| 1. |
|
|
| 2. |
|
|
| 3. |
- Klionsky, Daniel J., et al.
(author)
-
Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
-
In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
-
Research review (peer-reviewed)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
|
|
| 4. |
|
|
| 5. |
- Fischer, U., et al.
(author)
-
Early versus Later Anticoagulation for Stroke with Atrial Fibrillation
- 2023
-
In: New England Journal of Medicine. - 0028-4793. ; 388:26, s. 2411-2421
-
Journal article (peer-reviewed)abstract
- BackgroundThe effect of early as compared with later initiation of direct oral anticoagulants (DOACs) in persons with atrial fibrillation who have had an acute ischemic stroke is unclear.MethodsWe performed an investigator-initiated, open-label trial at 103 sites in 15 countries. Participants were randomly assigned in a 1:1 ratio to early anticoagulation (within 48 hours after a minor or moderate stroke or on day 6 or 7 after a major stroke) or later anticoagulation (day 3 or 4 after a minor stroke, day 6 or 7 after a moderate stroke, or day 12, 13, or 14 after a major stroke). Assessors were unaware of the trial-group assignments. The primary outcome was a composite of recurrent ischemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial hemorrhage, or vascular death within 30 days after randomization. Secondary outcomes included the components of the composite primary outcome at 30 and 90 days.ResultsOf 2013 participants (37% with minor stroke, 40% with moderate stroke, and 23% with major stroke), 1006 were assigned to early anticoagulation and 1007 to later anticoagulation. A primary-outcome event occurred in 29 participants (2.9%) in the early-treatment group and 41 participants (4.1%) in the later-treatment group (risk difference, -1.18 percentage points; 95% confidence interval [CI], -2.84 to 0.47) by 30 days. Recurrent ischemic stroke occurred in 14 participants (1.4%) in the early-treatment group and 25 participants (2.5%) in the later-treatment group (odds ratio, 0.57; 95% CI, 0.29 to 1.07) by 30 days and in 18 participants (1.9%) and 30 participants (3.1%), respectively, by 90 days (odds ratio, 0.60; 95% CI, 0.33 to 1.06). Symptomatic intracranial hemorrhage occurred in 2 participants (0.2%) in both groups by 30 days.ConclusionsIn this trial, the incidence of recurrent ischemic stroke, systemic embolism, major extracranial bleeding, symptomatic intracranial hemorrhage, or vascular death at 30 days was estimated to range from 2.8 percentage points lower to 0.5 percentage points higher (based on the 95% confidence interval) with early than with later use of DOACs. (Funded by the Swiss National Science Foundation and others; ELAN ClinicalTrials.gov number, .)
|
|
| 6. |
- Pfaller, M.A., et al.
(author)
-
Twelve years of fluconazole in clinical practice : Global-trends in species distribution and fluconazole susceptibility of bloodstream isolates of Candida
- 2004
-
In: Clinical Microbiology and Infection. - : Elsevier BV. - 1198-743X .- 1469-0691. ; 10:SUPPL. 1, s. 11-23
-
Journal article (peer-reviewed)abstract
- We determined the species distribution and in-vitro susceptibility of 6082 bloodstream infection (BSI) isolates of Candida spp. collected from 250 medical centres in 32 nations over a 10-year period from 1992 through 2001. The species included 3401 C. albicans, 984 C. glabrata, 796 C. parapsilosis, 585 C. tropicalis, 153 C. krusei, 67 C. lusitaniae, 48 C. guilliermondii, 10 C. famata, 10 C. kefyr, six C. pelliculosa, five C. rugosa, four C. lipolytica, three C. dubliniensis, three C. inconspicua, two C. sake and one isolate each of C. lambica, C. norvegensis and C. zeylanoides. Minimum inhibitory concentration determinations were made using the National Committee for Clinical Laboratory Standards reference broth microdilution method. Variation in the rank order and frequency of the different species of Candida was observed over time and by geographic area. The proportion of BSI due to C. albicans and C. glabrata increased and C. parapsilosis decreased over time in Canada, the USA and Europe. C. glabrata was an infrequent cause of BSI in Latin America and the Asia-Pacific region. Very little variation in fluconazole susceptibility was observed among isolates of C. albicans, C. tropicalis and C. parapsilosis. These species accounted for 78% of all BSI and remained highly susceptible (91-100% susceptible) to fluconazole from 1992 to 2001 irrespective of geographic origin. The prevalence of fluconazole resistance among C. glabrata isolates was variable both over time and among the various countries and regions. Resistance to fluconazole among C. glabrata isolates was greatest in the USA and varied by US census region (range 0-23%). These observations are generally encouraging relative to the sustained usefulness of fluconazole as a systemically active antifungal agent for the treatment of candida BSI. © 2004 Copyright by the European Society of Clinical Microbiology and Infectious Diseases.
|
|
| 7. |
|
|
| 8. |
- Antonova, M., et al.
(author)
-
Baby MIND : a magnetized segmented neutrino detector for the WAGASCI experiment
- 2017
-
In: Journal of Instrumentation. - : Institute of Physics (IOP). - 1748-0221. ; 12:07, s. 1-6
-
Journal article (peer-reviewed)abstract
- T2K (Tokai-to-Kamioka) is a long-baseline neutrino experiment in Japan designed to study various parameters of neutrino oscillations. A near detector complex (ND280) is located 280 m downstream of the production target and measures neutrino beam parameters before any oscillations occur. ND280’s measurements are used to predict the number and spectra of neutrinos in the Super-Kamiokande detector at the distance of 295 km. The difference in the target material between the far (water) and near (scintillator, hydrocarbon) detectors leads to the main non-cancelling systematic uncertainty for the oscillation analysis. In order to reduce this uncertainty a new WAter-Grid-And-SCintillator detector (WAGASCI) has been developed. A magnetized iron neutrino detector (Baby MIND) will be used to measure momentum and charge identification of the outgoing muons from charged current interactions. The Baby MIND modules are composed of magnetized iron plates and long plastic scintillator bars read out at the both ends with wavelength shifting fibers and silicon photomultipliers. The front-end electronics board has been developed to perform the readout and digitization of the signals from the scintillator bars. Detector elements were tested with cosmic rays and in the PS beam at CERN. The obtained results are presented in this paper.
|
|
| 9. |
- Antonova, M., et al.
(author)
-
Baby MIND : a magnetized segmented neutrino detector for the WAGASCI experiment
- 2017
-
In: Journal of Instrumentation. - : IOP PUBLISHING LTD. - 1748-0221. ; 12
-
Journal article (peer-reviewed)abstract
- T2K (Tokai-to-Kamioka) is a long-baseline neutrino experiment in Japan designed to study various parameters of neutrino oscillations. Anear detector complex (ND280) is located 280m downstream of the production target and measures neutrino beam parameters before any oscillations occur. ND280's measurements are used to predict the number and spectra of neutrinos in the Super-Kamiokande detector at the distance of 295 km. The difference in the target material between the far (water) and near (scintillator, hydrocarbon) detectors leads to the main non-cancelling systematic uncertainty for the oscillation analysis. In order to reduce this uncertainty a new WAter-Grid-And-SCintillator detector (WAGASCI) has been developed. A magnetized iron neutrino detector (Baby MIND) will be used to measure momentum and charge identification of the outgoing muons from charged current interactions. The Baby MIND modules are composed of magnetized iron plates and long plastic scintillator bars read out at the both ends with wavelength shifting fibers and silicon photomultipliers. The front-end electronics board has been developed to perform the readout and digitization of the signals from the scintillator bars. Detector elements were tested with cosmic rays and in the PS beam at CERN. The obtained results are presented in this paper.
|
|
| 10. |
- Antonova, M., et al.
(author)
-
Synchronization of the distributed readout frontend electronics of the Baby MIND detector
- 2017
-
In: 2017 XXVI International Scientific Conference Electronics (ET). - : IEEE. - 9781538617533
-
Conference paper (peer-reviewed)abstract
- Baby MIND is a new downstream muon range detector for the WGASCI experiment. This article discusses the distributed readout system and its timing requirements. The paper presents the design of the synchronization subsystem and the results of its test.
|
|
| 11. |
|
|
| 12. |
- Antonova, M., et al.
(author)
-
Proposal for characterization of muon spectrometers for neutrino beam lines with the Baby MIND
- 2015
-
Reports (other academic/artistic)abstract
- Neutrino detectors based on state-of-the-art plastic scintillators read out with solid state photo-sensors, as well as new magnetization schemes, have been developed in the framework of AIDA. Meaningful size prototypes are under construction. In the framework of the CERN neutrino platform, we propose to test a Totally Active Scintillator Detector (TASD) and a prototype of a Magnetized Iron Neutrino Detector (MIND), called Baby MIND in the H8 beam line in 2016-2018. The design of the detectors and the purpose and plans for the beam tests are presented. An opportunity to use the Baby MIND detector in a real neutrino beam at JPARC for the measurement of the cross-section ratio between Water and scintillator (WAGASCI experiment) is described.
|
|
| 13. |
- Richards, Stephen, et al.
(author)
-
Genome Sequence of the Pea Aphid Acyrthosiphon pisum
- 2010
-
In: PLoS biology. - : Public Library of Science (PLoS). - 1544-9173 .- 1545-7885. ; 8:2, s. e1000313-
-
Journal article (peer-reviewed)abstract
- Aphids are important agricultural pests and also biological models for studies of insect-plant interactions, symbiosis, virus vectoring, and the developmental causes of extreme phenotypic plasticity. Here we present the 464 Mb draft genome assembly of the pea aphid Acyrthosiphon pisum. This first published whole genome sequence of a basal hemimetabolous insect provides an outgroup to the multiple published genomes of holometabolous insects. Pea aphids are host-plant specialists, they can reproduce both sexually and asexually, and they have coevolved with an obligate bacterial symbiont. Here we highlight findings from whole genome analysis that may be related to these unusual biological features. These findings include discovery of extensive gene duplication in more than 2000 gene families as well as loss of evolutionarily conserved genes. Gene family expansions relative to other published genomes include genes involved in chromatin modification, miRNA synthesis, and sugar transport. Gene losses include genes central to the IMD immune pathway, selenoprotein utilization, purine salvage, and the entire urea cycle. The pea aphid genome reveals that only a limited number of genes have been acquired from bacteria; thus the reduced gene count of Buchnera does not reflect gene transfer to the host genome. The inventory of metabolic genes in the pea aphid genome suggests that there is extensive metabolite exchange between the aphid and Buchnera, including sharing of amino acid biosynthesis between the aphid and Buchnera. The pea aphid genome provides a foundation for post-genomic studies of fundamental biological questions and applied agricultural problems.
|
|
| 14. |
|
|
| 15. |
|
|
| 16. |
- Cabral, R.A., et al.
(author)
-
Volatile cycling of H2O, CO2, F, and Cl in the HIMU mantle: A new window provided by melt inclusions from oceanic hotspot lavas at Mangaia, Cook Islands.
- 2014
-
In: Geochemistry Geophysics Geosystems. - 1525-2027. ; 15, s. 4445-4467
-
Journal article (peer-reviewed)abstract
- Mangaia hosts the most radiogenic Pb-isotopic compositions observed in ocean island basalts and represents the HIMU (high µ = 238U/204Pb) mantle end-member, thought to result from recycled oceanic crust. Complete geochemical characterization of the HIMU mantle end-member has been inhibited due to a lack of deep submarine glass samples from HIMU localities. We homogenized olivine-hosted melt inclusions separated from Mangaia lavas and the resulting glassy inclusions made possible the first volatile abundances to be obtained from the HIMU mantle end-member. We also report major and trace element abundances and Pb-isotopic ratios on the inclusions, which have HIMU isotopic fingerprints. We evaluate the samples for processes that could modify the volatile and trace element abundances postmantle melting, including diffusive Fe and H2O loss, degassing, and assimilation. H2O/Ce ratios vary from 119 to 245 in the most pristine Mangaia inclusions; excluding an inclusion that shows evidence for assimilation, the primary magmatic H2O/Ce ratios vary up to ∼200, and are consistent with significant dehydration of oceanic crust during subduction and long-term storage in the mantle. CO2 concentrations range up to 2346 ppm CO2 in the inclusions. Relatively high CO2 in the inclusions, combined with previous observations of carbonate blebs in other Mangaia melt inclusions, highlight the importance of CO2 for the generation of the HIMU mantle. F/Nd ratios in the inclusions (30 ± 9; 2σ standard deviation) are higher than the canonical ratio observed in oceanic lavas, and Cl/K ratios (0.079 ± 0.028) fall in the range of pristine mantle (0.02–0.08).
|
|
| 17. |
- Hacke, W, et al.
(author)
-
Effects of alteplase for acute stroke according to criteria defining the European Union and United States marketing authorizations: Individual-patient-data meta-analysis of randomized trials
- 2018
-
In: International journal of stroke : official journal of the International Stroke Society. - : SAGE Publications. - 1747-4949. ; 13:2, s. 175-189
-
Journal article (peer-reviewed)abstract
- The recommended maximum age and time window for intravenous alteplase treatment of acute ischemic stroke differs between the Europe Union and United States. Aims We compared the effects of alteplase in cohorts defined by the current Europe Union or United States marketing approval labels, and by hypothetical revisions of the labels that would remove the Europe Union upper age limit or extend the United States treatment time window to 4.5 h. Methods We assessed outcomes in an individual-patient-data meta-analysis of eight randomized trials of intravenous alteplase (0.9 mg/kg) versus control for acute ischemic stroke. Outcomes included: excellent outcome (modified Rankin score 0–1) at 3–6 months, the distribution of modified Rankin score, symptomatic intracerebral hemorrhage, and 90-day mortality. Results Alteplase increased the odds of modified Rankin score 0–1 among 2449/6136 (40%) patients who met the current European Union label and 3491 (57%) patients who met the age-revised label (odds ratio 1.42, 95% CI 1.21−1.68 and 1.43, 1.23−1.65, respectively), but not in those outside the age-revised label (1.06, 0.90−1.26). By 90 days, there was no increased mortality in the current and age-revised cohorts (hazard ratios 0.98, 95% CI 0.76−1.25 and 1.01, 0.86–1.19, respectively) but mortality remained higher outside the age-revised label (1.19, 0.99–1.42). Similarly, alteplase increased the odds of modified Rankin score 0-1 among 1174/6136 (19%) patients who met the current US approval and 3326 (54%) who met a 4.5-h revised approval (odds ratio 1.55, 1.19−2.01 and 1.37, 1.17−1.59, respectively), but not for those outside the 4.5-h revised approval (1.14, 0.97−1.34). By 90 days, no increased mortality remained for the current and 4.5-h revised label cohorts (hazard ratios 0.99, 0.77−1.26 and 1.02, 0.87–1.20, respectively) but mortality remained higher outside the 4.5-h revised approval (1.17, 0.98–1.41). Conclusions An age-revised European Union label or 4.5-h-revised United States label would each increase the number of patients deriving net benefit from alteplase by 90 days after acute ischemic stroke, without excess mortality.
|
|
| 18. |
|
|
| 19. |
- Rose-Koga, E.F., et al.
(author)
-
Geochemical systematics of Pb isotopes, fluorine, and sulfur in melt inclusions from São Miguel, Azores.
- 2017
-
In: Chemical Geology. - : Elsevier BV. - 0009-2541 .- 1872-6836. ; 485, s. 22-37
-
Journal article (peer-reviewed)abstract
- Pb isotopic measurements in olivine-hosted melt inclusions of ocean island basalts (OIBs) from São Miguel, Azores, reflect the high 207Pb/204Pb and 208Pb/204Pb at a given 206Pb/204Pb of their host lavas. The data are consistent with mixing between two endmembers: the first (the Central Group) has relatively high 208Pb/206Pb and is similar to the component sampled by Graciosa and Faial, and the second is a radiogenic endmember (with low 208Pb/206Pb) that we refer to as the Nordeste component. F and Cl concentrations measured in the same melt inclusions from São Miguel represent parental abundances unmodified by crustal assimilation. Based on undegassed F and Cl concentrations, the source beneath São Miguel is volatile-rich. Pb-isotope composition of the melt inclusions correlates positively with S concentration: we attribute this correlation to the dissolution of oceanic crust sulfides in the S-undersaturated basaltic melt of the Nordeste component. These blebs were then assimilated by the São Miguel magma and the magma droplets were later trapped in olivines.When comparing melt inclusions from worldwide OIBs representing mantle endmembers, we find an overall negative correlation between F/Nd and 208Pb/206Pb for volcanic glasses and melt inclusions. The high F/Nd (up to 40) endmember is represented by HIMU melt inclusions and the low F/Nd (down to 14) by EM1 Pitcairn glasses. São Miguel melt inclusions have an intermediate F/Nd of 23.1 ± 3.4.
|
|
| 20. |
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
- Cabral, Rita A., et al.
(author)
-
Anomalous sulphur isotopes in plume lavas reveal deep mantle storage of Archaean crust
- 2013
-
In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 496:7446, s. 490-494
-
Journal article (peer-reviewed)abstract
- Basaltic lavas erupted at some oceanic intraplate hotspot volcanoes are thought to sample ancient subducted crustal materials(1,2). However, the residence time of these subducted materials in the mantle is uncertain and model-dependent(3), and compelling evidence for their return to the surface in regions of mantle upwelling beneath hotspots is lacking. Here we report anomalous sulphur isotope signatures indicating mass-independent fractionation (MIF) in olivine-hosted sulphides from 20-million-year-old ocean island basalts from Mangaia, Cook Islands (Polynesia), which have been suggested to sample recycled oceanic crust(3,4). Terrestrial MIF sulphur isotope signatures (in which the amount of fractionation does not scale in proportion with the difference in the masses of the isotopes) were generated exclusively through atmospheric photochemical reactions until about 2.45 billion years ago(5-7). Therefore, the discovery of MIF sulphur in these young plume lavas suggests that sulphur-probably derived from hydrothermally altered oceanic crust-was subducted into the mantle before 2.45 billion years ago and recycled into the mantle source of Mangaia lavas. These new data provide evidence for ancient materials, with negative Delta S-33 values, in the mantle source for Mangaia lavas. Our data also complement evidence for recycling of the sulphur content of ancient sedimentary materials to the subcontinental lithospheric mantle that has been identified in diamond-hosted sulphide inclusions(8,9). This Archaean age for recycled oceanic crust also provides key constraints on the length of time that subducted crustal material can survive in the mantle, and on the timescales of mantle convection from subduction to upwelling beneath hotspots.
|
|
| 24. |
|
|
| 25. |
|
|
| 26. |
- Zeichner, Sarah S., et al.
(author)
-
Polycyclic aromatic hydrocarbons in samples of Ryugu formed in the interstellar medium
- 2023
-
In: Science. - : AMER ASSOC ADVANCEMENT SCIENCE. - 0036-8075 .- 1095-9203. ; 382:6677, s. 1411-1415
-
Journal article (peer-reviewed)abstract
- Polycyclic aromatic hydrocarbons (PAHs) contain less than or similar to 20% of the carbon in the interstellar medium. They are potentially produced in circumstellar environments (at temperatures greater than or similar to 1000 kelvin), by (similar to 10 kelvin) interstellar clouds, or by processing of carbon-rich dust grains. We report isotopic properties of PAHs extracted from samples of the asteroid Ryugu and the meteorite Murchison. The doubly-C-13 substituted compositions (Delta 2x(13)C values) of the PAHs naphthalene, fluoranthene, and pyrene are 9 to 51 parts per thousand higher than values expected for a stochastic distribution of isotopes. The Delta 2x(13)C values are higher than expected if the PAHs formed in a circumstellar environment, but consistent with formation in the interstellar medium. By contrast, the PAHs phenanthrene and anthracene in Ryugu samples have Delta 2x(13)C values consistent with formation by higher-temperature reactions.
|
|
| 27. |
- Bisch, Gaelle, et al.
(author)
-
Genome Evolution of Bartonellaceae Symbionts of Ants at the Opposite Ends of the Trophic Scale
- 2018
-
In: Genome Biology and Evolution. - : Oxford University Press. - 1759-6653. ; 10:7, s. 1687-1704
-
Journal article (peer-reviewed)abstract
- Many insects rely on bacterial symbionts to supply essential amino acids and vitamins that are deficient in their diets, but metabolic comparisons of closely related gut bacteria in insects with different dietary preferences have not been performed. Here, we demonstrate that herbivorous ants of the genus Dolichoderus from the Peruvian Amazon host bacteria of the family Bartonellaceae, known for establishing chronic or pathogenic infections in mammals. We detected these bacteria in all studied Dolichoderus species, and found that they reside in the midgut wall, that is, the same location as many previously described nutritional endosymbionts of insects. The genomic analysis of four divergent strains infecting different Dolichoderus species revealed genes encoding pathways for nitrogen recycling and biosynthesis of several vitamins and all essential amino acids. In contrast, several biosynthetic pathways have been lost, whereas genes for the import and conversion of histidine and arginine to glutamine have been retained in the genome of a closely related gut bacterium of the carnivorous ant Harpegnathos saltator. The broad biosynthetic repertoire in Bartonellaceae of herbivorous ants resembled that of gut bacteria of honeybees that likewise feed on carbohydrate-rich diets. Taken together, the broad distribution of Bartonellaceae across Dolichoderus ants, their small genome sizes, the specific location within hosts, and the broad biosynthetic capability suggest that these bacteria are nutritional symbionts in herbivorous ants. The results highlight the important role of the host nutritional biology for the genomic evolution of the gut microbiota-and conversely, the importance of the microbiota for the nutrition of hosts.
|
|
| 28. |
|
|
| 29. |
|
|
| 30. |
- Koga, H., et al.
(author)
-
Development of an Oral Rehabilitation Robot
- 2008
-
In: Gerontechnology. - Eindhoven. - 1569-111X. ; 7:2, s. 142-142
-
Journal article (peer-reviewed)abstract
- It is well known that the massage therapy is useful for the rehabilitation of various diseases. Althoughvarious apparatus have been developed for the massage of the torso and limbs, a machineto perform precise massage therapy to maxillofacial region is not developed yet.Therefore, we developed a robot system that provides massage therapy to the maxillofacialregion. The name of our newly developed robot was WAO-1. WAO-1 has been designedto perform appropriate massage to the patients with dry mouth. System descriptionThe mechanism of WAO-1 consists of two main parts: robot arms and the plungerdevice. The robot arms consist of two 6-DOF (degrees of freedom) manipulators used tocontrol the movement of the plunger device attached to the end-effector of each manipulator(Figure 1). The plunger device is the only part of the robot having direct contact withthe patient face. In order to control the motion of the plungers attached at each arm ofWAO-1, a position control system is implemented. The control system of WAO-1 is composedby a Massage Pattern Generator and Virtual Compliance Control1. Method Anevaluation experiment of WAO-1 is performed. In this experiment, WAO-1 provides themassage to 6 healthy volunteers (without any maxillofacial disorders). Each subject isprovided the massage to its parotid gland for 2 minutes. In order to confirm the effectivenessof the massage provide by WAO-1, the production of saliva was considered as aperformance index. This index is measured by using the Saxon test2; which is a standardmethod to confirm the effectiveness of the massage therapy. Results and discussionThe average production of saliva was increased by 0.63 g after providing the massage. Byanalyzing the collected data with a t-test, we found a significant difference (p < 0.05). Thusthe effectiveness of the massage to the parotid gland by WAO-1 is confirmed. On theother hand, when the doctor gives the massage to the parotid gland of the people, productionof saliva increases 1.4 g (average of 6 people). Therefore, the effect of WAO-1’s massageis less than that of doctor’s massage. We developed a robot system (WAO-1) whichcan massage the face. We think clinical trial is necessary to collect the data to certify theeffectiveness of robotic massage. The goal of this study is to establish robot massagetherapy as physiotherapy.
|
|
| 31. |
- Koga, H., et al.
(author)
-
Development of an Oral Rehabilitation Robot for Massage Therapy
- 2007
-
In: Information Technology Applications in Biomedicine, 2007. ITAB 2007. 6th International Special Topic Conference on. - : IEEE. - 9781424418671 - 9781424418688 ; , s. 111-114
-
Conference paper (peer-reviewed)abstract
- It is well known that the massage therapy is useful for the rehabilitation of various diseases. Although various apparatus have been developed for the massage of the torso and limbs, a machine to perform precise massage therapy to maxillofacial region is not developed yet. Therefore, we developed a robot system that provides massage therapy to maxillofacial region. The name of our newly developed robot was WAO-1. WAO-1 has been designed to perform appropriate massage to the patients with dry mouth, etc. WAO-1 is composed by two 6-degree of freedom arms with plungers attached at the end-effectors. The massage is applied to the patient by controlling the force and position of the plunger (virtual compliance). As a preliminary step of the clinical application, a simulation therapy of robotic massage to stimulate salivary flow from parotid gland was performed. The dynamic force on patient's head during the massage using WAO-1 was evaluated. The results suggested that WAO-1 could perform equivalent massage to human hand. We expect that WAO-1 will be useful to provide massage therapy to several patients with oral health problems. This will aim in reducing the therapy costs due to the need of human efforts when long-time therapies are needed
|
|
| 32. |
|
|
| 33. |
- Ma, Jianhui, et al.
(author)
-
Inhibition of Nuclear PTEN Tyrosine Phosphorylation Enhances Glioma Radiation Sensitivity through Attenuated DNA Repair
- 2019
-
In: Cancer Cell. - : Elsevier BV. - 1535-6108 .- 1878-3686. ; 35:3, s. 504-518.e7
-
Journal article (peer-reviewed)abstract
- Ionizing radiation (IR) and chemotherapy are standard-of-care treatments for glioblastoma (GBM) patients and both result in DNA damage, however, the clinical efficacy is limited due to therapeutic resistance. We identified a mechanism of such resistance mediated by phosphorylation of PTEN on tyrosine 240 (pY240-PTEN) by FGFR2. pY240-PTEN is rapidly elevated and bound to chromatin through interaction with Ki-67 in response to IR treatment and facilitates the recruitment of RAD51 to promote DNA repair. Blocking Y240 phosphorylation confers radiation sensitivity to tumors and extends survival in GBM preclinical models. Y240F-Pten knockin mice showed radiation sensitivity. These results suggest that FGFR-mediated pY240-PTEN is a key mechanism of radiation resistance and is an actionable target for improving radiotherapy efficacy.
|
|
| 34. |
- Magnusson, Joel, 1991, et al.
(author)
-
Laser-Particle Collider for Multi-GeV Photon Production
- 2019
-
In: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 122:25
-
Journal article (peer-reviewed)abstract
- As an alternative to Compton backscattering and bremsstrahlung, the process of colliding high-energy electron beams with strong laser fields can more efficiently provide both a cleaner and brighter source of photons in the multi-GeV range for fundamental studies in nuclear and quark-gluon physics. In order to favor the emission of high-energy quanta and minimize their decay into electron-positron pairs, the fields must not only be sufficiently strong, but also well localized. We here examine these aspects and develop the concept of a laser-particle collider tailored for high-energy photon generation. We show that the use of multiple colliding laser pulses with 0.4 PW of total power is capable of converting more than 18% of multi-GeV electrons passing through the high-field region into photons, each of which carries more than half of the electron initial energy. © 2019 authors. Published by the American Physical Society.
|
|
| 35. |
- Nordenfelt, Pontus, et al.
(author)
-
Direction of actin flow dictates integrin LFA-1 orientation during leukocyte migration
- 2017
-
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 8:1
-
Journal article (peer-reviewed)abstract
- Integrin αβ heterodimer cell surface receptors mediate adhesive interactions that provide traction for cell migration. Here, we test whether the integrin, when engaged to an extracellular ligand and the cytoskeleton, adopts a specific orientation dictated by the direction of actin flow on the surface of migrating cells. We insert GFP into the rigid, ligand-binding head of the integrin, model with Rosetta the orientation of GFP and its transition dipole relative to the integrin head, and measure orientation with fluorescence polarization microscopy. Cytoskeleton and ligand-bound integrins orient in the same direction as retrograde actin flow with their cytoskeleton-binding β-subunits tilted by applied force. The measurements demonstrate that intracellular forces can orient cell surface integrins and support a molecular model of integrin activation by cytoskeletal force. Our results place atomic, Å-scale structures of cell surface receptors in the context of functional and cellular, μm-scale measurements.
|
|
| 36. |
- Ogaki, Kotaro, et al.
(author)
-
Multiple system atrophy and apolipoprotein E
- 2018
-
In: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257. ; 33:4, s. 647-650
-
Journal article (peer-reviewed)abstract
- Background: Dysregulation of the specialized lipid metabolism involved in myelin synthesis and maintenance by oligodendrocytes has been associated with the unique neuropathology of MSA. We hypothesized that apolipoprotein E, which is associated with neurodegeneration, may also play a role in the pathogenesis of MSA. Objective: This study evaluated genetic associations of Apolipoprotein E alleles with risk of MSA and -synuclein pathology, and also examined whether apolipoprotein E isoforms differentially affect -synuclein uptake in a oligodendrocyte cell.Methods: One hundred sixty-eight pathologically confirmed MSA patients, 89 clinically diagnosed MSA patients, and 1,277 control subjects were genotyped for Apolipoprotein E. Human oligodendrocyte cell lines were incubated with -synuclein and recombinant human apolipoprotein E, with internalized -synuclein imaged by confocal microscopy and cells analyzed by flow cytometry.Results: No significant association with risk of MSA or was observed for either Apolipoprotein E 2 or 4. -Synuclein burden was also not associated with Apolipoprotein E alleles in the pathologically confirmed patients. Interestingly, in our cell assays, apolipoprotein E 4 significantly reduced -synuclein uptake in the oligodendrocytic cell line.Conclusions: Despite differential effects of apolipoprotein E isoforms on -synuclein uptake in a human oligodendrocytic cell, we did not observe a significant association at the Apolipoprotein E locus with risk of MSA or -synuclein pathology.
|
|
| 37. |
- Swaminathan, Vinay, et al.
(author)
-
Actin retrograde flow actively aligns and orients ligand-engaged integrins in focal adhesions
- 2017
-
In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 114:40, s. 10648-10653
-
Journal article (peer-reviewed)abstract
- Integrins are transmembrane receptors that, upon activation, bind extracellular ligands and link them to the actin filament (F-actin) cytoskeleton to mediate cell adhesion and migration. Cytoskeletal forces in migrating cells generated by polymerization- or contractility-driven “retrograde flow” of F-actin from the cell leading edge have been hypothesized to mediate integrin activation for ligand binding. This predicts that these forces should align and orient activated, ligand-bound integrins at the leading edge. Here, polarization-sensitive fluorescence microscopy of GFP-αVβ3 integrins in fibroblasts shows that integrins are coaligned in a specific orientation within focal adhesions (FAs) in a manner dependent on binding immobilized ligand and a talin-mediated linkage to the F-actin cytoskeleton. These findings, together with Rosetta modeling, suggest that integrins in FA are coaligned and may be highly tilted by cytoskeletal forces. Thus, the F-actin cytoskeleton sculpts an anisotropic molecular scaffold in FAs, and this feature may underlie the ability of migrating cells to sense directional extracellular cues.
|
|
| 38. |
|
|
