment using a within-subjects design. A disorder-specific emotional-linguistic go/no-go fMRI paradigm was used to probe the interaction between negative emotional processing and inhibitory control. Results Analyses demonstrated significant treatment-related effects with relative increased dorsal prefrontal (dorsal anterior cingulate, dorsolateral prefrontal, and frontopolar cortices) activation, and relative decreased ventrolateral prefrontal cortex and hippocampal activation following treatment. Clinical improvement in constraint correlated positively with relative increased left dorsal anterior cingulate cortex activation. Clinical improvement in affective lability correlated positively with left posterior-medial orbitofrontal cortex/ventral striatum activation, and negatively with right amygdala/parahippocampal activation. Post-treatment improvements in constraint were predicted by pre-treatment right dorsal anterior cingulate cortex hypoactivation, and pre-treatment left posterior-medial orbitofrontal cortex/ventral striatum hypoactivation predicted improvements in affective lability. Conclusions These preliminary findings demonstrate potential TFP-associated alterations in frontolimbic circuitry and begin to identify neural mechanisms associated with a psychodynamically-oriented psychotherapy. PMID:26289141

Faculty development to improve teaching at a health sciences center: a needs assessment.

PubMed

Scarbecz, Mark; Russell, Cynthia K; Shreve, Robert G; Robinson, Melissa M; Scheid, Cheryl R

2011-02-01

There has been increasing interest at health science centers in improving the education of health professionals by offering faculty development activities. In 2007-08, as part of an effort to expand education-related faculty development offerings on campus, the University of Tennessee Health Science Center surveyed faculty members in an effort to identify faculty development activities that would be of interest. Factor analysis of survey data indicated that faculty interests in the areas of teaching and learning can be grouped into six dimensions: development of educational goals and objectives, the use of innovative teaching techniques, clinical teaching, improving traditional teaching skills, addressing teaching challenges, and facilitating participation. There were significant differences in the level of interest in education-related faculty development activities by academic rank and by the college of appointment. Full professors expressed somewhat less interest in faculty development activities than faculty members of lower ranks. Faculty members in the Colleges of Medicine and Dentistry expressed somewhat greater interest in faculty development to improve traditional teaching skills. The policy implications of the survey results are discussed, including the need for faculty development activities that target the needs of specific faculty groups.

Improvement in Therapeutic Efficacy and Reduction in Cellular Toxicity: Introduction of a Novel Anti-PSMA-Conjugated Hybrid Antiandrogen Nanoparticle.

PubMed

Thangavel, Chellappagounder; Perepelyuk, Maryna; Boopathi, Ettickan; Liu, Yi; Polischak, Steven; Deshpande, Deepak A; Rafiq, Khadija; Dicker, Adam P; Knudsen, Karen E; Shoyele, Sunday A; Den, Robert B

2018-05-07

Second generation antiandrogens have improved overall survival for men with metastatic castrate resistant prostate cancer; however, the antiandrogens result in suppression of androgen receptor (AR) activity in all tissues resulting in dose limiting toxicity. We sought to overcome this limitation through encapsulation in a prostate specific membrane antigen (PSMA)-conjugated nanoparticle. We designed and characterized a novel nanoparticle containing an antiandrogen, enzalutamide. Selectivity and enhanced efficacy was achieved through coating the particle with PSMA. The PSMA-conjugated nanoparticle was internalized selectively in AR expressing prostate cancer cells. It did not elicit an inflammatory effect. The efficacy of enzalutamide was not compromised through insertion into the nanoparticle; in fact, lower systemic drug concentrations of enzalutamide resulted in comparable clinical activity. Normal muscle cells were not impacted by the PSMA-conjugated containing antiandrogen. This approach represents a novel strategy to increase the specificity and effectiveness of antiandrogen treatment for men with castrate resistant prostate cancer. The ability to deliver higher drug concentrations in prostate cancer cells may translate into improved clinical end points including overall survival.

Robotic/virtual reality intervention program individualized to meet the specific sensorimotor impairments of an individual patient: a case study.

PubMed

Fluet, Gerard G; Merians, Alma S; Qiu, Qinyin; Saleh, Soha; Ruano, Viviana; Delmonico, Andrea R; Adamovich, Sergei V

2014-09-01

A majority of studies examining repetitive task practice facilitated by robots for the treatment of upper extremity paresis utilize standardized protocols applied to large groups. This study will describe a virtually simulated, robot-based intervention customized to match the goals and clinical presentation of a gentleman with upper extremity hemiparesis secondary to stroke. MP, the subject of this case, is an 85-year-old man with left hemiparesis secondary to an intracerebral hemorrhage 5 years prior to examination. Outcomes were measured before and after a 1-month period of home therapy and after a 1-month virtually simulated, robotic intervention. The intervention was designed to address specific impairments identified during his PT examination. When necessary, activities were modified based on MP's response to his first week of treatment. MP's home training program produced a 3-s decline in Wolf Motor Function Test (WMFT) time and a 5-s improvement in Jebsen Test of Hand Function (JTHF) time. He demonstrated an additional 35-s improvement in JTHF and an additional 44-s improvement in WMFT subsequent to the robotic training intervention. A 24-h activity measurement and the Hand and Activities of Daily Living scales of the Stroke Impact Scale improved following the robotic intervention. Based on his responses to training we feel that we have established that a customized program of virtually simulated, robotically facilitated rehabilitation was feasible and resulted in larger improvements than an intensive home training program in several measurements of upper extremity function in our patient with chronic hemiparesis.

Measuring Physical Activity in Outdoor Community Recreational Environments: Implications for Research, Policy, and Practice

PubMed Central

Jones, Sydney A.; Stransky, Michelle; Evenson, Kelly R.

2015-01-01

Chronic diseases such as cardiovascular disease (CVD) are major contributors to escalating health care costs in the USA. Physical activity is an important protective factor against CVD, and the National Prevention Strategy recognizes active living (defined as a way of life that integrates physical activity into everyday routines) as a priority for improving the nation’s health. This paper focuses on developing more inclusive measures of physical activity in outdoor community recreational environments, specifically parks and trails, to enhance their usability for at-risk populations such as persons with mobility limitations. We develop an integrated conceptual framework for measuring physical activity in outdoor community recreational environments, describe examples of evidence-based tools for measuring physical activity in these settings, and discuss strategies to improve measurement of physical activity for persons with mobility limitations. Addressing these measurement issues is critically important to making progress towards national CVD goals pertaining to active community environments. PMID:26005510

Youth fitness--problems and solutions.

PubMed

DiNubile, N A

1993-07-01

Review of the current data in the area of youth fitness reveals some alarming trends. Children in the United States are fatter, slower, and weaker than their counterparts in other developed nations. In addition, U.S. children seem to be adopting a sedentary lifestyle at earlier ages. Although there is no easy solution to this problem, there are specific recommendations that can ensure improvement in this area. The cornerstone for any meaningful change must involve programs that seek to increase physical activity both in school and at home. Daily, quality physical education in grades K-12 should be mandated in all states. Parents should be educated regarding the critical importance and the multitude of benefits to be derived from their involvement in fitness-related activities with their children. A healthy balance must be established between sedentary activities, e.g., television and video games, and physical activity. All schools should establish fitness testing programs for children and these should be based on health-fitness parameters rather than on athletic performance variables. To ensure improvements in youth fitness across our nation, other interventions are also necessary. These include appropriate involvement of local communities, state and federal governments, the medical health professions, and the media. Specific strategies are available for each group.

Protective antigens from El Tor vibrios

PubMed Central

Watanabe, Yoshikazu; Verwey, W. F.

1965-01-01

A biochemically and immunologically homogeneous antigenic fraction having the properties of a lipopolysaccharide has been isolated from the culture supernatant of an El Tor vibrio (Ogawa subtype). This antigen was very specifically protective for mice challenged with Ogawa strains of either El Tor vibrios or Vibrio cholerae. Rabbit antisera prepared against the antigen were passively protective for mice and highly vibriocidal but had little agglutinating activity. However, the antigen was able specifically to absorb agglutinins, as well as mouse-protective and vibriocidal antibody from serum prepared against whole bacterial cells. The specific protective activity of this lipopolysaccharide was much greater than that of vaccines made from whole bacterial cells, and its toxicity in animals was about equivalent to that of whole cells. The relationship of activity to toxicity therefore represented an improvement over the vaccines that were studied. ImagesFIG. 1FIG. 3FIG. 4FIG. 5 PMID:5294306

Drug conjugated nanoparticles activated by cancer cell specific mRNA.

PubMed

Gossai, Nathan P; Naumann, Jordan A; Li, Nan-Sheng; Zamora, Edward A; Gordon, David J; Piccirilli, Joseph A; Gordon, Peter M

2016-06-21

We describe a customizable approach to cancer therapy in which a gold nanoparticle (Au-NP) delivers a drug that is selectively activated within the cancer cell by the presence of an mRNA unique to the cancer cell. Fundamental to this approach is the observation that the amount of drug released from the Au-NP is proportional to both the presence and abundance of the cancer cell specific mRNA in a cell. As proof-of-principle, we demonstrate both the efficient delivery and selective release of the multi-kinase inhibitor dasatinib from Au-NPs in leukemia cells with resulting efficacy in vitro and in vivo. Furthermore, these Au-NPs reduce toxicity against hematopoietic stem cells and T-cells. This approach has the potential to improve the therapeutic efficacy of a drug and minimize toxicity while being highly customizable with respect to both the cancer cell specific mRNAs targeted and drugs activated.

Behaviour and Locomotor Activity of a Migratory Catostomid during Fishway Passage

PubMed Central

Silva, Ana T.; Hatry, Charles; Thiem, Jason D.; Gutowsky, Lee F. G.; Hatin, Daniel; Zhu, David Z.; W. Dawson, Jeffery; Katopodis, Christos; J. Cooke, Steven

2015-01-01

Fishways have been developed to restore longitudinal connectivity in rivers. Despite their potential for aiding fish passage, fishways may represent a source of significant energetic expenditure for fish as they are highly turbulent environments. Nonetheless, our understanding of the physiological mechanisms underpinning fishway passage of fish is still limited. We examined swimming behaviour and activity of silver redhorse (Moxostoma anisurum) during its upriver spawning migration in a vertical slot fishway. We used an accelerometer-derived instantaneous activity metric (overall dynamic body acceleration) to estimate location-specific swimming activity. Silver redhorse demonstrated progressive increases in activity during upstream fishway passage. Moreover, location-specific passage duration decreased with an increasing number of passage attempts. Turning basins and the most upstream basin were found to delay fish passage. No relationship was found between basin-specific passage duration and activity and the respective values from previous basins. The results demonstrate that successful fishway passage requires periods of high activity. The resultant energetic expenditure may affect fitness, foraging behaviour and increase susceptibility to predation, compromising population sustainability. This study highlights the need to understand the physiological mechanisms underpinning fishway passage to improve future designs and interpretation of biological evaluations. PMID:25853245

Palmitic acid mediates hypothalamic insulin resistance by altering PKC-theta subcellular localization in rodents.

PubMed

Benoit, Stephen C; Kemp, Christopher J; Elias, Carol F; Abplanalp, William; Herman, James P; Migrenne, Stephanie; Lefevre, Anne-Laure; Cruciani-Guglielmacci, Céline; Magnan, Christophe; Yu, Fang; Niswender, Kevin; Irani, Boman G; Holland, William L; Clegg, Deborah J

2009-09-01

Insulin signaling can be modulated by several isoforms of PKC in peripheral tissues. Here, we assessed whether one specific isoform, PKC-theta, was expressed in critical CNS regions that regulate energy balance and whether it mediated the deleterious effects of diets high in fat, specifically palmitic acid, on hypothalamic insulin activity in rats and mice. Using a combination of in situ hybridization and immunohistochemistry, we found that PKC-theta was expressed in discrete neuronal populations of the arcuate nucleus, specifically the neuropeptide Y/agouti-related protein neurons and the dorsal medial nucleus in the hypothalamus. CNS exposure to palmitic acid via direct infusion or by oral gavage increased the localization of PKC-theta to cell membranes in the hypothalamus, which was associated with impaired hypothalamic insulin and leptin signaling. This finding was specific for palmitic acid, as the monounsaturated fatty acid, oleic acid, neither increased membrane localization of PKC-theta nor induced insulin resistance. Finally, arcuate-specific knockdown of PKC-theta attenuated diet-induced obesity and improved insulin signaling. These results suggest that many of the deleterious effects of high-fat diets, specifically those enriched with palmitic acid, are CNS mediated via PKC-theta activation, resulting in reduced insulin activity.

Expression of single-chain Fv gene specific for gamma-seminoprotein by RTS and its biological activity identification.

PubMed

Han, Yuedong; Haun, Yi; Deng, Jinlan; Gao, Feng; Pan, Bifeng; Cui, Daxiang

2006-01-01

Fabricating a single-chain variable fragment specific for human seminoprotein is very important in antibody-directed enzyme prodrug therapy and NMR imaging for prostate cancer. Here a single-chain Fv specific for gamma-seminoprotein was expressed by RTS. Its activity and the efficiency of entry into prostate cancer cells are investigated by immunoprecipitation and Western blotting and immunofluorescent staining, as well as entry of conjugated magnetic beads into cells. Results showed that ScFv peptides specific for gamma-seminoprotein were successfully prepared, which can bind with the prostate cells specifically and can bring magnetic beads into prostate cancer cells within 15 min, the amount of magnetic beads inside prostate cancer cells increased as the culture time prolonged. ScFv-conjugated magnetic beads did not enter into control cells. In conclusion, the ScFv peptide against human gamma-seminoprotein with biological activity was successfully fabricated, which can take magnetic beads to prostate cancer cells specifically and not to the control cells. This ScFv peptide against human gamma-seminoprotein should be useful in improving the detection and therapy of prostate cancer at early stages and NMR imaging.

No Effect of Commercial Cognitive Training on Brain Activity, Choice Behavior, or Cognitive Performance.

PubMed

Kable, Joseph W; Caulfield, M Kathleen; Falcone, Mary; McConnell, Mairead; Bernardo, Leah; Parthasarathi, Trishala; Cooper, Nicole; Ashare, Rebecca; Audrain-McGovern, Janet; Hornik, Robert; Diefenbach, Paul; Lee, Frank J; Lerman, Caryn

2017-08-02

Increased preference for immediate over delayed rewards and for risky over certain rewards has been associated with unhealthy behavioral choices. Motivated by evidence that enhanced cognitive control can shift choice behavior away from immediate and risky rewards, we tested whether training executive cognitive function could influence choice behavior and brain responses. In this randomized controlled trial, 128 young adults (71 male, 57 female) participated in 10 weeks of training with either a commercial web-based cognitive training program or web-based video games that do not specifically target executive function or adapt the level of difficulty throughout training. Pretraining and post-training, participants completed cognitive assessments and functional magnetic resonance imaging during performance of the following validated decision-making tasks: delay discounting (choices between smaller rewards now vs larger rewards in the future) and risk sensitivity (choices between larger riskier rewards vs smaller certain rewards). Contrary to our hypothesis, we found no evidence that cognitive training influences neural activity during decision-making; nor did we find effects of cognitive training on measures of delay discounting or risk sensitivity. Participants in the commercial training condition improved with practice on the specific tasks they performed during training, but participants in both conditions showed similar improvement on standardized cognitive measures over time. Moreover, the degree of improvement was comparable to that observed in individuals who were reassessed without any training whatsoever. Commercial adaptive cognitive training appears to have no benefits in healthy young adults above those of standard video games for measures of brain activity, choice behavior, or cognitive performance. SIGNIFICANCE STATEMENT Engagement of neural regions and circuits important in executive cognitive function can bias behavioral choices away from immediate rewards. Activity in these regions may be enhanced through adaptive cognitive training. Commercial brain training programs claim to improve a broad range of mental processes; however, evidence for transfer beyond trained tasks is mixed. We undertook the first randomized controlled trial of the effects of commercial adaptive cognitive training (Lumosity) on neural activity and decision-making in young adults ( N = 128) compared with an active control (playing on-line video games). We found no evidence for relative benefits of cognitive training with respect to changes in decision-making behavior or brain response, or for cognitive task performance beyond those specifically trained. Copyright © 2017 the authors 0270-6474/17/377390-13$15.00/0.

No Effect of Commercial Cognitive Training on Brain Activity, Choice Behavior, or Cognitive Performance

PubMed Central

Caulfield, M. Kathleen; McConnell, Mairead; Bernardo, Leah; Parthasarathi, Trishala; Cooper, Nicole; Ashare, Rebecca; Audrain-McGovern, Janet; Lee, Frank J.; Lerman, Caryn

2017-01-01

Increased preference for immediate over delayed rewards and for risky over certain rewards has been associated with unhealthy behavioral choices. Motivated by evidence that enhanced cognitive control can shift choice behavior away from immediate and risky rewards, we tested whether training executive cognitive function could influence choice behavior and brain responses. In this randomized controlled trial, 128 young adults (71 male, 57 female) participated in 10 weeks of training with either a commercial web-based cognitive training program or web-based video games that do not specifically target executive function or adapt the level of difficulty throughout training. Pretraining and post-training, participants completed cognitive assessments and functional magnetic resonance imaging during performance of the following validated decision-making tasks: delay discounting (choices between smaller rewards now vs larger rewards in the future) and risk sensitivity (choices between larger riskier rewards vs smaller certain rewards). Contrary to our hypothesis, we found no evidence that cognitive training influences neural activity during decision-making; nor did we find effects of cognitive training on measures of delay discounting or risk sensitivity. Participants in the commercial training condition improved with practice on the specific tasks they performed during training, but participants in both conditions showed similar improvement on standardized cognitive measures over time. Moreover, the degree of improvement was comparable to that observed in individuals who were reassessed without any training whatsoever. Commercial adaptive cognitive training appears to have no benefits in healthy young adults above those of standard video games for measures of brain activity, choice behavior, or cognitive performance. SIGNIFICANCE STATEMENT Engagement of neural regions and circuits important in executive cognitive function can bias behavioral choices away from immediate rewards. Activity in these regions may be enhanced through adaptive cognitive training. Commercial brain training programs claim to improve a broad range of mental processes; however, evidence for transfer beyond trained tasks is mixed. We undertook the first randomized controlled trial of the effects of commercial adaptive cognitive training (Lumosity) on neural activity and decision-making in young adults (N = 128) compared with an active control (playing on-line video games). We found no evidence for relative benefits of cognitive training with respect to changes in decision-making behavior or brain response, or for cognitive task performance beyond those specifically trained. PMID:28694338

The SIRT1 activator SRT1720 extends lifespan and improves health of mice fed a standard diet

PubMed Central

Mitchell, Sarah J.; Martin-Montalvo, Alejandro; Mercken, Evi M.; Palacios, Hector H.; Ward, Theresa M.; Abulwerdi, Gelareh; Minor, Robin K.; Vlasuk, George P.; Ellis, James L.; Sinclair, David A.; Dawson, John; Allison, David B.; Zhang, Yongqing; Becker, Kevin G.; Bernier, Michel; de Cabo, Rafael

2014-01-01

The prevention or delay of the onset of age-related diseases prolongs survival and improves quality of life while reducing the burden on the health care system. Activation of sirtuin 1 (SIRT1), an NAD+ deacetylase, improves metabolism and confers protection against physiological and cognitive disturbances in old age. SRT1720 is a specific SIRT1 activator that has health and lifespan benefits in adult mice fed a high-fat diet. We found extension in lifespan, delayed onset of age-related metabolic diseases, and improved general health in mice fed a standard diet after SRT1720 supplementation. Inhibition of pro-inflammatory gene expression both in the liver and muscle of SRT1720-treated animals was noted. SRT1720 lowered phosphorylation of NF-κB pathway regulators in vitro only when SIRT1 was functionally present. Combined with our previous work, the current study further supports the beneficial effects of SRT1720 on health across the lifespan in mice. PMID:24582957

The Relationship between Listening Proficiency and Speaking Improvement in Higher Education: Considerations in Assessing Speaking and Listening

ERIC Educational Resources Information Center

Astorga-Cabezas, Erickzon D.

2015-01-01

This study examines the outcomes of having recourse to listening skills as support to improve oral skills in English language teaching. In this context, data from 120 students at a specific higher education institution was analyzed; 60 of whom were provided with totally listening-focused instruction and activities, while a separate group of 60…

The Implementation of Action Research for the Improvement of Biology Teaching and Learning in Senior Secondary Schools in Nigeria

ERIC Educational Resources Information Center

Udeani, U. N.; Atagana, H. I.; Esiobu, G. O.

2016-01-01

The main objective of the study was to implement an action research strategy to improve the teaching and learning of biology in senior secondary schools in Nigeria. Specifically the following research questions were raised: (1) What are the levels of intellectual challenge included in the activities used for classroom and laboratory instructions?…

Vestibular stimulation, spatial hemineglect and dysphasia, selective effects.

PubMed

Vallar, G; Papagno, C; Rusconi, M L; Bisiach, E

1995-09-01

The selectivity of the effects of vestibular stimulation was investigated in a left brain-damaged patient suffering from right visuo-spatial hemineglect and severe dysplasia. Vestibular stimulation temporarily improved the former but not the latter disorder. These results support the view that this treatment improves hemineglect by a specific effect, running counter the rightward distortion of egocentric co-ordinates, rather than by a general hemispheric activation.

Vagus Nerve Stimulation: A Non-Invasive Treatment to Improve the Health of Gulf Veterans with Gulf War Illness

DTIC Science & Technology

2017-05-01

Gulf War Illness (GWI) is a condition occurring in some veterans who served in the 1990-91 Gulf War. To date there is no specific treatment for it. A...device (which does not stimulate the vagus nerve). We will also test to see if the active device improves migraine which commonly occurs with widespread pain in GWI.

Portable Body Temperature Conditioner

DTIC Science & Technology

2013-12-01

thermal manikin. This research will identify specific design improvements to be implemented in a reiterative process , ultimately leading to an...activity in hot environmental conditions. Studies have shown that lowering the patient’s core body temperature rapidly to 38oC improves complications and...further attempts to hire a second technician, during the past year (Year 2) UNSOM began the process of hiring a bio-heat transfer engineering expert to

Protein Engineering and Homologous Expression of Serratia marcescens Lipase for Efficient Synthesis of a Pharmaceutically Relevant Chiral Epoxyester.

PubMed

Chen, Ke-Cai; Zheng, Ming-Min; Pan, Jiang; Li, Chun-Xiu; Xu, Jian-He

2017-10-01

The lipase isolated from Serratia marcescens (LipA) is a useful biocatalyst for kinetic resolution of a pharmaceutically relevant epoxyester, (±)-3-(4'-methoxyphenyl) glycidic acid methyl ester [(±)-MPGM], to afford optically pure (-)-MPGM, a key intermediate for the synthesis of diltiazem hydrochloride. Two mutants, LipA L315S and LipA S271F , were identified from the combinatorial saturation mutation library of 14 amino acid residues lining the substrate-binding pocket. LipA L315S , LipA S271F , and their combination LipA L315S/S271F showed 2.6-, 2.2-, and 4.6-fold improvements in their specific activities towards para-nitrophenyl butyrate (pNPB), respectively. Among these positive mutants, LipA S271F displayed a 3.5-fold higher specific activity towards the pharmaco substrate (±)-MPGM. Kinetic study showed that the improvement in catalytic efficiency of LipA S271F against (±)-MPGM was mainly resulted from the enhanced affinity between substrate and enzyme, as indicated by the decrease of K m . Furthermore, to address the insoluble expression issue in Escherichia coli, the homologous expression of LipA gene in S. marcescens was achieved by introducing it into an expression vector pUC18, resulting in ca. 20-fold higher lipase production. The significantly improved volumeric production and specific activity of S. marcescens lipase make it very attractive as a new-generation biocatalyst for more efficient and economical manufacturing of (-)-MPGM.

Sports Activity after Low-contact-stress Total Knee Arthroplasty – A long term follow-up study

PubMed Central

Vielgut, Ines; Leitner, Lukas; Kastner, Norbert; Radl, Roman; Leithner, Andreas; Sadoghi, Patrick

2016-01-01

The purpose of this study was to provide comprehensive long-term data about sports activity levels in patients following total knee arthroplasty (TKA) and to determine the impact of pre-operative function, pain and specific performed sports on the results. 236 patients who have undergone TKA for severe osteoarthritis of the knee were asked to provide specific information regarding exercised types of sports before surgery and after at least 10 years following TKA. Pre- and postoperative function and pain were evaluated by the use of Tegner-, WOMAC- and VAS Score. After a mean of 14.9 years, a significant improvement regarding pain and function was observed. Pre-operative Tegner- and WOMAC scores revealed significant positive correlations with the post-operative Tegner-Score. Accordingly, a high percentage of patients (70.9%) stayed actively involved in sports. Nevertheless, the number of performing patients has decreased according to the sports impact. 71.3% continued practising low-impact-, 43.7% intermediate-impact sports whereas only 16.4% kept performing high impact sports. We conclude that TKA is highly effective in long-time pain reduction as well as improvement of function. Additionally, we found considerable sports activities preserved in the investigated series. However, sports activities in particular, seem to decrease according to the impact of sports. PMID:27090945

Structural studies of the protein endostatin in fusion with BAX BH3 death domain, a hybrid that presents enhanced antitumoral activity.

PubMed

Chura-Chambi, Rosa Maria; Arcuri, Helen Andrade; Lino, Felipe; Versati, Natan; Palma, Mario Sergio; Favaro, Denize C; Morganti, Ligia

2017-05-01

Endostatin (ES) is an antiangiogenic protein that exhibits antitumor activity in animal models. However, the activity observed in animals was not observed in human clinical trials. ES-BAX is a fusion protein composed of two functional domains: ES, which presents specificity and is internalized by activated endothelial cells and the proapoptotic BH3 domain of the protein BAX, a peptide inductor of cellular death when internalized. We have previously shown (Chura-Chambi et al., Cell Death Dis, 5, e1371, 2014) that ES-BAX presents improved antitumor activity in relation to wild-type ES. Secondary and tertiary structures of ES-BAX are similar to ES, as indicated by homology-modeling studies and molecular dynamics simulations. Tryptophan intrinsic fluorescence and circular dichroism spectroscopy corroborate these data. 15 N HSQC NMR indicates that ES-BAX is structured, but some ES residues have suffered chemical shift perturbations, suggesting that the BH3 peptide interacts with some parts of the ES protein. ES and ES-BAX present similar stability to thermal denaturation. The production of stable hybrid proteins can be a new approach to the development of therapeutic agents presenting specificity for tumoral endothelium and improved antitumor effect. © 2016 International Union of Biochemistry and Molecular Biology, Inc.

Sports Activity after Low-contact-stress Total Knee Arthroplasty - A long term follow-up study.

PubMed

Vielgut, Ines; Leitner, Lukas; Kastner, Norbert; Radl, Roman; Leithner, Andreas; Sadoghi, Patrick

2016-04-19

The purpose of this study was to provide comprehensive long-term data about sports activity levels in patients following total knee arthroplasty (TKA) and to determine the impact of pre-operative function, pain and specific performed sports on the results. 236 patients who have undergone TKA for severe osteoarthritis of the knee were asked to provide specific information regarding exercised types of sports before surgery and after at least 10 years following TKA. Pre- and postoperative function and pain were evaluated by the use of Tegner-, WOMAC- and VAS Score. After a mean of 14.9 years, a significant improvement regarding pain and function was observed. Pre-operative Tegner- and WOMAC scores revealed significant positive correlations with the post-operative Tegner-Score. Accordingly, a high percentage of patients (70.9%) stayed actively involved in sports. Nevertheless, the number of performing patients has decreased according to the sports impact. 71.3% continued practising low-impact-, 43.7% intermediate-impact sports whereas only 16.4% kept performing high impact sports. We conclude that TKA is highly effective in long-time pain reduction as well as improvement of function. Additionally, we found considerable sports activities preserved in the investigated series. However, sports activities in particular, seem to decrease according to the impact of sports.

Visual Contrast Sensitivity Improvement by Right Frontal High-Beta Activity Is Mediated by Contrast Gain Mechanisms and Influenced by Fronto-Parietal White Matter Microstructure

PubMed Central

Quentin, Romain; Elkin Frankston, Seth; Vernet, Marine; Toba, Monica N.; Bartolomeo, Paolo; Chanes, Lorena; Valero-Cabré, Antoni

2016-01-01

Behavioral and electrophysiological studies in humans and non-human primates have correlated frontal high-beta activity with the orienting of endogenous attention and shown the ability of the latter function to modulate visual performance. We here combined rhythmic transcranial magnetic stimulation (TMS) and diffusion imaging to study the relation between frontal oscillatory activity and visual performance, and we associated these phenomena to a specific set of white matter pathways that in humans subtend attentional processes. High-beta rhythmic activity on the right frontal eye field (FEF) was induced with TMS and its causal effects on a contrast sensitivity function were recorded to explore its ability to improve visual detection performance across different stimulus contrast levels. Our results show that frequency-specific activity patterns engaged in the right FEF have the ability to induce a leftward shift of the psychometric function. This increase in visual performance across different levels of stimulus contrast is likely mediated by a contrast gain mechanism. Interestingly, microstructural measures of white matter connectivity suggest a strong implication of right fronto-parietal connectivity linking the FEF and the intraparietal sulcus in propagating high-beta rhythmic signals across brain networks and subtending top-down frontal influences on visual performance. PMID:25899709

Paving the Way for Speech: Voice-Training-Induced Plasticity in Chronic Aphasia and Apraxia of Speech—Three Single Cases

PubMed Central

Jungblut, Monika; Huber, Walter; Mais, Christiane

2014-01-01

Difficulties with temporal coordination or sequencing of speech movements are frequently reported in aphasia patients with concomitant apraxia of speech (AOS). Our major objective was to investigate the effects of specific rhythmic-melodic voice training on brain activation of those patients. Three patients with severe chronic nonfluent aphasia and AOS were included in this study. Before and after therapy, patients underwent the same fMRI procedure as 30 healthy control subjects in our prestudy, which investigated the neural substrates of sung vowel changes in untrained rhythm sequences. A main finding was that post-minus pretreatment imaging data yielded significant perilesional activations in all patients for example, in the left superior temporal gyrus, whereas the reverse subtraction revealed either no significant activation or right hemisphere activation. Likewise, pre- and posttreatment assessments of patients' vocal rhythm production, language, and speech motor performance yielded significant improvements for all patients. Our results suggest that changes in brain activation due to the applied training might indicate specific processes of reorganization, for example, improved temporal sequencing of sublexical speech components. In this context, a training that focuses on rhythmic singing with differently demanding complexity levels as concerns motor and cognitive capabilities seems to support paving the way for speech. PMID:24977055

Disulfide-crosslinked nanomicelles confer cancer-specific drug delivery and improve efficacy of paclitaxel in bladder cancer

NASA Astrophysics Data System (ADS)

Pan, Amy; Zhang, Hongyong; Li, Yuanpei; Lin, Tzu-yin; Wang, Fuli; Lee, Joyce; Cheng, Mingshan; Dall'Era, Marc; Li, Tianhong; deVere White, Ralph; Pan, Chong-Xian; Lam, Kit S.

2016-10-01

Chemotherapy commonly used in the treatment of advanced bladder cancer is only moderately effective and associated with significant toxicity. There has been no appreciable improvement in overall survival over the last three decades. The goal of this project is to develop and characterize bladder cancer-specific nanometer-scale micelles loaded with the chemotherapeutic drug paclitaxel (PTX) and determine the anti-tumor activity and toxicity. Micelle-building-material telodendrimers were synthesized through the stepwise conjugation of eight cholic acid units at one terminus of polyethylene glycol (PEG) and a bladder cancer-specific targeting peptide named PLZ4 at the other terminus. To synthesize disulfide-crosslinked PLZ4 nanomicelles (DC-PNM), cysteine was introduced between the cholic acid and PEG. DC-PNM-PTX was synthesized through the evaporation method by loading PTX in the core. The loading capacity of PTX in DC-PNM was 25% (W/W). The loading efficiency was over 99%. DC-PNM-PTX was spherical with the median size of 25 nm. The stability of DC-PNM-PTX was determined in a solution containing sodium docecyl sulfate (SDS). It was stable in a SDS solution, but dissolved within 5 min after the addition of glutathione at the physiological intracellular concentration of 10 mM. In vivo targeting and anti-tumor activity were determined in immunodeficient mice carrying patient-derived bladder cancer xenografts (PDXs). After intravenous administration, DC-PNM specifically targeted the bladder cancer PDXs, but very little to the lung cancer xenografts in the same mice (p < 0.001). DC-PNM loaded with PTX overcame cisplatin resistance, and improved the median survival from 55 d with free PTX to 69.5 d (p = 0.03) of mice carrying PDXs. In conclusion, DC-PNM remained stable in the SDS solution, specifically targeted the bladder cancer xenografts in vivo, and improved the anti-cancer efficacy of PTX.

Improved sensitivity and specificity for resting state and task fMRI with multiband multi-echo EPI compared to multi-echo EPI at 7 T.

PubMed

Boyacioğlu, Rasim; Schulz, Jenni; Koopmans, Peter J; Barth, Markus; Norris, David G

2015-10-01

A multiband multi-echo (MBME) sequence is implemented and compared to a matched standard multi-echo (ME) protocol to investigate the potential improvement in sensitivity and spatial specificity at 7 T for resting state and task fMRI. ME acquisition is attractive because BOLD sensitivity is less affected by variation in T2*, and because of the potential for separating BOLD and non-BOLD signal components. MBME further reduces TR thus increasing the potential reduction in physiological noise. In this study we used FSL-FIX to clean ME and MBME resting state and task fMRI data (both 3.5mm isotropic). After noise correction, the detection of resting state networks improves with more non-artifactual independent components being observed. Additional activation clusters for task data are discovered for MBME data (increased sensitivity) whereas existing clusters become more localized for resting state (improved spatial specificity). The results obtained indicate that MBME is superior to ME at high field strengths. Copyright © 2015 Elsevier Inc. All rights reserved.

Outcomes From Pediatric Gastroenterology Maintenance of Certification Using Web-based Modules.

PubMed

Sheu, Josephine; Chun, Stanford; O'Day, Emily; Cheung, Sara; Cruz, Rusvelda; Lightdale, Jenifer R; Fishman, Douglas S; Bousvaros, Athos; Huang, Jeannie S

2017-05-01

Beginning in 2013, the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) sponsored and developed subspecialty field-specific quality improvement (QI) activities to provide Part 4 Maintenance of Certification (MOC) credit for ongoing certification of pediatric gastroenterologists by the American Board of Pediatrics. Each activity was a Web-based module that measured clinical practice data repeatedly over at least 3 months as participants implemented rapid cycle change. Here, we examine existing variations in clinical practice among participating pediatric gastroenterologists and determine whether completion of Web-based MOC activities improves patient care processes and outcomes. We performed a cross-sectional and prospective analysis of physician and parent-reported clinical practice data abstracted from Web-based MOC modules on the topics of upper endoscopy, colonoscopy, and informed consent collected from pediatric gastroenterologists from North America from 2013 to 2016. Among 134 participating pediatric gastroenterologists, 56% practitioners practiced at an academic institution and most (94%) were NASPGHAN members. Participating physicians reported data from 6300 procedures. At baseline, notable practice variation across measured activities was demonstrated. Much of the rapid cycle changes implemented by participants involved individual behaviors, rather than system/team-based improvement activities. Participants demonstrated significant improvements on most targeted process and quality care outcomes. Pediatric gastroenterologists and parents reported baseline practice variation, and improvement in care processes and outcomes measured during NASPGHAN-sponsored Web-based MOC QI activities. Subspecialty-oriented Web-based MOC QI activities can reveal targets for reducing unwarranted variation in clinical pediatric practice, and can effectively improve care and patient outcomes.

Affective mediators of a physical activity intervention for depression in multiple sclerosis.

PubMed

Kratz, Anna L; Ehde, Dawn M; Bombardier, Charles H

2014-02-01

Previous analyses showed that a telephone-based intervention to increase physical activity in individuals with multiple sclerosis (MS) and depression resulted in significantly improved depressive symptoms compared to a wait-list control group. The aim of this study was to test positive affect and negative affect as mediators of the effect of the physical activity counseling on depressive symptoms. Ninety-two adults with MS, who met diagnostic criteria for either major depression or dysthymia and who reported low levels of physical activity, were randomized 1:1 to a 12-week telephone-based motivational interviewing (MI) intervention to improve physical activity (n = 44) or to a 12-week wait-list control group (n = 48). Self-reported positive and negative affect, physical activity, and depressive symptoms were gathered at baseline and postintervention. Path-analysis was used to test whether positive affect and negative affect mediated the positive effects of the intervention on depressive symptoms. Both positive and negative affect were significant mediators of the effects of the intervention on depressive symptoms; however, only positive affect mediated the association between changes in physical activity and improved depressive symptoms. Findings support physical activity and positive affect as key mediators of the MI treatment effect on improved mood. Decreases in negative affect were also evident in the treatment group, but were not related to improved physical activity. Findings may suggest the use of exercise-based interventions in conjunction with treatments that specifically target negative affective mechanisms for depression. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Adaptive Activation of a Stress Response Pathway Improves Learning and Memory Through Gs and β-Arrestin-1-Regulated Lactate Metabolism.

PubMed

Dong, Jun-Hong; Wang, Yi-Jing; Cui, Min; Wang, Xiao-Jing; Zheng, Wen-Shuai; Ma, Ming-Liang; Yang, Fan; He, Dong-Fang; Hu, Qiao-Xia; Zhang, Dao-Lai; Ning, Shang-Lei; Liu, Chun-Hua; Wang, Chuan; Wang, Yue; Li, Xiang-Yao; Yi, Fan; Lin, Amy; Kahsai, Alem W; Cahill, Thomas Joseph; Chen, Zhe-Yu; Yu, Xiao; Sun, Jin-Peng

2017-04-15

Stress is a conserved physiological response in mammals. Whereas moderate stress strengthens memory to improve reactions to previously experienced difficult situations, too much stress is harmful. We used specific β-adrenergic agonists, as well as β 2 -adrenergic receptor (β2AR) and arrestin knockout models, to study the effects of adaptive β2AR activation on cognitive function using Morris water maze and object recognition experiments. We used molecular and cell biological approaches to elucidate the signaling subnetworks. We observed that the duration of the adaptive β2AR activation determines its consequences on learning and memory. Short-term formoterol treatment, for 3 to 5 days, improved cognitive function; however, prolonged β2AR activation, for more than 6 days, produced harmful effects. We identified the activation of several signaling networks downstream of β2AR, as well as an essential role for arrestin and lactate metabolism in promoting cognitive ability. Whereas Gs-protein kinase A-cyclic adenosine monophosphate response element binding protein signaling modulated monocarboxylate transporter 1 expression, β-arrestin-1 controlled expression levels of monocarboxylate transporter 4 and lactate dehydrogenase A through the formation of a β-arrestin-1/phospho-mitogen-activated protein kinase/hypoxia-inducible factor-1α ternary complex to upregulate lactate metabolism in astrocyte-derived U251 cells. Conversely, long-term treatment with formoterol led to the desensitization of β2ARs, which was responsible for its decreased beneficial effects. Our results not only revealed that β-arrestin-1 regulated lactate metabolism to contribute to β2AR functions in improved memory formation, but also indicated that the appropriate management of one specific stress pathway, such as through the clinical drug formoterol, may exert beneficial effects on cognitive abilities. Copyright © 2016 Society of Biological Psychiatry. All rights reserved.

Improved Activity of a Thermophilic Cellulase, Cel5A, from Thermotoga maritima on Ionic Liquid Pretreated Switchgrass

PubMed Central

Chen, Zhiwei; Pereira, Jose H.; Liu, Hanbin; Tran, Huu M.; Hsu, Nathan S. Y.; Dibble, Dean; Singh, Seema; Adams, Paul D.; Sapra, Rajat; Hadi, Masood Z.; Simmons, Blake A.; Sale, Kenneth L.

2013-01-01

Ionic liquid pretreatment of biomass has been shown to greatly reduce the recalcitrance of lignocellulosic biomass, resulting in improved sugar yields after enzymatic saccharification. However, even under these improved saccharification conditions the cost of enzymes still represents a significant proportion of the total cost of producing sugars and ultimately fuels from lignocellulosic biomass. Much of the high cost of enzymes is due to the low catalytic efficiency and stability of lignocellulolytic enzymes, especially cellulases, under conditions that include high temperatures and the presence of residual pretreatment chemicals, such as acids, organic solvents, bases, or ionic liquids. Improving the efficiency of the saccharification process on ionic liquid pretreated biomass will facilitate reduced enzyme loading and cost. Thermophilic cellulases have been shown to be stable and active in ionic liquids but their activity is typically at lower levels. Cel5A_Tma, a thermophilic endoglucanase from Thermotoga maritima, is highly active on cellulosic substrates and is stable in ionic liquid environments. Here, our motivation was to engineer mutants of Cel5A_Tma with higher activity on 1-ethyl-3-methylimidazolium acetate ([C2mim][OAc]) pretreated biomass. We developed a robotic platform to screen a random mutagenesis library of Cel5A_Tma. Twelve mutants with 25–42% improvement in specific activity on carboxymethyl cellulose and up to 30% improvement on ionic-liquid pretreated switchgrass were successfully isolated and characterized from a library of twenty thousand variants. Interestingly, most of the mutations in the improved variants are located distally to the active site on the protein surface and are not directly involved with substrate binding. PMID:24244549

Improved activity of a thermophilic cellulase, Cel5A, from Thermotoga maritima on ionic liquid pretreated switchgrass.

PubMed

Chen, Zhiwei; Pereira, Jose H; Liu, Hanbin; Tran, Huu M; Hsu, Nathan S Y; Dibble, Dean; Singh, Seema; Adams, Paul D; Sapra, Rajat; Hadi, Masood Z; Simmons, Blake A; Sale, Kenneth L

2013-01-01

Ionic liquid pretreatment of biomass has been shown to greatly reduce the recalcitrance of lignocellulosic biomass, resulting in improved sugar yields after enzymatic saccharification. However, even under these improved saccharification conditions the cost of enzymes still represents a significant proportion of the total cost of producing sugars and ultimately fuels from lignocellulosic biomass. Much of the high cost of enzymes is due to the low catalytic efficiency and stability of lignocellulolytic enzymes, especially cellulases, under conditions that include high temperatures and the presence of residual pretreatment chemicals, such as acids, organic solvents, bases, or ionic liquids. Improving the efficiency of the saccharification process on ionic liquid pretreated biomass will facilitate reduced enzyme loading and cost. Thermophilic cellulases have been shown to be stable and active in ionic liquids but their activity is typically at lower levels. Cel5A_Tma, a thermophilic endoglucanase from Thermotoga maritima, is highly active on cellulosic substrates and is stable in ionic liquid environments. Here, our motivation was to engineer mutants of Cel5A_Tma with higher activity on 1-ethyl-3-methylimidazolium acetate ([C2mim][OAc]) pretreated biomass. We developed a robotic platform to screen a random mutagenesis library of Cel5A_Tma. Twelve mutants with 25-42% improvement in specific activity on carboxymethyl cellulose and up to 30% improvement on ionic-liquid pretreated switchgrass were successfully isolated and characterized from a library of twenty thousand variants. Interestingly, most of the mutations in the improved variants are located distally to the active site on the protein surface and are not directly involved with substrate binding.

Engineering NK Cells Modified With an EGFRvIII-specific Chimeric Antigen Receptor to Overexpress CXCR4 Improves Immunotherapy of CXCL12/SDF-1α-secreting Glioblastoma.

PubMed

Müller, Nadja; Michen, Susanne; Tietze, Stefanie; Töpfer, Katrin; Schulte, Alexander; Lamszus, Katrin; Schmitz, Marc; Schackert, Gabriele; Pastan, Ira; Temme, Achim

2015-06-01

Natural killer (NK) cells are promising effector cells for adjuvant immunotherapy of cancer. So far, several preclinical studies have shown the feasibility of gene-engineered NK cells, which upon expression of chimeric antigen receptors (CARs) are redirected to otherwise NK cell-resistant tumors. Yet, we reasoned that the efficiency of an immunotherapy using CAR-modified NK cells critically relies on efficient migration to the tumor site and might be improved by the engraftment of a receptor specific for a chemokine released by the tumor. On the basis of the DNAX-activation protein 12 (DAP12), a signaling adapter molecule involved in signal transduction of activating NK cell receptors, we constructed an epidermal growth factor variant III (EGFRvIII)-CAR, designated MR1.1-DAP12 which confers specific cytotoxicity of NK cell towards EGFRvIII glioblastoma cells in vitro and to established subcutaneous U87-MG tumor xenografts. So far, infusion of NK cells with expression of MR1.1-DAP12 caused a moderate but significantly delayed tumor growth and increased median survival time when compared with NK cells transduced with an ITAM-defective CAR. Notably, the further genetic engineering of these EGFRvIII-specific NK cells with the chemokine receptor CXCR4 conferred a specific chemotaxis to CXCL12/SDF-1α secreting U87-MG glioblastoma cells. Moreover, the administration of such NK cells resulted in complete tumor remission in a number of mice and a significantly increased survival when compared with the treatment of xenografts with NK cells expressing only the EGFRvIII-specific CAR or mock control. We conclude that chemokine receptor-engineered NK cells with concomitant expression of a tumor-specific CAR are a promising tool to improve adoptive tumor immunotherapy.

Preparatory neural activity predicts performance on a conflict task.

PubMed

Stern, Emily R; Wager, Tor D; Egner, Tobias; Hirsch, Joy; Mangels, Jennifer A

2007-10-24

Advance preparation has been shown to improve the efficiency of conflict resolution. Yet, with little empirical work directly linking preparatory neural activity to the performance benefits of advance cueing, it is not clear whether this relationship results from preparatory activation of task-specific networks, or from activity associated with general alerting processes. Here, fMRI data were acquired during a spatial Stroop task in which advance cues either informed subjects of the upcoming relevant feature of conflict stimuli (spatial or semantic) or were neutral. Informative cues decreased reaction time (RT) relative to neutral cues, and cues indicating that spatial information would be task-relevant elicited greater activity than neutral cues in multiple areas, including right anterior prefrontal and bilateral parietal cortex. Additionally, preparatory activation in bilateral parietal cortex and right dorsolateral prefrontal cortex predicted faster RT when subjects responded to spatial location. No regions were found to be specific to semantic cues at conventional thresholds, and lowering the threshold further revealed little overlap between activity associated with spatial and semantic cueing effects, thereby demonstrating a single dissociation between activations related to preparing a spatial versus semantic task-set. This relationship between preparatory activation of spatial processing networks and efficient conflict resolution suggests that advance information can benefit performance by leading to domain-specific biasing of task-relevant information.

Prebiotics and Inflammatory Bowel Disease.

PubMed

Rasmussen, Heather E; Hamaker, Bruce R

2017-12-01

Dietary fiber, specifically prebiotics, is the primary source of energy for the gut microbiota and thus has the potential to beneficially modify microbiota composition. Prebiotics have been used in both in vitro studies and with animal models of colitis with largely positive results. Human studies are few and have been conducted with only a few select prebiotics, primarily fructan-containing fibers. Although disease activity and inflammatory markers have improved, more needs to be learned about the specific prebiotic compounds and how they can be used to best improve the gut microbiota to counter changes induced by inflammatory bowel disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Effect of anti-TNF and conventional synthetic disease-modifying anti-rheumatic drug treatment on work disability and clinical outcome in a multicentre observational cohort study of psoriatic arthritis.

PubMed

Tillett, William; Shaddick, Gavin; Jobling, Amelia; Askari, Ayman; Cooper, Annie; Creamer, Paul; Clunie, Gavin; Helliwell, Philip S; James, Jana; Kay, Lesley; Korendowych, Eleanor; Lane, Suzanne; Packham, Jonathon; Shaban, Ragai; Thomas, Matthew L; Williamson, Lyn; McHugh, Neil

2017-04-01

To determine the effect of medical treatment on work disability in patients with active PsA in a real-world setting. Four hundred patients with active PsA commencing or switching to anti-TNF or conventional synthetic DMARD (csDMARD) were recruited to a multicentre UK prospective observational cohort study. Work disability was measured using the work productivity and activity-specific health problem instrument and peripheral joint activity was measured with the disease activity in PsA composite measure. Four hundred patients were recruited, of whom 229 (57.25%) were working (of any age). Sixty-two patients of working age (24%) were unemployed. At 6 months there was a 10% improvement in presenteeism ( P = 0.007) and a 15% improvement in work productivity ( P = 0.001) among working patients commenced on csDMARDs ( n = 164) vs a larger and more rapid 30% improvement in presenteeism ( P < 0.001) and 40% improvement in work productivity ( P < 0.001) among those commenced on anti-TNF therapy ( n = 65). Clinical response was poor among patients commenced on a csDMARD ( n = 272), with an 8.4 point improvement in disease activity in PsA ( P < 0.001) vs those commenced on anti-TNF therapy ( n = 121), who had a 36.8 point improvement ( P < 0.001). We report significant and clinically meaningful improvements in both work disability and clinical outcomes after commencement of anti-TNF therapy in a real-world setting. Improvements in all outcomes among those commencing csDMARDs were slower and of a smaller magnitude. © The Author 2016. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com

Videogame training strategy-induced change in brain function during a complex visuomotor task.

PubMed

Lee, Hyunkyu; Voss, Michelle W; Prakash, Ruchika Shaurya; Boot, Walter R; Vo, Loan T K; Basak, Chandramallika; Vanpatter, Matt; Gratton, Gabriele; Fabiani, Monica; Kramer, Arthur F

2012-07-01

Although changes in brain function induced by cognitive training have been examined, functional plasticity associated with specific training strategies is still relatively unexplored. In this study, we examined changes in brain function during a complex visuomotor task following training using the Space Fortress video game. To assess brain function, participants completed functional magnetic resonance imaging (fMRI) before and after 30 h of training with one of two training regimens: Hybrid Variable-Priority Training (HVT), with a focus on improving specific skills and managing task priority, or Full Emphasis Training (FET), in which participants simply practiced the game to obtain the highest overall score. Control participants received only 6 h of FET. Compared to FET, HVT learners reached higher performance on the game and showed less brain activation in areas related to visuo-spatial attention and goal-directed movement after training. Compared to the control group, HVT exhibited less brain activation in right dorsolateral prefrontal cortex (DLPFC), coupled with greater performance improvement. Region-of-interest analysis revealed that the reduction in brain activation was correlated with improved performance on the task. This study sheds light on the neurobiological mechanisms of improved learning from directed training (HVT) over non-directed training (FET), which is related to visuo-spatial attention and goal-directed motor planning, while separating the practice-based benefit, which is related to executive control and rule management. Copyright © 2012 Elsevier B.V. All rights reserved.

Mutants of Cre recombinase with improved accuracy

PubMed Central

Eroshenko, Nikolai; Church, George M.

2013-01-01

Despite rapid advances in genome engineering technologies, inserting genes into precise locations in the human genome remains an outstanding problem. It has been suggested that site-specific recombinases can be adapted towards use as transgene delivery vectors. The specificity of recombinases can be altered either with directed evolution or via fusions to modular DNA-binding domains. Unfortunately, both wildtype and altered variants often have detectable activities at off-target sites. Here we use bacterial selections to identify mutations in the dimerization surface of Cre recombinase (R32V, R32M, and 303GVSdup) that improve the accuracy of recombination. The mutants are functional in bacteria, in human cells, and in vitro (except for 303GVSdup, which we did not purify), and have improved selectivity against both model off-target sites and the entire E. coli genome. We propose that destabilizing binding cooperativity may be a general strategy for improving the accuracy of dimeric DNA-binding proteins. PMID:24056590

Configurations of a two-tiered amplified gene expression system in adenoviral vectors designed to improve the specificity of in vivo prostate cancer imaging

PubMed Central

Sato, M; Figueiredo, ML; Burton, JB; Johnson, M; Chen, M; Powell, R; Gambhir, SS; Carey, M; Wu, L

2009-01-01

Effective treatment for recurrent, disseminated prostate cancer is notably limited. We have developed adenoviral vectors with a prostate-specific two-step transcriptional amplification (TSTA) system that would express therapeutic genes at a robust level to target metastatic disease. The TSTA system employs the prostate-specific antigen (PSA) promoter/enhancer to drive a potent synthetic activator, which in turn activates the expression of the therapeutic gene. In this study, we explored different configurations of this bipartite system and discovered that physical separation of the two TSTA components into E1 and E3 regions of adenovirus was able to enhance androgen regulation and cell-discriminatory expression. The TSTA vectors that express imaging reporter genes were assessed by noninvasive imaging technologies in animal models. The improved selectivity of the E1E3 configured vector was reflected in silenced ectopic expression in the lung. Significantly, the enhanced specificity of the E1E3 vector enabled the detection of lung metastasis of prostate cancer. An E1E3 TSTA vector that expresses the herpes simplex virus thymidine kinase gene can effectively direct positron emission tomography (PET) imaging of the tumor. The prostate-targeted gene delivery vectors with robust and cell-specific expression capability will advance the development of safe and effective imaging guided therapy for recurrent metastatic stages of prostate cancer. PMID:18305574

Asthma in pregnancy: management strategies.

PubMed

McCallister, Jennifer W

2013-01-01

Asthma is one of the most prevalent chronic medical conditions to complicate pregnancy. With approximately one-third of women experiencing a worsening of control during the course of their pregnancy, identifying those at greatest risk has the potential to improve maternal and fetal outcomes for a large number of pregnancies. Similarly, active management strategies that prioritize asthma control in this vulnerable population can have a far-reaching impact. Demographic characteristics and patient noncompliance place certain populations of pregnant women at increased risk of poor asthma control during pregnancy. In addition, undertreatment and disparities in care of acute exacerbations during pregnancy likely contribute. Targeted educational interventions and treatment algorithms using objective markers of disease activity have shown improved outcomes in asthma control. Active management strategies which focus on identifying patient-specific risk factors, patient and provider education, and targeted treatment interventions can improve asthma care for women during pregnancy.

Attention improves encoding of task-relevant features in the human visual cortex

PubMed Central

Jehee, Janneke F.M.; Brady, Devin K.; Tong, Frank

2011-01-01

When spatial attention is directed towards a particular stimulus, increased activity is commonly observed in corresponding locations of the visual cortex. Does this attentional increase in activity indicate improved processing of all features contained within the attended stimulus, or might spatial attention selectively enhance the features relevant to the observer’s task? We used fMRI decoding methods to measure the strength of orientation-selective activity patterns in the human visual cortex while subjects performed either an orientation or contrast discrimination task, involving one of two laterally presented gratings. Greater overall BOLD activation with spatial attention was observed in areas V1-V4 for both tasks. However, multivariate pattern analysis revealed that orientation-selective responses were enhanced by attention only when orientation was the task-relevant feature, and not when the grating’s contrast had to be attended. In a second experiment, observers discriminated the orientation or color of a specific lateral grating. Here, orientation-selective responses were enhanced in both tasks but color-selective responses were enhanced only when color was task-relevant. In both experiments, task-specific enhancement of feature-selective activity was not confined to the attended stimulus location, but instead spread to other locations in the visual field, suggesting the concurrent involvement of a global feature-based attentional mechanism. These results suggest that attention can be remarkably selective in its ability to enhance particular task-relevant features, and further reveal that increases in overall BOLD amplitude are not necessarily accompanied by improved processing of stimulus information. PMID:21632942

Attention improves encoding of task-relevant features in the human visual cortex.

PubMed

Jehee, Janneke F M; Brady, Devin K; Tong, Frank

2011-06-01

When spatial attention is directed toward a particular stimulus, increased activity is commonly observed in corresponding locations of the visual cortex. Does this attentional increase in activity indicate improved processing of all features contained within the attended stimulus, or might spatial attention selectively enhance the features relevant to the observer's task? We used fMRI decoding methods to measure the strength of orientation-selective activity patterns in the human visual cortex while subjects performed either an orientation or contrast discrimination task, involving one of two laterally presented gratings. Greater overall BOLD activation with spatial attention was observed in visual cortical areas V1-V4 for both tasks. However, multivariate pattern analysis revealed that orientation-selective responses were enhanced by attention only when orientation was the task-relevant feature and not when the contrast of the grating had to be attended. In a second experiment, observers discriminated the orientation or color of a specific lateral grating. Here, orientation-selective responses were enhanced in both tasks, but color-selective responses were enhanced only when color was task relevant. In both experiments, task-specific enhancement of feature-selective activity was not confined to the attended stimulus location but instead spread to other locations in the visual field, suggesting the concurrent involvement of a global feature-based attentional mechanism. These results suggest that attention can be remarkably selective in its ability to enhance particular task-relevant features and further reveal that increases in overall BOLD amplitude are not necessarily accompanied by improved processing of stimulus information.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Peck, T; Sparkman, D; Storch, N

''The LLNL Site-Specific Advanced Simulation and Computing (ASCI) Software Quality Engineering Recommended Practices VI.I'' document describes a set of recommended software quality engineering (SQE) practices for ASCI code projects at Lawrence Livermore National Laboratory (LLNL). In this context, SQE is defined as the process of building quality into software products by applying the appropriate guiding principles and management practices. Continual code improvement and ongoing process improvement are expected benefits. Certain practices are recommended, although projects may select the specific activities they wish to improve, and the appropriate time lines for such actions. Additionally, projects can rely on the guidance ofmore » this document when generating ASCI Verification and Validation (VSrV) deliverables. ASCI program managers will gather information about their software engineering practices and improvement. This information can be shared to leverage the best SQE practices among development organizations. It will further be used to ensure the currency and vitality of the recommended practices. This Overview is intended to provide basic information to the LLNL ASCI software management and development staff from the ''LLNL Site-Specific ASCI Software Quality Engineering Recommended Practices VI.I'' document. Additionally the Overview provides steps to using the ''LLNL Site-Specific ASCI Software Quality Engineering Recommended Practices VI.I'' document. For definitions of terminology and acronyms, refer to the Glossary and Acronyms sections in the ''LLNL Site-Specific ASCI Software Quality Engineering Recommended Practices VI.I''.« less

Deep Sequencing-guided Design of a High Affinity Dual Specificity Antibody to Target Two Angiogenic Factors in Neovascular Age-related Macular Degeneration* ♦

PubMed Central

Koenig, Patrick; Lee, Chingwei V.; Sanowar, Sarah; Wu, Ping; Stinson, Jeremy; Harris, Seth F.; Fuh, Germaine

2015-01-01

The development of dual targeting antibodies promises therapies with improved efficacy over mono-specific antibodies. Here, we engineered a Two-in-One VEGF/angiopoietin 2 antibody with dual action Fab (DAF) as a potential therapeutic for neovascular age-related macular degeneration. Crystal structures of the VEGF/angiopoietin 2 DAF in complex with its two antigens showed highly overlapping binding sites. To achieve sufficient affinity of the DAF to block both angiogenic factors, we turned to deep mutational scanning in the complementarity determining regions (CDRs). By mutating all three CDRs of each antibody chain simultaneously, we were able not only to identify affinity improving single mutations but also mutation pairs from different CDRs that synergistically improve both binding functions. Furthermore, insights into the cooperativity between mutations allowed us to identify fold-stabilizing mutations in the CDRs. The data obtained from deep mutational scanning reveal that the majority of the 52 CDR residues are utilized differently for the two antigen binding function and permit, for the first time, the engineering of several DAF variants with sub-nanomolar affinity against two structurally unrelated antigens. The improved variants show similar blocking activity of receptor binding as the high affinity mono-specific antibodies against these two proteins, demonstrating the feasibility of generating a dual specificity binding surface with comparable properties to individual high affinity mono-specific antibodies. PMID:26088137

Organ-specific SPECT activity calibration using 3D printed phantoms for molecular radiotherapy dosimetry.

PubMed

Robinson, Andrew P; Tipping, Jill; Cullen, David M; Hamilton, David; Brown, Richard; Flynn, Alex; Oldfield, Christopher; Page, Emma; Price, Emlyn; Smith, Andrew; Snee, Richard

2016-12-01

Patient-specific absorbed dose calculations for molecular radiotherapy require accurate activity quantification. This is commonly derived from Single-Photon Emission Computed Tomography (SPECT) imaging using a calibration factor relating detected counts to known activity in a phantom insert. A series of phantom inserts, based on the mathematical models underlying many clinical dosimetry calculations, have been produced using 3D printing techniques. SPECT/CT data for the phantom inserts has been used to calculate new organ-specific calibration factors for (99m) Tc and (177)Lu. The measured calibration factors are compared to predicted values from calculations using a Gaussian kernel. Measured SPECT calibration factors for 3D printed organs display a clear dependence on organ shape for (99m) Tc and (177)Lu. The observed variation in calibration factor is reproduced using Gaussian kernel-based calculation over two orders of magnitude change in insert volume for (99m) Tc and (177)Lu. These new organ-specific calibration factors show a 24, 11 and 8 % reduction in absorbed dose for the liver, spleen and kidneys, respectively. Non-spherical calibration factors from 3D printed phantom inserts can significantly improve the accuracy of whole organ activity quantification for molecular radiotherapy, providing a crucial step towards individualised activity quantification and patient-specific dosimetry. 3D printed inserts are found to provide a cost effective and efficient way for clinical centres to access more realistic phantom data.

A Transplant-Specific Quality Initiative-Introducing TransQIP: A Joint Effort of the ASTS and ACS.

PubMed

Parekh, J; Ko, C; Lappin, J; Greenstein, S; Hirose, R

2017-07-01

In an attempt to improve surgical quality in the field of transplantation, the American College of Surgeons (ACS) and American Society of Transplant Surgeons have initiated a national quality improvement program in transplantation. This transplant-specific quality improvement program, called TransQIP, has been built from the ground up by transplant surgeons and captures detailed information on donor and recipient factors as well as transplant-specific outcomes. It is built upon the existing ACS/National Surgical Quality Improvement Program infrastructure and is designed to capture 100% of liver and kidney transplants performed at participating sites. TransQIP has completed its alpha pilot and will embark upon its beta phase at approximately 30 centers in the spring of 2017. Going forward, we anticipate TransQIP will help satisfy Centers for Medicare and Medicaid Services requirements for a quality improvement program, surgeon requirements for maintenance of certification, and qualify as a clinical practice improvement activity under the Merit-Based Incentive Payment System. Most importantly, we believe TransQIP will provide insight into surgical outcomes in transplantation that will allow the field to provide better care to our patients. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

Mitochondrial pharmacology: electron transport chain bypass as strategies to treat mitochondrial dysfunction.

PubMed

Atamna, Hani; Mackey, Jeanette; Dhahbi, Joseph M

2012-01-01

Mitochondrial dysfunction (primary or secondary) is detrimental to intermediary metabolism. Therapeutic strategies to treat/prevent mitochondrial dysfunction could be valuable for managing metabolic and age-related disorders. Here, we review strategies proposed to treat mitochondrial impairment. We then concentrate on redox-active agents, with mild-redox potential, who shuttle electrons among specific cytosolic or mitochondrial redox-centers. We propose that specific redox agents with mild redox potential (-0.1 V; 0.1 V) improve mitochondrial function because they can readily donate or accept electrons in biological systems, thus they enhance metabolic activity and prevent reactive oxygen species (ROS) production. These agents are likely to lack toxic effects because they lack the risk of inhibiting electron transfer in redox centers. This is different from redox agents with strong negative (-0.4 V; -0.2 V) or positive (0.2 V; 0.4 V) redox potentials who alter the redox status of redox-centers (i.e., become permanently reduced or oxidized). This view has been demonstrated by testing the effect of several redox active agents on cellular senescence. Methylene blue (MB, redox potential ≅10 mV) appears to readily cycle between the oxidized and reduced forms using specific mitochondrial and cytosolic redox centers. MB is most effective in delaying cell senescence and enhancing mitochondrial function in vivo and in vitro. Mild-redox agents can alter the biochemical activity of specific mitochondrial components, which then in response alters the expression of nuclear and mitochondrial genes. We present the concept of mitochondrial electron-carrier bypass as a potential result of mild-redox agents, a method to prevent ROS production, improve mitochondrial function, and delay cellular aging. Thus, mild-redox agents may prevent/delay mitochondria-driven disorders. Copyright © 2012 International Union of Biochemistry and Molecular Biology, Inc.

Improved design of hammerhead ribozyme for selective digestion of target RNA through recognition of site-specific adenosine-to-inosine RNA editing

PubMed Central

Fukuda, Masatora; Kurihara, Kei; Yamaguchi, Shota; Oyama, Yui; Deshimaru, Masanobu

2014-01-01

Adenosine-to-inosine (A-to-I) RNA editing is an endogenous regulatory mechanism involved in various biological processes. Site-specific, editing-state–dependent degradation of target RNA may be a powerful tool both for analyzing the mechanism of RNA editing and for regulating biological processes. Previously, we designed an artificial hammerhead ribozyme (HHR) for selective, site-specific RNA cleavage dependent on the A-to-I RNA editing state. In the present work, we developed an improved strategy for constructing a trans-acting HHR that specifically cleaves target editing sites in the adenosine but not the inosine state. Specificity for unedited sites was achieved by utilizing a sequence encoding the intrinsic cleavage specificity of a natural HHR. We used in vitro selection methods in an HHR library to select for an extended HHR containing a tertiary stabilization motif that facilitates HHR folding into an active conformation. By using this method, we successfully constructed highly active HHRs with unedited-specific cleavage. Moreover, using HHR cleavage followed by direct sequencing, we demonstrated that this ribozyme could cleave serotonin 2C receptor (HTR2C) mRNA extracted from mouse brain, depending on the site-specific editing state. This unedited-specific cleavage also enabled us to analyze the effect of editing state at the E and C sites on editing at other sites by using direct sequencing for the simultaneous quantification of the editing ratio at multiple sites. Our approach has the potential to elucidate the mechanism underlying the interdependencies of different editing states in substrate RNA with multiple editing sites. PMID:24448449

Stringency of substrate specificity of Escherichia coli malate dehydrogenase.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Boernke, W. E.; Millard, C. S.; Stevens, P. W.

1995-09-10

Malate dehydrogenase and lactate dehydrogenase are members of the structurally and functionally homologous family of 2-ketoacid dehydrogenases. Both enzymes display high specificity for their respective keto substrates, oxaloacetate and pyruvate. Closer analysis of their specificity, however, reveals that the specificity of malate dehydrogenase is much stricter and less malleable than that of lactate dehydrogenase. Site-specific mutagenesis of the two enzymes in an attempt to reverse their specificity has met with contrary results. Conversion of a specific active-site glutamine to arginine in lactate dehydrogenase from Bacillus stearothermophilus generated an enzyme that displayed activity toward oxaloacetate equal to that of the nativemore » enzyme toward pyruvate (H. M. Wilks et al. (1988) Science 242, 1541-1544). We have constructed a series of mutants in the mobile, active site loop of the Escherichia coli malate dehydrogenase that incorporate the complementary change, conversion of arginine 81 to glutamine, to evaluate the role of charge distribution and conformational flexibility within this loop in defining the substrate specificity of these enzymes. Mutants incorporating the change R81Q all had reversed specificity, displaying much higher activity toward pyruvate than to the natural substrate, oxaloacetate. In contrast to the mutated lactate dehydrogenase, these reversed-specificity mutants were much less active than the native enzyme. Secondary mutations within the loop of the E. coli enzyme (A80N, A80P, A80P/M85E/D86T) had either no or only moderately beneficial effects on the activity of the mutant enzyme toward pyruvate. The mutation A80P, which can be expected to reduce the overall flexibility of the loop, modestly improved activity toward pyruvate. The possible physiological relevance of the stringent specificity of malate dehydrogenase was investigated. In normal strains of E. coli, fermentative metabolism was not affected by expression of the mutant malate dehydrogenase. However, when expressed in a strain of E. coli unable to ferment glucose, the mutant enzyme restored growth and produced lactic acid as the sole fermentation product.« less

Well-Being and the Social Environment of Work: A Systematic Review of Intervention Studies.

PubMed

Daniels, Kevin; Watson, David; Gedikli, Cigdem

2017-08-16

There is consistent evidence that a good social environment in the workplace is associated with employee well-being. However, there has been no specific review of interventions to improve well-being through improving social environments at work. We conducted a systematic review of such interventions, and also considered performance as an outcome. We found eight studies of interventions. Six studies were of interventions that were based on introducing shared social activities into workgroups. Six out of the six studies demonstrated improvements in well-being across the sample (five studies), or for an identifiable sub-group (one study). Four out of the five studies demonstrated improvements in social environments, and four out of the five studies demonstrated improvements in indicators of performance. Analysis of implementation factors indicated that the interventions based on shared activities require some external facilitation, favorable worker attitudes prior to the intervention, and several different components. We found two studies that focused on improving fairness perceptions in the workplace. There were no consistent effects of these interventions on well-being or performance. We conclude that there is some evidence that interventions that increase the frequency of shared activities between workers can improve worker well-being and performance. We offer suggestions for improving the evidence base.

Well-Being and the Social Environment of Work: A Systematic Review of Intervention Studies

PubMed Central

Gedikli, Cigdem

2017-01-01

There is consistent evidence that a good social environment in the workplace is associated with employee well-being. However, there has been no specific review of interventions to improve well-being through improving social environments at work. We conducted a systematic review of such interventions, and also considered performance as an outcome. We found eight studies of interventions. Six studies were of interventions that were based on introducing shared social activities into workgroups. Six out of the six studies demonstrated improvements in well-being across the sample (five studies), or for an identifiable sub-group (one study). Four out of the five studies demonstrated improvements in social environments, and four out of the five studies demonstrated improvements in indicators of performance. Analysis of implementation factors indicated that the interventions based on shared activities require some external facilitation, favorable worker attitudes prior to the intervention, and several different components. We found two studies that focused on improving fairness perceptions in the workplace. There were no consistent effects of these interventions on well-being or performance. We conclude that there is some evidence that interventions that increase the frequency of shared activities between workers can improve worker well-being and performance. We offer suggestions for improving the evidence base. PMID:28813009

Exercise is medicine for patients with major depressive disorders: but only if the “pill” is taken!

PubMed Central

Gerber, Markus; Holsboer-Trachsler, Edith; Pühse, Uwe; Brand, Serge

2016-01-01

Major depressive disorders (MDDs) are a widespread and burdensome mental illness associated with a high comorbidity with other conditions and a significantly reduced life expectancy compared to the general population. Therefore, targeted actions are needed to improve physical health in people with MDDs, in addition to ongoing efforts to enhance psychological well-being. Meanwhile, the positive effects of exercise training on the treatment of MDDs are well documented, while compelling evidence exists that exercise interventions can improve cardiorespiratory fitness in clinically meaningful ways. On the flipside, the long-term effects of exercise therapy are still not well documented, and recent studies suggest that initial improvements in MDDs dissipate if regular exercise participation is discontinued after the end of interventions. A recent survey among Swiss psychiatric hospitals further shows that all institutions provide some form of physical activity and exercise program. However, only a limited number of patients participate in these programs, mainly because participation is voluntary and no particular efforts are undertaken to engage patients with the lowest physical activity levels. We argue that more systematic efforts are needed to fully exploit the potential of physical activity and exercise programs in psychiatric care. We also emphasize that initiating and maintaining regular physical activity among psychiatric patients is a major challenge because specific dysfunctional cognitive–emotional processes might interfere with their capacity to self-regulate health-related behaviors. Specifically, we claim that behavioral skill training should be used to support patients with MDDs in overcoming barriers to initiating and maintaining physical activity. Moreover, we suggest that the assessment of physical activity and cardiorespiratory fitness should become routine in psychiatric practice. PMID:27540294

Effect of an eccentrically biased hamstring strengthening home program on knee flexor strength and the length-tension relationship.

PubMed

Orishimo, Karl F; McHugh, Malachy P

2015-03-01

The purposes of this study were to document relative activation intensities of the hamstrings and gluteus maximus during 4 eccentric hamstring strengthening exercises and to assess the effects of a short-term strengthening program comprised of these exercises on knee flexor strength and the length-tension relationship. Twelve healthy subjects participated in this study. Electromyographic (EMG) activities from the biceps femoris, semitendinosus, and gluteus maximus were recorded as subjects performed (a) standing hip extension with elastic resistance, (b) trunk flexion in single limb stance (diver), (c) standing split (glider), and (d) supine sliding bridge (slider). Baseline isometric knee flexor strength was measured at 90, 70, 50, and 30° of flexion at the knee with the subject seated and the hip flexed to 50° from horizontal. After completing the 4-week training program, strength tests were repeated. Repeated-measures analysis of variance were used to compare EMG activity between muscles and to assess angle-specific strength improvements. Hamstring activity exceeded gluteus maximus activity for resisted hip extension, glider, and slider exercises (p < 0.001) but not for the diver (p = 0.087). Hamstring activation was greatest during the slider and resisted hip extension and lowest during the glider and the diver. Knee flexor strength improved by 9.0% (p = 0.005) but was not angle specific (training by angle p = 0.874). The short-term home training program effectively targeted the hamstrings and resulted in strength gains that were similar at short and long muscle lengths. These data demonstrate that hamstring strength can be improved using eccentrically biased unilateral exercises without the use of weights or other equipments.

Supercapacitors from Activated Carbon Derived from Granatum.

PubMed

Wang, Qiannan; Yang, Lin; Wang, Zhao; Chen, Kexun; Zhang, Lipeng

2015-12-01

Granatum carbon (GC) as electrode materials for supercapacitors is prepared via the chemical activation with different activating agent such as ZnC2 and KOH with an intention to improve the surface area and their electrochemical performance. The structure and electrochemical properties of GC materials are characterized with N2 adsorption/desorption measurements, scanning electron microscope (SEM), cyclic voltammetry (CV), galvanostatic charge/discharge cycling and electrochemical impedance spectroscopy (EIS). The obtained results show that the specific surface area of the granatum-based activated carbons increased obviously from 573 m2 x g(-1) to 1341 m2 x g(-1) by ZnC2 activation and to 930 m2 x g(-1) by KOH treatment. Furthermore, GCZ also delivers specific capacitance of 195.1 Fx g(-1) at the current density of 0.1 A x g(-1) in 30 wt.% KOH aqueous electrolyte and low capacitance loss of 28.5% when the current density increased by 10 times.

Vernier perceptual learning transfers to completely untrained retinal locations after double training: A “piggybacking” effect

PubMed Central

Wang, Rui; Zhang, Jun-Yun; Klein, Stanley A.; Levi, Dennis M.; Yu, Cong

2014-01-01

Perceptual learning, a process in which training improves visual discrimination, is often specific to the trained retinal location, and this location specificity is frequently regarded as an indication of neural plasticity in the retinotopic visual cortex. However, our previous studies have shown that “double training” enables location-specific perceptual learning, such as Vernier learning, to completely transfer to a new location where an irrelevant task is practiced. Here we show that Vernier learning can be actuated by less location-specific orientation or motion-direction learning to transfer to completely untrained retinal locations. This “piggybacking” effect occurs even if both tasks are trained at the same retinal location. However, piggybacking does not occur when the Vernier task is paired with a more location-specific contrast-discrimination task. This previously unknown complexity challenges the current understanding of perceptual learning and its specificity/transfer. Orientation and motion-direction learning, but not contrast and Vernier learning, appears to activate a global process that allows learning transfer to untrained locations. Moreover, when paired with orientation or motion-direction learning, Vernier learning may be “piggybacked” by the activated global process to transfer to other untrained retinal locations. How this task-specific global activation process is achieved is as yet unknown. PMID:25398974

Hospital management training and improvement in managerial skills: Serbian experience.

PubMed

Supic, Zorica Terzic; Bjegovic, Vesna; Marinkovic, Jelena; Milicevic, Milena Santric; Vasic, Vladimir

2010-06-01

The purpose of this study was to analyze the improvement of managerial skills of hospitals' top managers after a specific management training programme, and to explore possible predictors and relations. The study was conducted during the years 2006 and 2007 with cohort of 107 managers from 20 Serbian general hospitals. The managers self-assessed the improvement in their managerial skills before and after the training programme. After the training programme, all managers' skills had improved. The biggest improvement was in the following skills: organizing daily activities, motivating and guiding others, supervising the work of others, group discussion, and situation analysis. The least improved were: applying creative techniques, working well with peers, professional self-development, written communication, and operational planning. Identified predictors of improvement were: shorter years of managerial experience, type of manager, type of profession, and recognizing the importance of the managerial skills in oral communication, evidence-based decision making, and supervising the work of others. Specific training programme related to strategic management can increase managerial competencies, which are an important source of competitive advantage for organizations. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

Built environment interventions aimed at improving physical activity levels in rural Ontario health units: a descriptive qualitative study.

PubMed

Coghill, Cara-Lee; Valaitis, Ruta K; Eyles, John D

2015-05-03

Few studies to date have explored the relationship between the built environment and physical activity specifically in rural settings. The Ontario Public Health Standards policies mandate that health units in Ontario address the built environment; however, it is unclear how public health practitioners are integrating the built environment into public health interventions aimed at improving physical activity in chronic disease prevention programs. This descriptive qualitative study explored interventions that have or are being implemented which address the built environment specifically related to physical activity in rural Ontario health units, and the impact of these interventions. Data were collected through twelve in-depth semi-structured interviews with rural public health practitioners and managers representing 12 of 13 health units serving rural communities. Key themes were identified using qualitative content analysis. Themes that emerged regarding the types of interventions that health units are employing included: Engagement with policy work at a municipal level; building and working with community partners, committees and coalitions; gathering and providing evidence; developing and implementing programs; and social marketing and awareness raising. Evaluation of interventions to date has been limited. Public health interventions, and their evaluations, are complex. Health units who serve large rural populations in Ontario are engaging in numerous activities to address physical activity levels. There is a need to further evaluate the impact of these interventions on population health.

Developing a medication communication framework across continuums of care using the Circle of Care Modeling approach.

PubMed

Kitson, Nicole A; Price, Morgan; Lau, Francis Y; Showler, Grey

2013-10-17

Medication errors are a common type of preventable errors in health care causing unnecessary patient harm, hospitalization, and even fatality. Improving communication between providers and between providers and patients is a key aspect of decreasing medication errors and improving patient safety. Medication management requires extensive collaboration and communication across roles and care settings, which can reduce (or contribute to) medication-related errors. Medication management involves key recurrent activities (determine need, prescribe, dispense, administer, and monitor/evaluate) with information communicated within and between each. Despite its importance, there is a lack of conceptual models that explore medication communication specifically across roles and settings. This research seeks to address that gap. The Circle of Care Modeling (CCM) approach was used to build a model of medication communication activities across the circle of care. CCM positions the patient in the centre of his or her own healthcare system; providers and other roles are then modeled around the patient as a web of relationships. Recurrent medication communication activities were mapped to the medication management framework. The research occurred in three iterations, to test and revise the model: Iteration 1 consisted of a literature review and internal team discussion, Iteration 2 consisted of interviews, observation, and a discussion group at a Community Health Centre, and Iteration 3 consisted of interviews and a discussion group in the larger community. Each iteration provided further detail to the Circle of Care medication communication model. Specific medication communication activities were mapped along each communication pathway between roles and to the medication management framework. We could not map all medication communication activities to the medication management framework; we added Coordinate as a separate and distinct recurrent activity. We saw many examples of coordination activities, for instance, Medical Office Assistants acting as a liaison between pharmacists and family physicians to clarify prescription details. Through the use of CCM we were able to unearth tacitly held knowledge to expand our understanding of medication communication. Drawing out the coordination activities could be a missing piece for us to better understand how to streamline and improve multi-step communication processes with a goal of improving patient safety.

Developing a medication communication framework across continuums of care using the Circle of Care Modeling approach

PubMed Central

2013-01-01

Background Medication errors are a common type of preventable errors in health care causing unnecessary patient harm, hospitalization, and even fatality. Improving communication between providers and between providers and patients is a key aspect of decreasing medication errors and improving patient safety. Medication management requires extensive collaboration and communication across roles and care settings, which can reduce (or contribute to) medication-related errors. Medication management involves key recurrent activities (determine need, prescribe, dispense, administer, and monitor/evaluate) with information communicated within and between each. Despite its importance, there is a lack of conceptual models that explore medication communication specifically across roles and settings. This research seeks to address that gap. Methods The Circle of Care Modeling (CCM) approach was used to build a model of medication communication activities across the circle of care. CCM positions the patient in the centre of his or her own healthcare system; providers and other roles are then modeled around the patient as a web of relationships. Recurrent medication communication activities were mapped to the medication management framework. The research occurred in three iterations, to test and revise the model: Iteration 1 consisted of a literature review and internal team discussion, Iteration 2 consisted of interviews, observation, and a discussion group at a Community Health Centre, and Iteration 3 consisted of interviews and a discussion group in the larger community. Results Each iteration provided further detail to the Circle of Care medication communication model. Specific medication communication activities were mapped along each communication pathway between roles and to the medication management framework. We could not map all medication communication activities to the medication management framework; we added Coordinate as a separate and distinct recurrent activity. We saw many examples of coordination activities, for instance, Medical Office Assistants acting as a liaison between pharmacists and family physicians to clarify prescription details. Conclusions Through the use of CCM we were able to unearth tacitly held knowledge to expand our understanding of medication communication. Drawing out the coordination activities could be a missing piece for us to better understand how to streamline and improve multi-step communication processes with a goal of improving patient safety. PMID:24134454

New Developments in CRISPR Technology: Improvements in Specificity and Efficiency.

PubMed

Safari, Fatemeh; Farajnia, Safar; Ghasemi, Younes; Zarghami, Nosratollah

2017-01-01

RNA-guided endonuclease as a versatile genome editing technology opened new windows in various fields of biology. The simplicity of this revolutionary technique provides a promising future for its application in a broad range of approaches from functional annotation of genes to diseases, to genetic manipulation and gene therapy. Besides the site-specific activity of Cas9 endonuclease, the unintended cleavage known as off-target effect is still a major challenge for this genome editing technique. Various strategies have been developed to resolve this bottleneck including development of new softwares for designing optimized guide RNA (gRNA), engineering Cas9 enzyme, improvement in off-target detection assays, etc. Results: This review dedicated to discuss on methods that have been used for optimizing Cas9, specificity with the aim of improving this technology for therapeutic applications. In addition, the applications and novel breakthroughs in the field of CRISPR technology will be described. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Cost effective nuclear commercial grade dedication

DOE Office of Scientific and Technical Information (OSTI.GOV)

Maletz, J.J.; Marston, M.J.

1991-01-01

This paper describes a new computerized database method to create/edit/view specification technical data sheets (mini-specifications) for procurement of spare parts for nuclear facility maintenance and to develop information that could support possible future facility life extension efforts. This method may reduce cost when compared with current manual methods. The use of standardized technical data sheets (mini-specifications) for items of the same category improves efficiency. This method can be used for a variety of tasks, including: Nuclear safety-related procurement; Non-safety related procurement; Commercial grade item procurement/dedication; Evaluation of replacement items. This program will assist the nuclear facility in upgrading its procurementmore » activities consistent with the recent NUMARC Procurement Initiative. Proper utilization of the program will assist the user in assuring that the procured items are correct for the applications, provide data to assist in detecting fraudulent materials, minimize human error in withdrawing database information, improve data retrievability, improve traceability, and reduce long-term procurement costs.« less

Training and transfer effects of N-back training for brain-injured and healthy subjects.

PubMed

Lindeløv, Jonas Kristoffer; Dall, Jonas Olsen; Kristensen, Casper Daniel; Aagesen, Marie Holt; Olsen, Stine Almgren; Snuggerud, Therese Ruud; Sikorska, Anna

2016-10-01

Working memory impairments are prevalent among patients with acquired brain injury (ABI). Computerised training targeting working memory has been researched extensively using samples from healthy populations but this field remains isolated from similar research in ABI patients. We report the results of an actively controlled randomised controlled trial in which 17 patients and 18 healthy subjects completed training on an N-back task. The healthy group had superior improvements on both training tasks (SMD = 6.1 and 3.3) whereas the ABI group improved much less (SMD = 0.5 and 1.1). Neither group demonstrated transfer to untrained tasks. We conclude that computerised training facilitates improvement of specific skills rather than high-level cognition in healthy and ABI subjects alike. The acquisition of these specific skills seems to be impaired by brain injury. The most effective use of computer-based cognitive training may be to make the task resemble the targeted behaviour(s) closely in order to exploit the stimulus-specificity of learning.

Tobacco drought stress responses reveal new targets for Solanaceae crop improvement.

PubMed

Rabara, Roel C; Tripathi, Prateek; Reese, R Neil; Rushton, Deena L; Alexander, Danny; Timko, Michael P; Shen, Qingxi J; Rushton, Paul J

2015-06-30

The Solanaceae are an economically important family of plants that include tobacco (Nicotiana tabacum L.), tomato, and potato. Drought is a major cause of crop losses. We have identified major changes in physiology, metabolites, mRNA levels, and promoter activities during the tobacco response to drought. We have classified these as potential components of core responses that may be common to many plant species or responses that may be family/species-specific features of the drought stress response in tobacco or the Solanaceae. In tobacco the largest increase in any metabolite was a striking 70-fold increase in 4-hydroxy-2-oxoglutaric acid (KHG) in roots that appears to be tobacco/Solanaceae specific. KHG is poorly characterized in plants but is broken down to pyruvate and glyoxylate after the E. coli SOS response to facilitate the resumption of respiration. A similar process in tobacco would represent a mechanism to restart respiration upon water availability after drought. At the mRNA level, transcription factor gene induction by drought also showed both core and species/family specific responses. Many Group IX Subgroup 3 AP2/ERF transcription factors in tobacco appear to play roles in nicotine biosynthesis as a response to herbivory, whereas their counterparts in legume species appear to play roles in drought responses. We observed apparent Solanaceae-specific drought induction of several Group IId WRKY genes. One of these, NtWRKY69, showed ABA-independent drought stress-inducible promoter activity that moved into the leaf through the vascular tissue and then eventually into the surrounding leaf cells. We propose components of a core metabolic response to drought stress in plants and also show that some major responses to drought stress at the metabolome and transcriptome levels are family specific. We therefore propose that the observed family-specific changes in metabolism are regulated, at least in part, by family-specific changes in transcription factor activity. We also present a list of potential targets for the improvement of Solanaceae drought responses.

Challenges in performance of food safety management systems: a case of fish processing companies in Tanzania.

PubMed

Kussaga, Jamal B; Luning, Pieternel A; Tiisekwa, Bendantunguka P M; Jacxsens, Liesbeth

2014-04-01

This study provides insight for food safety (FS) performance in light of the current performance of core FS management system (FSMS) activities and context riskiness of these systems to identify the opportunities for improvement of the FSMS. A FSMS diagnostic instrument was applied to assess the performance levels of FSMS activities regarding context riskiness and FS performance in 14 fish processing companies in Tanzania. Two clusters (cluster I and II) with average FSMS (level 2) operating under moderate-risk context (score 2) were identified. Overall, cluster I had better (score 3) FS performance than cluster II (score 2 to 3). However, a majority of the fish companies need further improvement of their FSMS and reduction of context riskiness to assure good FS performance. The FSMS activity levels could be improved through hygienic design of equipment and facilities, strict raw material control, proper follow-up of critical control point analysis, developing specific sanitation procedures and company-specific sampling design and measuring plans, independent validation of preventive measures, and establishing comprehensive documentation and record-keeping systems. The risk level of the context could be reduced through automation of production processes (such as filleting, packaging, and sanitation) to restrict people's interference, recruitment of permanent high-skilled technological staff, and setting requirements on product use (storage and distribution conditions) on customers. However, such intervention measures for improvement could be taken in phases, starting with less expensive ones (such as sanitation procedures) that can be implemented in the short term to more expensive interventions (setting up assurance activities) to be adopted in the long term. These measures are essential for fish processing companies to move toward FSMS that are more effective.

Exercise enhances cognitive function and neurotrophin expression in the hippocampus accompanied by changes in epigenetic programming in senescence-accelerated mice.

PubMed

Maejima, Hiroshi; Kanemura, Naohiko; Kokubun, Takanori; Murata, Kenji; Takayanagi, Kiyomi

2018-02-05

Aerobic exercise is known to increase expression of neurotrophins, particularly brain-derived neurotrophic factor (BDNF), in the hippocampus and to improve cognitive function. Exercise exerts neuroprotective effects in the hippocampus by inducing epigenetic changes, which play crucial roles in aging and neurodegenerative diseases. Specifically, the activity levels of histone acetyltransferases (HATs) and histone deacetylases (HDACs) regulate histone acetylation and modulate gene transcription. The objective of the present study was to assess the interactive effects of exercise and aging on cognitive function, expression of neurotrophins (BDNF and neurotrophin-4) and their receptors (tyrosine receptor kinase B and p75), and epigenetic regulations, including the activity of HATs and HADCs in the hippocampus. We used the senescence-accelerated mouse (SAM) model, specifically 13-month-old SAM resistant 1(SAMR1) and SAM prone 1 (SAMP1) lines. Mice were distributed into four groups based on accelerated senescence and exercise status. Mice in the exercise groups exercised on a treadmill for approximately 60min a day, 5days a week. Aerobic exercise for 4 weeks improved cognitive function, accompanied by an increase in BDNF expression and a decrease in p75 transcription in both SAMR1 and SAMP1. In addition, the exercise regimen activated both HAT and HDAC in the hippocampus. Therefore, the present study reveals that despite accelerated senescence, long-term exercise improved cognitive function, upregulated the expression of BDNF, and downregulated p75, a receptor involved in apoptotic signaling. Furthermore, long-term exercise enhanced activity of both HAT and HDAC, which may contribute to the transcriptional regulation underlying the improvement of cognitive function. Copyright © 2017 Elsevier B.V. All rights reserved.

Improved Training Program for Fall Prevention of Warfighters with Lower Extremity Trauma

DTIC Science & Technology

2016-10-01

productive, active civilian life. The training program utilizes a microprocessor -controlled treadmill designed to deliver task- specific training...National Military Medical Center (WRNMMC), and Mayo. The fall prevention training program utilizes a microprocessor -controlled treadmill to deliver

Genetic engineering of microbial pesticides

Treesearch

Bruce C. Carlton

1985-01-01

Recent advances in genetics and molecular biology make possible the cloning and genetic manipulation of genes for insecticidal activities from natural insect pathogens. Using recombinant DNA methods and site-directed mutagenesis of specific gene regions, production of new and improved biorationals should be possible.

Membranes having aligned 1-D nanoparticles in a matrix layer for improved fluid separation

DOEpatents

Revanur, Ravindra; Lulevich, Valentin; Roh, Il Juhn; Klare, Jennifer E.; Kim, Sangil; Noy, Aleksandr; Bakajin, Olgica

2015-12-22

Membranes for fluid separation are disclosed. These membranes have a matrix layer sandwiched between an active layer and a porous support layer. The matrix layer includes 1-D nanoparticles that are vertically aligned in a porous polymer matrix, and which substantially extend through the matrix layer. The active layer provides species-specific transport, while the support layer provides mechanical support. A matrix layer of this type has favorable surface morphology for forming the active layer. Furthermore, the pores that form in the matrix layer tend to be smaller and more evenly distributed as a result of the presence of aligned 1-D nanoparticles. Improved performance of separation membranes of this type is attributed to these effects.

Behavior-Specific Influences for Physical Activity Among African American Women.

PubMed

Jackson, Hope; Yates, Bernice C; Blanchard, Shirley; Zimmerman, Lani M; Hudson, Diane; Pozehl, Bunny

2016-08-01

The purpose of this study was to describe physical activity (PA) behaviors and physical functioning of prehypertensive and Stage I hypertensive African American Women (AAW) and to examine the relationships between PA behavior, physical functioning, personal factors, and behavior-specific influences. Pender's Health Promotion Model was the conceptual framework for the study. A cross-sectional design and convenience sample were used. The PA domain where the greatest amount of time was spent was in work-related activity, followed by household, leisure time, and transportation activity. Personal factors most strongly correlated to lower PA were greater body mass index and waist circumference. AAW perceived moderate barriers to PA and minimal family and friend social support for PA. Future interventions need to focus on removing barriers to and improving social support for PA among AAW. © The Author(s) 2016.

Investigation of bypass fluid flow in an active magnetic regenerative liquefier

DOE PAGES

Holladay, Jamelyn; Teyber, Reed; Meinhardt, Kerry; ...

2018-05-19

Active magnetic regenerators (AMR) with second order magnetocaloric materials operating below the Curie temperature have a unique property where the magnetized specific heat is lower than the demagnetized specific heat. The associated thermal mass imbalance allows a fraction of heat transfer fluid in the cold heat exchanger to bypass the magnetized regenerator. This cold bypassed fluid can precool a process stream as it returns to the hot side, thereby increasing the efficiency of liquefaction and reducing the cost of liquid cryogens. In the present work, the net cooling power of an active magnetic regenerative liquefier is investigated as a functionmore » of the bypass flow fraction. In conclusion, experiments are performed at a fixed temperature span yielding a 30% improvement in net cooling power, affirming the potential of bypass flow in active magnetic regenerative liquefiers.« less

Investigation of bypass fluid flow in an active magnetic regenerative liquefier

DOE Office of Scientific and Technical Information (OSTI.GOV)

Holladay, Jamelyn; Teyber, Reed; Meinhardt, Kerry

Active magnetic regenerators (AMR) with second order magnetocaloric materials operating below the Curie temperature have a unique property where the magnetized specific heat is lower than the demagnetized specific heat. The associated thermal mass imbalance allows a fraction of heat transfer fluid in the cold heat exchanger to bypass the magnetized regenerator. This cold bypassed fluid can precool a process stream as it returns to the hot side, thereby increasing the efficiency of liquefaction and reducing the cost of liquid cryogens. In the present work, the net cooling power of an active magnetic regenerative liquefier is investigated as a functionmore » of the bypass flow fraction. Experiments are performed at a fixed temperature span yielding a 30% improvement in net cooling power, affirming the potential of bypass flow in active magnetic regenerative liquefiers.« less

Investigation of bypass fluid flow in an active magnetic regenerative liquefier

DOE Office of Scientific and Technical Information (OSTI.GOV)

Holladay, Jamelyn; Teyber, Reed; Meinhardt, Kerry

Active magnetic regenerators (AMR) with second order magnetocaloric materials operating below the Curie temperature have a unique property where the magnetized specific heat is lower than the demagnetized specific heat. The associated thermal mass imbalance allows a fraction of heat transfer fluid in the cold heat exchanger to bypass the magnetized regenerator. This cold bypassed fluid can precool a process stream as it returns to the hot side, thereby increasing the efficiency of liquefaction and reducing the cost of liquid cryogens. In the present work, the net cooling power of an active magnetic regenerative liquefier is investigated as a functionmore » of the bypass flow fraction. In conclusion, experiments are performed at a fixed temperature span yielding a 30% improvement in net cooling power, affirming the potential of bypass flow in active magnetic regenerative liquefiers.« less

Optimization of ultrasound-assisted extraction of pectinase enzyme from guava (Psidium guajava) peel: Enzyme recovery, specific activity, temperature, and storage stability.

PubMed

Amid, Mehrnoush; Murshid, Fara Syazana; Manap, Mohd Yazid; Islam Sarker, Zaidul

2016-01-01

This study aimed to investigate the effects of the ultrasound-assisted extraction conditions on the yield, specific activity, temperature, and storage stability of the pectinase enzyme from guava peel. The ultrasound variables studied were sonication time (10-30 min), ultrasound temperature (30-50 °C), pH (2.0-8.0), and solvent-to-sample ratio (2:1 mL/g to 6:1 mL/g). The main goal was to optimize the ultrasound-assisted extraction conditions to maximize the recovery of pectinase from guava peel with the most desirable enzyme-specific activity and stability. Under the optimum conditions, a high yield (96.2%), good specific activity (18.2 U/mg), temperature stability (88.3%), and storage stability (90.3%) of the extracted enzyme were achieved. The optimal conditions were 20 min sonication time, 40 °C temperature, at pH 5.0, using a 4:1 mL/g solvent-to-sample ratio. The study demonstrated that optimization of ultrasound-assisted process conditions for the enzyme extraction could improve the enzymatic characteristics and yield of the enzyme.

Rubisco activity and regulation as targets for crop improvement.

PubMed

Parry, Martin A J; Andralojc, P John; Scales, Joanna C; Salvucci, Michael E; Carmo-Silva, A Elizabete; Alonso, Hernan; Whitney, Spencer M

2013-01-01

Rubisco (ribulose-1,5-bisphosphate (RuBP) carboxylase/oxygenase) enables net carbon fixation through the carboxylation of RuBP. However, some characteristics of Rubisco make it surprisingly inefficient and compromise photosynthetic productivity. For example, Rubisco catalyses a wasteful reaction with oxygen that leads to the release of previously fixed CO(2) and NH(3) and the consumption of energy during photorespiration. Furthermore, Rubisco is slow and large amounts are needed to support adequate photosynthetic rates. Consequently, Rubisco has been studied intensively as a prime target for manipulations to 'supercharge' photosynthesis and improve both productivity and resource use efficiency. The catalytic properties of Rubiscos from diverse sources vary considerably, suggesting that changes in turnover rate, affinity, or specificity for CO(2) can be introduced to improve Rubisco performance in specific crops and environments. While attempts to manipulate plant Rubisco by nuclear transformation have had limited success, modifying its catalysis by targeted changes to its catalytic large subunit via chloroplast transformation have been much more successful. However, this technique is still in need of development for most major food crops including maize, wheat, and rice. Other bioengineering approaches for improving Rubisco performance include improving the activity of its ancillary protein, Rubisco activase, in addition to modulating the synthesis and degradation of Rubisco's inhibitory sugar phosphate ligands. As the rate-limiting step in carbon assimilation, even modest improvements in the overall performance of Rubisco pose a viable pathway for obtaining significant gains in plant yield, particularly under stressful environmental conditions.

Intralymphatic allergen-specific immunotherapy: an effective and safe alternative treatment route for pollen-induced allergic rhinitis.

PubMed

Hylander, Terese; Latif, Leith; Petersson-Westin, Ulla; Cardell, Lars Olaf

2013-02-01

Allergen-specific immunotherapy is the only causative treatment of IgE-mediated allergic disorders. The most common administration route is subcutaneous, which may necessitate more than 50 allergen injections during 3 to 5 years. Recent evidence suggests that direct intralymphatic injections could yield faster beneficial results with considerably lower allergen doses and markedly reduced numbers of injections. To evaluate the effects of intralymphatic allergen-specific immunotherapy in pollen-allergic patients. In an open pilot investigation followed by a double-blind, placebo-controlled study, patients with allergic rhinitis were treated with 3 intralymphatic inguinal injections of ALK Alutard (containing 1000 SQ-U birch pollen or grass pollen) or placebo (ALK diluent). Clinical pre- and posttreatment parameters were assessed, the inflammatory cell content in nasal lavage fluids estimated, and the activation pattern of peripheral T cells described. All patients tolerated the intralymphatic immunotherapy (ILIT) treatment well, and the injections did not elicit any severe adverse event. Patients receiving active treatment displayed an initial increase in allergen-specific IgE level and peripheral T-cell activation. A clinical improvement in nasal allergic symptoms upon challenge was recorded along with a decreased inflammatory response in the nose. In addition, these patients reported an improvement in their seasonal allergic disease. No such changes were seen in the placebo group. Although this study is based on a limited number of patients, ILIT with grass-pollen or birch-pollen extracts appears to reduce nasal allergic symptoms without causing any safety problems. Hence, ILIT might constitute a less time-consuming and more cost-effective alternative to conventional subcutaneous allergen-specific immunotherapy. Copyright © 2013 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

The path to cost transformation.

PubMed

Hill-Mischel, Jody; Morrissey, Walter W; Neese, Kimberly; Shoger, Timothy R

2016-06-01

A healthcare organization's efforts to strategically transform its cost structure in preparation for value-based payment invariably must begin with a systemwide assessment of cost and quality. Such an assessment should focus on three categories of performance improvement activities: margin improvement, business restructuring, and clinical transformation. A work-team approach is recommended, where teams with multidisciplinary representation assume responsibility for assessing specific areas (e.g., acute care enterprise, physician enterprise, business restructuring).

Restoring walking after spinal cord injury: operant conditioning of spinal reflexes can help.

PubMed

Thompson, Aiko K; Wolpaw, Jonathan R

2015-04-01

People with incomplete spinal cord injury (SCI) frequently suffer motor disabilities due to spasticity and poor muscle control, even after conventional therapy. Abnormal spinal reflex activity often contributes to these problems. Operant conditioning of spinal reflexes, which can target plasticity to specific reflex pathways, can enhance recovery. In rats in which a right lateral column lesion had weakened right stance and produced an asymmetrical gait, up-conditioning of the right soleus H-reflex, which increased muscle spindle afferent excitation of soleus, strengthened right stance and eliminated the asymmetry. In people with hyperreflexia due to incomplete SCI, down-conditioning of the soleus H-reflex improved walking speed and symmetry. Furthermore, modulation of electromyographic activity during walking improved bilaterally, indicating that a protocol that targets plasticity to a specific pathway can trigger widespread plasticity that improves recovery far beyond that attributable to the change in the targeted pathway. These improvements were apparent to people in their daily lives. They reported walking faster and farther, and noted less spasticity and better balance. Operant conditioning protocols could be developed to modify other spinal reflexes or corticospinal connections; and could be combined with other therapies to enhance recovery in people with SCI or other neuromuscular disorders. © The Author(s) 2014.

Severe progressive scoliosis in an adult female possibly secondary thoracic surgery in childhood treated with scoliosis specific Schroth physiotherapy: Case presentation.

PubMed

Lebel, Andrea; Lebel, Victoria Ashley

2016-01-01

Scoliosis is a complex three-dimensional (3D) spinal deformity. Acquired scoliosis in early childhood may progress into adulthood and pose an increased risk of health problems and reduction in quality of life. In Canada, patients with scoliosis are not referred for physiotherapeutic scoliosis-specific exercises (PSSE) despite the fact that Schroth physiotherapy, a scoliosis-specific 3D posture training and exercise program, can be effective in reducing pain and improving scoliosis curves, vital capacity, and overall quality of life in scoliosis patients. This case presentation shows that indeed adult curve progression can be stopped and even reversed with scoliosis specific Schroth physiotherapy (SSSPT) in an adult patient with scoliosis. This is a retrospective case presentation involving a 23-year-old female scoliosis patient who began an outpatient Schroth physiotherapy exercise program and was initially monitored monthly and then annually for improvement in measurements of angle of trunk rotation (ATR) and chest expansion and improvement in vital capacity measured with incentive spirometry. Photos were taken to document body image periodically throughout Schroth physiotherapy treatment. Additionally, the patient completed SRS-22 quality of life questionnaires every 2 years to evaluate daily function, pain, self-imagine, mental health, and scoliosis management satisfaction. Within one month of beginning SSSPT, the patient reported no more back pain and within 2 months, reported improved breathing. The patient also benefitted from improved chest expansion, reduced scoliosis curve angles (measured in Cobb degrees), increased vital capacity, decreased ATR, and higher SRS-22 scores. She became more active and resumed all athletic activity within 8 months of beginning Schroth physiotherapy. Adult scoliosis patients are not routinely referred for PSSE in Canada, even though Schroth physiotherapy, a form of PSSE, is shown to be effective in this case presentation. The patient in this case presentation was successfully treated with Schroth physiotherapy. Long-term comprehensive Schroth physiotherapy, to help correct and maintain proper posture in all aspects of daily living, should be part of scoliosis management for adult scoliosis patients in Canada to stop and reverse curve progression and to improve overall quality of life.

Homeopathy – what are the active ingredients? An exploratory study using the UK Medical Research Council's framework for the evaluation of complex interventions

PubMed Central

Thompson, Trevor DB; Weiss, Marjorie

2006-01-01

Background Research in homeopathy has traditionally addressed itself to defining the effectiveness of homeopathic potencies in comparison to placebo medication. There is now increasing awareness that the homeopathic consultation is in itself a therapeutic intervention working independently or synergistically with the prescribed remedy. Our objective was to identify and evalute potential "active ingredients" of the homeopathic approach as a whole, in a prospective formal case series, which draws on actual consultation data, and is based on the MRC framework for the evaluation of complex interventions. Methods Following on from a theoretical review of how homeopathic care might mediate its effects, 18 patients were prospectively recruited to a case series based at Bristol Homeopathic Hospital. Patients, who lived with one of three index conditions, were interviewed before and after a five visit "package of care". All consultations were recorded and transcribed verbatim. Additional data, including generic and condition-specific questionnaires, artwork and "significant other" reports were collected. Textual data was subject to thematic analysis and triangulated with other sources. Results We judged that around one third of patients had experienced a major improvement in their health over the study period, a third had some improvement and a third had no improvement. Putative active ingredients included the patients' "openness to the mind-body connection", consultational empathy, in-depth enquiry into bodily complaints, disclosure, the remedy matching process and, potentially, the homeopathic remedies themselves. Conclusion This study has has identified, using primary consultation and other data, a range of factors that might account for the effectiveness of homeopathic care. Some of these, such as empathy, are non-specific. Others, such as the remedy matching process, are specific to homeopathy. These findings counsel against the use of placebo-controlled RCT designs in which both arms would potentially be receiving specific active ingredients. Future research in homeopathy should focus on pragmatic trials and seek to confirm or refute the therapeutic role of constructs such as patient "openness", disclosure and homeopathicity. PMID:17101037

Effects of warm-up on vertical jump performance and muscle electrical activity using half-squats at low and moderate intensity.

PubMed

Sotiropoulos, Konstantinos; Smilios, Ilias; Christou, Marios; Barzouka, Karolina; Spaias, Angelos; Douda, Helen; Tokmakidis, Savvas P

2010-01-01

The purpose of this study was to determine the effects of a specific warm-up using half-squats at low and moderate intensity on vertical jump performance and electromyographic activity of the thigh muscles. The subjects were 26 men who were divided into a low intensity group (LIG; n = 13) and a moderate intensity group (MIG; n = 13). The LIG performed a specific warm-up protocol that included the explosive execution of half-squats with loads 25 and 35% of the one repetition maximum (1RM) and the MIG with loads 45 and 65% of the 1RM. The two groups performed a countermovement jump (CMJ) before and three minutes after the specific warm-up protocols. During the concentric phase of the CMJ a linear encoder connected to an A/D converter interfaced to a PC with a software for data acquisition and analysis allowed the calculation of average mechanical power. The electromyographic (EMG) activity of the vastus lateralis (VL), vastus medialis (VM) and rectus femoris (RF) were recorded during the concentric phase of the jumps. The average quadriceps (Qc) activity (mean value of the VL, VM and RF) was also calculated. A two way ANOVA (protocols X time) with repeated measures on the second factor was used to analyze the data. Following the specific warm-up procedure both groups improved (p ≤ 0.05) CMJ performance and mechanical power by 3.5% and 6.3%, respectively, with no differences observed between the two groups. EMG activity of the Qc and VL increased (p ≤ 0.05) for both groups by 5.9% and 8.5%, respectively. It is concluded that the use of a specific warm-up that includes half-squats, performed explosively with low to moderate intensity, improves CMJ performance. This may be due to increased muscle activation as evaluated by the surface EMG. Key pointsThe inclusion of two sets of explosively performed half squats with low to moderate loads in the warm up procedure elicited an acute performance en-hancement.The performance was enhanced regardless of the load used in the warm-up.The performance enhancement is accompanied by a greater electromyographic activity of the knee extensors muscles.

Effects of Warm-Up on Vertical Jump Performance and Muscle Electrical Activity Using Half-Squats at Low and Moderate Intensity

PubMed Central

Sotiropoulos, Konstantinos; Smilios, Ilias; Christou, Marios; Barzouka, Karolina; Spaias, Angelos; Douda, Helen; Tokmakidis, Savvas p.

2010-01-01

The purpose of this study was to determine the effects of a specific warm-up using half-squats at low and moderate intensity on vertical jump performance and electromyographic activity of the thigh muscles. The subjects were 26 men who were divided into a low intensity group (LIG; n = 13) and a moderate intensity group (MIG; n = 13). The LIG performed a specific warm-up protocol that included the explosive execution of half-squats with loads 25 and 35% of the one repetition maximum (1RM) and the MIG with loads 45 and 65% of the 1RM. The two groups performed a countermovement jump (CMJ) before and three minutes after the specific warm-up protocols. During the concentric phase of the CMJ a linear encoder connected to an A/D converter interfaced to a PC with a software for data acquisition and analysis allowed the calculation of average mechanical power. The electromyographic (EMG) activity of the vastus lateralis (VL), vastus medialis (VM) and rectus femoris (RF) were recorded during the concentric phase of the jumps. The average quadriceps (Qc) activity (mean value of the VL, VM and RF) was also calculated. A two way ANOVA (protocols X time) with repeated measures on the second factor was used to analyze the data. Following the specific warm-up procedure both groups improved (p ≤ 0.05) CMJ performance and mechanical power by 3.5% and 6.3%, respectively, with no differences observed between the two groups. EMG activity of the Qc and VL increased (p ≤ 0.05) for both groups by 5.9% and 8.5%, respectively. It is concluded that the use of a specific warm-up that includes half-squats, performed explosively with low to moderate intensity, improves CMJ performance. This may be due to increased muscle activation as evaluated by the surface EMG. Key points The inclusion of two sets of explosively performed half squats with low to moderate loads in the warm up procedure elicited an acute performance en-hancement. The performance was enhanced regardless of the load used in the warm-up. The performance enhancement is accompanied by a greater electromyographic activity of the knee extensors muscles. PMID:24149703

Hepatic overexpression of steroid sulfatase ameliorates mouse models of obesity and type 2 diabetes through sex-specific mechanisms.

PubMed

Jiang, Mengxi; He, Jinhan; Kucera, Heidi; Gaikwad, Nilesh W; Zhang, Bin; Xu, Meishu; O'Doherty, Robert M; Selcer, Kyle W; Xie, Wen

2014-03-21

The steroid sulfatase (STS)-mediated desulfation is a critical metabolic mechanism that regulates the chemical and functional homeostasis of endogenous and exogenous molecules. In this report, we first showed that the liver expression of Sts was induced in both the high fat diet (HFD) and ob/ob models of obesity and type 2 diabetes and during the fed to fasting transition. In defining the functional relevance of STS induction in metabolic disease, we showed that overexpression of STS in the liver of transgenic mice alleviated HFD and ob/ob models of obesity and type 2 diabetes, including reduced body weight, improved insulin sensitivity, and decreased hepatic steatosis and inflammation. Interestingly, STS exerted its metabolic benefit through sex-specific mechanisms. In female mice, STS may have increased hepatic estrogen activity by converting biologically inactive estrogen sulfates to active estrogens and consequently improved the metabolic functions, whereas ovariectomy abolished this protective effect. In contrast, the metabolic benefit of STS in males may have been accounted for by the male-specific decrease of inflammation in white adipose tissue and skeletal muscle as well as a pattern of skeletal muscle gene expression that favors energy expenditure. The metabolic benefit in male STS transgenic mice was retained after castration. Treatment with the STS substrate estrone sulfate also improved metabolic functions in both the HFD and ob/ob models. Our results have uncovered a novel function of STS in energy metabolism and type 2 diabetes. Liver-specific STS induction or estrogen/estrogen sulfate delivery may represent a novel approach to manage metabolic syndrome.

Preliminary definition of improvement in juvenile arthritis.

PubMed

Giannini, E H; Ruperto, N; Ravelli, A; Lovell, D J; Felson, D T; Martini, A

1997-07-01

To identify a core set of outcome variables for the assessment of children with juvenile arthritis (JA), to use the core set to develop a definition of improvement to determine whether individual patients demonstrate clinically important improvement, and to promote this definition as a single efficacy measure in JA clinical trials. A core set of outcome variables was established using a combination of statistical and consensus formation techniques. Variables in the core set consisted of 1) physician global assessment of disease activity; 2) parent/patient assessment of overall well-being; 3) functional ability; 4) number of joints with active arthritis; 5) number of joints with limited range of motion; and 6) erythrocyte sedimentation rate. To establish a definition of improvement using this core set, 21 pediatric rheumatologists from 14 countries met, and, using consensus formation techniques, scored each of 72 patient profiles as improved or not improved. Using the physicians' consensus as the gold standard, the chi-square, sensitivity, and specificity were calculated for each of 240 possible definitions of improvement. Definitions with sensitivity or specificity of <80% were eliminated. The ability of the remaining definitions to discriminate between the effects of active agent and those of placebo, using actual trial data, was then observed. Each definition was also ranked for face validity, and the sum of the ranks was then multiplied by the kappa statistic. The definition of improvement with the highest final score was as follows: at least 30% improvement from baseline in 3 of any 6 variables in the core set, with no more than 1 of the remaining variables worsening by >30%. The second highest scoring definition was closely related to the first; the third highest was similar to the Paulus criteria used in adult rheumatoid arthritis trials, except with different variables. This indicates convergent validity of the process used. We propose a definition of improvement for JA. Use of a uniform definition will help standardize the conduct and reporting of clinical trials, and should help practitioners decide if a child with JA has responded adequately to therapy. We are in the process of prospectively validating this definition and several others that scored highly.

[The specific features of the blood gas transport system in patients with postinfarction cardiosclerosis].

PubMed

Mikashinovich, Z I; Suroedova, R A; Olempieva, E V

2009-10-01

The specific features of blood gas transport system functioning were analyzed in patients with cardiovascular diseases. In patients with postinfarction cardiosclerosis (PICS), the quantitative mechanism for hypoxia adaptation tended to decrease, which may be considered to be a compensatory-adaptive reaction aimed at eliminating the sludge phenomenon and improving the rheological characteristics of blood. Acute myocardial reinfarction developed in patents with PICS is characterized by the lower functional activity of red blood cells, and developing hypoxia is an important link of activation of apoptotic cell death. The degree of hypoxia may be believed to correlate with the sizes of a myocardial necrosis focus.

The use of an active learning approach in a SCALE-UP learning space improves academic performance in undergraduate General Biology.

PubMed

Hacisalihoglu, Gokhan; Stephens, Desmond; Johnson, Lewis; Edington, Maurice

2018-01-01

Active learning is a pedagogical approach that involves students engaging in collaborative learning, which enables them to take more responsibility for their learning and improve their critical thinking skills. While prior research examined student performance at majority universities, this study focuses on specifically Historically Black Colleges and Universities (HBCUs) for the first time. Here we present work that focuses on the impact of active learning interventions at Florida A&M University, where we measured the impact of active learning strategies coupled with a SCALE-UP (Student Centered Active Learning Environment with Upside-down Pedagogies) learning environment on student success in General Biology. In biology sections where active learning techniques were employed, students watched online videos and completed specific activities before class covering information previously presented in a traditional lecture format. In-class activities were then carefully planned to reinforce critical concepts and enhance critical thinking skills through active learning techniques such as the one-minute paper, think-pair-share, and the utilization of clickers. Students in the active learning and control groups covered the same topics, took the same summative examinations and completed identical homework sets. In addition, the same instructor taught all of the sections included in this study. Testing demonstrated that these interventions increased learning gains by as much as 16%, and students reported an increase in their positive perceptions of active learning and biology. Overall, our results suggest that active learning approaches coupled with the SCALE-UP environment may provide an added opportunity for student success when compared with the standard modes of instruction in General Biology.

Strategies for prevention and management of musculoskeletal conditions. Low back pain (non-specific).

PubMed

Krismer, M; van Tulder, M

2007-02-01

Low back pain (LBP) is defined as pain localised between the 12th rib and the inferior gluteal folds, with or without leg pain. Most cases are non-specific, but in about 10% of cases a specific cause is identified. Red flags are typical signs or symptoms that are frequently associated with specific LBP. Yellow flags are prognostic factors associated with a more unfavourable and often chronic disabling course of the disease. LBP has a lifetime prevalence of 60-85%. At any one time, about 15% of adults have LBP. LBP poses an economic burden to society, mainly in terms of the large number of work days lost (indirect costs) and less so by direct treatment costs. A substantial proportion of individuals with chronic LBP has been found to have chronic widespread pain. LBP is often associated with other pain manifestations such as headache, abdominal pain and pain in different locations of the extremities. Widespread pain is associated with a worse prognosis compared to localised LBP. Treatment targets are reduction of pain and better activity/participation, including prevention of disability as well as maintainance of work capacity. The evidence from selected and appraised guidelines, systematic reviews and major clinical studies was classified into four levels, level Ia being the best level with evidence from meta-analysis of randomised controlled trials. Key recommendations (level Ia): fitness programmes and advice to stay active can reduce pain, improve function and can prevent LBP becoming chronic. Simple analgesics, NSAIDs and muscle relaxants can reduce pain and can improve and maintain function. Maintaining physical activity, avoiding rest and manual therapy can reduce pain and maintain and restore function in acute LBP. Behavioural treatment can prevent LBP becoming chronic. Aerobic fitness and endurance training, behavioural treatment and multi-disciplinary treatment programmes can reduce pain and can improve/maintain function in chronic LBP.

Multiple division cycles and long-term survival of hepatocytes are distinctly regulated by extracellular signal-regulated kinases ERK1 and ERK2.

PubMed

Frémin, Christophe; Bessard, Anne; Ezan, Frédéric; Gailhouste, Luc; Régeard, Morgane; Le Seyec, Jacques; Gilot, David; Pagès, Gilles; Pouysségur, Jacques; Langouët, Sophie; Baffet, Georges

2009-03-01

We investigated the specific role of the mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase 1 (ERK1)/ERK2 pathway in the regulation of multiple cell cycles and long-term survival of normal hepatocytes. An early and sustained epidermal growth factor (EGF)-dependent MAPK activation greatly improved the potential of cell proliferation. In this condition, almost 100% of the hepatocytes proliferated, and targeting ERK1 or ERK2 via RNA interference revealed the specific involvement of ERK2 in this regulation. However, once their first cell cycle was performed, hepatocytes failed to undergo a second round of replication and stayed blocked in G1 phase. We demonstrated that sustained EGF-dependent activation of the MAPK/ERK kinase (MEK)/ERK pathway was involved in this blockage as specific transient inhibition of the cascade repotentiated hepatocytes to perform a new wave of replication and multiple cell cycles. We identified this mechanism by showing that this blockage was in part supported by ERK2-dependent p21 expression. Moreover, continuous MEK inhibition was associated with a lower apoptotic engagement, leading to an improvement of survival up to 3 weeks. Using RNA interference and ERK1 knockout mice, we extended these results by showing that this improved survival was due to the specific inhibition of ERK1 expression/phosphorylation and did not involve ERK2. Our results emphasize that transient MAPK inhibition allows multiple cell cycles in primary cultures of hepatocytes and that ERK2 has a key role in the regulation of S phase entry. Moreover, we revealed a major and distinct role of ERK1 in the regulation of hepatocyte survival. Taken together, our results represent an important advance in understanding long-term survival and cell cycle regulation of hepatocytes.

Probing the molecular determinants of aniline dioxygenase substrate specificity by saturation mutagenesis.

PubMed

Ang, Ee L; Obbard, Jeffrey P; Zhao, Huimin

2007-02-01

Aniline dioxygenase is a multicomponent Rieske nonheme-iron dioxygenase enzyme isolated from Acinetobacter sp. strain YAA. Saturation mutagenesis of the substrate-binding pocket residues, which were identified using a homology model of the alpha subunit of the terminal dioxygenase (AtdA3), was used to probe the molecular determinants of AtdA substrate specificity. The V205A mutation widened the substrate specificity of aniline dioxygenase to include 2-isopropylaniline, for which the wild-type enzyme has no activity. The V205A mutation also made 2-isopropylaniline a better substrate for the enzyme than 2,4-dimethylaniline, a native substrate of the wild-type enzyme. The I248L mutation improved the activity of aniline dioxygenase against aniline and 2,4-dimethylaniline approximately 1.7-fold and 2.1-fold, respectively. Thus, it is shown that the alpha subunit of the terminal dioxygenase indeed plays a part in the substrate specificity as well as the activity of aniline dioxygenase. Interestingly, the equivalent residues of V205 and I248 have not been previously reported to influence the substrate specificity of other Rieske dioxygenases. These results should facilitate future engineering of the enzyme for bioremediation and industrial applications.

Tissue-Specific Regulation of Chromatin Insulator Function

PubMed Central

Matzat, Leah H.; Dale, Ryan K.; Moshkovich, Nellie; Lei, Elissa P.

2012-01-01

Chromatin insulators organize the genome into distinct transcriptional domains and contribute to cell type–specific chromatin organization. However, factors regulating tissue-specific insulator function have not yet been discovered. Here we identify the RNA recognition motif-containing protein Shep as a direct interactor of two individual components of the gypsy insulator complex in Drosophila. Mutation of shep improves gypsy-dependent enhancer blocking, indicating a role as a negative regulator of insulator activity. Unlike ubiquitously expressed core gypsy insulator proteins, Shep is highly expressed in the central nervous system (CNS) with lower expression in other tissues. We developed a novel, quantitative tissue-specific barrier assay to demonstrate that Shep functions as a negative regulator of insulator activity in the CNS but not in muscle tissue. Additionally, mutation of shep alters insulator complex nuclear localization in the CNS but has no effect in other tissues. Consistent with negative regulatory activity, ChIP–seq analysis of Shep in a CNS-derived cell line indicates substantial genome-wide colocalization with a single gypsy insulator component but limited overlap with intact insulator complexes. Taken together, these data reveal a novel, tissue-specific mode of regulation of a chromatin insulator. PMID:23209434

Recovery of neuronal and network excitability after spinal cord injury and implications for spasticity

PubMed Central

D'Amico, Jessica M.; Condliffe, Elizabeth G.; Martins, Karen J. B.; Bennett, David J.; Gorassini, Monica A.

2014-01-01

The state of areflexia and muscle weakness that immediately follows a spinal cord injury (SCI) is gradually replaced by the recovery of neuronal and network excitability, leading to both improvements in residual motor function and the development of spasticity. In this review we summarize recent animal and human studies that describe how motoneurons and their activation by sensory pathways become hyperexcitable to compensate for the reduction of functional activation of the spinal cord and the eventual impact on the muscle. Specifically, decreases in the inhibitory control of sensory transmission and increases in intrinsic motoneuron excitability are described. We present the idea that replacing lost patterned activation of the spinal cord by activating synaptic inputs via assisted movements, pharmacology or electrical stimulation may help to recover lost spinal inhibition. This may lead to a reduction of uncontrolled activation of the spinal cord and thus, improve its controlled activation by synaptic inputs to ultimately normalize circuit function. Increasing the excitation of the spinal cord with spared descending and/or peripheral inputs by facilitating movement, instead of suppressing it pharmacologically, may provide the best avenue to improve residual motor function and manage spasticity after SCI. PMID:24860447

Electrode-active material for electrochemical batteries and method of preparation

DOEpatents

Varma, R.

1983-11-07

A battery electrode material comprises a non-stoichiometric electrode-active material which forms a redox pair with the battery electrolyte, an electrically conductive polymer present in the range of from about 2% by weight to about 5% by weight of the electrode-active material, and a binder. The conductive polymer provides improved proton or ion conductivity and is a ligand resulting in metal ion or negative ion vacancies of less than about 0.1 atom percent. Specific electrodes of nickel and lead are disclosed.

Electrode-active material for electrochemical batteries and method of preparation

DOEpatents

Varma, Ravi

1987-01-01

A battery electrode material comprising a non-stoichiometric electrode-active material which forms a redox pair with the battery electrolyte, an electrically conductive polymer present in the range of from about 2% by weight to about 5% by weight of the electrode-active material, and a binder. The conductive polymer provides improved proton or ion conductivity and is a ligand resulting in metal ion or negative ion vacancies of less than about 0.1 atom percent. Specific electrodes of nickel and lead are disclosed.

Teaching Intercultural Management Communication: Where Are We? Where Do We Go?

ERIC Educational Resources Information Center

Varner, Iris I.

2001-01-01

Outlines three major challenges faced in teaching intercultural business communication, and discusses how teachers can meet these challenges to assure that students become effective intercultural managers and communicators. Outlines several specific activities to improve students' intercultural business communication skills. (SR)

Effective Teamwork: The EVA NBL Experience

NASA Technical Reports Server (NTRS)

Crocker, Lori

2007-01-01

This viewgraph presentation reviews the experience of improving the operation of the ExtraVehiclar Activity (EVA) Neutral Buoyancy Laboratory as a team of NASA employees and contractors. It reviews specific recommendations to use in turning a struggling organization around as a NASA/contractor team

Fusion of an oligopeptide to the N terminus of an alkaline α-amylase from Alkalimonas amylolytica simultaneously improves the enzyme's catalytic efficiency, thermal stability, and resistance to oxidation.

PubMed

Yang, Haiquan; Lu, Xinyao; Liu, Long; Li, Jianghua; Shin, Hyun-dong; Chen, Rachel R; Du, Guocheng; Chen, Jian

2013-05-01

In this study, we constructed and expressed six fusion proteins composed of oligopeptides attached to the N terminus of the alkaline α-amylase (AmyK) from Alkalimonas amylolytica. The oligopeptides had various effects on the functional and structural characteristics of AmyK. AmyK-p1, the fusion protein containing peptide 1 (AEAEAKAKAEAEAKAK), exhibited improved specific activity, catalytic efficiency, alkaline stability, thermal stability, and oxidative stability compared with AmyK. Compared with AmyK, the specific activity and catalytic constant (kcat) of AmyK-p1 were increased by 4.1-fold and 3.5-fold, respectively. The following properties were also improved in AmyK-p1 compared with AmyK: kcat/Km increased from 1.8 liter/(g·min) to 9.7 liter/(g·min), stable pH range was extended from 7.0 to 11.0 to 7.0 to 12.0, optimal temperature increased from 50°C to 55°C, and the half-life at 60°C increased by ∼2-fold. Moreover, AmyK-p1 showed improved resistance to oxidation and retained 54% of its activity after incubation with H2O2, compared with 20% activity retained by AmyK. Finally, AmyK-p1 was more compatible than AmyK with the commercial solid detergents tested. The mechanisms responsible for these changes were analyzed by comparing the three-dimensional (3-D) structural models of AmyK and AmyK-p1. The significantly enhanced catalytic efficiency and stability of AmyK-p1 suggests its potential as a detergent ingredient. In addition, the oligopeptide fusion strategy described here may be useful for improving the catalytic efficiency and stability of other industrial enzymes.

Fusion of an Oligopeptide to the N Terminus of an Alkaline α-Amylase from Alkalimonas amylolytica Simultaneously Improves the Enzyme's Catalytic Efficiency, Thermal Stability, and Resistance to Oxidation

PubMed Central

Yang, Haiquan; Lu, Xinyao; Li, Jianghua; Shin, Hyun-dong; Chen, Rachel R.; Du, Guocheng

2013-01-01

In this study, we constructed and expressed six fusion proteins composed of oligopeptides attached to the N terminus of the alkaline α-amylase (AmyK) from Alkalimonas amylolytica. The oligopeptides had various effects on the functional and structural characteristics of AmyK. AmyK-p1, the fusion protein containing peptide 1 (AEAEAKAKAEAEAKAK), exhibited improved specific activity, catalytic efficiency, alkaline stability, thermal stability, and oxidative stability compared with AmyK. Compared with AmyK, the specific activity and catalytic constant (kcat) of AmyK-p1 were increased by 4.1-fold and 3.5-fold, respectively. The following properties were also improved in AmyK-p1 compared with AmyK: kcat/Km increased from 1.8 liter/(g·min) to 9.7 liter/(g·min), stable pH range was extended from 7.0 to 11.0 to 7.0 to 12.0, optimal temperature increased from 50°C to 55°C, and the half-life at 60°C increased by ∼2-fold. Moreover, AmyK-p1 showed improved resistance to oxidation and retained 54% of its activity after incubation with H2O2, compared with 20% activity retained by AmyK. Finally, AmyK-p1 was more compatible than AmyK with the commercial solid detergents tested. The mechanisms responsible for these changes were analyzed by comparing the three-dimensional (3-D) structural models of AmyK and AmyK-p1. The significantly enhanced catalytic efficiency and stability of AmyK-p1 suggests its potential as a detergent ingredient. In addition, the oligopeptide fusion strategy described here may be useful for improving the catalytic efficiency and stability of other industrial enzymes. PMID:23455344

PEGylation, increasing specific activity and multiple dosing as strategies to improve the risk-benefit profile of targeted radionuclide therapy with 177Lu-DOTA-bombesin analogues

PubMed Central

2012-01-01

Background Radiolabelled bombesin (BN) conjugates are promising radiotracers for imaging and therapy of breast and prostate tumours, in which BN2/gastrin-releasing peptide receptors are overexpressed. We describe the influence of the specific activity of a 177Lu-DOTA-PEG5k-Lys-B analogue on its therapeutic efficacy and compare it with its non-PEGylated counterpart. Methods Derivatisation of a stabilised DOTA-BN(7–14)[Cha13,Nle14] analogue with a linear PEG molecule of 5 kDa (PEG5k) was performed by PEGylation of the ϵ-amino group of a β3hLys-βAla-βAla spacer between the BN sequence and the DOTA chelator. The non-PEGylated and the PEGylated analogues were radiolabelled with 177Lu. In vitro evaluation was performed in human prostate carcinoma PC-3 cells, and in vivo studies were carried out in nude mice bearing PC-3 tumour xenografts. Different specific activities of the PEGylated BN analogue and various dose regimens were evaluated concerning their therapeutic efficacy. Results The specificity and the binding affinity of the BN analogue for BN2/GRP receptors were only slightly reduced by PEGylation. In vitro binding kinetics of the PEGylated analogue was slower since steady-state condition was reached after 4 h. PEGylation improved the stability of BN conjugate in vitro in human plasma by a factor of 5.6. The non-PEGylated BN analogue showed favourable pharmacokinetics already, i.e. fast blood clearance and renal excretion, but PEGylation improved the in vivo behaviour further. One hour after injection, the tumour uptake of the PEG5k-BN derivative was higher compared with that of the non-PEGylated analogue (3.43 ± 0.63% vs. 1.88 ± 0.4% ID/g). Moreover, the increased tumour retention resulted in a twofold higher tumour accumulation at 24 h p.i., and increased tumour-to-non-target ratios (tumour-to-kidney, 0.6 vs. 0.4; tumour-to-liver, 8.8 vs. 5.9, 24 h p.i.). In the therapy study, both 177Lu-labelled BN analogues significantly inhibited tumour growth. The therapeutic efficacy was highest for the PEGylated derivative of high specific activity administered in two fractions (2 × 20 MBq = 40 MBq) at day 0 and day 7 (73% tumour growth inhibition, 3 weeks after therapy). Conclusions PEGylation and increasing the specific activity enhance the pharmacokinetic properties of a 177Lu-labelled BN-based radiopharmaceutical and provide a protocol for targeted radionuclide therapy with a beneficial anti-tumour effectiveness and a favourable risk-profile at the same time. PMID:22681935

Aerospace Safety Advisory Panel

NASA Technical Reports Server (NTRS)

1992-01-01

The results of the Panel's activities are presented in a set of findings and recommendations. Highlighted here are both improvements in NASA's safety and reliability activities and specific areas where additional gains might be realized. One area of particular concern involves the curtailment or elimination of Space Shuttle safety and reliability enhancements. Several findings and recommendations address this area of concern, reflecting the opinion that safety and reliability enhancements are essential to the continued successful operation of the Space Shuttle. It is recommended that a comprehensive and continuing program of safety and reliability improvements in all areas of Space Shuttle hardware/software be considered an inherent component of ongoing Space Shuttle operations.

CBT Specific Process in Exposure-Based Treatments: Initial Examination in a Pediatric OCD Sample

PubMed Central

Benito, Kristen Grabill; Conelea, Christine; Garcia, Abbe M.; Freeman, Jennifer B.

2012-01-01

Cognitive-Behavioral theory and empirical support suggest that optimal activation of fear is a critical component for successful exposure treatment. Using this theory, we developed coding methodology for measuring CBT-specific process during exposure. We piloted this methodology in a sample of young children (N = 18) who previously received CBT as part of a randomized controlled trial. Results supported the preliminary reliability and predictive validity of coding variables with 12 week and 3 month treatment outcome data, generally showing results consistent with CBT theory. However, given our limited and restricted sample, additional testing is warranted. Measurement of CBT-specific process using this methodology may have implications for understanding mechanism of change in exposure-based treatments and for improving dissemination efforts through identification of therapist behaviors associated with improved outcome. PMID:22523609

Entrapment of hepatocyte spheroids in a hollow fiber bioreactor as a potential bioartificial liver.

PubMed

Wu, F J; Peshwa, M V; Cerra, F B; Hu, W S

1995-01-01

A bioartificial liver (BAL) employing xenogeneic hepatocytes has been developed as a potential interim support for patients in hepatic failure. For application in human therapy, the BAL requires a substantial increase in liver-specific functions. Cultivation of hepatocytes as spheroids leads to enhanced liver specific functions. We explored the possibility of entrapping spheroids into the BAL in order to improve device performance. Rat hepatocyte spheroids were entrapped in collagen gel within the lumen fibers of the BAL. The morphology and ultrastructure of collagen-entrapped spheroids resembled those of suspended spheroids formed on petri dishes. Albumin synthesis and P-450 enzyme activity were measured as markers of liver specific functions of spheroids entrapped in the BAL. At least a 4-fold improvement in these functions was observed compared to BAL devices entrapped with dispersed hepatocytes in collagen gels.

Assimilation of passive and active CCI soil moisture products into hydrological modelling: an intercomparison study in Europe

NASA Astrophysics Data System (ADS)

Maggioni, V.; Massari, C.; Camici, S.; Brocca, L.; Marchesini, I.

2017-12-01

Soil moisture (SM) is a key variable in rainfall-runoff partitioning since it acts on the main hydrological processes taking part within a catchment. Modeling SM is often a difficult task due to its large variability at different temporal and spatial scales. Ground soil moisture measurements are a valuable tool for improving runoff prediction but are often limited and suffer from spatial representativeness issues. Remotely sensed observations offer a new source of data able to cope the latter issues thus opening new possibilities for improving flood simulations worldwide. Today, several different SM products are available at increased accuracy with respect to the past. Some interesting products are those derived from the Climate Change Initiative (CCI) which offer the most complete and most consistent global SM data record based on active and passive microwave sensors.Thanks to the combination of multiple sensors within an active, a passive and an active+passive products, the CCI SM is expected to provide a significant benefit for the improvement of rainfall-runoff simulations through data assimilation. However, previous studies have shown that the success of the assimilation is not only related to the accuracy of the observations but also to the specific climate and the catchment physical and hydrological characteristics as well as to many necessary choices related to the assimilation technique. These choices along with the type of SM observations (i.e. passive or active) might play an important role for the success or the failure of the assimilation exercise which is not still clear. In this study, based on a large dataset of catchments covering large part of the Europe, we assimilated satellite SM observations from the passive and the active CCI SM products into Modello Idrologico Semiditribuito in Continuo (MISDc, Brocca et al. 2011). Rainfall and temperature data were collected from the European Climate Assessment & Dataset (E-OBS) while discharge data were obtained from the Global Runoff Data Centre (GRDC). Preliminary results show a general improvement of the hydrological simulations for catchments located in the Mediterranean areas specifically for the active product while lower performance is obtained at northern latitudes due to the presence of snow and ice.

A robust activity marking system for exploring active neuronal ensembles

PubMed Central

Sørensen, Andreas T; Cooper, Yonatan A; Baratta, Michael V; Weng, Feng-Ju; Zhang, Yuxiang; Ramamoorthi, Kartik; Fropf, Robin; LaVerriere, Emily; Xue, Jian; Young, Andrew; Schneider, Colleen; Gøtzsche, Casper René; Hemberg, Martin; Yin, Jerry CP; Maier, Steven F; Lin, Yingxi

2016-01-01

Understanding how the brain captures transient experience and converts it into long lasting changes in neural circuits requires the identification and investigation of the specific ensembles of neurons that are responsible for the encoding of each experience. We have developed a Robust Activity Marking (RAM) system that allows for the identification and interrogation of ensembles of neurons. The RAM system provides unprecedented high sensitivity and selectivity through the use of an optimized synthetic activity-regulated promoter that is strongly induced by neuronal activity and a modified Tet-Off system that achieves improved temporal control. Due to its compact design, RAM can be packaged into a single adeno-associated virus (AAV), providing great versatility and ease of use, including application to mice, rats, flies, and potentially many other species. Cre-dependent RAM, CRAM, allows for the study of active ensembles of a specific cell type and anatomical connectivity, further expanding the RAM system’s versatility. DOI: http://dx.doi.org/10.7554/eLife.13918.001 PMID:27661450

Engineering of isoamylase: improvement of protein stability and catalytic efficiency through semi-rational design.

PubMed

Li, Youran; Zhang, Liang; Ding, Zhongyang; Gu, Zhenghua; Shi, Guiyang

2016-01-01

Isoamylase catalyzes the hydrolysis of α-1,6-glycosidic linkages in glycogen, amylopectin and α/β-limit dextrins. A semi-rational design strategy was performed to improve catalytic properties of isoamylase from Bacillus lentus. Three residues in vicinity of the essential residues, Arg505, Asn513, and Gly608, were chosen as the mutation sites and were substituted by Ala, Pro, Glu, and Lys, respectively. Thermal stability of the mutant R505P and acidic stability of the mutant R505E were enhanced. The k cat /K m values of the mutant G608V have been promoted by 49%, and the specific activity increased by 33%. This work provides an effective strategy for improving the catalytic activity and stability of isoamylase, and the results obtained here may be useful for the improvement of catalytic properties of other α/β barrel enzymes.

Improved GMP-compliant multi-dose production and quality control of 6-[18F]fluoro-L-DOPA.

PubMed

Luurtsema, G; Boersma, H H; Schepers, M; de Vries, A M T; Maas, B; Zijlma, R; de Vries, E F J; Elsinga, P H

2017-01-01

6-[ 18 F]Fluoro-L-3,4-dihydroxyphenylalanine (FDOPA) is a frequently used radiopharmaceutical for detecting neuroendocrine and brain tumors and for the differential diagnosis of Parkinson's disease. To meet the demand for FDOPA, a high-yield GMP-compliant production method is required. Therefore, this study aimed to improve the FDOPA production and quality control procedures to enable distribution of the radiopharmaceutical over distances.FDOPA was prepared by electrophilic fluorination of the trimethylstannyl precursor with [ 18 F]F 2 , produced from [ 18 O] 2 via the double-shoot approach, leading to FDOPA with higher specific activity as compared to FDOPA which was synthesized, using [ 18 F]F 2 produced from 20 Ne, leading to FDOPA with a lower specific activity. The quality control of the product was performed using a validated UPLC system and compared with quality control with a conventional HPLC system. Impurities were identified using UPLC-MS. The [ 18 O] 2 double-shoot radionuclide production method yielded significantly more [ 18 F]F 2 with less carrier F 2 than the conventional method starting from 20 Ne. After adjustment of radiolabeling parameters substantially higher amounts of FDOPA with higher specific activity could be obtained. Quality control by UPLC was much faster and detected more side-products than HPLC. UPLC-MS showed that the most important side-product was FDOPA-quinone, rather than 6-hydroxydopa as suggested by the European Pharmacopoeia. The production and quality control of FDOPA were significantly improved by introducing the [ 18 O] 2 double-shoot radionuclide production method, and product analysis by UPLC, respectively. As a result, FDOPA is now routinely available for clinical practice and for distribution over distances.

Surface Plasmon Resonance kinetic analysis of the interaction between G-quadruplex nucleic acids and an anti-G-quadruplex monoclonal antibody.

PubMed

Lago, Sara; Nadai, Matteo; Rossetto, Monica; Richter, Sara N

2018-06-01

G-quadruplexes (G4s) are nucleic acids secondary structures formed in guanine-rich sequences. Anti-G4 antibodies represent a tool for the direct investigation of G4s in cells. Surface Plasmon Resonance (SPR) is a highly sensitive technology, suitable for assessing the affinity between biomolecules. We here aimed at improving the orientation of an anti-G4 antibody on the SPR sensor chip to optimize detection of binding antigens. SPR was employed to characterize the anti-G4 antibody interaction with G4 and non-G4 oligonucleotides. Dextran-functionalized sensor chips were used both in covalent coupling and capturing procedures. The use of two leading molecule for orienting the antibody of interest allowed to improve its activity from completely non-functional to 65% active. The specificity of the anti-G4 antobody for G4 structures could thus be assessed with high sensitivity and reliability. Optimization of the immobilization protocol for SPR biosensing, allowed us to determine the anti-G4 antibody affinity and specificity for G4 antigens with higher sensitivity with respect to other in vitro assays such as ELISA. Anti-G4 antibody specificity is a fundamental assumption for the future utilization of this kind of antibodies for monitoring G4s directly in cells. The heterogeneous orientation of amine-coupling immobilized ligands is a general problem that often leads to partial or complete inactivation of the molecules. Here we describe a new strategy for improving ligand orientation: driving it from two sides. This principle can be virtually applied to every molecule that loses its activity or is poorly immobilized after standard coupling to the SPR chip surface. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Effects of Exercise on Bone Status in Female Subjects, from Young Girls to Postmenopausal Women: An Overview of Systematic Reviews and Meta-Analyses.

PubMed

Xu, Jincheng; Lombardi, Giovanni; Jiao, Wei; Banfi, Giuseppe

2016-08-01

Osteoporosis and postmenopausal bone loss pose a huge social and economic burden worldwide. Regular exercise and physical activity are effective interventions for maximizing or maintaining peak bone mass and preventing bone loss in the elderly; however, most recommendations are addressed to the general public and lack specific indications for girls and women, the segment of the population most at risk for developing osteoporosis. The aim of this overview of systematic reviews and meta-analyses was to summarize current evidence for the effects of exercise and physical activity interventions on bone status in girls and women, and to explore whether specific exercise programs exist for improving or maintaining bone mass or bone strength in females. The PubMed, EMBASE, PEDro, and Cochrane Library databases were searched from January 2009, updated to 22 June 2015, using the following groups of search terms: (i) 'physical activity' and 'exercise'; and (ii) 'bone', 'bone health', 'bone strength', 'bone structure', 'bone metabolism', 'bone turnover', and 'bone biomarkers'. Searches and screening were limited to systematic reviews or meta-analyses of studies in females and published in English. Our final analysis included 12 articles that met the inclusion criteria. Combined-impact exercise protocols (impact exercise with resistance training) are the best choice to preserve/improve bone mineral density in pre- and postmenopausal women. Peak bone mass in young girls can be improved with short bouts of school-based high-impact plyometric exercise programs. Whole-body vibration exercises have no beneficial effects on bone in postmenopausal or elderly women. Lifelong exercise, specific for age, is an effective way to sustain bone health in girls and women.

Directions for Optimization of Photosynthetic Carbon Fixation: RuBisCO's Efficiency May Not Be So Constrained After All.

PubMed

Cummins, Peter L; Kannappan, Babu; Gready, Jill E

2018-01-01

The ubiquitous enzyme Ribulose 1,5-bisphosphate carboxylase-oxygenase (RuBisCO) fixes atmospheric carbon dioxide within the Calvin-Benson cycle that is utilized by most photosynthetic organisms. Despite this central role, RuBisCO's efficiency surprisingly struggles, with both a very slow turnover rate to products and also impaired substrate specificity, features that have long been an enigma as it would be assumed that its efficiency was under strong evolutionary pressure. RuBisCO's substrate specificity is compromised as it catalyzes a side-fixation reaction with atmospheric oxygen; empirical kinetic results show a trend to tradeoff between relative specificity and low catalytic turnover rate. Although the dominant hypothesis has been that the active-site chemistry constrains the enzyme's evolution, a more recent study on RuBisCO stability and adaptability has implicated competing selection pressures. Elucidating these constraints is crucial for directing future research on improving photosynthesis, as the current literature casts doubt on the potential effectiveness of site-directed mutagenesis to improve RuBisCO's efficiency. Here we use regression analysis to quantify the relationships between kinetic parameters obtained from empirical data sets spanning a wide evolutionary range of RuBisCOs. Most significantly we found that the rate constant for dissociation of CO 2 from the enzyme complex was much higher than previous estimates and comparable with the corresponding catalytic rate constant. Observed trends between relative specificity and turnover rate can be expressed as the product of negative and positive correlation factors. This provides an explanation in simple kinetic terms of both the natural variation of relative specificity as well as that obtained by reported site-directed mutagenesis results. We demonstrate that the kinetic behaviour shows a lesser rather than more constrained RuBisCO, consistent with growing empirical evidence of higher variability in relative specificity. In summary our analysis supports an explanation for the origin of the tradeoff between specificity and turnover as due to competition between protein stability and activity, rather than constraints between rate constants imposed by the underlying chemistry. Our analysis suggests that simultaneous improvement in both specificity and turnover rate of RuBisCO is possible.

Palmitic acid mediates hypothalamic insulin resistance by altering PKC-θ subcellular localization in rodents

PubMed Central

Benoit, Stephen C.; Kemp, Christopher J.; Elias, Carol F.; Abplanalp, William; Herman, James P.; Migrenne, Stephanie; Lefevre, Anne-Laure; Cruciani-Guglielmacci, Céline; Magnan, Christophe; Yu, Fang; Niswender, Kevin; Irani, Boman G.; Holland, William L.; Clegg, Deborah J.

2009-01-01

Insulin signaling can be modulated by several isoforms of PKC in peripheral tissues. Here, we assessed whether one specific isoform, PKC-θ, was expressed in critical CNS regions that regulate energy balance and whether it mediated the deleterious effects of diets high in fat, specifically palmitic acid, on hypothalamic insulin activity in rats and mice. Using a combination of in situ hybridization and immunohistochemistry, we found that PKC-θ was expressed in discrete neuronal populations of the arcuate nucleus, specifically the neuropeptide Y/agouti-related protein neurons and the dorsal medial nucleus in the hypothalamus. CNS exposure to palmitic acid via direct infusion or by oral gavage increased the localization of PKC-θ to cell membranes in the hypothalamus, which was associated with impaired hypothalamic insulin and leptin signaling. This finding was specific for palmitic acid, as the monounsaturated fatty acid, oleic acid, neither increased membrane localization of PKC-θ nor induced insulin resistance. Finally, arcuate-specific knockdown of PKC-θ attenuated diet-induced obesity and improved insulin signaling. These results suggest that many of the deleterious effects of high-fat diets, specifically those enriched with palmitic acid, are CNS mediated via PKC-θ activation, resulting in reduced insulin activity. PMID:19726875

Effect of core stabilization exercises versus conventional exercises on pain and functional status in patients with non-specific low back pain: a randomized clinical trial.

PubMed

Inani, Sumit B; Selkar, Sohan P

2013-01-01

Low Back Pain (LBP) results in significant level of disability, producing significant restriction on usual activity such as an inability to work. Nearly two third of the adults are affected by non-specific low back pain at some point in their lives. The purpose of the study was to determine the effect of core stabilization exercises in comparison with conventional exercises on pain, functional status in patients with non-specific LBP. Thirty patients diagnosed with non-specific LBP participated with age group between 20-50 years and divided in to 2 groups, one with core stabilization exercises and other conventional exercises, 15 subjects each. Three months study, pre and post treatment outcome measures used were VAS for pain intensity and Modified Oswestry Low Back Pain Disability Index for functional status (disability). Data were analyzed using student 't' test (paired and unpaired). Whereas both groups improved significantly from the initiation of treatment, a between-group comparison revealed significantly greater (p<0.001) improvements regarding pain and functional status for experimental group compared to control group. Core stabilization exercises were found to be more effective in reducing pain and improving functional status by decreasing disability of patients with non-specific low back pain in comparison with conventional exercises.

Evaluation of a new geriatric foot versus the Solid Ankle Cushion Heel foot for low-activity amputees.

PubMed

Bonnet, Xavier; Adde, Jean N; Blanchard, François; Gedouin-Toquet, Annick; Eveno, Dominique

2015-04-01

It is always a challenge to rehabilitate geriatric amputees to perform self-care skills at home with limited ambulation. A new geriatric foot (with a lower effective foot length) has been specifically designed to reduce residual limb stress and to ease the step completion. The aim of this study is to evaluate the benefit of a new geriatric foot versus a Solid Ankle Cushion Heel foot for low-activity persons with transtibial amputation. Crossover study. A total of 12 patients were included in this study. 2-min walking test, Quebec User Evaluation of Satisfaction with Assistive Technology 2.0 questionnaire and pressure socket measurements. The geriatric foot allows for greater patient satisfaction. The maximal pressure was significantly lower in the proximal anterior stump area. No statistical differences were obtained from the 2-min walking test. A geriatric foot designed with a low effective foot length improves the satisfaction and reduces proximal anterior socket pressures for poor-performing persons with transtibial amputation. The development and evaluation of feet specifically designed for geriatric persons with transtibial amputation could improve their specific requirements and satisfaction. © The International Society for Prosthetics and Orthotics 2014.

Idiopathic inflammatory myositis.

PubMed

Tieu, Joanna; Lundberg, Ingrid E; Limaye, Vidya

2016-02-01

Knowledge on idiopathic inflammatory myopathy (IIM) has evolved with the identification of myositis-associated and myositis-specific antibodies, development of histopathological classification and the recognition of how these correlate with clinical phenotype and response to therapy. In this paper, we outline key advances in diagnosis and histopathology, including the more recent identification of antibodies associated with immune-mediated necrotising myopathy (IMNM) and inclusion body myositis (IBM). Ongoing longitudinal observational cohorts allow further classification of these patients with IIM, their predicted clinical course and response to specific therapies. Registries have been developed worldwide for this purpose. A challenging aspect in IIM, a multisystem disease with multiple clinical subtypes, has been defining disease status and clinically relevant improvement. Tools for assessing activity and damage are now recognised to be important in determining disease activity and guiding therapeutic decision-making. The International Myositis Assessment and Clinical Studies (IMACS) group has developed such tools for use in research and clinical settings. There is limited evidence for specific treatment strategies in IIM. With significant development in the understanding of IIM and improved classification, longitudinal observational cohorts and trials using validated outcome measures are necessary, to provide important information for evidence-based care in the clinical setting. Crown Copyright © 2016. Published by Elsevier Ltd. All rights reserved.

Degenerate Pax2 and Senseless binding motifs improve detection of low-affinity sites required for enhancer specificity

PubMed Central

Zandvakili, Arya; Campbell, Ian; Weirauch, Matthew T.

2018-01-01

Cells use thousands of regulatory sequences to recruit transcription factors (TFs) and produce specific transcriptional outcomes. Since TFs bind degenerate DNA sequences, discriminating functional TF binding sites (TFBSs) from background sequences represents a significant challenge. Here, we show that a Drosophila regulatory element that activates Epidermal Growth Factor signaling requires overlapping, low-affinity TFBSs for competing TFs (Pax2 and Senseless) to ensure cell- and segment-specific activity. Testing available TF binding models for Pax2 and Senseless, however, revealed variable accuracy in predicting such low-affinity TFBSs. To better define parameters that increase accuracy, we developed a method that systematically selects subsets of TFBSs based on predicted affinity to generate hundreds of position-weight matrices (PWMs). Counterintuitively, we found that degenerate PWMs produced from datasets depleted of high-affinity sequences were more accurate in identifying both low- and high-affinity TFBSs for the Pax2 and Senseless TFs. Taken together, these findings reveal how TFBS arrangement can be constrained by competition rather than cooperativity and that degenerate models of TF binding preferences can improve identification of biologically relevant low affinity TFBSs. PMID:29617378

Hospital clinical pharmacy services in Vietnam.

PubMed

Trinh, Hieu T; Nguyen, Huong T L; Pham, Van T T; Ba, Hai L; Dong, Phuong T X; Cao, Thao T B; Nguyen, Hanh T H; Brien, Jo-Anne

2018-04-07

Background Clinical pharmacy is key to the quality use of medicines. While there are different approaches in different countries, international perspectives may inform health service development. The Vietnamese Ministry of Health introduced a legal regulation of clinical pharmacy services in December 2012. Objective To describe the services, and to explore reported barriers and facilitators in implementing clinical pharmacy activities in Vietnamese hospitals after the introduction of Vietnamese Ministry of Health legal regulation. Setting Thirty-nine hospitals in Hanoi, Vietnam, including 22 provincial and 17 district hospitals. Method A mixed methods study was utilized. An online questionnaire was sent to the hospitals. In-depth interviews were conducted with pairs of nominated pharmacists at ten of these hospitals. The questionnaire focused on four areas: facilities, workforce, policies and clinical pharmacy activities. Main outcome measure Proportion of clinical pharmacy activities in hospitals. Themes in clinical pharmacy practice. Results 34/39 (87%) hospitals had established clinical pharmacy teams. Most activities were non-patient-specific (87%) while the preliminary patient-specific clinical pharmacy services were available in only 8/39 hospitals (21%). The most common non-patient-specific activities were providing medicines information (97%), reporting adverse drug reactions (97%), monitoring medication usage (97%). The patient specific activities varied widely between hospitals and were ad hoc. The main challenges reported were: lack of workforce and qualified clinical pharmacists. Conclusion While most hospitals had hospital-based pharmacy activities, the direct patient care was limited. Training, education and an expanded work forces are needed to improve clinical pharmacy services.

Expression of Bacillus protease (Protease BYA) from Bacillus sp. Y in Bacillus subtilis and enhancement of its specific activity by site-directed mutagenesis-improvement in productivity of detergent enzyme-.

PubMed

Tobe, Seiichi; Shimogaki, Hisao; Ohdera, Motoyasu; Asai, Yoshio; Oba, Kenkichi; Iwama, Masanori; Irie, Masachika

2006-01-01

An attempt was made to express protease BYA produced by an alkalophilic Bacillus sp. Y in Bacillus subtilis by gene engineering methods. The gene encoding protease BYA was cloned from Bacillus sp. Y, and expression vector pTA71 was constructed from the amylase promoter of Bacillus licheniformis, DNA fragments encoding the open reading frame of protease BYA, and pUB110. Protease BYA was secreted at an activity level of 5100 APU/ml in the common industrial culture medium of Bacillus subtilis transformed with pTA71. We then attempted to increase the specific activity of protease BYA by site-directed mutagenesis. Amino acid residue Ala29 next to catalytic Asp30 was replaced by one of three uncharged amino acid residues (Val29, Leu29, Ile29), and each mutant enzyme was expressed and isolated from the culture medium. Val29 mutant enzyme was secreted at an activity level of greater than 7000 APU/ml in culture medium, and its specific activity was 1.5-fold higher than that of the wild-type enzyme. Other mutant enzymes had specific activity similar to that of the original one and were less stabile than the wild-type enzyme. It can be thought that the substitution at amino acid residue 29 affects the level of activity and stability of protease BYA.

NASA Fixed Wing Project Propulsion Research and Technology Development Activities to Reduce Thrust Specific Energy Consumption

NASA Technical Reports Server (NTRS)

Hathaway, Michael D.; Rosario, Ruben Del; Madavan, Nateri K.

2013-01-01

This paper presents an overview of the propulsion research and technology portfolio of NASA Fundamental Aeronautics Program Fixed Wing Project. The research is aimed at significantly reducing the thrust specific fuel/energy consumption of notional advanced fixed wing aircraft (by 60 percent relative to a baseline Boeing 737-800 aircraft with CFM56-7B engines) in the 2030 to 2035 time frame. The research investments described herein are aimed at improving propulsive efficiency through higher bypass ratio fans, improving thermal efficiency through compact high overall pressure ratio gas generators, and exploring the potential benefits of boundary layer ingestion propulsion and hybrid gas-electric propulsion concepts.

NASA Fixed Wing Project Propulsion Research and Technology Development Activities to Reduce Thrust Specific Energy Consumption

NASA Technical Reports Server (NTRS)

Hathaway, Michael D.; DelRasario, Ruben; Madavan, Nateri K.

2013-01-01

This paper presents an overview of the propulsion research and technology portfolio of NASA Fundamental Aeronautics Program Fixed Wing Project. The research is aimed at significantly reducing the thrust specific fuel/energy consumption of notional advanced fixed wing aircraft (by 60 % relative to a baseline Boeing 737-800 aircraft with CFM56-7B engines) in the 2030-2035 time frame. The research investments described herein are aimed at improving propulsive efficiency through higher bypass ratio fans, improving thermal efficiency through compact high overall pressure ratio gas generators, and exploring the potential benefits of boundary layer ingestion propulsion and hybrid gas-electric propulsion concepts.

An active learning curriculum improves fellows' knowledge and faculty teaching skills.

PubMed

Inra, Jennifer A; Pelletier, Stephen; Kumar, Navin L; Barnes, Edward L; Shields, Helen M

2017-01-01

Traditional didactic lectures are the mainstay of teaching for graduate medical education, although this method may not be the most effective way to transmit information. We created an active learning curriculum for Brigham and Women's Hospital (BWH) gastroenterology fellows to maximize learning. We evaluated whether this new curriculum improved perceived knowledge acquisition and knowledge base. In addition, our study assessed whether coaching faculty members in specific methods to enhance active learning improved their perceived teaching and presentation skills. We compared the Gastroenterology Training Exam (GTE) scores before and after the implementation of this curriculum to assess whether an improved knowledge base was documented. In addition, fellows and faculty members were asked to complete anonymous evaluations regarding their learning and teaching experiences. Fifteen fellows were invited to 12 lectures over a 2-year period. GTE scores improved in the areas of stomach ( p <0.001), general gastroenterology ( p =0.005), esophagus ( p <0.001), and small bowel ( p =0.001), and the total score ( p =0.001) between pre- and postimplementation of the active learning curriculum. Scores in hepatology, as well as biliary and pancreatic study, showed a trend toward improvement ( p >0.05). All fellows believed the lectures were helpful, felt more prepared to take the GTE, and preferred the interactive format to traditional didactic lectures. All lecturers agreed that they acquired new teaching skills, improved teaching and presentation skills, and learned new tools that could help them teach better in the future. An active learning curriculum is preferred by GI fellows and may be helpful for improving transmission of information in any specialty in medical education. Individualized faculty coaching sessions demonstrating new ways to transmit information may be important for an individual faculty member's teaching excellence.

Activation of Salmonella Typhi-specific regulatory T cells in typhoid disease in a wild-type S. Typhi challenge model.

PubMed

McArthur, Monica A; Fresnay, Stephanie; Magder, Laurence S; Darton, Thomas C; Jones, Claire; Waddington, Claire S; Blohmke, Christoph J; Dougan, Gordon; Angus, Brian; Levine, Myron M; Pollard, Andrew J; Sztein, Marcelo B

2015-05-01

Salmonella Typhi (S. Typhi), the causative agent of typhoid fever, causes significant morbidity and mortality worldwide. Currently available vaccines are moderately efficacious, and identification of immunological responses associated with protection or disease will facilitate the development of improved vaccines. We investigated S. Typhi-specific modulation of activation and homing potential of circulating regulatory T cells (Treg) by flow and mass cytometry using specimens obtained from a human challenge study. Peripheral blood mononuclear cells were obtained from volunteers pre- and at multiple time-points post-challenge with wild-type S. Typhi. We identified differing patterns of S. Typhi-specific modulation of the homing potential of circulating Treg between volunteers diagnosed with typhoid (TD) and those who were not (No TD). TD volunteers demonstrated up-regulation of the gut homing molecule integrin α4ß7 pre-challenge, followed by a significant down-regulation post-challenge consistent with Treg homing to the gut. Additionally, S. Typhi-specific Treg from TD volunteers exhibited up-regulation of activation molecules post-challenge (e.g., HLA-DR, LFA-1). We further demonstrate that depletion of Treg results in increased S. Typhi-specific cytokine production by CD8+ TEM in vitro. These results suggest that the tissue distribution of activated Treg, their characteristics and activation status may play a pivotal role in typhoid fever, possibly through suppression of S. Typhi-specific effector T cell responses. These studies provide important novel insights into the regulation of immune responses that are likely to be critical in protection against typhoid and other enteric infectious diseases.

Consolidated fuel reprocessing program

NASA Astrophysics Data System (ADS)

1985-02-01

Improved processes and components for the Breeder Reprocessing Engineering Test (BRET) were identified and developed as well as the design, procurement and development of prototypic equipment. The integrated testing of process equipment and flowsheets prototypical of a pilot scale full reprocessing plant, and also for testing prototypical remote features of specific complex components in the system are provided. Information to guide the long range activities of the Consolidated Fuel Reprocessing Program (CERP), a focal point for foreign exchange activities, and support in specialized technical areas are described. Research and development activities in HTGR fuel treatment technology are being conducted. Head-end process and laboratory scale development efforts, as well as studies specific to HTGR fuel, are reported. The development of off-gas treatment processes has generic application to fuel reprocessing, progress in this work is also reported.

Visible light-induced degradation of acetone over SO42-/MoOx/MgF2 catalysts.

PubMed

He, Yiming; Sheng, Tianlu; Wu, Ying; Chen, Jianshan; Fu, Ruibiao; Hu, Shengming; Wu, Xintao

2009-08-30

A visible light active photodegration catalyst was prepared by doping MoO(3) into MgF(2) matrix. The addition of SO(4)(2-) into MoO(x)/MgF(2) could improve the catalytic activity greatly and an acetone conversion of 96.1% under visible light was obtained on the SO(4)(2-)/5%MoO(x)/MgF(2) (SMM) catalyst. By BET, XRD, Raman, FT-IR, XPS, UV-vis technology the specific area, structure and photoadsorption ability of the catalysts were characterized. The high photocatlaytic activity of the SMM catalyst is attributed to its large specific area, the high dispersal of MoO(3) domains in MgF(2) and the inhibiting effect of MgF(2) matrix on the electron-hole pair recombination.

Directed evolution of new and improved enzyme functions using an evolutionary intermediate and multidirectional search.

PubMed

Porter, Joanne L; Boon, Priscilla L S; Murray, Tracy P; Huber, Thomas; Collyer, Charles A; Ollis, David L

2015-02-20

The ease with which enzymes can be adapted from their native roles and engineered to function specifically for industrial or commercial applications is crucial to enabling enzyme technology to advance beyond its current state. Directed evolution is a powerful tool for engineering enzymes with improved physical and catalytic properties and can be used to evolve enzymes where lack of structural information may thwart the use of rational design. In this study, we take the versatile and diverse α/β hydrolase fold framework, in the form of dienelactone hydrolase, and evolve it over three unique sequential evolutions with a total of 14 rounds of screening to generate a series of enzyme variants. The native enzyme has a low level of promiscuous activity toward p-nitrophenyl acetate but almost undetectable activity toward larger p-nitrophenyl esters. Using p-nitrophenyl acetate as an evolutionary intermediate, we have generated variants with altered specificity and catalytic activity up to 3 orders of magnitude higher than the native enzyme toward the larger nonphysiological p-nitrophenyl ester substrates. Several variants also possess increased stability resulting from the multidimensional approach to screening. Crystal structure analysis and substrate docking show how the enzyme active site changes over the course of the evolutions as either a direct or an indirect result of mutations.

Quality of life benefits of paid work activity in schizophrenia.

PubMed

Bryson, Gary; Lysaker, Paul; Bell, Morris

2002-01-01

In a study of work rehabilitation, 97 participants with schizophrenia or schizoaffective disorder were randomized into either a Pay or a No Pay condition to determine the impact of work activity and pay on rehabilitation outcomes. This report specifically investigates the relationship between work rehabilitation and quality of life (QOL) measures for people with schizophrenia. Previous reports have described improvements in symptoms and work outcomes for participants in the Pay condition. Results in this report reveal that randomization to the Pay condition improved ratings on the Heinrichs Quality of Life Scale (QLS). The improvements are found both in overall QLS and in the domain of Intrapsychic Foundations (motivation, sense of purpose, anhedonia, and empathy). For a larger sample (n = 114) we assessed the relationship between amount of participation and QLS improvement. Degree of participation was related to improvement on the QLS total and Intrapsychic Foundations domain. Finally, improvement in the Interpersonal Relations scale was associated with weeks of participation for the most consistent participants. How participation in work rehabilitation and its interaction with pay improves motivation, interpersonal relatedness, and overall quality of life is discussed.

Physical activity promotion in business and industry: evidence, context, and recommendations for a national plan.

PubMed

Pronk, Nicolaas P

2009-11-01

The contemporary workplace setting is in need of interventions that effectively promote higher levels of occupational and habitual physical activity. It is the purpose of this paper to outline an evidence-based approach to promote physical activity in the business and industry sector in support of a National Physical Activity Plan. Comprehensive literature searches identified systematic reviews, comprehensive reviews, and consensus documents on the impact of physical activity interventions in the business and industry sector. A framework for action and priority recommendations for practice and research were generated. Comprehensive, multicomponent work-site programs that include physical activity components generate significant improvements in health, reduce absenteeism and sick leave, and can generate a positive financial return. Specific evidence-based physical activity interventions are presented. Recommendations for practice include implementing comprehensive, multicomponent programs that make physical activity interventions possible, simple, rewarding and relevant in the context of a social-ecological model. The business and industry sector has significant opportunities to improve physical activity among employees, their dependents, and the community at-large and to reap important benefits related to worker health and business performance.

Physical Activity Promotion in Business and Industry: Evidence, Context, and Recommendations for a National Plan.

PubMed

Pronk, Nicolaas P

2009-11-01

The contemporary workplace setting is in need of interventions that effectively promote higher levels of occupational and habitual physical activity. It is the purpose of this paper to outline an evidence-based approach to promote physical activity in the business and industry sector in support of a National Physical Activity Plan. Comprehensive literature searches identified systematic reviews, comprehensive reviews, and consensus documents on the impact of physical activity interventions in the business and industry sector. A framework for action and priority recommendations for practice and research were generated. Comprehensive, multicomponent worksite programs that include physical activity components generate significant improvements in health, reduce absenteeism and sick leave, and can generate a positive financial return. Specific evidence-based physical activity interventions are presented. Recommendations for practice include implementing comprehensive, multicomponent programs that make physical activity interventions possible, simple, rewarding and relevant in the context of a social-ecological model. The business and industry sector has significant opportunities to improve physical activity among employees, their dependents, and the community at-large and to reap important benefits related to worker health and business performance.

In situ identification of nocardioform actinomycetes in activated sludge using fluorescent rRNA-targeted oligonucleotide probes.

PubMed

Schuppler, M; Wagner, M; Schön, G; Göbel, U B

1998-01-01

Hitherto, few environmental samples have been investigated by a 'full cycle rRNA analysis'. Here the results of in situ hybridization experiments with specific rRNA-targeted oligonucleotide probes developed on the basis of new sequences derived from a previously described comparative 16S rRNA analysis of nocardioform actinomycetes in activated sludge are reported. Application of the specific probes enabled identification and discrimination of the distinct populations of nocardioform actinomycetes in activated sludge. One of the specific probes (DLP) detected rod-shaped bacteria which were found in 13 of the 16 investigated sludge samples from various wastewater treatment plants, suggesting their importance in the wastewater treatment process. Another probe (GLP2) hybridized with typically branched filaments of nocardioforms mainly found in samples from enhanced biological phosphorus removal plants, suggesting that these bacteria are involved in sludge foaming. The combination of in situ hybridization with fluorescently labelled rRNA-targeted oligonucleotide probes and confocal laser scanning microscopy improved the detection of nocardioform actinomycetes, which often showed only weak signals inside the activated-sludge flocs.

Improved fluorescent labeling of chitin oligomers: Chitinolytic properties of acidic mammalian chitinase under somatic tissue pH conditions.

PubMed

Wakita, Satoshi; Kimura, Masahiro; Kato, Naoki; Kashimura, Akinori; Kobayashi, Shunsuke; Kanayama, Naoto; Ohno, Misa; Honda, Shotaro; Sakaguchi, Masayoshi; Sugahara, Yasusato; Bauer, Peter O; Oyama, Fumitaka

2017-05-15

Acidic mammalian chitinase (AMCase) has been implicated in various pathophysiological conditions including asthma, allergic inflammation and food processing. AMCase is most active at pH 2.0, and its activity gradually decreases to up to pH 8. Here we analyzed chitin degradation by AMCase in weak acidic to neutral conditions by fluorophore-assisted carbohydrate electrophoresis established originally for oligosaccharides analysis. We found that specific fragments with slower-than-expected mobility as defined by chitin oligosaccharide markers were generated at pH 5.0∼8.0 as by-products of the reaction. We established an improved method for chitin oligosaccharides suppressing this side reaction by pre-acidification of the fluorophore-labeling reaction mixture. Our improved method specifically detects chitin oligosaccharides and warrants quantification of up to 50nmol of the material. Using this strategy, we found that AMCase produced dimer of N-acetyl-d-glucosamine (GlcNAc) at strong acidic to neutral condition. Moreover, we found that AMCase generates (GlcNAc) 2 as well as (GlcNAc) 3 under physiological conditions. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Transitions of Care in Medical Education: A Compilation of Effective Teaching Methods.

PubMed

McBryde, Meagan; Vandiver, Jeremy W; Onysko, Mary

2016-04-01

Transitioning patients safely from the inpatient environment back to an outpatient environment is an important component of health care, and multidisciplinary cooperation and formal processes are necessary to accomplish this task. This Transitions of Care (TOC) process is constantly being shaped in health care systems to improve patient safety, outcomes, and satisfaction. While there are many models that have been published on methods to improve the TOC process systematically, there is no clear roadmap for educators to teach TOC concepts to providers in training. This article reviews published data to highlight specific methods shown to effectively instill these concepts and values into medical students and residents. Formal, evidence-based, TOC curriculum should be developed within medical schools and residency programs. TOC education should ideally begin early in the education process, and its importance should be reiterated throughout the curriculum longitudinally. Curriculum should have a specific focus on recognition of common causes of hospital readmissions, such as medication errors, lack of adequate follow-up visits, and social/economic barriers. Use of didactic lectures, case-based workshops, role-playing activities, home visits, interprofessional activities, and resident-led quality improvement projects have all be shown to be effective ways to teach TOC concepts.

Evaluation of Three State-of-the-Art Classifiers for Recognition of Activities of Daily Living from Smart Home Ambient Data

PubMed Central

Nef, Tobias; Urwyler, Prabitha; Büchler, Marcel; Tarnanas, Ioannis; Stucki, Reto; Cazzoli, Dario; Müri, René; Mosimann, Urs

2012-01-01

Smart homes for the aging population have recently started attracting the attention of the research community. The “health state” of smart homes is comprised of many different levels; starting with the physical health of citizens, it also includes longer-term health norms and outcomes, as well as the arena of positive behavior changes. One of the problems of interest is to monitor the activities of daily living (ADL) of the elderly, aiming at their protection and well-being. For this purpose, we installed passive infrared (PIR) sensors to detect motion in a specific area inside a smart apartment and used them to collect a set of ADL. In a novel approach, we describe a technology that allows the ground truth collected in one smart home to train activity recognition systems for other smart homes. We asked the users to label all instances of all ADL only once and subsequently applied data mining techniques to cluster in-home sensor firings. Each cluster would therefore represent the instances of the same activity. Once the clusters were associated to their corresponding activities, our system was able to recognize future activities. To improve the activity recognition accuracy, our system preprocessed raw sensor data by identifying overlapping activities. To evaluate the recognition performance from a 200-day dataset, we implemented three different active learning classification algorithms and compared their performance: naive Bayesian (NB), support vector machine (SVM) and random forest (RF). Based on our results, the RF classifier recognized activities with an average specificity of 96.53%, a sensitivity of 68.49%, a precision of 74.41% and an F-measure of 71.33%, outperforming both the NB and SVM classifiers. Further clustering markedly improved the results of the RF classifier. An activity recognition system based on PIR sensors in conjunction with a clustering classification approach was able to detect ADL from datasets collected from different homes. Thus, our PIR-based smart home technology could improve care and provide valuable information to better understand the functioning of our societies, as well as to inform both individual and collective action in a smart city scenario. PMID:26007727

Evaluation of Three State-of-the-Art Classifiers for Recognition of Activities of Daily Living from Smart Home Ambient Data.

PubMed

Nef, Tobias; Urwyler, Prabitha; Büchler, Marcel; Tarnanas, Ioannis; Stucki, Reto; Cazzoli, Dario; Müri, René; Mosimann, Urs

2015-05-21

Smart homes for the aging population have recently started attracting the attention of the research community. The "health state" of smart homes is comprised of many different levels; starting with the physical health of citizens, it also includes longer-term health norms and outcomes, as well as the arena of positive behavior changes. One of the problems of interest is to monitor the activities of daily living (ADL) of the elderly, aiming at their protection and well-being. For this purpose, we installed passive infrared (PIR) sensors to detect motion in a specific area inside a smart apartment and used them to collect a set of ADL. In a novel approach, we describe a technology that allows the ground truth collected in one smart home to train activity recognition systems for other smart homes. We asked the users to label all instances of all ADL only once and subsequently applied data mining techniques to cluster in-home sensor firings. Each cluster would therefore represent the instances of the same activity. Once the clusters were associated to their corresponding activities, our system was able to recognize future activities. To improve the activity recognition accuracy, our system preprocessed raw sensor data by identifying overlapping activities. To evaluate the recognition performance from a 200-day dataset, we implemented three different active learning classification algorithms and compared their performance: naive Bayesian (NB), support vector machine (SVM) and random forest (RF). Based on our results, the RF classifier recognized activities with an average specificity of 96.53%, a sensitivity of 68.49%, a precision of 74.41% and an F-measure of 71.33%, outperforming both the NB and SVM classifiers. Further clustering markedly improved the results of the RF classifier. An activity recognition system based on PIR sensors in conjunction with a clustering classification approach was able to detect ADL from datasets collected from different homes. Thus, our PIR-based smart home technology could improve care and provide valuable information to better understand the functioning of our societies, as well as to inform both individual and collective action in a smart city scenario.

The Literature Review of Analytical Support to Defence Transformation: Lessons Learned from Turkish Air Force Transformation Activities

DTIC Science & Technology

2010-04-01

available [11]. Additionally, Table-3 is a guide for DMAIC methodology including 29 different methods [12]. RTO-MP-SAS-081 6 - 4 NATO UNCLASSIFIED NATO...Table 3: DMAIC Methodology (5-Phase Methodology). Define Measure Analyze Improve Control Project Charter Prioritization Matrix 5 Whys Analysis...Methodology Scope [13] DMAIC PDCA Develop performance priorities This is a preliminary stage that precedes specific improvement projects, and the aim

Student Peer Review as a Tool for Efficiently Achieving Subject-Specific and Generic Learning Outcomes: Examples in Botany at the Faculty of Agriculture, University of Belgrade

ERIC Educational Resources Information Center

Quarrie, Sofija Pekic

2007-01-01

Several teachers at the Faculty of Agriculture at the University of Belgrade recognised the need to improve teaching methods in order to actively involve students in the teaching process, help them learn more effectively, and reduce the low exam pass rate. This led to a purpose-designed course on improving academic skills, after which the author…

Permeable reactive barrier of surface hydrophobic granular activated carbon coupled with elemental iron for the removal of 2,4-dichlorophenol in water.

PubMed

Yang, Ji; Cao, Limei; Guo, Rui; Jia, Jinping

2010-12-15

Granular activated carbon was modified with dimethyl dichlorosilane to improve its surface hydrophobicity, and therefore to improve the performance of permeable reactive barrier constructed with the modified granular activated carbon and elemental iron. X-ray photoelectron spectroscopy shows that the surface silicon concentration of the modified granular activated carbon is higher than that of the original one, leading to the increased surface hydrophobicity. Although the specific surface area decreased from 895 to 835 m(2)g(-1), the modified granular activated carbon could adsorb 20% more 2,4-dichlorophenol than the original one did in water. It is also proven that the permeable reactive barrier with the modified granular activated carbon is more efficient at 2,4-dichlorophenol dechlorination, in which process 2,4-dichlorophenol is transformed to 2-chlorophenol or 4-chlorophenol then to phenol, or to phenol directly. Copyright © 2010 Elsevier B.V. All rights reserved.

The effect of combined somatosensory stimulation and task-specific training on upper limb function in chronic stroke: a double-blind randomized controlled trial.

PubMed

Fleming, Melanie K; Sorinola, Isaac O; Roberts-Lewis, Sarah F; Wolfe, Charles D; Wellwood, Ian; Newham, Di J

2015-02-01

Somatosensory stimulation (SS) is a potential adjuvant to stroke rehabilitation, but the effect on function needs further investigation. To explore the effect of combining SS with task-specific training (TST) on upper limb function and arm use in chronic stroke survivors and determine underlying mechanisms. In this double-blinded randomized controlled trial (ISRCTN 05542931), 33 patients (mean 37.7 months poststroke) were block randomized to 2 groups: active or sham SS. They received 12 sessions of 2 hours of SS (active or sham) to all 3 upper limb nerves immediately before 30 minutes of TST. The primary outcome was the Action Research Arm Test (ARAT) score. Secondary outcomes were time to perform the ARAT, Fugl-Meyer Assessment score (FM), Motor Activity Log (MAL), and Goal Attainment Scale (GAS). Underlying mechanisms were explored using transcranial magnetic stimulation stimulus-response curves and intracortical inhibition. Outcomes were assessed at baseline, immediately following the intervention (mean 2 days), and 3 and 6 months (mean 96 and 190 days) after the intervention. The active group (n = 16) demonstrated greater improvement in ARAT score and time immediately postintervention (between-group difference; P < .05), but not at 3- or 6-month follow-ups (P > .2). Within-group improvements were seen for both groups for ARAT and GAS, but for the active group only for FM and MAL (P < .05). Corticospinal excitability did not change. Long-lasting improvements in upper limb function were observed following TST. Additional benefit of SS was seen immediately post treatment, but did not persist and the underlying mechanisms remain unclear. © The Author(s) 2014.

Deep Sequencing-guided Design of a High Affinity Dual Specificity Antibody to Target Two Angiogenic Factors in Neovascular Age-related Macular Degeneration.

PubMed

Koenig, Patrick; Lee, Chingwei V; Sanowar, Sarah; Wu, Ping; Stinson, Jeremy; Harris, Seth F; Fuh, Germaine

2015-09-04

The development of dual targeting antibodies promises therapies with improved efficacy over mono-specific antibodies. Here, we engineered a Two-in-One VEGF/angiopoietin 2 antibody with dual action Fab (DAF) as a potential therapeutic for neovascular age-related macular degeneration. Crystal structures of the VEGF/angiopoietin 2 DAF in complex with its two antigens showed highly overlapping binding sites. To achieve sufficient affinity of the DAF to block both angiogenic factors, we turned to deep mutational scanning in the complementarity determining regions (CDRs). By mutating all three CDRs of each antibody chain simultaneously, we were able not only to identify affinity improving single mutations but also mutation pairs from different CDRs that synergistically improve both binding functions. Furthermore, insights into the cooperativity between mutations allowed us to identify fold-stabilizing mutations in the CDRs. The data obtained from deep mutational scanning reveal that the majority of the 52 CDR residues are utilized differently for the two antigen binding function and permit, for the first time, the engineering of several DAF variants with sub-nanomolar affinity against two structurally unrelated antigens. The improved variants show similar blocking activity of receptor binding as the high affinity mono-specific antibodies against these two proteins, demonstrating the feasibility of generating a dual specificity binding surface with comparable properties to individual high affinity mono-specific antibodies. © 2015 by The American Society for Biochemistry and Molecular Biology, Inc.

Effect of epithalon on age-specific changes in the retina in rats with hereditary pigmentary dystrophy.

PubMed

Khavinson, V Kh; Razumovskii, M I; Trofimova, S V; Grigor'yan, R A; Chaban, T V; Oleinik, T L; Razumovskaya, A M

2002-01-01

The effect of peptide bioregulator Epithalon on the course of hereditary pigmentary retinal degeneration was studied in Campbell rats. Administration of epithalon starting from birth protected morphological structure, increased its bioelectrical activity, and improved its function.

Female sexual function and the clitoral complex using pelvic MRI assessment.

PubMed

Vaccaro, Christine M; Fellner, Angela N; Pauls, Rachel N

2014-09-01

To report basic measurements of clitoral anatomy, and explore potential relationships between the clitoral complex and female sexual function using MRI assessment. In this retrospective descriptive study, 20 sexually active women (≥18 years) who had a recent pelvic MRI for various gynecologic concerns were invited to participate. Outcome measures included demographic data, medical and sexual history, quality of life questionnaires: Female Sexual Function Index (FSFI), Body Exposure during Sexual Activities Questionnaire (BESAQ), and Short Form Quality of Life Questionnaire (SF-12). These data were then compared to detailed clitoral MRI measurements and analyzed using the Pearson correlation and Chi square test. FSFI domains of desire, arousal, lubrication, and orgasm were inversely correlated with clitoral size (p=0.01-0.04), as were SF-12 physical composite scores (p=0.003), suggesting improved sexual function and physical health in women with smaller clitoral structures (specifically the clitoral body and crus). Sexual function was improved in women with a smaller-sized clitoris, specifically the clitoral body and crus. Published by Elsevier Ireland Ltd.

The SIRT1 activator SRT1720 extends lifespan and improves health of mice fed a standard diet.

PubMed

Mitchell, Sarah J; Martin-Montalvo, Alejandro; Mercken, Evi M; Palacios, Hector H; Ward, Theresa M; Abulwerdi, Gelareh; Minor, Robin K; Vlasuk, George P; Ellis, James L; Sinclair, David A; Dawson, John; Allison, David B; Zhang, Yongqing; Becker, Kevin G; Bernier, Michel; de Cabo, Rafael

2014-03-13

The prevention or delay of the onset of age-related diseases prolongs survival and improves quality of life while reducing the burden on the health care system. Activation of sirtuin 1 (SIRT1), an NAD(+)-dependent deacetylase, improves metabolism and confers protection against physiological and cognitive disturbances in old age. SRT1720 is a specific SIRT1 activator that has health and lifespan benefits in adult mice fed a high-fat diet. We found extension in lifespan, delayed onset of age-related metabolic diseases, and improved general health in mice fed a standard diet after SRT1720 supplementation. Inhibition of proinflammatory gene expression in both liver and muscle of SRT1720-treated animals was noted. SRT1720 lowered the phosphorylation of NF-κB pathway regulators in vitro only when SIRT1 was functionally present. Combined with our previous work, the current study further supports the beneficial effects of SRT1720 on health across the lifespan in mice. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Quantifying in situ growth rate of a filamentous bacterial species in activated sludge using rRNA:rDNA ratio.

PubMed

Nguyen, Vivi L; He, Xia; de Los Reyes, Francis L

2016-11-01

If the in situ growth rate of filamentous bacteria in activated sludge can be quantified, researchers can more accurately assess the effect of operating conditions on the growth of filaments and improve the mathematical modeling of filamentous bulking. We developed a method to quantify the in situ specific growth rate of Sphaerotilus natans (a model filament) in activated sludge using the species-specific 16S rRNA:rDNA ratio. Primers targeting the 16S rRNA of S. natans were designed, and real-time PCR and RT-PCR were used to quantify DNA and RNA levels of S. natans, respectively. A positive linear relationship was found between the rRNA:rDNA ratio (from 440 to 4500) and the specific growth rate of S. natans (from 0.036 to 0.172 h -1 ) using chemostat experiments. The in situ growth rates of S. natans in activated sludge samples from three water reclamation facilities were quantified, illustrating how the approach can be applied in a complex environment such as activated sludge. © FEMS 2016. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The RNA-binding protein Rumpelstiltskin antagonizes gypsy chromatin insulator function in a tissue-specific manner

PubMed Central

King, Matthew R.; Matzat, Leah H.; Dale, Ryan K.; Lim, Su Jun; Lei, Elissa P.

2014-01-01

ABSTRACT Chromatin insulators are DNA–protein complexes that are situated throughout the genome that are proposed to contribute to higher-order organization and demarcation into distinct transcriptional domains. Mounting evidence in different species implicates RNA and RNA-binding proteins as regulators of chromatin insulator activities. Here, we identify the Drosophila hnRNP M homolog Rumpelstiltskin (Rump) as an antagonist of gypsy chromatin insulator enhancer-blocking and barrier activities. Despite ubiquitous expression of Rump, decreasing Rump levels leads to improvement of barrier activity only in tissues outside of the central nervous system (CNS). Furthermore, rump mutants restore insulator body localization in an insulator mutant background only in non-CNS tissues. Rump associates physically with core gypsy insulator proteins, and chromatin immunoprecipitation and sequencing analysis of Rump demonstrates extensive colocalization with a subset of insulator sites across the genome. The genome-wide binding profile and tissue specificity of Rump contrast with that of Shep, a recently identified RNA-binding protein that antagonizes gypsy insulator activity primarily in the CNS. Our findings indicate parallel roles for RNA-binding proteins in mediating tissue-specific regulation of chromatin insulator activity. PMID:24706949

Improved microautoradiographic method to determine individual microorganisms active in substrate uptake in natural waters.

PubMed

Tabor, P S; Neihof, R A

1982-10-01

We report a method which combines epifluorescence microscopy and microautoradiography to determine both the total number of microorganisms in natural water populations and those individual organisms active in the uptake of specific substrates. After incubation with H-labeled substrate, the sample is filtered and, while still on the filter, mounted directly in a film of autoradiographic emulsion on a microscope slide. The microautoradiogram is processed and stained with acridine orange, and, subsequently, the filter is removed before microscopic observation. This novel preparation resulted in increased accuracy in direct counts made from the autoradiogram, improved sensitivity in the recognition of uptake-active (H-labeled) organisms, and enumeration of a significantly greater number of labeled organisms compared with corresponding samples prepared by a previously reported method.

Improved Microautoradiographic Method to Determine Individual Microorganisms Active in Substrate Uptake in Natural Waters

PubMed Central

Tabor, Paul S.; Neihof, Rex A.

1982-01-01

We report a method which combines epifluorescence microscopy and microautoradiography to determine both the total number of microorganisms in natural water populations and those individual organisms active in the uptake of specific substrates. After incubation with 3H-labeled substrate, the sample is filtered and, while still on the filter, mounted directly in a film of autoradiographic emulsion on a microscope slide. The microautoradiogram is processed and stained with acridine orange, and, subsequently, the filter is removed before microscopic observation. This novel preparation resulted in increased accuracy in direct counts made from the autoradiogram, improved sensitivity in the recognition of uptake-active (3H-labeled) organisms, and enumeration of a significantly greater number of labeled organisms compared with corresponding samples prepared by a previously reported method. Images PMID:16346120

Improvement of polyphenol properties upon glucosylation in a UV-induced skin cell ageing model.

PubMed

Nadim, M; Auriol, D; Lamerant-FayeL, N; Lefèvre, F; Dubanet, L; Redziniak, G; Kieda, C; Grillon, C

2014-12-01

Polyphenols are strong antioxidant molecules allowing prevention of skin photo-ageing damages, but their use is limited due to low solubility and toxicity towards skin cells. We postulated that enzymatic glucosylation could improve their solubility, stability and, consequently, their efficacy. The aim of this work was to study changes induced by addition of a glucose moiety on two polyphenols displaying very different chemical structures [caffeic acid (CA), epigallocatechin-3-gallate (EGCG) and there glucosylated form, Glc-CA and Glc-EGCG] by assessing their cytotoxic properties and their antioxidant and anti-inflammatory activities. Their antioxidant effect was assessed first by the classical DPPH radical-scavenging method. Then, a panel of human skin cells (keratinocytes, melanocytes, fibroblasts and endothelial cells) was used to evaluate their effect on cell toxicity and their antioxidant activities. With this aim, a photo-ageing model based on UV irradiation of skin cells was established. Molecule activity was assessed on reactive oxygen species (ROS) production, on superoxide dismutase (SOD) and catalase activities and, finally, on inflammatory factor production IL-6, IL-8 and IL-1β. In an acellular model, antioxidant activity assessed by DPPH method was strongly reduced for Glc-CA compared to CA, whereas it remained the same for Glc-EGCG compared to EGCG. Glucosylated derivatives did not display more toxic effect on various skin cells. Moreover, toxicity was even strongly reduced for caffeic acid upon glucosylation. The efficacy of glucosyl-compounds against UV-induced ROS production was preserved, both with pre- and post-UV treatments. Particularly, a better antioxidant efficacy was shown by Glc-EGCG, vs. EGCG, on keratinocytes. In addition, an induction of SOD and catalase activity was clearly observed for Glc-CA. Both glucosyl-polyphenols display the same activity as their parent molecule in decreasing inflammatory factor production. Our results demonstrated that enzymatic glucosylation of CA and EGCG led to an improved or preserved antioxidant activity in a cellular model of UV-induced skin ageing, despite the decrease in instantaneous antioxidant properties observed for Glc-CA. Glc-EGCG is specifically more active on keratinocytes, suggesting a specific targeting. Such glucosylated polyphenols displaying improved physicochemical and biological properties should be better candidates than natural ones for use in food additives and cosmetics. © 2014 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

Does outpatient physical therapy with the aim of improving health-related physical fitness influence the level of physical activity in patients with long-term musculoskeletal conditions?

PubMed

Holm, I; Tveter, A T; Moseng, T; Dagfinrud, H

2015-09-01

To evaluate any change in self-reported level of physical activity in patients receiving a general physical exercise programme in addition to disease-specific physiotherapy treatment. Pre-post-intervention study. Outpatient physiotherapy clinics. One hundred and ninety patients with long-term musculoskeletal conditions attending outpatient physiotherapy were recruited from seven physiotherapy clinics. Physiotherapy including disease-specific modalities and a general individually tailored exercise programme. Patients were evaluated at baseline and at the end of the programme. International Physical Activity Questionnaire short form (IPAQ-sf) and COOP WONCA functional assessment charts. Forty-two patients were excluded from the analysis because they did not complete the IPAQ-sf correctly or dropped out during the treatment period. There was a significant increase in the number of metabolic equivalent task (MET)-min/week for vigorous and moderate-intensity activities, walking and total physical activity. The number of exercise sessions per week increased from 1.8 [standard deviation (SD) 0.9] to 2.2 (SD 1.2) (P=0.001). The proportion of patients with a low level of physical activity decreased by 12%, and the proportion of the participants who did not/could not exercise decreased from 26% to 8%. The COOP WONCA charts showed significant improvements in the physical fitness, feelings, daily activities and social activities items. A significant increase was found in the number of MET-min/week for all activity levels. Therefore, a general physical exercise programme initiated by a physiotherapist led to a positive change in level of physical activity. Copyright © 2014 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

Exploring the specific features of interfacial enzymology based on lipase studies.

PubMed

Aloulou, Ahmed; Rodriguez, Jorge A; Fernandez, Sylvie; van Oosterhout, Dirk; Puccinelli, Delphine; Carrière, Frédéric

2006-09-01

Many enzymes are active at interfaces in the living world (such as in the signaling processes at the surface of cell membranes, digestion of dietary lipids, starch and cellulose degradation, etc.), but fundamental enzymology remains largely focused on the interactions between enzymes and soluble substrates. The biochemical and kinetic characterization of lipolytic enzymes has opened up new paths of research in the field of interfacial enzymology. Lipases are water-soluble enzymes hydrolyzing insoluble triglyceride substrates, and studies on these enzymes have led to the development of specific interfacial kinetic models. Structure-function studies on lipases have thrown light on the interfacial recognition sites present in the molecular structure of these enzymes, the conformational changes occurring in the presence of lipids and amphiphiles, and the stability of the enzymes present at interfaces. The pH-dependent activity, substrate specificity and inhibition of these enzymes can all result from both "classical" interactions between a substrate or inhibitor and the active site, as well as from the adsorption of the enzymes at the surface of aggregated substrate particles such as oil drops, lipid bilayers or monomolecular lipid films. The adsorption step can provide an alternative target for improving substrate specificity and developing specific enzyme inhibitors. Several data obtained with gastric lipase, classical pancreatic lipase, pancreatic lipase-related protein 2 and phosphatidylserine-specific phospholipase A1 were chosen here to illustrate these specific features of interfacial enzymology.

Improving the activity of the subtilisin nattokinase by site-directed mutagenesis and molecular dynamics simulation.

PubMed

Weng, Meizhi; Deng, Xiongwei; Bao, Wei; Zhu, Li; Wu, Jieyuan; Cai, Yongjun; Jia, Yan; Zheng, Zhongliang; Zou, Guolin

2015-09-25

Nattokinase (NK), a bacterial serine protease from Bacillus subtilis var. natto, is a potential cardiovascular drug exhibiting strong fibrinolytic activity. To broaden its commercial and medical applications, we constructed a single-mutant (I31L) and two double-mutants (M222A/I31L and T220S/I31L) by site-directed mutagenesis. Active enzymes were expressed in Escherichia coli with periplasmic secretion and were purified to homogeneity. The kinetic parameters of enzymes were examined by spectroscopy assay and isothermal titration calorimetry (ITC), and their fibrinolytic activities were determined by fibrin plate method. The substitution of Leu(31) for Ile(31) resulted in about 2-fold enhancement of catalytic efficiency (Kcat/KM) compared with wild-type NK. The specific activities of both double-mutants (M222A/I31L and T220S/I31L) were significantly increased when compared with the single-mutants (M222A and T220S) and the oxidative stability of M222A/I31L mutant was enhanced with respect to wild-type NK. This study demonstrates the feasibility of improving activity of NK by site-directed mutagenesis and shows successful protein engineering cases to improve the activity of NK as a potent therapeutic agent. Copyright © 2015 Elsevier Inc. All rights reserved.

Platelet Activating Factor Receptor Activation Improves siRNA Uptake and RNAi Responses in Well-differentiated Airway Epithelia.

PubMed

Krishnamurthy, Sateesh; Behlke, Mark A; Apicella, Michael A; McCray, Paul B; Davidson, Beverly L

2014-07-15

Well-differentiated human airway epithelia present formidable barriers to efficient siRNA delivery. We previously reported that treatment of airway epithelia with specific small molecules improves oligonucleotide uptake and facilitates RNAi responses. Here, we exploited the platelet activating factor receptor (PAFR) pathway, utilized by specific bacteria to transcytose into epithelia, as a trigger for internalization of Dicer-substrate siRNAs (DsiRNA). PAFR is a G-protein coupled receptor which can be engaged and activated by phosphorylcholine residues on the lipooligosaccharide (LOS) of nontypeable Haemophilus influenzae and the teichoic acid of Streptococcus pneumoniae as well as by its natural ligand, platelet activating factor (PAF). When well-differentiated airway epithelia were simultaneously treated with either nontypeable Haemophilus influenzae LOS or PAF and transduced with DsiRNA formulated with the peptide transductin, we observed silencing of both endogenous and exogenous targets. PAF receptor antagonists prevented LOS or PAF-assisted DsiRNA silencing, demonstrating that ligand engagement of PAFR is essential for this process. Additionally, PAF-assisted DsiRNA transfection decreased CFTR protein expression and function and reduced exogenous viral protein levels and titer in human airway epithelia. Treatment with spiperone, a small molecule identified using the Connectivity map database to correlate gene expression changes in response to drug treatment with those associated with PAFR stimulation, also induced silencing. These results suggest that the signaling pathway activated by PAFR binding can be manipulated to facilitate siRNA entry and function in difficult to transfect well-differentiated airway epithelial cells.

Long term cancer-specific anxiety in men undergoing active surveillance for prostate cancer: findings from a large prospective cohort.

PubMed

Marzouk, Karim; Assel, Melissa; Ehdaie, Behfar; Vickers, Andrew

2018-06-07

Active surveillance is the preferred management of men with low-risk prostate cancer. Cancer-specific anxiety during active surveillance remains understudied. We sought to report long-term anxiety for men on active surveillance to determine if interventions need to be tailored to improve adherence. Four hundred and thirteen men enrolled in active surveillance at a single tertiary care center completed quality of life surveys as part of routine care. A modified version of the Memorial Anxiety Scale for Prostate Cancer was used to determine cancer-specific anxiety. Generalized estimating equations evaluated the association between anxiety and length of time on surveillance. Additionally, we examined associations between anxiety and patient age, marital status, Gleason score, number of positive cores, family history, and overall health. The median age of men was 61 years with a median PSA at diagnosis 4.4 ng/ml; 95% of patients had Gleason 6 disease. The median time from initiation of active surveillance to last survey was 3.7 years. There was a 29% risk of reporting cancer-specific anxiety within the first year. Anxiety significantly decreased over time (OR=0.87; 95% CI: 0.79, 0.95; p=0.003). Pathologic and demographic characteristics were not associated with anxiety after adjusting for time on surveillance. In men undergoing active surveillance, we observed a moderate risk of cancer-specific anxiety that significantly decreases over time. Those considering conservative management can be informed that, although it is common experience some anxiety initially, most patients rapidly adjust and report low levels of anxiety within 2 years. Copyright © 2018 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Trypsin pre-treatment corrects SRID over-estimation of immunologically active, pre-fusion HA caused by mixed immunoprecipitin rings.

PubMed

Wen, Yingxia; Palladino, Giuseppe; Xie, Yuhong; Ferrari, Annette; Ma, Xiuwen; Han, Liqun; Dormitzer, Philip R; Settembre, Ethan C

2016-06-17

Influenza vaccines are the primary intervention to prevent the substantial health burden of seasonal and pandemic influenza. Subunit and split influenza vaccines are formulated, released for clinical use, and tested for stability based on their content of immunologically active (capable of eliciting functional antibodies) hemagglutinin (HA). Single-radial immunodiffusion (SRID), the standard in vitro potency assay in the field, is believed to specifically detect immunologically active HA. We confirmed that, with conformationally homogeneous HA preparations, SRID specifically detected native, pre-fusion HA, which elicited influenza neutralizing and hemagglutination inhibiting (HI) antibodies in mice, and it did not detect low-pH stressed, post-fusion HA, which was selectively removed from the SRID gel during a blotting step and was significantly less immunologically active. This selective detection was due to the SRID format, not a conformational specificity of the sheep antiserum used in the SRID, as the same antiserum detected non-stressed and low-pH stressed HA similarly when used in an ELISA format. However, when low-pH stressed HA was mixed with non-stressed HA, SRID detected both forms in mixed immunoprecipitin rings, leading to over-quantification of pre-fusion HA. We previously reported that trypsin digestion of antigen samples selectively degrade stressed HA, so that an otherwise conformationally insensitive biophysical quantification technique, reversed-phase high pressure liquid chromatography (RP-HPLC), can specifically quantify trypsin-resistant, immunologically active, pre-fusion HA. Here, we report that trypsin digestion can also improve the specificity of SRID so that it can quantify immunologically active, pre-fusion HA when it is mixed with less immunologically active, post-fusion HA. Copyright © 2016 Elsevier Ltd. All rights reserved.

Specific Uptake of Lipid-Antibody-Functionalized LbL Microcarriers by Cells.

PubMed

Göse, Martin; Scheffler, Kira; Reibetanz, Uta

2016-11-14

The modular construction of Layer-by-Layer biopolymer microcarriers facilitates a highly specific design of drug delivery systems. A supported lipid bilayer (SLB) contributes to biocompatibility and protection of sensitive active agents. The addition of a lipid anchor equipped with PEG (shielding from opsonins) and biotin (attachment of exchangeable outer functional molecules) enhances the microcarrier functionality even more. However, a homogeneously assembled supported lipid bilayer is a prerequisite for a specific binding of functional components. Our investigations show that a tightly packed SLB improves the efficiency of functional components attached to the microcarrier's surface, as illustrated with specific antibodies in cellular application. Only a low quantity of antibodies is needed to obtain improved cellular uptake rates independent from cell type as compared to an antibody-functionalized loosely packed lipid bilayer or directly assembled antibody onto the multilayer. A fast disassembly of the lipid bilayer within endolysosomes exposing the underlying drug delivering multilayer structure demonstrates the suitability of LbL-microcarriers as a multifunctional drug delivery system.

Effects of belimumab, a B lymphocyte stimulator-specific inhibitor, on disease activity across multiple organ domains in patients with systemic lupus erythematosus: combined results from two phase III trials.

PubMed

Manzi, Susan; Sánchez-Guerrero, Jorge; Merrill, Joan T; Furie, Richard; Gladman, Dafna; Navarra, Sandra V; Ginzler, Ellen M; D'Cruz, David P; Doria, Andrea; Cooper, Simon; Zhong, Z John; Hough, Douglas; Freimuth, William; Petri, Michelle A

2012-11-01

To evaluate the effects of belimumab versus placebo, plus standard systemic lupus erythematosus (SLE) therapy, on organ domain-specific SLE disease activity. Data obtained after 52 weeks of treatment from two phase III trials (BLISS-52 and BLISS-76) comparing belimumab 1 and 10 mg/kg versus placebo, plus standard therapy, in 1684 autoantibody-positive patients were analysed post hoc for changes in British Isles Lupus Assessment Group (BILAG) and Safety of Estrogens in Lupus National Assessment-Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) organ domain scores. At baseline, the domains involved in the majority of patients were musculoskeletal and mucocutaneous by both BILAG and SELENA-SLEDAI, and immunological by SELENA-SLEDAI. At 52 weeks, significantly more patients treated with belimumab versus placebo had improvement in BILAG musculoskeletal and mucocutaneous domains (1 and 10 mg/kg), and in SELENA-SLEDAI mucocutaneous (10 mg/kg), musculoskeletal (1 mg/kg) and immunological (1 and 10 mg/kg) domains. Improvement was also observed in other organ systems with a low prevalence (≤16%) at baseline, including the SELENA-SLEDAI vasculitis and central nervous system domains. Significantly fewer patients treated with belimumab versus placebo had worsening in the BILAG haematological domain (1 mg/kg) and in the SELENA-SLEDAI immunological (10 mg/kg), haematological (10 mg/kg) and renal (1 mg/kg) domains. Belimumab treatment improved overall SLE disease activity in the most common musculoskeletal and mucocutaneous organ domains. Less worsening occurred in the haematological, immunological and renal domains.

Neuroprotective Effects of Exercise Treatments After Injury: The Dual Role of Neurotrophic Factors

PubMed Central

Cobianchi, Stefano; Arbat-Plana, Ariadna; López-Álvarez, Víctor M.; Navarro, Xavier

2017-01-01

Background Shared connections between physical activity and neuroprotection have been studied for decades, but the mechanisms underlying this effect of specific exercise were only recently brought to light. Several evidences suggest that physical activity may be a reasonable and beneficial method to improve functional recovery in both peripheral and central nerve injuries and to delay functional decay in neurodegenerative diseases. In addition to improving cardiac and immune functions, physical activity may represent a multifunctional approach not only to improve cardiocirculatory and immune functions, but potentially modulating trophic factors signaling and, in turn, neuronal function and structure at times that may be critical for neurodegeneration and regeneration. Methods Research content related to the effects of physical activity and specific exercise programs in normal and injured nervous system have been reviewed. Results Sustained exercise, particularly if applied at moderate intensity and early after injury, exerts anti-inflammatory and pro-regenerative effects, and may boost cognitive and motor functions in aging and neurological disorders. However, newest studies show that exercise modalities can differently affect the production and function of brain-derived neurotrophic factor and other neurotrophins involved in the generation of neuropathic conditions. These findings suggest the possibility that new exercise strategies can be directed to nerve injuries with therapeutical benefits. Conclusion Considering the growing burden of illness worldwide, understanding of how modulation of neurotrophic factors contributes to exercise-induced neuroprotection and regeneration after peripheral nerve and spinal cord injuries is a relevant topic for research, and represents the beginning of a new non-pharmacological therapeutic approach for better rehabilitation of neural disorders. PMID:27026050

A Facile Stable-Isotope Dilution Method for Determination of Sphingosine Phosphate Lyase Activity

PubMed Central

Suh, Jung H.; Eltanawy, Abeer; Rangan, Apoorva; Saba, Julie D.

2015-01-01

A new technique for quantifying sphingosine phosphate lyase activity in biological samples is described. In this procedure, 2-hydrazinoquinoline is used to convert (2E)-hexadecenal into the corresponding hydrazone derivative to improve ionization efficiency and selectivity of detection. Combined utilization of liquid chromatographic separation and multiple reaction monitoring-mass spectrometry allows for simultaneous quantification of the substrate S1P and product (2E)-hexadecenal. Incorporation of (2E)-d5-hexadecenal as an internal standard improves detection accuracy and precision. A simple one-step derivatization procedure eliminates the need for further extractions. Limits of quantification for (2E)-hexadecenal and sphingosine-1-phosphate are 100 and 50 fmol, respectively. The assay displays a wide dynamic detection range useful for detection of low basal sphingosine phosphate lyase activity in wild type cells, SPL-overexpressing cell lines, and wild type mouse tissues. Compared to current methods, the capacity for simultaneous detection of sphingosine-1-phosphate and (2E)-hexadecenal greatly improves the accuracy of results and shows excellent sensitivity and specificity for sphingosine phosphate lyase activity detection. PMID:26408264

Making sense: Dopamine activates conscious self‐monitoring through medial prefrontal cortex

PubMed Central

Joensson, Morten; Thomsen, Kristine Rømer; Andersen, Lau M.; Gross, Joachim; Mouridsen, Kim; Sandberg, Kristian; Østergaard, Leif

2015-01-01

Abstract When experiences become meaningful to the self, they are linked to synchronous activity in a paralimbic network of self‐awareness and dopaminergic activity. This network includes medial prefrontal and medial parietal/posterior cingulate cortices, where transcranial magnetic stimulation may transiently impair self‐awareness. Conversely, we hypothesize that dopaminergic stimulation may improve self‐awareness and metacognition (i.e., the ability of the brain to consciously monitor its own cognitive processes). Here, we demonstrate improved noetic (conscious) metacognition by oral administration of 100 mg dopamine in minimal self‐awareness. In a separate experiment with extended self‐awareness dopamine improved the retrieval accuracy of memories of self‐judgment (autonoetic, i.e., explicitly self‐conscious) metacognition. Concomitantly, magnetoencephalography (MEG) showed increased amplitudes of oscillations (power) preferentially in the medial prefrontal cortex. Given that electromagnetic activity in this region is instrumental in self‐awareness, this explains the specific effect of dopamine on explicit self‐awareness and autonoetic metacognition. Hum Brain Mapp 36:1866–1877, 2015. © 2015 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.. PMID:25627861

Improved non-destructive method for 90Sr activity determination in aqueous solutions using Monte Carlo simulation.

PubMed

Samardžić, Selena; Milošević, Miodrag; Todorović, Nataša; Lakatoš, Robert

2018-04-04

The development of new methods and improvements of existing methods for the specific activity determination of 90 Sr and other distinct beta emitters has been of considerable interest. The reason for this interest is that the notably small number of methods that are able to meet all the set criteria, such as reliability of the results, measurement uncertainty and time, and minimum production of radioactive waste, as well as applicability to various samples with reference to their nature, geometry and composition. In this paper, two methods for rapid 90 Sr activity determination based on Monte Carlo simulations are used, one for a Si semiconductor detector for beta spectrometric measurements and the other for the Geiger-Muller (GM) ionization probe. To improve the reliability of the measurement results, samples with high and low strontium activity solutions were prepared in the form of dry residues. The results of the proposed methodology were verified with a standard method using a liquid scintillation counter, and notably good agreements are achieved. Copyright © 2018 Elsevier Ltd. All rights reserved.

Specific disruption of Lnk in murine endothelial progenitor cells promotes dermal wound healing via enhanced vasculogenesis, activation of myofibroblasts, and suppression of inflammatory cell recruitment.

PubMed

Lee, Jun Hee; Ji, Seung Taek; Kim, Jaeho; Takaki, Satoshi; Asahara, Takayuki; Hong, Young-Joon; Kwon, Sang-Mo

2016-10-28

Although endothelial progenitor cells (EPCs) contribute to wound repair by promoting neovascularization, the mechanism of EPC-mediated wound healing remains poorly understood due to the lack of pivotal molecular targets of dermal wound repair. We found that genetic targeting of the Lnk gene in EPCs dramatically enhances the vasculogenic potential including cell proliferation, migration, and tubule-like formation as well as accelerates in vivo wound healing, with a reduction in fibrotic tissue and improved neovascularization via significant suppression of inflammatory cell recruitment. When injected into wound sites, Lnk -/- EPCs gave rise to a significant number of new vessels, with remarkably increased survival of transplanted cells and decreased recruitment of cytotoxic T cells, macrophages, and neutrophils, but caused activation of fibroblasts in the wound-remodeling phase. Notably, in a mouse model of type I diabetes, transplanted Lnk -/- EPCs induced significantly better wound healing than Lnk +/+ EPCs did. The specific targeting of Lnk may be a promising EPC-based therapeutic strategy for dermal wound healing via improvement of neovascularization but inhibition of excessive inflammation as well as activation of myofibroblasts during dermal tissue remodeling.

Acute moderate exercise improves mnemonic discrimination in young adults.

PubMed

Suwabe, Kazuya; Hyodo, Kazuki; Byun, Kyeongho; Ochi, Genta; Yassa, Michael A; Soya, Hideaki

2017-03-01

Increasing evidence suggests that regular moderate exercise increases neurogenesis in the dentate gyrus (DG) of the hippocampus and improves memory functions in both humans and animals. The DG is known to play a role in pattern separation, which is the ability to discriminate among similar experiences, a fundamental component of episodic memory. While long-term voluntary exercise improves pattern separation, there is little evidence of alterations in DG function after an acute exercise session. Our previous studies showing acute moderate exercise-enhanced DG activation in rats, and acute moderate exercise-enhanced prefrontal activation and executive function in humans, led us to postulate that acute moderate exercise may also activate the hippocampus, including more specifically the DG, thus improving pattern separation. We thus investigated the effects of a 10-min moderate exercise (50% V̇O 2peak ) session, the recommended intensity for health promotion, on mnemonic discrimination (a behavioral index of pattern separation) in young adults. An acute bout of moderate exercise improved mnemonic discrimination performance in high similarity lures. These results support our hypothesis that acute moderate exercise improves DG-mediated pattern separation in humans, proposing a useful human acute-exercise model for analyzing the neuronal substrate underlying acute and regular exercise-enhanced episodic memory based on the hippocampus. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Acute Moderate Exercise Improves Mnemonic Discrimination in Young Adults

PubMed Central

Suwabe, Kazuya; Hyodo, Kazuki; Byun, Kyeongho; Ochi, Genta; Yassa, Michael A.; Soya, Hideaki

2018-01-01

Increasing evidence suggests that regular moderate exercise increases neurogenesis in the dentate gyrus (DG) of the hippocampus and improves memory functions in both humans and animals. The DG is known to play a role in pattern separation, which is the ability to discriminate among similar experiences, a fundamental component of episodic memory. While long-term voluntary exercise improves pattern separation, there is little evidence of alterations in DG function after an acute exercise session. Our previous studies showing acute moderate exercise-enhanced DG activation in rats, and acute moderate exercise-enhanced prefrontal activation and executive function in humans, led us to postulate that acute moderate exercise may also activate the hippocampus, including more specifically the DG, thus improving pattern separation. We thus investigated the effects of a 10-min moderate exercise (50% V̇O2peak) session, the recommended intensity for health promotion, on mnemonic discrimination (a behavioral index of pattern separation) in young adults. An acute bout of moderate exercise improved mnemonic discrimination performance in high similarity lures. These results support our hypothesis that acute moderate exercise improves DG-mediated pattern separation in humans, proposing a useful human acute-exercise model for analyzing the neuronal substrate underlying acute and regular exercise-enhanced episodic memory based on the hippocampus. PMID:27997992

Interventions for coordination of walking following stroke: systematic review.

PubMed

Hollands, Kristen L; Pelton, Trudy A; Tyson, Sarah F; Hollands, Mark A; van Vliet, Paulette M

2012-03-01

Impairments in gait coordination may be a factor in falls and mobility limitations after stroke. Therefore, rehabilitation targeting gait coordination may be an effective way to improve walking post-stroke. This review sought to examine current treatments that target impairments of gait coordination, the theoretical basis on which they are derived and the effects of such interventions. Few high quality RCTs with a low risk of bias specifically targeting and measuring restoration of coordinated gait were found. Consequently, we took a pragmatic approach to describing and quantifying the available evidence and included non-randomised study designs and limited the influence of heterogeneity in experimental design and control comparators by restricting meta-analyses to pre- and post-test comparisons of experimental interventions only. Results show that physiotherapy interventions significantly improved gait function and coordination. Interventions involving repetitive task-specific practice and/or auditory cueing appeared to be the most promising approaches to restore gait coordination. The fact that overall improvements in gait coordination coincided with increased walking speed lends support to the hypothesis that targeting gait coordination gait may be a way of improving overall walking ability post-stroke. However, establishing the mechanism for improved locomotor control requires a better understanding of the nature of both neuroplasticity and coordination deficits in functional tasks after stroke. Future research requires the measurement of impairment, activity and cortical activation in an effort to establish the mechanism by which functional gains are achieved. Copyright © 2011 Elsevier B.V. All rights reserved.

Novel in Vitro Modification of Bone for an Allograft with Improved Toughness Osteoconductivity

DTIC Science & Technology

2013-10-01

col1a1 by RT-PCR. High-performance liquid chromatography and fluorescence microscopy will be used to quantify AGEs and crosslinks. BODY The...molecular markers of mineralization, osteocalcin, Runx2 and col1a1 using quantitative RT-PCR with specific primers. (Months 14-15.) 5a. Preperation of...cellular activity and differentiation but not bone specific Collagen, type I, alpha 1 ( COL1A1 ) Associated with cell adhesion, proliferation and

Masked Chimeric Antigen Receptor for Tumor-Specific Activation.

PubMed

Han, Xiaolu; Bryson, Paul D; Zhao, Yifan; Cinay, Gunce E; Li, Si; Guo, Yunfei; Siriwon, Natnaree; Wang, Pin

2017-01-04

Adoptive cellular therapy based on chimeric antigen receptor (CAR)-engineered T (CAR-T) cells is a powerful form of cancer immunotherapy. CAR-T cells can be redirected to specifically recognize tumor-associated antigens (TAAs) and induce high levels of antitumor activity. However, they may also display "on-target off-tumor" toxicities, resulting from low-level expression of TAAs in healthy tissues. These adverse effects have raised considerable safety concerns and limited the clinical application of this otherwise promising therapeutic modality. To minimize such side effects, we have designed an epidermal growth factor receptor (EGFR)-specific masked CAR (mCAR), which consists of a masking peptide that blocks the antigen-binding site and a protease-sensitive linker. Proteases commonly active in the tumor microenvironment can cleave the linker and disengage the masking peptide, thereby enabling CAR-T cells to recognize target antigens only at the tumor site. In vitro mCAR showed dramatically reduced antigen binding and antigen-specific activation in the absence of proteases, but normal levels of binding and activity upon treatment with certain proteases. Masked CAR-T cells also showed antitumor efficacy in vivo comparable to that of unmasked CAR. Our study demonstrates the feasibility of improving the safety profile of conventional CARs and may also inspire future design of CAR molecules targeting broadly expressed TAAs. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

Mutation design of a thermophilic Rubisco based on three-dimensional structure enhances its activity at ambient temperature.

PubMed

Fujihashi, Masahiro; Nishitani, Yuichi; Kiriyama, Tomohiro; Aono, Riku; Sato, Takaaki; Takai, Tomoyuki; Tagashira, Kenta; Fukuda, Wakao; Atomi, Haruyuki; Imanaka, Tadayuki; Miki, Kunio

2016-10-01

Ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) plays a central role in carbon dioxide fixation on our planet. Rubisco from a hyperthermophilic archaeon Thermococcus kodakarensis (Tk-Rubisco) shows approximately twenty times the activity of spinach Rubisco at high temperature, but only one-eighth the activity at ambient temperature. We have tried to improve the activity of Tk-Rubisco at ambient temperature, and have successfully constructed several mutants which showed higher activities than the wild-type enzyme both in vitro and in vivo. Here, we designed new Tk-Rubisco mutants based on its three-dimensional structure and a sequence comparison of thermophilic and mesophilic plant Rubiscos. Four mutations were introduced to generate new mutants based on this strategy, and one of the four mutants, T289D, showed significantly improved activity compared to that of the wild-type enzyme. The crystal structure of the Tk-Rubisco T289D mutant suggested that the increase in activity was due to mechanisms distinct from those involved in the improvement in activity of Tk-Rubisco SP8, a mutant protein previously reported to show the highest activity at ambient temperature. Combining the mutations of T289D and SP8 successfully generated a mutant protein (SP8-T289D) with the highest activity to date both in vitro and in vivo. The improvement was particularly pronounced for the in vivo activity of SP8-T289D when introduced into the mesophilic, photosynthetic bacterium Rhodopseudomonas palustris, which resulted in a strain with nearly two-fold higher specific growth rates compared to that of a strain harboring the wild-type enzyme at ambient temperature. Proteins 2016; 84:1339-1346. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

34 CFR 607.7 - What definitions apply?

Code of Federal Regulations, 2013 CFR

2013-07-01

... incorporated into an implementation plan designed to meet one or more objectives. An activity is a part of a..., specifically designed to improve the self sufficiency of the school. Educational and general expenditures means the total amount expended by an institution of higher education for instruction, research, public...

34 CFR 607.7 - What definitions apply?

Code of Federal Regulations, 2012 CFR

2012-07-01

... incorporated into an implementation plan designed to meet one or more objectives. An activity is a part of a..., specifically designed to improve the self sufficiency of the school. Educational and general expenditures means the total amount expended by an institution of higher education for instruction, research, public...

34 CFR 607.7 - What definitions apply?

Code of Federal Regulations, 2010 CFR

2010-07-01

... incorporated into an implementation plan designed to meet one or more objectives. An activity is a part of a..., specifically designed to improve the self sufficiency of the school. Educational and general expenditures means the total amount expended by an institution of higher education for instruction, research, public...

34 CFR 607.7 - What definitions apply?

Code of Federal Regulations, 2014 CFR

2014-07-01

... incorporated into an implementation plan designed to meet one or more objectives. An activity is a part of a..., specifically designed to improve the self sufficiency of the school. Educational and general expenditures means the total amount expended by an institution of higher education for instruction, research, public...

34 CFR 607.7 - What definitions apply?

Code of Federal Regulations, 2011 CFR

2011-07-01

... incorporated into an implementation plan designed to meet one or more objectives. An activity is a part of a..., specifically designed to improve the self sufficiency of the school. Educational and general expenditures means the total amount expended by an institution of higher education for instruction, research, public...

Prodrugs for Improving Tumor Targetability and Efficiency

PubMed Central

Mahato, Rubi; Tai, Wanyi; Cheng, Kun

2011-01-01

As the mainstay in the treatment of various cancers for several decades, chemotherapy is successful but still faces challenges including non-selectivity and high toxicity. Improving the selectivity is therefore a critical step to improve the therapeutic efficacy of chemotherapy. Prodrug is one of the most promising approaches to increase the selectivity and efficacy of a chemotherapy drug. The classical prodrug approach is to improve the pharmaceutical properties (solubility, stability, permeability, irritation, distribution, etc.) via a simple chemical modification. This review will focus on various targeted prodrug designs that have been developed to increase the selectivity of chemotherapy drugs. Various tumor-targeting ligands, transporter-associated ligands, and polymers can be incorporated in a prodrug to enhance the tumor uptake. Prodrugs can also be activated by enzymes that are specifically expressed at a higher level in tumors, leading to a selective anti-tumor effect. This can be achieved by conjugating the enzyme to a tumor-specific antibody, or delivering a vector expressing the enzyme into tumor cells. PMID:21333700

Protective antitumor activity through dendritic cell immunization is mediated by NK cell as well as CTL activation.

PubMed

Kim, K D; Kim, J K; Kim, S J; Choe, I S; Chung, T H; Choe, Y K; Lim, J S

1999-08-01

Dendritic cells (DCs) are potent professional antigen-presenting cells (APC) capable of inducing the primary T cell response to antigen. Although tumor cells express target antigens, they are incapable of stimulating a tumor-specific immune response due to a defect in the costimulatory signal that is required for optimal activation of T cells. In this work, we describe a new approach using tumor-DC coculture to improve the antigen presenting capacity of tumor cells, which does not require a source of tumor-associated antigen. Immunization of a weakly immunogenic and progressive tumor cocultured with bone marrow-derived DCs generated an effective tumor vaccine. Immunization with the cocultured DCs was able to induce complete protective immunity against tumor challenges and was effective for the induction of tumor-specific CTL (cytotoxic T lymphocyte) activity. Furthermore, high NK cell activity was observed in mice in which tumors were rejected. In addition, immunization with tumor-pulsed DCs induced delayed tumor growth, but not tumor eradication in tumor-bearing mice. Our results demonstrate that coculture of DCs with tumors generated antitumor immunity due to the NK cell activation as well as tumor-specific T cell. This approach would be useful for designing tumor vaccines using DCs when the information about tumor antigens is limited.

Rational design and validation of a Tip60 histone acetyltransferase inhibitor

NASA Astrophysics Data System (ADS)

Gao, Chunxia; Bourke, Emer; Scobie, Martin; Famme, Melina Arcos; Koolmeister, Tobias; Helleday, Thomas; Eriksson, Leif A.; Lowndes, Noel F.; Brown, James A. L.

2014-06-01

Histone acetylation is required for many aspects of gene regulation, genome maintenance and metabolism and dysfunctional acetylation is implicated in numerous diseases, including cancer. Acetylation is regulated by histone acetyltransferases (HATs) and histone deacetylases and currently, few general HAT inhibitors have been described. We identified the HAT Tip60 as an excellent candidate for targeted drug development, as Tip60 is a key mediator of the DNA damage response and transcriptional co-activator. Our modeling of Tip60 indicated that the active binding pocket possesses opposite charges at each end, with the positive charges attributed to two specific side chains. We used structure based drug design to develop a novel Tip60 inhibitor, TH1834, to fit this specific pocket. We demonstrate that TH1834 significantly inhibits Tip60 activity in vitro and treating cells with TH1834 results in apoptosis and increased unrepaired DNA damage (following ionizing radiation treatment) in breast cancer but not control cell lines. Furthermore, TH1834 did not affect the activity of related HAT MOF, as indicated by H4K16Ac, demonstrating specificity. The modeling and validation of the small molecule inhibitor TH1834 represents a first step towards developing additional specific, targeted inhibitors of Tip60 that may lead to further improvements in the treatment of breast cancer.

Systematic identification of substrates for profiling of secreted proteases from Aspergillus species.

PubMed

Schaal, René; Kupfahl, Claudio; Buchheidt, Dieter; Neumaier, Michael; Findeisen, Peter

2007-11-01

Reliable and early diagnosis of life-threatening invasive mycoses in neutropenic patients caused by fungi of the Aspergillus species remains challenging because current clinical diagnostic tools lack in sensitivity and/or specificity. During invasive growth a variety of fungal proteases are secreted into the bloodstream and protease profiling with reporter peptides might improve diagnosis of invasive aspergillosis in serum specimens. To characterise the specific protease activity of Aspergillus fumigatus and Aspergillus niger we analyzed Aspergillus culture supernatants, human serum and the mixture of both. A systematic screening for optimised protease substrates was performed using a random peptide library consisting of 360 synthetic peptides featuring fluorescence resonance energy transfer (FRET). We could identify numerous peptides that are selectively cleaved by fungus-specific proteases. These reporter peptides might be feasible for future protease profiling of serum specimens to improve diagnosis and monitoring of invasive aspergillosis.

Detailed Structural Analyses of KOH Activated Carbon from Waste Coffee Beans

NASA Astrophysics Data System (ADS)

Takahata, Tomokazu; Toda, Ikumi; Ono, Hiroki; Ohshio, Shigeo; Akasaka, Hiroki; Himeno, Syuji; Kokubu, Toshinori; Saitoh, Hidetoshi

2009-11-01

The relationship of the detailed structural change of KOH activated carbon and hydrogen storage ability was investigated in activated carbon materials fabricated from waste coffee beans. The specific surface area of porous carbon materials calculated from N2 adsorption isotherms stood at 2070 m2/g when the weight ratio of KOH to carbon materials was 5:1, and pore size was in the range of approximately 0.6 to 1.1 nm as micropores. In the structural analysis, X-ray diffraction analysis and Raman spectroscopy indicated structural change in these carbon materials through KOH activation. The order of the graphite structure changed to a smaller scale with this activation. It is theorized that specific surface area increased using micropores provided by carbon materials developed from the descent of the graphite structure. Hydrogen storage ability improved with these structural changes, and reached 0.6 wt % at 2070 m2/g. These results suggest that hydrogen storage ability is conferred by the chemical effect on graphite of carbon materials.

Angiotensin-I converting enzyme (ACE): structure, biological roles, and molecular basis for chloride ion dependence.

PubMed

Masuyer, Geoffrey; Yates, Christopher J; Sturrock, Edward D; Acharya, K Ravi

2014-10-01

Somatic angiotensin-I converting enzyme (sACE) has an essential role in the regulation of blood pressure and electrolyte fluid homeostasis. It is a zinc protease that cleaves angiotensin-I (AngI), bradykinin, and a broad range of other signalling peptides. The enzyme activity is provided by two homologous domains (N- and C-), which display clear differences in substrate specificities and chloride activation. The presence of chloride ions in sACE and its unusual role in activity was identified early on in the characterisation of the enzyme. The molecular mechanisms of chloride activation have been investigated thoroughly through mutagenesis studies and shown to be substrate-dependent. Recent results from X-ray crystallography structural analysis have provided the basis for the intricate interactions between ACE, its substrate and chloride ions. Here we describe the role of chloride ions in human ACE and its physiological consequences. Insights into the chloride activation of the N- and C-domains could impact the design of improved domain-specific ACE inhibitors.

Expanding the Bioactive Chemical Space of Anthrabenzoxocinones through Engineering the Highly Promiscuous Biosynthetic Modification Steps.

PubMed

Mei, Xianyi; Yan, Xiaoli; Zhang, Hui; Yu, Mingjia; Shen, Guangqing; Zhou, Linjun; Deng, Zixin; Lei, Chun; Qu, Xudong

2018-01-19

Anthrabenzoxocinones (ABXs) including (-)-ABXs and (+)-ABXs are a group of bacterial FabF-specific inhibitors with potent antimicrobial activity of resistant strains. Optimization of their chemical structures is a promising method to develop potent antibiotics. Through biosynthetic investigation, we herein identified and characterized two highly promiscuous enzymes involved in the (-)-ABX structural modification. The promiscuous halogenase and methyltransferase can respectively introduce halogen-modifications into various positions of the ABX scaffolds and methylation to highly diverse substrates. Manipulation of their activity in both of the (-)-ABXs and (+)-ABXs biosyntheses led to the generation of 14 novel ABX analogues of both enantiomers. Bioactivity assessment revealed that a few of the analogues showed significantly improved antimicrobial activity, with the C3-hydroxyl and chlorine substitutions critical for their activity. This study enormously expands the bioactive chemical space of the ABX family and FabF-specific inhibitors. The disclosed broad-selective biosynthetic machineries and structure-activity relationship provide a solid basis for further generation of potent antimicrobial agents.

Voluntary control of intracortical oscillations for reconfiguration of network activity

PubMed Central

Corlier, Juliana; Valderrama, Mario; Navarrete, Miguel; Lehongre, Katia; Hasboun, Dominique; Adam, Claude; Belaid, Hayat; Clémenceau, Stéphane; Baulac, Michel; Charpier, Stéphane; Navarro, Vincent; Le Van Quyen, Michel

2016-01-01

Voluntary control of oscillatory activity represents a key target in the self-regulation of brain function. Using a real-time closed-loop paradigm and simultaneous macro- and micro-electrode recordings, we studied the effects of self-induced intracortical oscillatory activity (4–8 Hz) in seven neurosurgical patients. Subjects learned to robustly and specifically induce oscillations in the target frequency, confirmed by increased oscillatory event density. We have found that the session-to-session variability in performance was explained by the functional long-range decoupling of the target area suggesting a training-induced network reorganization. Downstream effects on more local activities included progressive cross-frequency-coupling with gamma oscillations (30–120 Hz), and the dynamic modulation of neuronal firing rates and spike timing, indicating an improved temporal coordination of local circuits. These findings suggest that effects of voluntary control of intracortical oscillations can be exploited to specifically target plasticity processes to reconfigure network activity, with a particular relevance for memory function or skill acquisition. PMID:27808225

Identification of New Drug Targets in Multi-Drug Resistant Bacterial Infections

DTIC Science & Technology

2013-10-01

observation allowed us to improve the substrate specificity assay and identify that threonine serves as an optimal substrate in the pyrophosphate exchange...activity was obtained, and the activity now seems to be optimal with the small hydroxyl containing amino acids threonine and serine. These... diabetic ulcers are favored sites of infection (6, 7). A. baumannii has also been shown to cause infections outside the health care setting, namely, severe

Robots integrated with virtual reality simulations for customized motor training in a person with upper extremity hemiparesis: a case report

PubMed Central

Fluet, Gerard G.; Merians, Alma S.; Qiu, Qinyin; Lafond, Ian; Saleh, Soha; Ruano, Viviana; Delmonico, Andrea R.; Adamovich, Sergei V.

2014-01-01

Background and Purpose A majority of studies examining repetitive task practice facilitated by robots for the treatment of upper extremity paresis utilize standardized protocols applied to large groups. Others utilize interventions tailored to patients but don't describe the clinical decision making process utilized to develop and modify interventions. This case report will describe a robot-based intervention customized to match the goals and clinical presentation of a gentleman with upper extremity hemiparesis secondary to stroke. Methods PM is an 85 year-old man with left hemiparesis secondary to an intracerebral hemorrhage five years prior to examination. Outcomes were measured before and after a one month period of home therapy and after a one month robotic intervention. The intervention was designed to address specific impairments identified during his PT examination. When necessary, activities were modified based on the patient's response to his first week of treatment. Outcomes PM trained twelve sessions using six virtually simulated activities. Modifications to original configurations of these activities resulted in performance improvements in five of these activities. PM demonstrated a 35 second improvement in Jebsen Test of Hand Function time and a 44 second improvement in Wolf Motor Function Test time subsequent to the robotic training intervention. Reaching kinematics, 24 hour activity measurement and the Hand and Activities of Daily Living scales of the Stroke Impact Scale all improved as well. Discussion A customized program of robotically facilitated rehabilitation resulted in large short-term improvements in several measurements of upper extremity function in a patient with chronic hemiparesis. PMID:22592063

Enhancement of a prosthetic knee with a microprocessor-controlled gait phase switch reduces falls and improves balance confidence and gait speed in community ambulators with unilateral transfemoral amputation.

PubMed

Fuenzalida Squella, Sara Agueda; Kannenberg, Andreas; Brandão Benetti, Ângelo

2018-04-01

Despite the evidence for improved safety and function of microprocessor stance and swing-controlled prosthetic knees, non-microprocessor-controlled prosthetic knees are still standard of care for persons with transfemoral amputations in most countries. Limited feature microprocessor-control enhancement of such knees could stand to significantly improve patient outcomes. To evaluate gait speed, balance, and fall reduction benefits of the new 3E80 default stance hydraulic knee compared to standard non-microprocessor-controlled prosthetic knees. Comparative within-subject clinical study. A total of 13 young, high-functioning community ambulators with a transfemoral amputation underwent assessment of performance-based (e.g. 2-min walk test, timed ramp/stair tests) and self-reported (e.g. falls, Activities-Specific Balance Confidence scale, Prosthesis Evaluation Questionnaire question #1, Satisfaction with the Prosthesis) outcome measures for their non-microprocessor-controlled prosthetic knees and again after 8 weeks of accommodation to the 3E80 microprocessor-enhanced knee. Self-reported falls significantly declined 77% ( p = .04), Activities-Specific Balance Confidence scores improved 12 points ( p = .005), 2-min walk test walking distance increased 20 m on level ( p = .01) and uneven ( p = .045) terrain, and patient satisfaction significantly improved ( p < .01) when using the 3E80 knee. Slope and stair ambulation performance did not differ between knee conditions. The 3E80 knee reduced self-reported fall incidents and improved balance confidence. Walking performance on both level and uneven terrains also improved compared to non-microprocessor-controlled prosthetic knees. Subjects' satisfaction was significantly higher than with their previous non-microprocessor-controlled prosthetic knees. The 3E80 may be considered a prosthetic option for improving gait performance, balance confidence, and safety in highly active amputees. Clinical relevance This study compared performance-based and self-reported outcome measures when using non-microprocessor and a new microprocessor-enhanced, default stance rotary hydraulic knee. The results inform rehabilitation professionals about the functional benefits of a limited-feature, microprocessor-enhanced hydraulic prosthetic knee over standard non-microprocessor-controlled prosthetic knees.

SPECIFICITY OF IMPROVED METHODS FOR MYCOBACTIN BIOASSAY BY ARTHROBACTER TERREGENS

PubMed Central

Antoine, Alan D.; Morrison, Norman E.; Hanks, John H.

1964-01-01

Antoine, Alan D. (Johns Hopkins University-Leonard Wood Memorial Leprosy Research Laboratory, Baltimore, Md.), Norman E. Morrison, and John H. Hanks. Specificity of improved methods for mycobactin bioassay by Arthrobacter terregens. J. Bacteriol. 88:1672–1677. 1964.—Arthrobacter terregens was used to assay mycobactin, a growth factor for Mycobacterium paratuberculosis. Improved techniques permit the assay of mycobactin within 3 to 4 days by agarplate or liquid-medium methods. For the agarplate method, Arthrobacter terregens gave linear increases in zonal growth at mycobactin concentrations of 0.07 to 0.30 μg per spot; for the liquid-medium method, linear increases in turbidimetric growth occurred at 0.05 to 0.27 μg/ml. Specificity studies show that the mycobactin hydrolytic products, cobactin and mycobactic acid, function as growth stimulators, but the high concentrations required would produce only minimal interference in mycobactin assays. Furthermore, the response to mycobactic acid is characterized by a delayed response of 3 days. Various synthetic hydroxylamine-containing compounds and metalchelating agents cannot replace the biological activity of mycobactin. Diacetylmycobactin is 7.4 times more effective than mycobactin as a growth stimulator. PMID:14240956

Acceptance and Commitment Therapy modules: Differential impact on treatment processes and outcomes.

PubMed

Villatte, Jennifer L; Vilardaga, Roger; Villatte, Matthieu; Plumb Vilardaga, Jennifer C; Atkins, David C; Hayes, Steven C

2016-02-01

A modular, transdiagnostic approach to treatment design and implementation may increase the public health impact of evidence-based psychosocial interventions. Such an approach relies on algorithms for selecting and implementing treatment components intended to have a specific therapeutic effect, yet there is little evidence for how components function independent of their treatment packages when employed in clinical service settings. This study aimed to demonstrate the specificity of treatment effects for two components of Acceptance and Commitment Therapy (ACT), a promising candidate for modularization. A randomized, nonconcurrent, multiple-baseline across participants design was used to examine component effects on treatment processes and outcomes in 15 adults seeking mental health treatment. The ACT OPEN module targeted acceptance and cognitive defusion; the ACT ENGAGED module targeted values-based activation and persistence. According to Tau-U analyses, both modules produced significant improvements in psychiatric symptoms, quality of life, and targeted therapeutic processes. ACT ENGAGED demonstrated greater improvements in quality of life and values-based activation. ACT OPEN showed greater improvements in symptom severity, acceptance, and defusion. Both modules improved awareness and non-reactivity, which were mutually targeted, though using distinct intervention procedures. Both interventions demonstrated high treatment acceptability, completion, and patient satisfaction. Treatment effects were maintained at 3-month follow up. ACT components should be considered for inclusion in a modular approach to implementing evidence-based psychosocial interventions for adults. Copyright © 2015 Elsevier Ltd. All rights reserved.

Improving Diversity and Educational Outreach at the K-14 level: A Call to Action for the AGU Membership

NASA Astrophysics Data System (ADS)

Hall, F. R.; Johnson, R.

2002-12-01

In 2002, the Subcommittee on Diversity (SD) of the Committee on Education and Human Resources (CEHR) submitted a Diversity Plan to the leadership of AGU. This plan outlines specific programs and goals that AGU can follow to help improve diversity in the Earth and space sciences. Diversity issues are key components to improve the human resource potential in the geosciences. As women are the majority population, and racial and ethnic minorities are experiencing the largest growing segment of the United States population, it is within our best interest to actively recruit and retain these populations into our dynamic fields of study. The SD recognizes that the strength of the AGU lies within its membership. Composed of some of the brightest and talented scientists in the world, the AGU members are leaders and pioneers in our understanding of the Earth System. Yet, many, if not most, people within underrepresented communities are not aware of the relevance that the Earth and space sciences play in their lives. In this discussion, we will discuss the importance of the AGU membership in the Diversity Plan. In addition, we will outline specific things that AGU members can do to improve access of US students and citizenry to Earth and space science education. These steps require that AGU members become active advocates in the public, especially at the K-14 level.

CD28z CARs and Armored CARs

PubMed Central

Pegram, Hollie J.; Park, Jae H.; Brentjens, Renier J.

2015-01-01

CD19-targeted chimeric antigen receptor (CAR) T cells are currently being tested in the clinic with very promising outcomes. However, limitations to CAR T cell therapy exist. These include lack of efficacy against some tumors, specific targeting of tumor cells without affecting normal tissue and retaining activity within the suppressive tumor microenvironment. Whilst promising clinical trials are in progress, preclinical development is focused on optimizing CAR design, to generate “armored CAR T cells” which are protected from the inhibitory tumor microenvironment. Studies investigating the expression of cytokine transgenes, combination therapy with small molecule inhibitors or monoclonal antibodies are aimed at improving the anti-tumor efficacy of CAR T cell therapy. Other strategies aimed at improving CAR T cell therapy include utilizing dual CARs and chemokine receptors to more specifically target tumor cells. This review will describe the current clinical data and some novel “armored CAR T cell” approaches for improving anti-tumor efficacy therapy. PMID:24667958

CD28z CARs and armored CARs.

PubMed

Pegram, Hollie J; Park, Jae H; Brentjens, Renier J

2014-01-01

CD19-targeted chimeric antigen receptor (CAR) T cells are currently being tested in the clinic with very promising outcomes. However, limitations to CAR T cell therapy exist. These include lack of efficacy against some tumors, specific targeting of tumor cells without affecting normal tissue and retaining activity within the suppressive tumor microenvironment. Whereas promising clinical trials are in progress, preclinical development is focused on optimizing CAR design, to generate "armored CAR T cells," which are protected from the inhibitory tumor microenvironment. Studies investigating the expression of cytokine transgenes, combination therapy with small molecule inhibitors, or monoclonal antibodies, are aimed at improving the antitumor efficacy of CAR T cell therapy. Other strategies aimed at improving CAR T cell therapy include using dual CARs and chemokine receptors to more specifically target tumor cells. This review will describe the current clinical data and some novel armored CAR T cell approaches for improving antitumor efficacy therapy.

The effect of a Lean quality improvement implementation program on surgical pathology specimen accessioning and gross preparation error frequency.

PubMed

Smith, Maxwell L; Wilkerson, Trent; Grzybicki, Dana M; Raab, Stephen S

2012-09-01

Few reports have documented the effectiveness of Lean quality improvement in changing anatomic pathology patient safety. We used Lean methods of education; hoshin kanri goal setting and culture change; kaizen events; observation of work activities, hand-offs, and pathways; A3-problem solving, metric development, and measurement; and frontline work redesign in the accessioning and gross examination areas of an anatomic pathology laboratory. We compared the pre- and post-Lean implementation proportion of near-miss events and changes made in specific work processes. In the implementation phase, we documented 29 individual A3-root cause analyses. The pre- and postimplementation proportions of process- and operator-dependent near-miss events were 5.5 and 1.8 (P < .002) and 0.6 and 0.6, respectively. We conclude that through culture change and implementation of specific work process changes, Lean implementation may improve pathology patient safety.

Physical activity discrimination improvement using accelerometers and wireless sensor network localization - biomed 2013.

PubMed

Bashford, Gregory R; Burnfield, Judith M; Perez, Lance C

2013-01-01

Automating documentation of physical activity data (e.g., duration and speed of walking or propelling a wheelchair) into the electronic medical record (EMR) offers promise for improving efficiency of documentation and understanding of best practices in the rehabilitation and home health settings. Commercially available devices which could be used to automate documentation of physical activities are either cumbersome to wear or lack the specificity required to differentiate activities. We have designed a novel system to differentiate and quantify physical activities, using inexpensive accelerometer-based biomechanical data technology and wireless sensor networks, a technology combination that has not been used in a rehabilitation setting to date. As a first step, a feasibility study was performed where 14 healthy young adults (mean age = 22.6 ± 2.5 years, mean height = 173 ± 10.0 cm, mean mass = 70.7 ± 11.3 kg) carried out eight different activities while wearing a biaxial accelerometer sensor. Activities were performed at each participant’s self-selected pace during a single testing session in a controlled environment. Linear discriminant analysis was performed by extracting spectral parameters from the subjects’ accelerometer patterns. It is shown that physical activity classification alone results in an average accuracy of 49.5%, but when combined with rule-based constraints using a wireless sensor network with localization capabilities in an in silico simulated room, accuracy improves to 99.3%. When fully implemented, our technology package is expected to improve goal setting, treatment interventions and patient outcomes by enhancing clinicians’ understanding of patients’ physical performance within a day and across the rehabilitation program.

Activity measurement and effective dose modelling of natural radionuclides in building material.

PubMed

Maringer, F J; Baumgartner, A; Rechberger, F; Seidel, C; Stietka, M

2013-11-01

In this paper the assessment of natural radionuclides' activity concentration in building materials, calibration requirements and related indoor exposure dose models is presented. Particular attention is turned to specific improvements in low-level gamma-ray spectrometry to determine the activity concentration of necessary natural radionuclides in building materials with adequate measurement uncertainties. Different approaches for the modelling of the effective dose indoor due to external radiation resulted from natural radionuclides in building material and results of actual building material assessments are shown. Copyright © 2013 Elsevier Ltd. All rights reserved.

Active Travel Behavior in a Border Region of Texas and New Mexico: Motivators, Deterrents, and Characteristics.

PubMed

Sener, Ipek N; Lee, Richard J

2017-08-01

Active travel has been linked with improved transportation and health outcomes, such as reduced traffic congestion and air pollution, improved mobility, accessibility, and equity, and increased physical and mental health. The purpose of this study was to better understand active travel characteristics, motivators, and deterrents in the El Paso, TX, region. A multimodal transportation survey brought together elements of transportation and health, with a focus on attitudinal characteristics. The analysis consisted of an initial descriptive analysis, spatial analysis, and multivariate binary and ordered-response models of walking and bicycling behavior. The motivators and deterrents of active travel differed for walkers, bicyclists, and noncyclists interested in bicycling. The link between active travel and life satisfaction was moderated by age, with a negative association for older travelers. This effect was stronger for bicycling than it was for walking. Based on the findings, several interventions to encourage walking and bicycling were suggested. These included infrastructure and built environment enhancements, workplace programs, and interventions targeting specific subpopulations.

Respiratory motor training and neuromuscular plasticity in patients with chronic obstructive pulmonary disease: A pilot study.

PubMed

Ovechkin, Alexander V; Sayenko, Dimitry G; Ovechkina, Elena N; Aslan, Sevda C; Pitts, Teresa; Folz, Rodney J

2016-07-15

The objective of this study was to examine the feasibility of a full-scale investigation of the neurophysiological mechanisms of COPD-induced respiratory neuromuscular control deficits. Characterization of respiratory single- and multi-muscle activation patterns using surface electromyography (sEMG) were assessed along with functional measures at baseline and following 21±2 (mean±SD) sessions of respiratory motor training (RMT) performed during a one-month period in four patients with GOLD stage II or III COPD. Pre-training, the individuals with COPD showed significantly increased (p<0.05) overall respiratory muscle activity and disorganized multi-muscle activation patterns in association with lowered spirometrical measures and decreased fast- and slow-twitch fiber activity as compared to healthy controls (N=4). Following RMT, functional and respiratory sEMG activation outcomes during quite breathing and forced expiratory efforts were improved suggesting that functional improvements, induced by task-specific RMT, are evidence respiratory neuromuscular networks re-organization. Published by Elsevier B.V.

Systematic Review of the Effectiveness of Occupational Therapy–Related Interventions for People With Parkinson’s Disease

PubMed Central

Foster, Erin R.; Bedekar, Mayuri

2014-01-01

We describe the results of a systematic review of the literature on occupational therapy–related interventions for people with Parkinson’s disease (PD). Three broad categories of intervention emerged: (1) exercise or physical activity; (2) environmental cues, stimuli, and objects; and (3) self-management and cognitive–behavioral strategies. Moderate to strong evidence exists for task-specific benefits of targeted physical activity training on motor performance, postural stability, and balance. Low to moderate evidence indicates that more complex, multimodal activity training supports improvement in functional movement activities. The evidence is moderate that the use of external supports during functional mobility or other movement activities has positive effects on motor control. In addition, moderate evidence is available that individualized interventions focused on promoting participant wellness initiatives and personal control by means of cognitive–behavioral strategies can improve targeted areas of quality of life. The implications for practice, education, and research are discussed. PMID:24367954

Cytochrome P450 Bioconjugate as a Nanovehicle for Improved Chemotherapy Treatment.

PubMed

Quester, Katrin; Juarez-Moreno, Karla; Secundino, Isamel; Roseinstein, Yvonne; Alejo, Karla P; Huerta-Saquero, Alejandro; Vazquez-Duhalt, Rafael

2017-05-01

Cancer is still a growing public health problem, especially breast cancer that is one of the most important cancers in women. Chemotherapy, even though a successful treatment, is accompanied by severe side effects. Moreover, most of the drugs used for chemotherapy are administered as prodrugs and need to be transformed to the active form by cytochromes P450 (CYPs). In addition, increasing numbers of cancer tissues show lower CYP activity than the surrounding healthy tissues in which prodrugs are preferentially activated causing cytotoxicity. Here, the design of a functionalized cytochrome P450 bioconjugate is reported as nanovehicle for the enzyme direct delivery to the tumor tissue in order to improve the local drug activation. MCF-7 breast cancer cells are treated with CYP-polyethylene glycol bioconjugate functionalized folic acid, where it activates the prodrug tamoxifen and significantly reduces the dose of tamoxifen needed to kill the tumor cells. The CYP bioconjugate covered with polyethylene glycol shows no immunogenic activity. The advantages of increasing the site-specific CYP activity in tumor tissues are discussed. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

An investigation into non-invasive physical activity recognition using smartphones.

PubMed

Kelly, Daniel; Caulfield, Brian

2012-01-01

Technology utilized to automatically monitor Activities of Daily Living (ADL) could be a key component in identifying deviations from normal functional profiles and providing feedback on interventions aimed at improving health. However, if activity recognition systems are to be implemented in real world scenarios such as health and wellness monitoring, the activity sensing modality must unobtrusively fit the human environment rather than forcing humans to adhere to sensor specific conditions. Modern smart phones represent a ubiquitous computing device which has already undergone mainstream adoption. In this paper, we investigate the feasibility of using a modern smartphone, with limited placement constraints, as the sensing modality for an activity recognition system. A dataset of 4 subjects performing 7 activities, using varying sensor placement conditions, is utilized to investigate this. Initial experiments show that a decision tree classifier performs activity classification with precision and recall scores of 0.75 and 0.73 respectively. More importantly, as part of this initial experiment, 3 main problems, and subsequently 3 solutions, relating to unconstrained sensor placement were identified. Using our proposed solutions, classification precision and recall scores were improved by +13% and +14.6% respectively.

The minimum information about a genome sequence (MIGS) specification

PubMed Central

Field, Dawn; Garrity, George; Gray, Tanya; Morrison, Norman; Selengut, Jeremy; Sterk, Peter; Tatusova, Tatiana; Thomson, Nicholas; Allen, Michael J; Angiuoli, Samuel V; Ashburner, Michael; Axelrod, Nelson; Baldauf, Sandra; Ballard, Stuart; Boore, Jeffrey; Cochrane, Guy; Cole, James; Dawyndt, Peter; De Vos, Paul; dePamphilis, Claude; Edwards, Robert; Faruque, Nadeem; Feldman, Robert; Gilbert, Jack; Gilna, Paul; Glöckner, Frank Oliver; Goldstein, Philip; Guralnick, Robert; Haft, Dan; Hancock, David; Hermjakob, Henning; Hertz-Fowler, Christiane; Hugenholtz, Phil; Joint, Ian; Kagan, Leonid; Kane, Matthew; Kennedy, Jessie; Kowalchuk, George; Kottmann, Renzo; Kolker, Eugene; Kravitz, Saul; Kyrpides, Nikos; Leebens-Mack, Jim; Lewis, Suzanna E; Li, Kelvin; Lister, Allyson L; Lord, Phillip; Maltsev, Natalia; Markowitz, Victor; Martiny, Jennifer; Methe, Barbara; Mizrachi, Ilene; Moxon, Richard; Nelson, Karen; Parkhill, Julian; Proctor, Lita; White, Owen; Sansone, Susanna-Assunta; Spiers, Andrew; Stevens, Robert; Swift, Paul; Taylor, Chris; Tateno, Yoshio; Tett, Adrian; Turner, Sarah; Ussery, David; Vaughan, Bob; Ward, Naomi; Whetzel, Trish; Gil, Ingio San; Wilson, Gareth; Wipat, Anil

2008-01-01

With the quantity of genomic data increasing at an exponential rate, it is imperative that these data be captured electronically, in a standard format. Standardization activities must proceed within the auspices of open-access and international working bodies. To tackle the issues surrounding the development of better descriptions of genomic investigations, we have formed the Genomic Standards Consortium (GSC). Here, we introduce the minimum information about a genome sequence (MIGS) specification with the intent of promoting participation in its development and discussing the resources that will be required to develop improved mechanisms of metadata capture and exchange. As part of its wider goals, the GSC also supports improving the ‘transparency’ of the information contained in existing genomic databases. PMID:18464787

Challenges and prospects of chimeric antigen receptor T cell therapy in solid tumors.

PubMed

Jindal, Vishal; Arora, Ena; Gupta, Sorab

2018-05-05

Chimeric antigen receptor (CAR) T cell therapy is a novel and innovative immunotherapy. CAR-T cells are genetically engineered T cells, carrying MHC independent specific antigen receptor and co-stimulatory molecule which can activate an immune response to a cancer specific antigen. This therapy showed great results in hematological malignancies but were unable to prove their worth in solid tumors. Likely reasons for their failure are lack of antigens, poor trafficking, and hostile tumor microenvironment. Excessive amount of research is going on to improve the efficacy of CAR T cell therapy in solid tumors. In this article, we will discuss the challenges faced in improving the outcome of CAR T cell therapy in solid tumors and various strategies adopted to curb them.

Designing and Assessing Learning

ERIC Educational Resources Information Center

Quan, Hong; Liu, Dandan; Cun, Xiangqin; Lu, Yingchun

2009-01-01

This paper analyses the design, implementation and assessment of a level 2 module for non-English major students in higher vocational and professional education. 1132001 is a code of module that uses active methods to teach college English in China. It specifically reflects on the module's advantage and defect for developing and improving learning…

75 FR 9220 - Meeting of the Advisory Committee on Minority Health

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-01

... each racial and ethnic minority group and on the development of goals and specific program activities... to improve the health of racial and ethnic minority populations through the development of health... designated contact person at least fourteen (14) business days prior to the meeting. Members of the public...

48 CFR 1602.170-14 - FEHB-specific medical loss ratio threshold calculation.

Code of Federal Regulations, 2014 CFR

2014-10-01

... issuer's expenditures for activities that improve health care quality, to total premium revenue determined by OPM, as defined by the Department of Health and Human Services in 45 CFR part 158. (b) The FEHB... OFFICE OF PERSONNEL MANAGEMENT FEDERAL EMPLOYEES HEALTH BENEFITS ACQUISITION REGULATION GENERAL...

48 CFR 1602.170-14 - FEHB-specific medical loss ratio threshold calculation.

Code of Federal Regulations, 2013 CFR

2013-10-01

... issuer's expenditures for activities that improve health care quality, to total premium revenue determined by OPM, as defined by the Department of Health and Human Services in 45 CFR part 158. (b) The FEHB... OFFICE OF PERSONNEL MANAGEMENT FEDERAL EMPLOYEES HEALTH BENEFITS ACQUISITION REGULATION GENERAL...

48 CFR 1602.170-14 - FEHB-specific medical loss ratio threshold calculation.

Code of Federal Regulations, 2012 CFR

2012-10-01

... issuer's expenditures for activities that improve health care quality, to total premium revenue determined by OPM, as defined by the Department of Health and Human Services in 45 CFR part 158. (b) The FEHB... OFFICE OF PERSONNEL MANAGEMENT FEDERAL EMPLOYEES HEALTH BENEFITS ACQUISITION REGULATION GENERAL...

78 FR 48472 - Notice of Entering into a Compact with Georgia

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-08

... assessments. The project consists of three activities, which were targeted to specifically improve math and... approximately 23,400 math, science, information and communications technology, and English teachers in grades 7... approximately six national assessments focused on math and science, and the development of a system of classroom...

A Unique Approach to Programming for the Preschool Child.

ERIC Educational Resources Information Center

Bert, Diane K.; Levenson, Joan

This short paper describes the Parent Readiness Education Project (PREP), a successful innovative effort to ameliorate the deficiencies of preschool children by training parents to enrich their home environment and improve interactions with their children through a specific program of daily home activities. PREP identifies 4-year-old children with…

The Effects of Peer-Administered Token Reinforcement on Jump Rope Behaviors of Elementary Physical Education Students

ERIC Educational Resources Information Center

Alstot, Andrew E.

2012-01-01

Token economies have a long research and applied history within clinical settings and classroom education (Kazdin, 1982). However, despite reported successes in improving physical activity behaviors (Alstot, 2012), research examining token reinforcement implemented specifically in physical education is virtually nonexistent. Therefore, the purpose…

Cross-Curricular Skills Development in Final-Year Dissertation by Active and Collaborative Methodologies

ERIC Educational Resources Information Center

Etaio, Iñaki; Churruca, Itziar; Rada, Diego; Miranda, Jonatan; Saracibar, Amaia; Sarrionandia, Fernando; Lasa, Arrate; Simón, Edurne; Labayen, Idoia; Martinez, Olaia

2018-01-01

European Frame for Higher Education has led universities to adapt their teaching schemes. Degrees must train students in competences including specific and cross-curricular skills. Nevertheless, there are important limitations to follow skill improvement through the consecutive academic years. Final-year dissertation (FYD) offers the opportunity…

A Practical Approach to Sex Fair Performance Evaluation in Secondary Physical Education.

ERIC Educational Resources Information Center

McGonagle, Kenneth; Stevens, Ann

A method of sex-fair performance evaluation is presented which can be used in coeducational secondary school physical education classes. This method tallies specific skill areas associated with athletic activities, disregarding such concepts as student improvement, level of competition, participation, effort, and exact skill measurement.…

Using a Wiki to Produce Journalistic Best Practices

ERIC Educational Resources Information Center

Hoewe, Jennifer; Bowe, Brian J.; Zeldes, Geri Alumit

2012-01-01

The difficult nature of reporting accurately and objectively on religion, coupled with world events and discrimination against Muslims, motivated a pilot course called "Reporting on Islam." The activity detailed in this article addressed two issues--improving the coverage of religion, specifically Islam, in the news media and using communication…

Improving Attachments of Non-Invasive (Type III) Electronic Data Loggers to Cetaceans

DTIC Science & Technology

2014-09-30

the assessment tag impact on animal health and well-being. Specifically, we are working to develop methods that will enable the accurate estimates...currently not available for any marine mammal, about animal health and activity has the potential to revolutionize how animals are cared for in these

Engineered and Other Wood Products - An Opportunity to "Grow the Pie"

Treesearch

Albert Schuler; Craig Adair

2003-01-01

The market for engineered wood products (EWP) is being driven by a number of factors including: technology; reduced availability of old-growth timber; construction activity, and globalization. Specifically, technological developments have allowed the industry to "engineer" or "design" improved performance properties and to utilize former "weed...

Developing Confidence within Girls through Self-Defense Education

ERIC Educational Resources Information Center

Banks, Aaron L.

2012-01-01

Through physical activity, physical educators have long sought to improve the self-efficacy and self-esteem in girls and young woman. Current research indicates that self-defense education may have a positive psychological impact on female participants, specifically regarding the development of self-efficacy and self-esteem. Through participation…

DESIGNS FOR ESTIMATING VARIABILITY STRUCTURE AND IMPLICATIONS FOR DETECTING WATERSHED RESTORATION EFFECTIVENESS

EPA Science Inventory

The evaluation of stream restoration projects is moving from a focus on project specific effectiveness to a more holistic evaluation of the array of restoration activities that are or might be imposed to improve conditions across the stream network. Part of evaluating how the con...

Use and Analysis of Finite Element Methods for Problems of Solid Mechanics and Fracture

DTIC Science & Technology

1993-01-19

improve global accuracy and convergence rates, specific activities such as mesh refinement may be undertaken local to the crack tips. A criticism ...Sciences, Centro Internacional de Metodos Numnericos en Ingenieria, Barcelona, 1992 11 1 |l!avacek, J Rosenberg, A E Beagles and J R Whiteman

Comparative Staffing Units as a Measure of University Instructional Workload. Second Edition.

ERIC Educational Resources Information Center

Colorado State Univ., Ft. Collins.

A project was undertaken to devise an improved method for determining the workload generated by each direct instructional, instructional-related, and professional-related activity carried out at Colorado State University and the estimated workload expected of each instructional faculty member. These load factors specifically recognize the input…

Carbon accounting rules and guidelines for the United States Forest Sector

Treesearch

Richard A. Birdsey

2006-01-01

The United States Climate Change initiative includes improvements to the U.S. Department of Energy's Voluntary Greenhouse Gas Reporting Program. The program includes specific accounting rules and guidelines for reporting and registering forestry activities that reduce atmospheric CO2 by increasing carbon sequestration or reducing emissions....

Human lactoferricin derived di-peptides deploying loop structures induce apoptosis specifically in cancer cells through targeting membranous phosphatidylserine.

PubMed

Riedl, Sabrina; Leber, Regina; Rinner, Beate; Schaider, Helmut; Lohner, Karl; Zweytick, Dagmar

2015-11-01

Host defense-derived peptides have emerged as a novel strategy for the development of alternative anticancer therapies. In this study we report on characteristic features of human lactoferricin (hLFcin) derivatives which facilitate specific killing of cancer cells of melanoma, glioblastoma and rhabdomyosarcoma compared with non-specific derivatives and the synthetic peptide RW-AH. Changes in amino acid sequence of hLFcin providing 9-11 amino acids stretched derivatives LF11-316, -318 and -322 only yielded low antitumor activity. However, the addition of the repeat (di-peptide) and the retro-repeat (di-retro-peptide) sequences highly improved cancer cell toxicity up to 100% at 20 μM peptide concentration. Compared to the complete parent sequence hLFcin the derivatives showed toxicity on the melanoma cell line A375 increased by 10-fold and on the glioblastoma cell line U-87mg by 2-3-fold. Reduced killing velocity, apoptotic blebbing, activation of caspase 3/7 and formation of apoptotic DNA fragments proved that the active and cancer selective peptides, e.g. R-DIM-P-LF11-322, trigger apoptosis, whereas highly active, though non-selective peptides, such as DIM-LF11-318 and RW-AH seem to kill rapidly via necrosis inducing membrane lyses. Structural studies revealed specific toxicity on cancer cells by peptide derivatives with loop structures, whereas non-specific peptides comprised α-helical structures without loop. Model studies with the cancer membrane mimic phosphatidylserine (PS) gave strong evidence that PS only exposed by cancer cells is an important target for specific hLFcin derivatives. Other negatively charged membrane exposed molecules as sialic acid, heparan and chondroitin sulfate were shown to have minor impact on peptide activity. Copyright © 2015. Published by Elsevier B.V.

Screening glycosynthase libraries with a fluoride chemosensor assay independently of enzyme specificity: identification of a transitional hydrolase to synthase mutant.

PubMed

Andrés, Eduardo; Aragunde, Hugo; Planas, Antoni

2014-03-01

Glycosynthases have become efficient tools for the enzymatic synthesis of oligosaccharides, glycoconjugates and polysaccharides. Enzyme-directed evolution approaches are applied to improve the performance of current glycosynthases and engineer specificity for non-natural substrates. However, simple and general screening methods are required since most of the reported assays are specific for each particular enzyme. In the present paper, we report a general screening assay that is independent of enzyme specificity, and implemented in an HTS (high-throughput screening) format for the screening of cell extracts in directed evolution experiments. Fluoride ion is a general by-product released in all glycosynthase reactions with glycosyl fluoride donors. The new assay is based on the use of a specific chemical sensor (a silyl ether of a fluorogenic methylumbelliferone) to transduce fluoride concentration into a fluorescence signal. As a proof-of-concept, it has been applied to a nucleophile saturation mutant library of Bacillus licheniformis 1,3-1,4-β-glucanase. Beyond the expected mutations at the glutamic acid (catalytic) nucleophile, other variants have been shown to acquire glycosynthase activity. Surprisingly, an aspartic acid for glutamic acid replacement renders a highly active glycosynthase, but still retains low hydrolase activity. It appears as an intermediate state between glycosyl hydrolase and glycosynthase.

Engineering the DNA cytosine-5 methyltransferase reaction for sequence-specific labeling of DNA

PubMed Central

Lukinavičius, Gražvydas; Lapinaitė, Audronė; Urbanavičiūtė, Giedrė; Gerasimaitė, Rūta; Klimašauskas, Saulius

2012-01-01

DNA methyltransferases catalyse the transfer of a methyl group from the ubiquitous cofactor S-adenosyl-L-methionine (AdoMet) onto specific target sites on DNA and play important roles in organisms from bacteria to humans. AdoMet analogs with extended propargylic side chains have been chemically produced for methyltransferase-directed transfer of activated groups (mTAG) onto DNA, although the efficiency of reactions with synthetic analogs remained low. We performed steric engineering of the cofactor pocket in a model DNA cytosine-5 methyltransferase (C5-MTase), M.HhaI, by systematic replacement of three non-essential positions, located in two conserved sequence motifs and in a variable region, with smaller residues. We found that double and triple replacements lead to a substantial improvement of the transalkylation activity, which manifests itself in a mild increase of cofactor binding affinity and a larger increase of the rate of alkyl transfer. These effects are accompanied with reduction of both the stability of the product DNA–M.HhaI–AdoHcy complex and the rate of methylation, permitting competitive mTAG labeling in the presence of AdoMet. Analogous replacements of two conserved residues in M.HpaII and M2.Eco31I also resulted in improved transalkylation activity attesting a general applicability of the homology-guided engineering to the C5-MTase family and expanding the repertoire of sequence-specific tools for covalent in vitro and ex vivo labeling of DNA. PMID:23042683

Radon control activities for lung cancer prevention in national comprehensive cancer control program plans, 2005-2011.

PubMed

Neri, Antonio; Stewart, Sherri L; Angell, William

2013-08-08

Radon is the second leading cause of lung cancer among smokers and the leading cause among nonsmokers. The US Environmental Protection Agency recommends that every home be tested for radon. Comprehensive Cancer Control (CCC) programs develop cancer coalitions that coordinate funding and resources to focus on cancer activities that are recorded in cancer plans. Radon tests, remediation, and radon mitigation techniques are relatively inexpensive, but it is unclear whether coalitions recognize radon as an important carcinogen. We reviewed 65 cancer plans created from 2005 through 2011 for the terms "radon," "radiation," or "lung." Plan activities were categorized as radon awareness, home testing, remediation, supporting radon policy activities, or policy evaluation. We also reviewed each CCC program's most recent progress report. Cancer plan content was reviewed to assess alignment with existing radon-specific policies in each state. Twenty-seven of the plans reviewed (42%) had radon-specific terminology. Improving awareness of radon was included in all 27 plans; also included were home testing (n=21), remediation (n=11), support radon policy activities (n=13), and policy evaluation (n=1). Three plans noted current engagement in radon activities. Thirty states had radon-specific laws; most (n=21) were related to radon professional licensure. Eleven states had cancer plan activities that aligned with existing state radon laws. Although several states have radon-specific policies, approximately half of cancer coalitions may not be aware of radon as a public health issue. CCC-developed cancer coalitions and plans should prioritize tobacco control to address lung cancer but should consider addressing radon through partnership with existing radon control programs.

In vitro assessment of TAT — Ciliary Neurotrophic Factor therapeutic potential for peripheral nerve regeneration

DOE Office of Scientific and Technical Information (OSTI.GOV)

Barbon, Silvia, E-mail: silvia.barbon@yahoo.it

In regenerative neurobiology, Ciliary Neurotrophic Factor (CNTF) is raising high interest as a multifunctional neurocytokine, playing a key role in the regeneration of injured peripheral nerves. Despite its promising trophic and regulatory activity, its clinical application is limited by the onset of severe side effects, due to the lack of efficient intracellular trafficking after administration. In this study, recombinant CNTF linked to the transactivator transduction domain (TAT) was investigated in vitro and found to be an optimized fusion protein which preserves neurotrophic activity, besides enhancing cellular uptake for therapeutic advantage. Moreover, a compelling protein delivery method was defined, in themore » future perspective of improving nerve regeneration strategies. Following determination of TAT-CNTF molecular weight and concentration, its specific effect on neural SH-SY5Y and PC12 cultures was assessed. Cell proliferation assay demonstrated that the fusion protein triggers PC12 cell growth within 6 h of stimulation. At the same time, the activation of signal transduction pathway and enhancement of cellular trafficking were found to be accomplished in both neural cell lines after specific treatment with TAT-CNTF. Finally, the recombinant growth factor was successfully loaded on oxidized polyvinyl alcohol (PVA) scaffolds, and more efficiently released when polymer oxidation rate increased. Taken together, our results highlight that the TAT domain addiction to the protein sequence preserves CNTF specific neurotrophic activity in vitro, besides improving cellular uptake. Moreover, oxidized PVA could represent an ideal biomaterial for the development of nerve conduits loaded with the fusion protein to be delivered to the site of nerve injury. - Highlights: • TAT-CNTF is an optimized fusion protein that preserves neurotrophic activity. • In neural cell lines, TAT-CNTF triggers the activation of signal transduction. • Fast cellular uptake of TAT-CNTF was accomplished after cell treatment. • TAT-CNTF can be efficiently loaded on oxidized PVA cylinders for local delivery. • TAT-CNTF features make it ideal for peripheral nerve regeneration therapies.« less

The effect of an integrated perceived competence and motor intervention in children with developmental coordination disorder.

PubMed

Noordstar, Johannes J; van der Net, Janjaap; Voerman, Lia; Helders, Paul J M; Jongmans, Marian J

2017-01-01

Children with DCD have lower self-perceptions and are less physically active than typically developing children. The aim of this quasi-experimental study was to investigate whether an integrated perceived competence and motor intervention affects DCD children's motor performance, self-perceptions, and physical activity compared with a motor intervention only. The intervention group consisted of 20 children and the care-as-usual group consisted of 11 children, all aged 7-10 years. The perceived competence component of the intervention focused primarily on providing positive, specific, and progress feedback to enhance self-perceptions. We assessed children at baseline, after 12 treatment sessions (trial end-point), and at 3-month follow-up. Mixed linear models revealed no differences between the intervention and the care-as-usual group on any of the outcome measures. Children improved their motor performance and increased their perceived athletic competence, global self-esteem, and perceived motor competence after 12 treatment sessions. This improvement was maintained at 3-month follow-up. Motor task values and physical activity remained unchanged for all children. A perceived competence and motor intervention is as effective as care-as-usual in children with DCD. Future research should focus on improving physical activity in children with DCD. This is the first study that has investigated the effect of an integrated perceived competence and motor intervention (intervention group) on motor performance, self-perceptions, and physical activity compared with a motor intervention (care-as-usual group) in children with DCD. We made the perceived competence component explicit by providing positive, specific, and progress feedback to enhance children's self-perceptions. Also, this is one of the first studies that has investigated the effect after both 12 treatment sessions (trial end-point) and after 3 months of no intervention (3-month follow-up). We found no differences between the intervention and the care-as-usual group, but children improved their motor performance and increased (most) of their self-perceptions after 12 treatment sessions, while physical activity remained the same. The improvement was still present at the 3-month follow-up. We also benchmarked our results about self-perceptions and physical activity to a group of typically developing children. Self-perceptions in children with DCD had improved to the level of typically developing children after 12 treatment sessions, but their physical activity levels remained significantly lower. This result was the same at the 3-month follow-up, except for perceived athletic competence, which was lower in children with DCD at the 3-month follow-up. In accordance with previous intervention studies that have investigated children with DCD, we found large intra-group variability in the change in motor performance and self-perceptions in children with DCD. We argue that we need to better understand why some children with DCD improve and others do not after a motor intervention. Copyright © 2016 Elsevier Ltd. All rights reserved.

Improved Killing of Ovarian Cancer Stem Cells by Combining a Novel Chimeric Antigen Receptor-Based Immunotherapy and Chemotherapy.

PubMed

Klapdor, Rüdiger; Wang, Shuo; Hacker, Ulrich; Büning, Hildegard; Morgan, Michael; Dörk, Thilo; Hillemanns, Peter; Schambach, Axel

2017-10-01

Ovarian cancer represents the most lethal gynecological cancer. Although cytoreductive chemotherapy and surgery lead to complete macroscopic tumor removal, most of the patients in advanced stages suffer from recurrent disease and subsequently die. This may be explained by the activity of cancer stem cells (CSC), which are a subpopulation of cells with an elevated chemoresistance and an increased capacity for self-renewal and metastatic spread. Specifically targeting these cells by adoptive immunotherapy represents a promising strategy to reduce the risk for recurrent disease. This study selected the widely accepted CSC marker CD133 as a target for a chimeric antigen receptor (CAR)-based immunotherapeutic approach to treat ovarian cancer. A lentiviral vector was generated encoding a third-generation anti-CD133-CAR, and clinically used NK92 cells were transduced. These engineered natural killer (NK) cells showed specific killing against CD133-positive ovarian cancer cell lines and primary ovarian cancer cells cultured from sequential ascites harvests. Additionally, specific activation of these engineered NK cells was demonstrated via interferon-gamma secretion assays. To improve clinical efficacy of ovarian cancer treatment, the effect of the chemotherapeutic agent cisplatin was evaluated together with CAR-transduced NK cell treatment. It was demonstrated that NK cells remain cytotoxic and active under cisplatin treatment and, importantly, that sequential treatment with cisplatin followed by CAR-NK cells led to the strongest killing effect. The specific eradication of ovarian CSCs by anti-CD133-CAR expressing NK92 cells represents a promising strategy and, when confirmed in vivo, shall be the basis of future clinical studies with the aim to prevent recurrent disease.

Muscarinic cholinergic receptor binding: in vivo depiction using single photon emission computed tomography and radioiodinated quinuclidinyl benzilate

DOE Office of Scientific and Technical Information (OSTI.GOV)

Drayer, B.; Jaszczak, R.; Coleman, E.

1982-06-01

An attempt was made to characterize, in vivo, specific binding to the muscarinic cholinergic receptor in the calf using the radioiodinated ligand quinuclidinyl benzilate (/sup 123/I-OH-QNB) and single photon detection emission computed tomography (SPECT). The supratentorial brain activity was significantly increased after the intravenous infusion of /sup 123/I-OH-QNB as compared to free /sup 123/I. Scopolamine, a muscarinic cholinergic receptor antagonist, decreased the measured brain activity when infused prior to /sup 123/I-OH-QNB consistent with pharmacologic blockade of specific receptor binding. Quantitative in vitro tissue distribution studies obtained following SPECT imaging were consistent with regionally distinct specific receptor binding in the striatummore » and cortical gray matter, nonspecific binding in the cerebellum, and pharmacologic blockade of specific binding sites with scopolamine. Although /sup 123/I-OH-QNB is not the ideal radioligand, our limited success will hopefully encourage the development of improved binding probes for SPECT imaging and quantitation.« less

Rilmenidine improves hepatic steatosis through p38-dependent pathway to higher the expression of farnesoid X receptor.

PubMed

Yang, Po-Sheng; Wu, Hung-Tsung; Chung, Hsien-Hui; Chen, Chun-Ta; Chi, Chin-Wen; Yeh, Ching-Hua; Cheng, Juei-Tang

2012-01-01

The nuclear receptor farnesoid X receptor (FXR) regulates pathways in lipid, glucose, and energy metabolism. Activation of FXR in mice significantly improved high-fat diet-induced hepatic steatosis. It has been reported that activation of imidazoline I-1 receptor by rilmenidine increases the expression of FXR in human hepatoma cell line, Hep G2 cell, to regulate the target genes relating to lipid metabolism; activation of FXR by rilmenidine exerts an antihyperlipidemic action. However, signals for this action of rilmenidine are still unknown. In the present study, hepatic steatosis induced in mice by high-fat diet was improved by rilmenidine after intraperitoneal injection at 1 mg/kg daily for 12 weeks. Also, mediation of I-1 receptors was identified using the specific antagonist efaroxan. Moreover, rilmenidine decreased the oleic acid-induced lipid accumulation in Hep G2 cells. Otherwise, rilmenidine increased the phosphorylation of p38 to increase the expression of FXR. Deletion of calcium ions by BAPTA-AM reversed the rilmenidine-induced p38 phosphorylation. In conclusion, we suggest that rilmenidine activates I-1 receptor to increase intracellular calcium ions that may enhance the phosphorylation of p38 to higher the expression of FXR for improvement of hepatic steatosis in both animals and cells.

New Surface-Enhanced Raman Sensing Chip Designed for On-Site Detection of Active Ricin in Complex Matrices Based on Specific Depurination.

PubMed

Tang, Ji-Jun; Sun, Jie-Fang; Lui, Rui; Zhang, Zong-Mian; Liu, Jing-Fu; Xie, Jian-Wei

2016-01-27

Quick and accurate on-site detection of active ricin has very important realistic significance in view of national security and defense. In this paper, optimized single-stranded oligodeoxynucleotides named poly(21dA), which function as a depurination substrate of active ricin, were screened and chemically attached on gold nanoparticles (AuNPs, ∼100 nm) via the Au-S bond [poly(21dA)-AuNPs]. Subsequently, poly(21dA)-AuNPs were assembled on a dihydrogen lipoic-acid-modified Si wafer (SH-Si), thus forming the specific surface-enhanced Raman spectroscopy (SERS) chip [poly(21dA)-AuNPs@SH-Si] for depurination of active ricin. Under optimized conditions, active ricin could specifically hydrolyze multiple adenines from poly(21dA) on the chip. This depurination-induced composition change could be conveniently monitored by measuring the distinct attenuation of the SERS signature corresponding to adenine. To improve sensitivity of this method, a silver nanoshell was deposited on post-reacted poly(21dA)-AuNPs, which lowered the limit of detection to 8.9 ng mL(-1). The utility of this well-controlled SERS chip was successfully demonstrated in food and biological matrices spiked with different concentrations of active ricin, thus showing to be very promising assay for reliable and rapid on-site detection of active ricin.

Atmospheric Electrical Activity and the Prospects for Improving Short-Term, Weather Forcasting

NASA Technical Reports Server (NTRS)

Goodman, Steven J.

2003-01-01

How might lightning measurements be used to improve short-term (0-24 hr) weather forecasting? We examine this question under two different prediction strategies. These include integration of lightning data into short-term forecasts (nowcasts) of convective (including severe) weather hazards and the assimilation of lightning data into cloud-resolving numerical weather prediction models. In each strategy we define specific metrics of forecast improvement and a progress assessment. We also address the conventional observing system deficiencies and potential gap-filling information that can be addressed through the use of the lightning measurement.

Characterization of Site-Specific Mutations in a Short-Chain-Length/Medium-Chain-Length Polyhydroxyalkanoate Synthase: In Vivo and In Vitro Studies of Enzymatic Activity and Substrate Specificity

PubMed Central

Chuah, Jo-Ann; Tomizawa, Satoshi; Yamada, Miwa; Tsuge, Takeharu; Doi, Yoshiharu

2013-01-01

Saturation point mutagenesis was carried out at position 479 in the polyhydroxyalkanoate (PHA) synthase from Chromobacterium sp. strain USM2 (PhaCCs) with specificities for short-chain-length (SCL) [(R)-3-hydroxybutyrate (3HB) and (R)-3-hydroxyvalerate (3HV)] and medium-chain-length (MCL) [(R)-3-hydroxyhexanoate (3HHx)] monomers in an effort to enhance the specificity of the enzyme for 3HHx. A maximum 4-fold increase in 3HHx incorporation and a 1.6-fold increase in PHA biosynthesis, more than the wild-type synthase, was achieved using selected mutant synthases. These increases were subsequently correlated with improved synthase activity and increased preference of PhaCCs for 3HHx monomers. We found that substitutions with uncharged residues were beneficial, as they resulted in enhanced PHA production and/or 3HHx incorporation. Further analysis led to postulations that the size and geometry of the substrate-binding pocket are determinants of PHA accumulation, 3HHx fraction, and chain length specificity. In vitro activities for polymerization of 3HV and 3HHx monomers were consistent with in vivo substrate specificities. Ultimately, the preference shown by wild-type and mutant synthases for either SCL (C4 and C5) or MCL (C6) substrates substantiates the fundamental classification of PHA synthases. PMID:23584780

Activity classification based on inertial and barometric pressure sensors at different anatomical locations.

PubMed

Moncada-Torres, A; Leuenberger, K; Gonzenbach, R; Luft, A; Gassert, R

2014-07-01

Miniature, wearable sensor modules are a promising technology to monitor activities of daily living (ADL) over extended periods of time. To assure both user compliance and meaningful results, the selection and placement site of sensors requires careful consideration. We investigated these aspects for the classification of 16 ADL in 6 healthy subjects under laboratory conditions using ReSense, our custom-made inertial measurement unit enhanced with a barometric pressure sensor used to capture activity-related altitude changes. Subjects wore a module on each wrist and ankle, and one on the trunk. Activities comprised whole body movements as well as gross and dextrous upper-limb activities. Wrist-module data outperformed the other locations for the three activity groups. Specifically, overall classification accuracy rates of almost 93% and more than 95% were achieved for the repeated holdout and user-specific validation methods, respectively, for all 16 activities. Including the altitude profile resulted in a considerable improvement of up to 20% in the classification accuracy for stair ascent and descent. The gyroscopes provided no useful information for activity classification under this scheme. The proposed sensor setting could allow for robust long-term activity monitoring with high compliance in different patient populations.

Surface engineered magnetic nanoparticles for specific immunotargeting of cadherin expressing cells

NASA Astrophysics Data System (ADS)

Moros, Maria; Delhaes, Flavien; Puertas, Sara; Saez, Berta; de la Fuente, Jesús M.; Grazú, Valeria; Feracci, Helene

2016-02-01

In spite of historic advances in cancer biology and recent development of sophisticated chemotherapeutics, the outlook for patients with advanced cancer is still grim. In this sense nanoparticles (NPs), through their unique physical properties, enable the development of new approaches for cancer diagnosis and treatment. Thus far the most used active targeting scheme involves NPs functionalization with antibodies specific to molecules overexpressed on cancer cell’s surface. Therefore, such active targeting relies on differences in NPs uptake kinetics rates between tumor and healthy cells. Many cancers of epithelial origin are associated with the inappropriate expression of non-epithelial cadherins (e.g. N-, P-, -11) with concomitant loss of E-cadherin. Such phenomenon named cadherin switching favors tumor development and metastasis via interactions of tumor cells with stromal components. That is why we optimized the oriented functionalization of fluorescently labelled magnetic NPs with a novel antibody specific for the extracellular domain of cadherin-11. The obtained Ab-NPs exhibited high specificity when incubated with two cell lines used as models of tumor and healthy cells. Thus, cadherin switching offers a great opportunity for the development of active targeting strategies aimed to improve the early detection and treatment of cancer.

The Evaluation of Triphenyl Phosphate as a Flame Retardant Additive to Improve the Safety of Lithium-Ion Battery Electrolytes

NASA Technical Reports Server (NTRS)

Smart, M. C.; Krause, F. C.; Hwang, C.; Westa, W. C.; Soler, J.; Prakash, G. K. S.; Ratnakumar, B. V.

2011-01-01

NASA is actively pursuing the development of advanced electrochemical energy storage and conversion devices for future lunar and Mars missions. The Exploration Technology Development Program, Energy Storage Project is sponsoring the development of advanced Li-ion batteries and PEM fuel cell and regenerative fuel cell systems for the Altair Lunar Lander, Extravehicular Activities (EVA), and rovers and as the primary energy storage system for Lunar Surface Systems. At JPL, in collaboration with NASA-GRC, NASA-JSC and industry, we are actively developing advanced Li-ion batteries with improved specific energy, energy density and safety. One effort is focused upon developing Li-ion battery electrolyte with enhanced safety characteristics (i.e., low flammability). A number of commercial applications also require Li-ion batteries with enhanced safety, especially for automotive applications.

Gender-related impacts of improved agricultural technologies: identification of indicators from a case study.

PubMed

Kolli, R D; Bantilan, C

1997-01-01

This study examines the gender-related consequences of adoption of a groundnut production technology (GPT) package introduced in Umra village for increasing the production of legumes in India. GPT affected household labor activity patterns, decision making, and distribution of benefits. The package offered improved varieties and improved practices. Data were obtained from surveys conducted among 26 farm households in each Umra and Karanji village during 1992-94 and among 15 agricultural wage laborer households from Umra and 21 from Karanji. Men and women both cooperated in certain groundnut production activities and specialized in other activities. Men used agricultural equipment and tools and performed hard labor. Women used hand skills or small tools. Villages differed in gender task specificity. Umra women after GPT reported more work in field cleaning, fertilizer application, and sowing by hand dibbling. A new GPT activity of gypsum application was handled in almost 60% of farm households by women. Large yield gains changed harvesting activities in Umra. The number of exclusive activities performed only by women rose after GPT. GPT was not designed to eliminate drudgery performed by women. Umra women spent more time than Karanji women in production. More labor was needed with GPT. Wage rates for women workers were similar in both villages. Wages were less in Umra for men compared to Karanji. Men and women jointly decided on resource allocations in 53% of households in Karanji and only 36% in Umra. The adoption of GPT reduced the control of women over resource use. More joint and sole decisions by women were made in Umra on the use of the main product. Women gained control over products for home use in Umra. Men retained control over the value of 80% of the crop. Both men and women were satisfied with GPT, but specific perceptions differed by gender.

Co-Stimulation through 4-1BB/CD137 Improves the Expansion and Function of CD8+ Melanoma Tumor-Infiltrating Lymphocytes for Adoptive T-Cell Therapy

PubMed Central

Chacon, Jessica Ann; Wu, Richard C.; Sukhumalchandra, Pariya; Molldrem, Jeffrey J.; Sarnaik, Amod; Pilon-Thomas, Shari; Weber, Jeffrey; Hwu, Patrick; Radvanyi, Laszlo

2013-01-01

Adoptive T-cell therapy (ACT) using tumor-infiltrating lymphocytes (TIL) can induce tumor regression in up to 50% or more of patients with unresectable metastatic melanoma. However, current methods to expand melanoma TIL, especially the “rapid expansion protocol” (REP) were not designed to enhance the generation of optimal effector-memory CD8+ T cells for infusion. One approach to this problem is to manipulate specific co-stimulatory signaling pathways to enhance CD8+ effector-memory T-cell expansion. In this study, we determined the effects of activating the TNF-R family member 4-1BB/CD137, specifically induced in activated CD8+ T cells, on the yield, phenotype, and functional activity of expanded CD8+ T cells during the REP. We found that CD8+ TIL up-regulate 4-1BB expression early during the REP after initial TCR stimulation, but neither the PBMC feeder cells in the REP or the activated TIL expressed 4-1BB ligand. However, addition of an exogenous agonistic anti-4-1BB IgG4 (BMS 663513) to the REP significantly enhanced the frequency and total yield of CD8+ T cells as well as their maintenance of CD28 and increased their anti-tumor CTL activity. Gene expression analysis found an increase in bcl-2 and survivin expression induced by 4-1BB that was associated with an enhanced survival capability of CD8+ post-REP TIL when re-cultured in the absence or presence of cytokines. Our findings suggest that adding an agonistic anti-4-1BB antibody during the time of TIL REP initiation produces a CD8+ T cell population capable of improved effector function and survival. This may greatly improve TIL persistence and anti-tumor activity in vivo after adoptive transfer into patients. PMID:23560068

The Grass Might Be Greener: Medical Marijuana Patients Exhibit Altered Brain Activity and Improved Executive Function after 3 Months of Treatment

PubMed Central

Gruber, Staci A.; Sagar, Kelly A.; Dahlgren, Mary K.; Gonenc, Atilla; Smith, Rosemary T.; Lambros, Ashley M.; Cabrera, Korine B.; Lukas, Scott E.

2018-01-01

The vast majority of states have enacted full or partial medical marijuana (MMJ) programs, causing the number of patients seeking certification for MMJ use to increase dramatically in recent years. Despite increased use of MMJ across the nation, no studies thus far have examined the specific impact of MMJ on cognitive function and related brain activation. In the present study, MMJ patients seeking treatment for a variety of documented medical conditions were assessed prior to initiating MMJ treatment and after 3 months of treatment as part of a larger longitudinal study. In order to examine the effect of MMJ treatment on task-related brain activation, MMJ patients completed the Multi-Source Interference Test (MSIT) while undergoing functional magnetic resonance imaging (fMRI). We also collected data regarding conventional medication use, clinical state, and health-related measures at each visit. Following 3 months of treatment, MMJ patients demonstrated improved task performance accompanied by changes in brain activation patterns within the cingulate cortex and frontal regions. Interestingly, after MMJ treatment, brain activation patterns appeared more similar to those exhibited by healthy controls from previous studies than at pre-treatment, suggestive of a potential normalization of brain function relative to baseline. These findings suggest that MMJ use may result in different effects relative to recreational marijuana (MJ) use, as recreational consumers have been shown to exhibit decrements in task performance accompanied by altered brain activation. Moreover, patients in the current study also reported improvements in clinical state and health-related measures as well as notable decreases in prescription medication use, particularly opioids and benzodiapezines after 3 months of treatment. Further research is needed to clarify the specific neurobiologic impact, clinical efficacy, and unique effects of MMJ for a range of indications and how it compares to recreational MJ use. PMID:29387010

The Grass Might Be Greener: Medical Marijuana Patients Exhibit Altered Brain Activity and Improved Executive Function after 3 Months of Treatment.

PubMed

Gruber, Staci A; Sagar, Kelly A; Dahlgren, Mary K; Gonenc, Atilla; Smith, Rosemary T; Lambros, Ashley M; Cabrera, Korine B; Lukas, Scott E

2017-01-01

The vast majority of states have enacted full or partial medical marijuana (MMJ) programs, causing the number of patients seeking certification for MMJ use to increase dramatically in recent years. Despite increased use of MMJ across the nation, no studies thus far have examined the specific impact of MMJ on cognitive function and related brain activation. In the present study, MMJ patients seeking treatment for a variety of documented medical conditions were assessed prior to initiating MMJ treatment and after 3 months of treatment as part of a larger longitudinal study. In order to examine the effect of MMJ treatment on task-related brain activation, MMJ patients completed the Multi-Source Interference Test (MSIT) while undergoing functional magnetic resonance imaging (fMRI). We also collected data regarding conventional medication use, clinical state, and health-related measures at each visit. Following 3 months of treatment, MMJ patients demonstrated improved task performance accompanied by changes in brain activation patterns within the cingulate cortex and frontal regions. Interestingly, after MMJ treatment, brain activation patterns appeared more similar to those exhibited by healthy controls from previous studies than at pre-treatment, suggestive of a potential normalization of brain function relative to baseline. These findings suggest that MMJ use may result in different effects relative to recreational marijuana (MJ) use, as recreational consumers have been shown to exhibit decrements in task performance accompanied by altered brain activation. Moreover, patients in the current study also reported improvements in clinical state and health-related measures as well as notable decreases in prescription medication use, particularly opioids and benzodiapezines after 3 months of treatment. Further research is needed to clarify the specific neurobiologic impact, clinical efficacy, and unique effects of MMJ for a range of indications and how it compares to recreational MJ use.

Specific inhibition of c-Jun N-terminal kinase delays preterm labour and reduces mortality

PubMed Central

Pirianov, Grisha; MacIntyre, David A; Lee, Yun; Waddington, Simon N; Terzidou, Vasso; Mehmet, Huseyin; Bennett, Phillip R

2015-01-01

Preterm labour (PTL) is commonly associated with infection and/or inflammation. Lipopolysaccharide (LPS) from different bacteria can be used to independently or mutually activate Jun N-terminal kinase (JNK)/AP1- or NF-κB-driven inflammatory pathways that lead to PTL. Previous studies using Salmonella abortus LPS, which activates both JNK/AP-1 and NF-κB, showed that selective inhibition of NF-κB delays labour and improves pup outcome. Where labour is induced using Escherichia coli LPS (O111), which upregulates JNK/AP-1 but not NF-κB, inhibition of JNK/AP-1 activation also delays labour. In this study, to determine the potential role of JNK as a therapeutic target in PTL, we investigated the specific contribution of JNK signalling to S. Abortus LPS-induced PTL in mice. Intrauterine administration of S. Abortus LPS to pregnant mice resulted in the activation of JNK in the maternal uterus and fetal brain, upregulation of pro-inflammatory proteins COX-2, CXCL1, and CCL2, phosphorylation of cPLA2 in myometrium, and induction of PTL. Specific inhibition of JNK by co-administration of specific D-JNK inhibitory peptide (D-JNKI) delayed LPS-induced preterm delivery and reduced fetal mortality. This is associated with inhibition of myometrial cPLA2 phosphorylation and proinflammatory proteins synthesis. In addition, we report that D-JNKI inhibits the activation of JNK/JNK3 and caspase-3, which are important mediators of neural cell death in the neonatal brain. Our data demonstrate that specific inhibition of TLR4-activated JNK signalling pathways has potential as a therapeutic approach in the management of infection/inflammation-associated PTL and prevention of the associated detrimental effects to the neonatal brain. PMID:26183892

Improvement of oxygen-containing functional groups on olive stones activated carbon by ozone and nitric acid for heavy metals removal from aqueous phase.

PubMed

Bohli, Thouraya; Ouederni, Abdelmottaleb

2016-08-01

Recently, modification of surface structure of activated carbons in order to improve their adsorption performance toward especial pollutants has gained great interest. Oxygen-containing functional groups have been devoted as the main responsible for heavy metal binding on the activated carbon surface; their introduction or enhancement needs specific modification and impregnation methods. In the present work, olive stones activated carbon (COSAC) undergoes surface modifications in gaseous phase using ozone (O3) and in liquid phase using nitric acid (HNO3). The activated carbon samples were characterized using N2 adsorption-desorption isotherm, SEM, pHpzc, FTIR, and Boehm titration. The activated carbon parent (COSAC) has a high surface area of 1194 m(2)/g and shows a predominantly microporous structure. Oxidation treatments with nitric acid and ozone show a decrease in both specific surface area and micropore volumes, whereas these acidic treatments have led to a fixation of high amount of surface oxygen functional groups, thus making the carbon surface more hydrophilic. Activated carbon samples were used as an adsorbent matrix for the removal of Co(II), Ni(II), and Cu(II) heavy metal ions from aqueous solutions. Adsorption isotherms were obtained at 30 °C, and the data are well fitted to the Redlich-Peterson and Langmuir equation. Results show that oxidized COSACs, especially COSAC(HNO3), are capable to remove more Co(II), Cu(II), and Ni(II) from aqueous solution. Nitric acid-oxidized olive stones activated carbon was tested in its ability to remove metal ions from binary systems and results show an important maximum adsorbed amount as compared to single systems.

Nonhuman TRIM5 Variants Enhance Recognition of HIV-1-Infected Cells by CD8+ T Cells

PubMed Central

Jimenez-Moyano, Esther; Ruiz, Alba; Kløverpris, Henrik N.; Rodriguez-Plata, Maria T.; Peña, Ruth; Blondeau, Caroline; Selwood, David L.; Izquierdo-Useros, Nuria; Moris, Arnaud; Clotet, Bonaventura; Goulder, Philip; Towers, Greg J.

2016-01-01

ABSTRACT Tripartite motif-containing protein 5 (TRIM5) restricts human immunodeficiency virus type 1 (HIV-1) in a species-specific manner by uncoating viral particles while activating early innate responses. Although the contribution of TRIM5 proteins to cellular immunity has not yet been studied, their interactions with the incoming viral capsid and the cellular proteasome led us to hypothesize a role for them. Here, we investigate whether the expression of two nonhuman TRIM5 orthologs, rhesus TRIM5α (RhT5) and TRIM-cyclophilin A (TCyp), both of which are potent restrictors of HIV-1, could enhance immune recognition of infected cells by CD8+ T cells. We illustrate how TRIM5 restriction improves CD8+ T-cell-mediated HIV-1 inhibition. Moreover, when TRIM5 activity was blocked by the nonimmunosuppressive analog of cyclosporine (CsA), sarcosine-3(4-methylbenzoate)–CsA (SmBz-CsA), we found a significant reduction in CD107a/MIP-1β expression in HIV-1-specific CD8+ T cells. This finding underscores the direct link between TRIM5 restriction and activation of CD8+ T-cell responses. Interestingly, cells expressing RhT5 induced stronger CD8+ T-cell responses through the specific recognition of the HIV-1 capsid by the immune system. The underlying mechanism of this process may involve TRIM5-specific capsid recruitment to cellular proteasomes and increase peptide availability for loading and presentation of HLA class I antigens. In summary, we identified a novel function for nonhuman TRIM5 variants in cellular immunity. We hypothesize that TRIM5 can couple innate viral sensing and CD8+ T-cell activation to increase species barriers against retrovirus infection. IMPORTANCE New therapeutics to tackle HIV-1 infection should aim to combine rapid innate viral sensing and cellular immune recognition. Such strategies could prevent seeding of the viral reservoir and the immune damage that occurs during acute infection. The nonhuman TRIM5 variants, rhesus TRIM5α (RhT5) and TRIM-cyclophilin A (TCyp), are attractive candidates owing to their potency in sensing HIV-1 and blocking its activity. Here, we show that expression of RhT5 and TCyp in HIV-1-infected cells improves CD8+ T-cell-mediated inhibition through the direct activation of HIV-1-specific CD8+ T-cell responses. We found that the potency in CD8+ activation was stronger for RhT5 variants and capsid-specific CD8+ T cells in a mechanism that relies on TRIM5-dependent particle recruitment to cellular proteasomes. This novel mechanism couples innate viral sensing with cellular immunity in a single protein and could be exploited to develop innovative therapeutics for control of HIV-1 infection. PMID:27440884

Neural activity during emotion recognition after combined cognitive plus social cognitive training in schizophrenia.

PubMed

Hooker, Christine I; Bruce, Lori; Fisher, Melissa; Verosky, Sara C; Miyakawa, Asako; Vinogradov, Sophia

2012-08-01

Cognitive remediation training has been shown to improve both cognitive and social cognitive deficits in people with schizophrenia, but the mechanisms that support this behavioral improvement are largely unknown. One hypothesis is that intensive behavioral training in cognition and/or social cognition restores the underlying neural mechanisms that support targeted skills. However, there is little research on the neural effects of cognitive remediation training. This study investigated whether a 50 h (10-week) remediation intervention which included both cognitive and social cognitive training would influence neural function in regions that support social cognition. Twenty-two stable, outpatient schizophrenia participants were randomized to a treatment condition consisting of auditory-based cognitive training (AT) [Brain Fitness Program/auditory module ~60 min/day] plus social cognition training (SCT) which was focused on emotion recognition [~5-15 min per day] or a placebo condition of non-specific computer games (CG) for an equal amount of time. Pre and post intervention assessments included an fMRI task of positive and negative facial emotion recognition, and standard behavioral assessments of cognition, emotion processing, and functional outcome. There were no significant intervention-related improvements in general cognition or functional outcome. fMRI results showed the predicted group-by-time interaction. Specifically, in comparison to CG, AT+SCT participants had a greater pre-to-post intervention increase in postcentral gyrus activity during emotion recognition of both positive and negative emotions. Furthermore, among all participants, the increase in postcentral gyrus activity predicted behavioral improvement on a standardized test of emotion processing (MSCEIT: Perceiving Emotions). Results indicate that combined cognition and social cognition training impacts neural mechanisms that support social cognition skills. Copyright © 2012 Elsevier B.V. All rights reserved.

Neural activity during emotion recognition after combined cognitive plus social-cognitive training in schizophrenia

PubMed Central

Hooker, Christine I.; Bruce, Lori; Fisher, Melissa; Verosky, Sara C.; Miyakawa, Asako; Vinogradov, Sophia

2012-01-01

Cognitive remediation training has been shown to improve both cognitive and social-cognitive deficits in people with schizophrenia, but the mechanisms that support this behavioral improvement are largely unknown. One hypothesis is that intensive behavioral training in cognition and/or social-cognition restores the underlying neural mechanisms that support targeted skills. However, there is little research on the neural effects of cognitive remediation training. This study investigated whether a 50 hour (10-week) remediation intervention which included both cognitive and social-cognitive training would influence neural function in regions that support social-cognition. Twenty-two stable, outpatient schizophrenia participants were randomized to a treatment condition consisting of auditory-based cognitive training (AT) [Brain Fitness Program/auditory module ~60 minutes/day] plus social-cognition training (SCT) which was focused on emotion recognition [~5–15 minutes per day] or a placebo condition of non-specific computer games (CG) for an equal amount of time. Pre and post intervention assessments included an fMRI task of positive and negative facial emotion recognition, and standard behavioral assessments of cognition, emotion processing, and functional outcome. There were no significant intervention-related improvements in general cognition or functional outcome. FMRI results showed the predicted group-by-time interaction. Specifically, in comparison to CG, AT+SCT participants had a greater pre-to-post intervention increase in postcentral gyrus activity during emotion recognition of both positive and negative emotions. Furthermore, among all participants, the increase in postcentral gyrus activity predicted behavioral improvement on a standardized test of emotion processing (MSCEIT: Perceiving Emotions). Results indicate that combined cognition and social-cognition training impacts neural mechanisms that support social-cognition skills. PMID:22695257

The spatiotemporal MEG covariance matrix modeled as a sum of Kronecker products.

PubMed

Bijma, Fetsje; de Munck, Jan C; Heethaar, Rob M

2005-08-15

The single Kronecker product (KP) model for the spatiotemporal covariance of MEG residuals is extended to a sum of Kronecker products. This sum of KP is estimated such that it approximates the spatiotemporal sample covariance best in matrix norm. Contrary to the single KP, this extension allows for describing multiple, independent phenomena in the ongoing background activity. Whereas the single KP model can be interpreted by assuming that background activity is generated by randomly distributed dipoles with certain spatial and temporal characteristics, the sum model can be physiologically interpreted by assuming a composite of such processes. Taking enough terms into account, the spatiotemporal sample covariance matrix can be described exactly by this extended model. In the estimation of the sum of KP model, it appears that the sum of the first 2 KP describes between 67% and 93%. Moreover, these first two terms describe two physiological processes in the background activity: focal, frequency-specific alpha activity, and more widespread non-frequency-specific activity. Furthermore, temporal nonstationarities due to trial-to-trial variations are not clearly visible in the first two terms, and, hence, play only a minor role in the sample covariance matrix in terms of matrix power. Considering the dipole localization, the single KP model appears to describe around 80% of the noise and seems therefore adequate. The emphasis of further improvement of localization accuracy should be on improving the source model rather than the covariance model.

Measurement of Physical Activity and Energy Expenditure in Wheelchair Users: Methods, Considerations and Future Directions.

PubMed

Nightingale, Tom E; Rouse, Peter C; Thompson, Dylan; Bilzon, James L J

2017-12-01

Accurately measuring physical activity and energy expenditure in persons with chronic physical disabilities who use wheelchairs is a considerable and ongoing challenge. Quantifying various free-living lifestyle behaviours in this group is at present restricted by our understanding of appropriate measurement tools and analytical techniques. This review provides a detailed evaluation of the currently available measurement tools used to predict physical activity and energy expenditure in persons who use wheelchairs. It also outlines numerous considerations specific to this population and suggests suitable future directions for the field. Of the existing three self-report methods utilised in this population, the 3-day Physical Activity Recall Assessment for People with Spinal Cord Injury (PARA-SCI) telephone interview demonstrates the best reliability and validity. However, the complexity of interview administration and potential for recall bias are notable limitations. Objective measurement tools, which overcome such considerations, have been validated using controlled laboratory protocols. These have consistently demonstrated the arm or wrist as the most suitable anatomical location to wear accelerometers. Yet, more complex data analysis methodologies may be necessary to further improve energy expenditure prediction for more intricate movements or behaviours. Multi-sensor devices that incorporate physiological signals and acceleration have recently been adapted for persons who use wheelchairs. Population specific algorithms offer considerable improvements in energy expenditure prediction accuracy. This review highlights the progress in the field and aims to encourage the wider scientific community to develop innovative solutions to accurately quantify physical activity in this population.

A modified single-tube one-step product-enhanced reverse transcriptase (mSTOS-PERT) assay with heparin as DNA polymerase inhibitor for specific detection of RTase activity.

PubMed

Fan, Xiao-Yong; Lü, Guo-Zhen; Wu, Li-Na; Chen, Jing-Hua; Xu, Wen-Qing; Zhao, Chun-Nü; Guo, Sheng-Qi

2006-12-01

Current regulations and recommendations proposed for the production of vaccines in continuous cell lines of any origin demand that these be free of exogenous viruses, particularly retroviruses. Recently, the ultra-sensitive product-enhanced reverse transcriptase (PERT) assay can be used to detect minute of reverse transcriptase (RTase) in single retroviral particle and is 10(6) times more sensitive than the conventional RTase assays. However, coincidental with this increase in sensitivity is an increase in false-positive reactions derived from contaminating cellular DNA polymerases, which are known to have RTase-like activities. To develop a modified single-tube one-step PERT (mSTOS-PERT) assay with improvements on decreasing significantly the level of false-positive reactions, and to evaluate the mSTOS-PERT assay for sensitivity and specificity. Ampliwaxtrade mark was used to compartmentalize the reverse transcription (RT) and PCR step in the same micro-tube with more efficiency and reproducibility, while maintaining the high sensitivity. The DNA amplification products were separated by 2% agarose gel electrophoresis, and then analyzed by non-isotopic Southern blot hybridization. A wide variety of cell lines used in biologicals production were detected to validate the improved mSTOS-PERT assay. The detection limit for the mSTOS-PERT assay was at least 10(-9)U, when using AMV-RTase as a positive control. Furthermore, heparin involvement in the RT step can eliminate completely the false-positive PERT signals which are exhibited by cellular polymerases such as DNA-dependent DNA polymerase alpha, gamma released by cell death. Most mammalian cells (MRC-5, Vero, WISH, 2BS, RK-13, MDCK, etc.) are PERT-negative in cell supernatants. Some PERT-positive signals in cell lysates were found to be introduced by the cellular DNA polymerases and could be inhibited specifically by heparin. Chick cells derived from either chick embryo fibroblasts (CEF) or allantoic fluid from SPF embryonated eggs, murine hybridoma cell SP2/0, etc., contained authentic RTase activities, which could not be inactivated by heparin. The improved mSTOS-PERT assay described here may distinguish the genuine RTase activity from cellular polymerases with high sensitivity and specificity, and is rapid and easy to perform to screen for the possible contamination of minute retroviruses in the cell substrates used in vaccine production.

Explorations of Substituted Urea Functionality for Discovery of New Activators of the Heme Regulated Inhibitor Kinase

PubMed Central

Chen, Ting; Takrouri, Khuloud; Hee-Hwang, Sung; Rana, Sandeep; Yefidoff-Freedman, Revital; Halperin, Jose; Natarajan, Amarnath; Morisseau, Christophe; Hammock, Bruce; Chorev, Michael; Aktas, Bertal H.

2014-01-01

Heme-regulated inhibitor kinase (HRI), an eukaryotic translation initiation factor 2 alpha (eIF2α) kinase, plays critical roles in cell proliferation, differentiation, and adaptation to cytoplasmic stress. HRI is also a critical modifier of hemoglobin disorders such as β-thalassemia. We previously identified N,N′-diarylureas as potent activators of HRI suitable for studying biology of this important kinase. To expand the repertoire of chemotypes that activate HRI we screened a ~1,900 member N,N′-disubstituted urea library in the surrogate eIF2α phosphorylation assay identifying N-aryl,N′-cyclohexylphenoxyurea as a promising scaffold. We validated hit compounds as a bona-fide HRI activators in secondary assays and explored contributions of substitutions on the N-aryl and N′-cyclohexylphenoxy groups to their activity by studying focused libraries of complementing analogs. We tested these N-aryl,N′-cyclohexylphenoxyureas in the surrogate eIF2α phosphorylation and cell proliferation assays, demonstrating significantly improved bioactivities and specificities. We consider these compounds to represent lead candidates for the development of potent and specific HRI activators. PMID:24261904

Attention improves memory by suppressing spiking-neuron activity in the human anterior temporal lobe.

PubMed

Wittig, John H; Jang, Anthony I; Cocjin, John B; Inati, Sara K; Zaghloul, Kareem A

2018-06-01

We identify a memory-specific attention mechanism in the human anterior temporal lobe, an area implicated in semantic processing and episodic memory formation. Spiking neuron activity is suppressed and becomes more reliable in preparation for verbal memory formation. Intracranial electroencephalography signals implicate this region as a source of executive control for attentional selection. Consistent with this interpretation, its surgical removal causes significant memory impairment for attended words relative to unattended words.

Cellular and molecular mechanisms of HIV-1 integration targeting.

PubMed

Engelman, Alan N; Singh, Parmit K

2018-07-01

Integration is central to HIV-1 replication and helps mold the reservoir of cells that persists in AIDS patients. HIV-1 interacts with specific cellular factors to target integration to interior regions of transcriptionally active genes within gene-dense regions of chromatin. The viral capsid interacts with several proteins that are additionally implicated in virus nuclear import, including cleavage and polyadenylation specificity factor 6, to suppress integration into heterochromatin. The viral integrase protein interacts with transcriptional co-activator lens epithelium-derived growth factor p75 to principally position integration within gene bodies. The integrase additionally senses target DNA distortion and nucleotide sequence to help fine-tune the specific phosphodiester bonds that are cleaved at integration sites. Research into virus-host interactions that underlie HIV-1 integration targeting has aided the development of a novel class of integrase inhibitors and may help to improve the safety of viral-based gene therapy vectors.

Music improves verbal memory encoding while decreasing prefrontal cortex activity: an fNIRS study.

PubMed

Ferreri, Laura; Aucouturier, Jean-Julien; Muthalib, Makii; Bigand, Emmanuel; Bugaiska, Aurelia

2013-01-01

Listening to music engages the whole brain, thus stimulating cognitive performance in a range of non-purely musical activities such as language and memory tasks. This article addresses an ongoing debate on the link between music and memory for words. While evidence on healthy and clinical populations suggests that music listening can improve verbal memory in a variety of situations, it is still unclear what specific memory process is affected and how. This study was designed to explore the hypothesis that music specifically benefits the encoding part of verbal memory tasks, by providing a richer context for encoding and therefore less demand on the dorsolateral prefrontal cortex (DLPFC). Twenty-two healthy young adults were subjected to functional near-infrared spectroscopy (fNIRS) imaging of their bilateral DLPFC while encoding words in the presence of either a music or a silent background. Behavioral data confirmed the facilitating effect of music background during encoding on subsequent item recognition. fNIRS results revealed significantly greater activation of the left hemisphere during encoding (in line with the HERA model of memory lateralization) and a sustained, bilateral decrease of activity in the DLPFC in the music condition compared to silence. These findings suggest that music modulates the role played by the DLPFC during verbal encoding, and open perspectives for applications to clinical populations with prefrontal impairments, such as elderly adults or Alzheimer's patients.

Photocatalytic activity of titania coatings synthesised by a combined laser/sol–gel technique

DOE Office of Scientific and Technical Information (OSTI.GOV)

Adraider, Y.; Pang, Y.X., E-mail: F6098038@tees.ac.uk; Nabhani, F.

2014-06-01

Highlights: • Sol–gel method was used to prepare titania coatings. • Titania thin films were coated on substrate surface by dip coating. • Fibre laser was employed to irradiate the titania coated surfaces. • Photocatalytic efficiency of titania coatings was significantly improved after laser processing. - Abstract: Titania coatings were prepared using sol–gel method and then applied on the substrate surface by dip coating. Fibre laser (λ = 1064 nm) in continuous wave mode was used to irradiate the titania coated surfaces at different specific energies. The ATR-FTIR, XRD, SEM, EDS and contact angle measurement were employed to analyse surfacemore » morphology, phase composition and crystalline structure of laser-irradiated titania coatings, whilst the photocatalytic activity was evaluated by measuring the decomposition of methylene blue (MB) after exposure to the visible light for various illumination times. Results showed that the laser-irradiated titania coatings demonstrate significant different composition and microstructure in comparison with the as-coated from the same sol–gel titania. Photocatalytic efficiency of titania coatings was significantly improved after laser processing. The photocatalytic activity of laser-irradiated titania coatings was higher than that of the as-coated titania. The titania coating processed at laser specific energy of 6.5 J/mm{sup 2} exhibited the highest photocatalytic activity among all titania samples.« less

Effect of monophasic pulsed current on heel pain and functional activities caused by plantar fasciitis.

PubMed

Alotaibi, Abdullah K; Petrofsky, Jerrold S; Daher, Noha S; Lohman, Everett; Laymon, Michael; Syed, Hasan M

2015-03-20

Plantar fasciitis (PF) is a soft tissue disorder considered to be one of the most common causes of inferior heel pain. The aim of this study was to investigate the effect of monophasic pulsed current (MPC) and MPC coupled with plantar fascia-specific stretching exercises (SE) on the treatment of PF. Forty-four participants (22 women and 22 men, with a mean age of 49 years) diagnosed with PF were randomly assigned to receive MPC (n=22) or MPC coupled with plantar fascia-specific SE (n=22). Prior to and after 4 weeks of treatment, participants underwent baseline evaluation; heel pain was evaluated using a visual analogue scale (VAS), heel tenderness threshold was quantified using a handheld pressure algometer (PA), and functional activities level was assessed using the Activities of Daily Living subscale of the Foot and Ankle Ability Measure (ADL/FAAM). Heel pain scores showed a significant reduction in both groups compared to baseline VAS scores (P<0.001). Heel tenderness improved significantly in both groups compared with baseline PA scores (P<0.001). Functional activity level improved significantly in both groups compared with baseline (ADL/FAAM) scores (P<0.001). However, no significant differences existed between the 2 treatment groups in all post-intervention outcome measures. This trial showed that MPC is useful in treating inferior heel symptoms caused by PF.

Magnetic Photocatalyst BiVO₄/Mn-Zn ferrite/Reduced Graphene Oxide: Synthesis Strategy and Its Highly Photocatalytic Activity.

PubMed

Xie, Taiping; Li, Hui; Liu, Chenglun; Yang, Jun; Xiao, Tiancun; Xu, Longjun

2018-05-29

Magnetic photocatalyst BiVO₄/Mn-Zn ferrite (Mn 1- x Zn x Fe₂O₄)/reduced graphene oxide (RGO) was synthesized by a simple calcination and reduction method. The magnetic photocatalyst held high visible light-absorption ability with low band gap energy and wide absorption wavelength range. Electrochemical impedance spectroscopies illustrated good electrical conductivity which indicated low charge-transfer resistance due to incorporation of Mn 1- x Zn x Fe₂O₄ and RGO. The test of photocatalytic activity showed that the degradation ratio of rhodamine B (RhB) reached 96.0% under visible light irradiation after only 1.5 h reaction. The photocatalytic mechanism for the prepared photocatalyst was explained in detail. Here, the incorporation of RGO enhanced the specific surface area compared with BiVO4/Mn 1- x Zn x Fe₂O₄.The larger specific surface area provided more active surface sites, more free space to improve the mobility of photo-induced electrons, and further facilitated the effective migration of charge carriers, leading to the remarkable improvement of photocatalytic performance. Meanwhile, RGO was the effective acceptor as well as transporter of photo-generated electron hole pairs. •O₂ - was the most active species in the photocatalytic reaction. BiVO₄/Mn 1- x Zn x Fe₂O₄/RGO had quite a wide application in organic contaminants removal or environmental pollution control.

Effect of Monophasic Pulsed Current on Heel Pain and Functional Activities caused by Plantar Fasciitis

PubMed Central

Alotaibi, Abdullah K.; Petrofsky, Jerrold S.; Daher, Noha S.; Lohman, Everett; Laymon, Michael; Syed, Hasan M.

2015-01-01

Background Plantar fasciitis (PF) is a soft tissue disorder considered to be one of the most common causes of inferior heel pain. The aim of this study was to investigate the effect of monophasic pulsed current (MPC) and MPC coupled with plantar fascia-specific stretching exercises (SE) on the treatment of PF. Material/Methods Forty-four participants (22 women and 22 men, with a mean age of 49 years) diagnosed with PF were randomly assigned to receive MPC (n=22) or MPC coupled with plantar fascia-specific SE (n=22). Prior to and after 4 weeks of treatment, participants underwent baseline evaluation; heel pain was evaluated using a visual analogue scale (VAS), heel tenderness threshold was quantified using a handheld pressure algometer (PA), and functional activities level was assessed using the Activities of Daily Living subscale of the Foot and Ankle Ability Measure (ADL/FAAM). Results Heel pain scores showed a significant reduction in both groups compared to baseline VAS scores (P<0.001). Heel tenderness improved significantly in both groups compared with baseline PA scores (P<0.001). Functional activity level improved significantly in both groups compared with baseline (ADL/FAAM) scores (P<0.001). However, no significant differences existed between the 2 treatment groups in all post-intervention outcome measures. Conclusions This trial showed that MPC is useful in treating inferior heel symptoms caused by PF. PMID:25791231

Music improves verbal memory encoding while decreasing prefrontal cortex activity: an fNIRS study

PubMed Central

Ferreri, Laura; Aucouturier, Jean-Julien; Muthalib, Makii; Bigand, Emmanuel; Bugaiska, Aurelia

2013-01-01

Listening to music engages the whole brain, thus stimulating cognitive performance in a range of non-purely musical activities such as language and memory tasks. This article addresses an ongoing debate on the link between music and memory for words. While evidence on healthy and clinical populations suggests that music listening can improve verbal memory in a variety of situations, it is still unclear what specific memory process is affected and how. This study was designed to explore the hypothesis that music specifically benefits the encoding part of verbal memory tasks, by providing a richer context for encoding and therefore less demand on the dorsolateral prefrontal cortex (DLPFC). Twenty-two healthy young adults were subjected to functional near-infrared spectroscopy (fNIRS) imaging of their bilateral DLPFC while encoding words in the presence of either a music or a silent background. Behavioral data confirmed the facilitating effect of music background during encoding on subsequent item recognition. fNIRS results revealed significantly greater activation of the left hemisphere during encoding (in line with the HERA model of memory lateralization) and a sustained, bilateral decrease of activity in the DLPFC in the music condition compared to silence. These findings suggest that music modulates the role played by the DLPFC during verbal encoding, and open perspectives for applications to clinical populations with prefrontal impairments, such as elderly adults or Alzheimer’s patients. PMID:24339807

Use of a consumer market activity monitoring and feedback device improves exercise capacity and activity levels in COPD.

PubMed

Caulfield, Brian; Kaljo, Indira; Donnelly, Seamas

2014-01-01

COPD is associated with a gradual decline in physical activity, which itself contributes to a worsening of the underlying condition. Strategies that improve physical activity levels are critical to halt this cycle. Wearable sensor based activity monitoring and persuasive feedback might offer a potential solution. However it is not clear just how much intervention might be needed in this regard - i.e. whether programmes need to be tailored specifically for the target clinical population or whether more simple activity monitoring and feedback solutions, such as that offered in consumer market devices, might be sufficient. This research was carried out to investigate the impact of 4 weeks of using an off the shelf consumer market activity monitoring and feedback application on measures of physical activity, exercise capacity, and health related quality of life in a population of 10 Stage I and II COPD patients. Results demonstrate a significant and positive effect on exercise capacity (measured using a 6-minute walk test) and activity levels (measured in terms of average number of steps per hour) yet no impact on health related quality of life (St Georges Respiratory Disease Questionnaire).

A truly healthy bottom line: improving financial results through effective health and productivity programs.

PubMed

Wolff, Shelly

2008-01-01

Financially speaking, an effective, comprehensive, properly executed health and productivity (H&P) program can drive significant business results. Unfortunately, many companies are not getting the same return on their investments in H&P programs as their peers. This article defines program effectiveness and describes the specific activities of employers that have implemented successful H&P strategies leading to improved health, increased productivity and lower benefit costs-and, in turn, higher levels of performance, returns to shareholders and market premium.

Research in Computational Aeroscience Applications Implemented on Advanced Parallel Computing Systems

NASA Technical Reports Server (NTRS)

Wigton, Larry

1996-01-01

Improving the numerical linear algebra routines for use in new Navier-Stokes codes, specifically Tim Barth's unstructured grid code, with spin-offs to TRANAIR is reported. A fast distance calculation routine for Navier-Stokes codes using the new one-equation turbulence models is written. The primary focus of this work was devoted to improving matrix-iterative methods. New algorithms have been developed which activate the full potential of classical Cray-class computers as well as distributed-memory parallel computers.

Viral Vector-Based Targeting of miR-21 in Cardiac Nonmyocyte Cells Reduces Pathologic Remodeling of the Heart

PubMed Central

Ramanujam, Deepak; Sassi, Yassine; Laggerbauer, Bernhard; Engelhardt, Stefan

2016-01-01

Systemic inhibition of miR-21 has proven effective against myocardial fibrosis and dysfunction, while studies in cardiac myocytes suggested a protective role in this cell type. Considering potential implications for therapy, we aimed to determine the cell fraction where miR-21 exerts its pathological activity. We developed a viral vector-based strategy for gene targeting of nonmyocyte cardiac cells in vivo and compared global to cardiac myocyte-specific and nonmyocyte-specific deletion of miR-21 in chronic left ventricular pressure overload. Murine moloney virus and serotype 9 of adeno-associated virus were engineered to encode improved Cre recombinase for genetic deletion in miR-21fl/fl mice. Pericardial injection of murine moloney virus-improved Cre recombinase to neonates achieved highly selective genetic ablation of miR-21 in nonmyocyte cardiac cells, identified as cardiac fibroblasts and endothelial cells. Upon left ventricular pressure overload, cardiac function was only preserved in mice with miR-21 deficiency in nonmyocyte cardiac cells, but not in mice with global or cardiac myocyte-specific ablation. Our data demonstrate that miR-21 exerts its pathologic activity directly in cardiac nonmyocytes and encourage further development of antimiR-21 therapy toward cellular tropism. PMID:27545313

Modular and selective biosynthesis of gasoline-range alkanes.

PubMed

Sheppard, Micah J; Kunjapur, Aditya M; Prather, Kristala L J

2016-01-01

Typical renewable liquid fuel alternatives to gasoline are not entirely compatible with current infrastructure. We have engineered Escherichia coli to selectively produce alkanes found in gasoline (propane, butane, pentane, heptane, and nonane) from renewable substrates such as glucose or glycerol. Our modular pathway framework achieves carbon-chain extension by two different mechanisms. A fatty acid synthesis route is used to generate longer chains heptane and nonane, while a more energy efficient alternative, reverse-β-oxidation, is used for synthesis of propane, butane, and pentane. We demonstrate that both upstream (thiolase) and intermediate (thioesterase) reactions can act as control points for chain-length specificity. Specific free fatty acids are subsequently converted to alkanes using a broad-specificity carboxylic acid reductase and a cyanobacterial aldehyde decarbonylase (AD). The selectivity obtained by different module pairings provides a foundation for tuning alkane product distribution for desired fuel properties. Alternate ADs that have greater activity on shorter substrates improve observed alkane titer. However, even in an engineered host strain that significantly reduces endogenous conversion of aldehyde intermediates to alcohol byproducts, AD activity is observed to be limiting for all chain lengths. Given these insights, we discuss guiding principles for pathway selection and potential opportunities for pathway improvement. Copyright © 2015 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.

Photon up-conversion increases biomass yield in Chlorella vulgaris.

PubMed

Menon, Kavya R; Jose, Steffi; Suraishkumar, Gadi K

2014-12-01

Photon up-conversion, a process whereby lower energy radiations are converted to higher energy levels via the use of appropriate phosphor systems, was employed as a novel strategy for improving microalgal growth and lipid productivity. Photon up-conversion enables the utilization of regions of the solar spectrum, beyond the typical photosynthetically active radiation, that are usually wasted or are damaging to the algae. The effects of up-conversion of red light by two distinct sets of up-conversion phosphors were studied in the model microalgae Chlorella vulgaris. Up-conversion by set 1 phosphors led to a 2.85 fold increase in biomass concentration and a 3.2 fold increase in specific growth rate of the microalgae. While up-conversion by set 2 phosphors resulted in a 30% increase in biomass and 12% increase in specific intracellular neutral lipid, while the specific growth rates were comparable to that of the control. Furthermore, up-conversion resulted in higher levels of specific intracellular reactive oxygen species in C. vulgaris. Up-conversion of red light (654 nm) was shown to improve biomass yields in C. vulgaris. In principle, up-conversion can be used to increase the utilization range of the electromagnetic spectrum for improved cultivation of photosynthetic systems such as plants, algae, and microalgae. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Participation of National Medical Associations in quality improvement activities - International comparison and the Israeli case

PubMed Central

2014-01-01

Background Many countries have devoted considerable efforts in an attempt to improve the performance of their health care systems. National Medical Associations (NMAs), along with other stakeholders, play a part in the promotion of such activities. The purpose of this paper is to explore the nature and level of participation of NMAs in activities of quality improvement in medicine, with a specific emphasis on Israel. Methods The authors conducted a survey among NMAs around the world inquiring as to their involvement in three central aspects of quality improvement: clinical guidelines, quality measurement and continuing medical education (CME). In addition, they conducted a review of the literature in order to gather more information and complete the data collected in the survey. The findings were processed and analyzed comparatively. Results Most of the NMAs surveyed participate in quality improvement activities at least to some extent. NMAs' main involvement is in the regulation of CME and they are involved to a much lesser extent in the preparation of clinical guidelines and in quality measurement. In Israel, the Israeli Medical Association (IMA) has a dominant role in both the preparation of clinical guidelines and the regulation of CME credits. Discussion It is possible that the expertise maintained by the profession, coupled with the organizational power of the NMA as a union, is viewed as beneficial for regulating educational activities in medicine such as CME. Conversely, the issuing of clinical guidelines is usually regarded as a typical scientific activity, and therefore often rests in the hands of professional medical societies. Quality measurement is regarded as a distinctive administrative tool and is usually found in the province of governments. Based on the typology that we introduced in our previous paper, we discovered that the extent of NMAs’ involvement in quality improvement coincides with the mode of governance of the health care system. Conclusions The nature and level of participation of NMAs in activities of quality improvement varies widely. Collaboration of NMAs in this field with other stakeholders is not uncommon, and may contribute to the further development of quality improvement in medicine. PMID:24808940

Optimization of extraction of novel pectinase enzyme discovered in red pitaya (Hylocereus polyrhizus) peel.

PubMed

Zohdi, Nor Khanani; Amid, Mehrnoush

2013-11-20

Plant peels could be a potential source of novel pectinases for use in various industrial applications due to their broad substrate specificity with high stability under extreme conditions. Therefore, the extraction conditions of a novel pectinase enzyme from pitaya peel was optimized in this study. The effect of extraction variables, namely buffer to sample ratio (2:1 to 8:1, X₁), extraction temperature (-15 to +25 °C, X₂) and buffer pH (4.0 to 12.0, X₃) on specific activity, temperature stability, storage stability and surfactant agent stability of pectinase from pitaya peel was investigated. The study demonstrated that the optimum conditions for the extraction of pectinase from pitaya sources could improve the enzymatic characteristics of the enzyme and protect its activity and stability during the extraction procedure. The optimum extraction conditions cause the pectinase to achieve high specific activity (15.31 U/mg), temperature stability (78%), storage stability (88%) and surfactant agent stability (83%). The most desirable conditions to achieve the highest activity and stability of pectinase enzyme from pitaya peel were the use of 5:1 buffer to sample ratio at 5 °C and pH 8.0.

Enhancing learning in geosciences and water engineering via lab activities

NASA Astrophysics Data System (ADS)

Valyrakis, Manousos; Cheng, Ming

2016-04-01

This study focuses on the utilisation of lab based activities to enhance the learning experience of engineering students studying Water Engineering and Geosciences. In particular, the use of modern highly visual and tangible presentation techniques within an appropriate laboratory based space are used to introduce undergraduate students to advanced engineering concepts. A specific lab activity, namely "Flood-City", is presented as a case study to enhance the active engagement rate, improve the learning experience of the students and better achieve the intended learning objectives of the course within a broad context of the engineering and geosciences curriculum. Such activities, have been used over the last few years from the Water Engineering group @ Glasgow, with success for outreach purposes (e.g. Glasgow Science Festival and demos at the Glasgow Science Centre and Kelvingrove museum). The activity involves a specific setup of the demonstration flume in a sand-box configuration, with elements and activities designed so as to gamely the overall learning activity. Social media platforms can also be used effectively to the same goals, particularly in cases were the students already engage in these online media. To assess the effectiveness of this activity a purpose designed questionnaire is offered to the students. Specifically, the questionnaire covers several aspects that may affect student learning, performance and satisfaction, such as students' motivation, factors to effective learning (also assessed by follow-up quizzes), and methods of communication and assessment. The results, analysed to assess the effectiveness of the learning activity as the students perceive it, offer a promising potential for the use of such activities in outreach and learning.

Predictors of participation in sports after hip and knee arthroplasty.

PubMed

Williams, Daniel H; Greidanus, Nelson V; Masri, Bassam A; Duncan, Clive P; Garbuz, Donald S

2012-02-01

While the primary objective of joint arthroplasty is to improve patient quality of life, pain, and function, younger active patients often demand a return to higher function that includes sporting activity. Knowledge of rates and predictors of return to sports will help inform expectations in patients anticipating return to sports after joint arthroplasty. We measured the rate of sports participation at 1 year using the UCLA activity score and explored 11 variables, including choice of procedure/prosthesis, that might predict return to a high level of sporting activity, when controlling for potential confounding variables. We retrospectively evaluated 736 patients who underwent primary metal-on-polyethylene THA, metal-on-metal THA, hip resurfacing arthroplasty, revision THA, primary TKA, unicompartmental knee arthroplasty, and revision TKA between May 2005 and June 2007. We obtained UCLA activity scores on all patients; we defined high activity as a UCLA score of 7 or more. We evaluated patient demographics (age, sex, BMI, comorbidity), quality of life (WOMAC score, Oxford Hip Score, SF-12 score), and surgeon- and procedural/implant-specific variables to identify factors associated with postoperative activity score. Minimum followup was 11 months (mean, 12.1 months; range, 11-13 months). Preoperative UCLA activity score, age, male sex, and BMI predicted high activity scores. The type of operation and implant characteristics did not predict return to high activity sports. Our data suggest patient-specific factors predict postoperative activity rather than factors specific to type of surgery, implant, or surgeon factors. Level II, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.

Dance and Hometown Associations are Promising Strategies to Improve Physical Activity Participation Among US Nigerian Transnational Immigrants.

PubMed

Ibe-Lamberts, Kelechi; Tshiswaka, Daudet Ilunga; Onyenekwu, Ifeyinwa; Schwingel, Andiara; Iwelunmor, Juliet

2018-04-01

Lack of physical activity participation has been identified as a determinant for negative health outcomes across various ethnicities worldwide and within the USA. We investigated the perceptions of the prospects of promoting dancing within hometown associations as a form for improving physical activity participation for Nigerian Transnational Immigrants (NTIs) in the USA: a migrant cohort subset of individuals who maintain cross-border ties with their indigenous communities of origin. Using PEN-3 cultural model, we conducted semi-structured interviews with 24 transnational African migrants (11 males and 13 females) living in Chicago to explore culturally sensitive strategies to promote physical activity participation among our target population. The findings revealed positive perceptions related to dancing that might help to promote physical activity (PA) among NTI, existential or unique perceptions related to Nigerian parties that may also play a role with PA promotion, and negative perception in the form of limited discussions about PA in Nigerian hometown associations in the USA. Results from this study highlight the need for further investigation on culturally sensitive strategies to improve physical activity and participation in diverse Black immigrant populations, specifically in the form of cultural dance and activities such as parties in which this population frequently participate in. Furthermore, hometown associations may also serve as a platform for the implementation of PA programs due to its large reach to a rather covert group.

Platelet Activating Factor Receptor Activation Improves siRNA Uptake and RNAi Responses in Well-differentiated Airway Epithelia

PubMed Central

Krishnamurthy, Sateesh; Behlke, Mark A; Apicella, Michael A; McCray, Paul B; Davidson, Beverly L

2014-01-01

Well-differentiated human airway epithelia present formidable barriers to efficient siRNA delivery. We previously reported that treatment of airway epithelia with specific small molecules improves oligonucleotide uptake and facilitates RNAi responses. Here, we exploited the platelet activating factor receptor (PAFR) pathway, utilized by specific bacteria to transcytose into epithelia, as a trigger for internalization of Dicer-substrate siRNAs (DsiRNA). PAFR is a G-protein coupled receptor which can be engaged and activated by phosphorylcholine residues on the lipooligosaccharide (LOS) of nontypeable Haemophilus influenzae and the teichoic acid of Streptococcus pneumoniae as well as by its natural ligand, platelet activating factor (PAF). When well-differentiated airway epithelia were simultaneously treated with either nontypeable Haemophilus influenzae LOS or PAF and transduced with DsiRNA formulated with the peptide transductin, we observed silencing of both endogenous and exogenous targets. PAF receptor antagonists prevented LOS or PAF-assisted DsiRNA silencing, demonstrating that ligand engagement of PAFR is essential for this process. Additionally, PAF-assisted DsiRNA transfection decreased CFTR protein expression and function and reduced exogenous viral protein levels and titer in human airway epithelia. Treatment with spiperone, a small molecule identified using the Connectivity map database to correlate gene expression changes in response to drug treatment with those associated with PAFR stimulation, also induced silencing. These results suggest that the signaling pathway activated by PAFR binding can be manipulated to facilitate siRNA entry and function in difficult to transfect well-differentiated airway epithelial cells. PMID:25025465

Improvement of Processing Speed in Executive Function Immediately following an Increase in Cardiovascular Activity.

PubMed

Tam, Nicoladie D

2013-01-01

This study aims to identify the acute effects of physical exercise on specific cognitive functions immediately following an increase in cardiovascular activity. Stair-climbing exercise is used to increase the cardiovascular output of human subjects. The color-naming Stroop Test was used to identify the cognitive improvements in executive function with respect to processing speed and error rate. The study compared the Stroop results before and immediately after exercise and before and after nonexercise, as a control. The results show that there is a significant increase in processing speed and a reduction in errors immediately after less than 30 min of aerobic exercise. The improvements are greater for the incongruent than for the congruent color tests. This suggests that physical exercise induces a better performance in a task that requires resolving conflict (or interference) than a task that does not. There is no significant improvement for the nonexercise control trials. This demonstrates that an increase in cardiovascular activity has significant acute effects on improving the executive function that requires conflict resolution (for the incongruent color tests) immediately following aerobic exercise more than similar executive functions that do not require conflict resolution or involve the attention-inhibition process (for the congruent color tests).

Make Gestures to Learn: Reproducing Gestures Improves the Learning of Anatomical Knowledge More than Just Seeing Gestures

PubMed Central

Cherdieu, Mélaine; Palombi, Olivier; Gerber, Silvain; Troccaz, Jocelyne; Rochet-Capellan, Amélie

2017-01-01

Manual gestures can facilitate problem solving but also language or conceptual learning. Both seeing and making the gestures during learning seem to be beneficial. However, the stronger activation of the motor system in the second case should provide supplementary cues to consolidate and re-enact the mental traces created during learning. We tested this hypothesis in the context of anatomy learning by naïve adult participants. Anatomy is a challenging topic to learn and is of specific interest for research on embodied learning, as the learning content can be directly linked to learners' body. Two groups of participants were asked to look at a video lecture on the forearm anatomy. The video included a model making gestures related to the content of the lecture. Both groups see the gestures but only one also imitate the model. Tests of knowledge were run just after learning and few days later. The results revealed that imitating gestures improves the recall of structures names and their localization on a diagram. This effect was however significant only in long-term assessments. This suggests that: (1) the integration of motor actions and knowledge may require sleep; (2) a specific activation of the motor system during learning may improve the consolidation and/or the retrieval of memories. PMID:29062287

Comprehensive Proteomics Analysis of Laticifer Latex Reveals New Insights into Ethylene Stimulation of Natural Rubber Production.

PubMed

Wang, Xuchu; Wang, Dan; Sun, Yong; Yang, Qian; Chang, Lili; Wang, Limin; Meng, Xueru; Huang, Qixing; Jin, Xiang; Tong, Zheng

2015-09-08

Ethylene is a stimulant to increase natural rubber latex. After ethylene application, both fresh yield and dry matter of latex are substantially improved. Moreover, we found that ethylene improves the generation of small rubber particles. However, most genes involved in rubber biosynthesis are inhibited by exogenous ethylene. Therefore, we conducted a proteomics analysis of ethylene-stimulated rubber latex, and identified 287 abundant proteins as well as 143 ethylene responsive latex proteins (ERLPs) with mass spectrometry from the 2-DE and DIGE gels, respectively. In addition, more than 1,600 proteins, including 404 ERLPs, were identified by iTRAQ. Functional classification of ERLPs revealed that enzymes involved in post-translational modification, carbohydrate metabolism, hydrolase activity, and kinase activity were overrepresented. Some enzymes for rubber particle aggregation were inhibited to prolong latex flow, and thus finally improved latex production. Phosphoproteomics analysis identified 59 differential phosphoproteins; notably, specific isoforms of rubber elongation factor and small rubber particle protein that were phosphorylated mainly at serine residues. This post-translational modification and isoform-specific phosphorylation might be important for ethylene-stimulated latex production. These results not only deepen our understanding of the rubber latex proteome but also provide new insights into the use of ethylene to stimulate rubber latex production.

Memory traces of long-range coordinated oscillations in the sleeping human brain.

PubMed

Piantoni, Giovanni; Van Der Werf, Ysbrand D; Jensen, Ole; Van Someren, Eus J W

2015-01-01

Cognition involves coordinated activity across distributed neuronal networks. Neuronal activity during learning triggers cortical plasticity that allows for reorganization of the neuronal network and integration of new information. Animal studies have shown post-learning reactivation of learning-elicited neuronal network activity during subsequent sleep, supporting consolidation of the reorganization. However, no previous studies, to our knowledge, have demonstrated reactivation of specific learning-elicited long-range functional connectivity during sleep in humans. We here show reactivation of learning-induced long-range synchronization of magnetoencephalography power fluctuations in human sleep. Visuomotor learning elicited a specific profile of long-range cortico-cortical synchronization of slow (0.1 Hz) fluctuations in beta band (12-30 Hz) power. The parieto-occipital part of this synchronization profile reappeared in delta band (1-3.5 Hz) power fluctuations during subsequent sleep, but not during the intervening wakefulness period. Individual differences in the reactivated synchronization predicted postsleep performance improvement. The presleep resting-state synchronization profile was not reactivated during sleep. The findings demonstrate reactivation of long-range coordination of neuronal activity in humans, more specifically of reactivation of coupling of infra-slow fluctuations in oscillatory power. The spatiotemporal profile of delta power fluctuations during sleep may subserve memory consolidation by echoing coordinated activation elicited by prior learning. © 2014 Wiley Periodicals, Inc.

The process evaluation of It's Your Move!, an Australian adolescent community-based obesity prevention project.

PubMed

Mathews, Louise B; Moodie, Marj M; Simmons, Annie M; Swinburn, Boyd A

2010-07-30

Evidence on interventions for preventing unhealthy weight gain in adolescents is urgently needed. The aim of this paper is to describe the process evaluation for a three-year (2005-2008) project conducted in five secondary schools in the East Geelong/Bellarine region of Victoria, Australia. The project, 'It's Your Move!' aimed to reduce unhealthy weight gain by promoting healthy eating patterns, regular physical activity, healthy body weight, and body size perception amongst youth; and improve the capacity of families, schools, and community organisations to sustain the promotion of healthy eating and physical activity in the region. The project was supported by Deakin University (training and evaluation), a Reference Committee (strategic direction, budgetary approval and monitoring) and a Project Management Committee (project delivery). A workshop of students, teachers and other stakeholders formulated a 10-point action plan, which was then translated into strategies and initiatives specific to each school by the School Project Officers (staff members released from teaching duties one day per week) and trained Student Ambassadors. Baseline surveys informed intervention development. Process data were collected on all intervention activities and these were collated and enumerated, where possible, into a set of mutually exclusive tables to demonstrate the types of strategies and the dose, frequency and reach of intervention activities. The action plan included three guiding objectives, four on nutrition, two on physical activity and one on body image. The process evaluation data showed that a mix of intervention strategies were implemented, including social marketing, one-off events, lunch time and curriculum programs, improvements in infrastructure, and healthy school food policies. The majority of the interventions were implemented in schools and focused on capacity building and healthy eating strategies as physical activity practices were seen by the teachers as already meeting students' needs. While substantial health-promoting activities were conducted (especially related to healthy eating), there remain further opportunities for secondary schools to use a whole-of-school approach through the school curriculum, environment, policies and ethos to improve healthy eating, physical activity and healthy body perceptions in youth. To achieve this, significant, sustained leadership will be required within the education sector generally and within schools specifically.

Combined chemical and structural signals of biomaterials synergistically activate cell-cell communications for improving tissue regeneration.

PubMed

Xu, Yachen; Peng, Jinliang; Dong, Xin; Xu, Yuhong; Li, Haiyan; Chang, Jiang

2017-06-01

Biomaterials are only used as carriers of cells in the conventional tissue engineering. Considering the multi-cell environment and active cell-biomaterial interactions in tissue regeneration process, in this study, structural signals of aligned electrospun nanofibers and chemical signals of bioglass (BG) ionic products in cell culture medium are simultaneously applied to activate fibroblast-endothelial co-cultured cells in order to obtain an improved skin tissue engineering construct. Results demonstrate that the combined biomaterial signals synergistically activate fibroblast-endothelial co-culture skin tissue engineering constructs through promotion of paracrine effects and stimulation of gap junctional communication between cells, which results in enhanced vascularization and extracellular matrix protein synthesis in the constructs. Structural signals of aligned electrospun nanofibers play an important role in stimulating both of paracrine and gap junctional communication while chemical signals of BG ionic products mainly enhance paracrine effects. In vivo experiments reveal that the activated skin tissue engineering constructs significantly enhance wound healing as compared to control. This study indicates the advantages of synergistic effects between different bioactive signals of biomaterials can be taken to activate communication between different types of cells for obtaining tissue engineering constructs with improved functions. Tissue engineering can regenerate or replace tissue or organs through combining cells, biomaterials and growth factors. Normally, for repairing a specific tissue, only one type of cells, one kind of biomaterials, and specific growth factors are used to support cell growth. In this study, we proposed a novel tissue engineering approach by simply using co-cultured cells and combined biomaterial signals. Using a skin tissue engineering model, we successfully proved that the combined biomaterial signals such as surface nanostructures and bioactive ions could synergistically stimulate the cell-cell communication in co-culture system through paracrine effects and gap junction activation, and regulated expression of growth factors and extracellular matrix proteins, resulting in an activated tissue engineering constructs that significantly enhanced skin regeneration. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Relapse Prevention in Major Depressive Disorder: Mindfulness-Based Cognitive Therapy Versus an Active Control Condition

PubMed Central

Shallcross, Amanda J.; Gross, James J.; Visvanathan, Pallavi D.; Kumar, Niketa; Palfrey, Amy; Ford, Brett Q.; Dimidjian, Sona; Shirk, Stephen; Holm-Denoma, Jill; Goode, Kari M.; Cox, Erica; Chaplin, William; Mauss, Iris B.

2015-01-01

Objective We evaluated the comparative effectiveness of Mindfulness-based cognitive therapy (MBCT) versus an active control condition (ACC) for depression relapse prevention, depressive symptom reduction, and improvement in life satisfaction. Method Ninety-two participants in remission from Major Depressive Disorder with residual depressive symptoms were randomized to either an 8-week MBCT or a validated ACC that is structurally equivalent to MBCT and controls for non-specific effects (e.g., interaction with a facilitator, perceived social support, treatment outcome expectations). Both interventions were delivered according to their published manuals. Results Intention-to-treat analyses indicated no differences between MBCT and ACC in depression relapse rates or time to relapse over a 60-week follow-up. Both groups experienced significant and equal reductions in depressive symptoms and improvements in life satisfaction. A significant quadratic interaction (group x time) indicated that the pattern of depressive symptom reduction differed between groups. The ACC experienced immediate symptom reduction post-intervention and then a gradual increase over the 60-week follow-up. The MBCT group experienced a gradual linear symptom reduction. The pattern for life satisfaction was identical but only marginally significant. Conclusions MBCT did not differ from an ACC on rates of depression relapse, symptom reduction, or life satisfaction, suggesting that MBCT is no more effective for preventing depression relapse and reducing depressive symptoms than the active components of the ACC. Differences in trajectory of depressive symptom improvement suggest that the intervention-specific skills acquired may be associated with differential rates of therapeutic benefit. This study demonstrates the importance of comparing psychotherapeutic interventions to active control conditions. PMID:26371618

Impact of physical therapy for Parkinson's disease: a critical review of the literature.

PubMed

Kwakkel, G; de Goede, C J T; van Wegen, E E H

2007-01-01

A systematic review of the literature found 23 randomized clinical trials reflecting specific core areas of physical therapy (PT), that is, transfer, posture, balance, reaching and grasping, gait, and physical condition. All studies were of moderate methodological quality. Important limitations of the studies were: (1) insufficient statistical power (type II error); (2) poor methodological quality due to inadequate randomization and blinding procedures; (3) insufficient contrast in dosage and treatment between experimental and control groups; and (4) lack of appropriate measurement instruments able to identify clinically meaningful changes according to the International Classification of Functioning (ICF). In the last 5 years, the methodological quality of RCTs has shown substantial improvement. Most high-quality studies investigated the effects of exercise therapy, including the use of external rhythms to improve gait and gait-related activities. The results of these trials suggest that the effects of PT are task- and context-specific. This indicates that the tasks that are trained tend not to generalize to related activities that are not directly trained in the rehabilitation programme itself, and suggests that future programmes should train meaningful tasks preferably in patients' home environment. In addition, the decline in treatment effects after an intervention has ended suggests the need for permanent treatment of patients with PD, i.e. chronic treatment for this chronic disease. Future studies should aim to develop responsive measurement instruments able to monitor meaningful changes in activities, as well as better understanding of insufficiently understood symptoms such as freezing, rigidity and bradykinesia and greater insight into neurophysiological mechanisms underlying training-induced changes in activities such as improved gait performance by rhythmic cueing.

Novel Method to Detect and Characterize 18F-FDG Infiltration at the Injection Site: A Single-Institution Experience.

PubMed

Muzaffar, Razi; Frye, Sarah A; McMunn, Anna; Ryan, Kelley; Lattanze, Ron; Osman, Medhat M

2017-12-01

A novel quality control and quality assurance device provides time-activity curves that can identify and characterize PET/CT radiotracer infiltration at the injection site during the uptake phase. The purpose of this study was to compare rates of infiltration detected by the device with rates detected by physicians. We also assessed the value of using the device to improve injection results in our center. Methods: 109 subjects consented to the study. All had passive device sensors applied to their skin near the injection site and mirrored on the contralateral arm during the entire uptake period. Nuclear medicine physicians reviewed standard images for the presence of dose infiltration. Sensor-generated time-activity curves were independently examined and then compared with the physician reports. Injection data captured by the software were analyzed, and the results were provided to the technologists. Improvement measures were implemented, and rates were remeasured. Results: Physician review of the initial 40 head-to-toe field-of-view images identified 15 cases (38%) of dose infiltration (9 minor, 5 moderate, and 1 significant). Sensor time-activity curves on these 40 cases independently identified 22 cases (55%) of dose infiltration (16 minor, 5 moderate, and 1 significant). After the time-activity curve results and the contributing factor analysis were shared with technologists, injection techniques were modified and an additional 69 cases were studied. Of these, physician review identified 17 cases (25%) of infiltration (13 minor, 3 moderate, and 1 significant), a 34% decline. Sensor time-activity curves identified 4 cases (6%) of infiltration (2 minor and 2 moderate), an 89% decline. Conclusion: The device provides valuable quality control information for each subject. Time-activity curves can further characterize visible infiltration. Even when the injection site was out of the field of view, the time-activity curves could still detect and characterize infiltration. Our initial experience showed that the quality assurance information obtained from the device helped reduce the rate and severity of infiltration. The device revealed site-specific contributing factors that helped nuclear medicine physicians and technologists customize their quality improvement efforts to these site-specific issues. Reducing infiltration can improve image quality and SUV quantification, as well as the ability to minimize variability in a site's PET/CT results. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Investigation on the Activity Activation and Cementitious Property of Coal Gangue with High Iron and Silica Contents

NASA Astrophysics Data System (ADS)

Wu, Hong; Li, Yu; Teng, Min; Yang, Yu

2017-11-01

The activity of coal gangue by thermal activation and composite activation technologies was investigated. The crystal composition, framework structure and morphology change were analyzed by XRD, FT-IR and SEM, respectively. The cementitious property of coal gangue was measured by strength test. The results showed that thermal activation decomposed kaolinite in coal gangue, and formed the metastable structure with a porous state, multiple internal broken bonds and large specific surface areas. Based on thermal activation, the added lime provided the alkaline environment, then this reduced the bond energy of reactant particles and the degree of crystallinity of quartz in coal gangue. The two activation methods could effectively improve the cementitious property of coal gangue based unburned bricks, and that the composite activation technology was superior performance.

Making cognitive decision support work: Facilitating adoption, knowledge and behavior change through QI.

PubMed

Weir, Charlene; Brunker, Cherie; Butler, Jorie; Supiano, Mark A

2017-07-01

This paper evaluates the role of facilitation in the successful implementation of Computerized Decision Support (CDS). Facilitation processes include education, specialized computerized decision support, and work process reengineering. These techniques, as well as modeling and feedback enhance self-efficacy, which we propose is one of the factors that mediate the effectiveness of any CDS. In this study, outpatient clinics implemented quality improvement (QI) projects focused on improving geriatric care. Quality Improvement is the systematic process of improving quality through continuous measurement and targeted actions. The program, entitled "Advancing Geriatric Education through Quality Improvement" (AGE QI), consisted of a 6-month, QI based, intervention: (1) 2h didactic session, (2) 1h QI planning session, (3) computerized decision support design and implementation, (4) QI facilitation activities, (5) outcome feedback, and (6) 20h of CME. Specifically, we examined the impact of the QI based program on clinician's perceived self-efficacy in caring for older adults and the relationship of implementation support and facilitation on perceived success. The intervention was implemented at 3 institutions, 27 community healthcare system clinics, and 134 providers. This study reports the results of pre/post surveys for the forty-nine clinicians who completed the full CME program. Self-efficacy ratings for specific clinical behaviors related to care of older adults were assessed using a Likert based instrument. Self-ratings of efficacy improved across the following domains (depression, falls, end-of-life, functional status and medication management) and specifically in QI targeted domains and were associated with overall clinic improvements. Published by Elsevier Inc.

Evaluation of infrared thermography body temperature and collar-mounted accelerometer and acoustic technology for predicting time of ovulation of cows in a pasture-based system.

PubMed

Talukder, S; Thomson, P C; Kerrisk, K L; Clark, C E F; Celi, P

2015-03-01

This study was conducted to test the hypothesis that the specificity of infrared thermography (IRT) in detecting cows about to ovulate could be improved using different body parts that are less likely to be contaminated by fecal matter. In addition, the combined activity and rumination data captured by accelerometers were evaluated to provide a more accurate indication of ovulation than the activity and rumination data alone. Thermal images of 30 cows were captured for different body areas (eye, ear, muzzle, and vulva) twice daily after AM and PM milking sessions during the entire experimental period. Milk progesterone data and insemination records were used to determine the date of ovulation. Cows were fitted with SCR heat and rumination long-distance tags (SCR HR LD) for 1 month. Activity- and rumination-based estrus alerts were initially identified using default threshold values set by the manufacturer; however, a range of thresholds was also created and tested for both activity and rumination to determine the potential for higher levels of accuracy of ovulation detection. Visual assessment of mounting indicators resulted in 75% sensitivity (Se), 100% specificity (Sp), and 100% positive predictive value (PPV). Overall, IRT showed poor performance for detecting cows about to ovulate. Vulval temperature resulted in the greatest (80%) Sp but the poorest (21%) Se compared with the IRT temperatures of other body areas. The SCR HR LD tags default threshold value resulted in 78% Se, 57% Sp, and 70% PPV. Lowering the activity threshold from the default value improved the sensitivity but created a large number of false positives, which resulted in a decrease in specificity. Lowering the activity threshold to 20 resulted in a detection performance of 80% Se, 94% Sp, and 67% PPV, whereas the rumination levels achieved 35% Se, 69% Sp, and 14% PPV. The area under the curve for the activity level, rumination level, and the combined measures of activity and rumination levels were 0.82, 0.54, and 0.75, respectively. Alerts generated by SCR HR LD tags based on a lower activity threshold level had high sensitivity and may be able to detect a high proportion of cows in ovulatory periods in pasture-based system; however, the specificities and positive predictive value were lower than the visual assessment of mounting indicators. Copyright © 2015 Elsevier Inc. All rights reserved.

EthA, a Common Activator of Thiocarbamide-Containing Drugs Acting on Different Mycobacterial Targets▿

PubMed Central

Dover, Lynn G.; Alahari, Anuradha; Gratraud, Paul; Gomes, Jessica M.; Bhowruth, Veemal; Reynolds, Robert C.; Besra, Gurdyal S.; Kremer, Laurent

2007-01-01

Many of the current antimycobacterial agents require some form of cellular activation unmasking reactive groups, which in turn will bind to their specific targets. Therefore, understanding the mechanisms of activation of current antimycobacterials not only helps to decipher mechanisms of drug resistance but may also facilitate the development of alternative activation strategies or of analogues that do not require such processes. Herein, through the use of genetically defined strains of Mycobacterium bovis BCG we provide evidence that EthA, previously shown to activate ethionamide, also converts isoxyl (ISO) and thiacetazone (TAC) into reactive species. These results were further supported by the development of an in vitro assay using purified recombinant EthA, which allowed direct assessment of the metabolism of ISO. Interestingly, biochemical analysis of [14C]acetate-labeled cultures suggested that all of these EthA-activated drugs inhibit mycolic acid biosynthesis via different mechanisms through binding to specific targets. This report is also the first description of the molecular mechanism of action of TAC, a thiosemicarbazone antimicrobial agent that is still used in the treatment of tuberculosis as a second-line drug in many developing countries. Altogether, the results suggest that EthA is a common activator of thiocarbamide-containing drugs. The broad specificity of EthA can now be used to improve the activation process of these drugs, which may help overcome the toxicity problems associated with clinical thiocarbamide use. PMID:17220416

Antigen-Specific CD8 Lytic Phenotype Induced by Sipuleucel-T in Hormone-Sensitive or Castration-Resistant Prostate Cancer and Association With Overall Survival.

PubMed

Antonarakis, Emmanuel S; Small, Eric J; Petrylak, Daniel; Quinn, David I; Kibel, Adam S; Chang, Nancy; Dearstyne, Erica; Harmon, Matthew; Campogan, Dwayne; Haynes, Heather; Vu, Tuyen; Sheikh, Nadeem A; Drake, Charles G

2018-06-01

Sipuleucel-T is FDA-approved for the treatment of metastatic castration-resistant prostate cancer (mCRPC) based on the IMPACT trial showing a 4.1-month benefit in median overall survival (OS) for patients receiving sipuleucel-T vs control. Although efficacy of sipuleucel-T is well-established, its mechanism remains incompletely understood. Patient samples from three sipuleucel-T trials were assessed for peripheral cellular immune responses to the immunogen PA2024 and the target antigen prostatic acid phosphatase (PAP). PAP- and PA2024-specific proliferative and cytolytic responses were characterized to delineate sipuleucel-T-induced immune responses. To quantify potential cytotoxic T lymphocyte (CTL) activity, cell-surface CD107a expression on PAP- or PA2024-specific CD8+ T cells was measured in sipuleucel-T-treated patient and healthy volunteer samples. Increased PA2024-specific CD4+ (p=0.030) and CD8+ (p=0.052) T-cell proliferation from baseline to week 6 was observed (N=14) post-sipuleucel-T, with greater magnitude of PA2024-specific responses compared to PAP. PAP- and PA2024-CTL activity (CD107a positivity) significantly increased at weeks 6 and 26 after sipuleucel-T treatment (p<0.0001; N=22). At 26 weeks post-sipuleucel-T, OS correlated with the magnitude of PAP (Pearson's R, 0.52; p=0.013) or PA2024 (Pearson's R, 0.67; p=0.0006) CTL activity. Higher PA2024-CTL activity at week 26 was significantly associated with longer OS using tertile analysis (p=0.0005; N=22), with PA2024 responses correlating with PAP responses at week 26 (R=0.90; p=1.53E -08 ). This study is the first to report PAP-specific CD8+ T-cell responses elicited by sipuleucel-T treatment. Increased and persistent potential PA2024-specific CTL activity correlated with PAP-specific CTL activity and associated with improved OS following sipuleucel-T treatment. Copyright ©2018, American Association for Cancer Research.

[Improving prevention activities of infectious diseases during preparation and holding of the XXII Olympic Winter Games and XI Paralympic Winter Games 2014 in Sochi].

PubMed

Onishchenko, G G; Bragina, I V; Ezhlova, E B; Demina, Iu V; Grechanaia, T V; Nikolaevich, P N; Balaeva, M I; Tesheva, S Ch; Biriukov, V A; Kulichenko, A N; Vasilenko, N F; Maletskaia, O V; Manin, E A; Orobeĭ, V G

2015-01-01

The article presents data on the implementation of a set of preventive activities to ensure sanitation and epidemiological welfare during the XXII Olympic Winter Games and XI Paralympic Winter Games 2014 in Sochi. The importance of monitoring and evaluation of epidemiological risk, as the basis of formation of preventive measures is noticed. The questions of specific, and nonspecific prevention of infectious diseases, especially the work done during the pre-Olympic period are considered. The importance of specifically developed regulatory basis, and health education are emphasized. The conclusion about the effectiveness of the measures taken, which led to a significant reduction of infectious diseases in the region is made.