| 1. |
- Klionsky, Daniel J., et al.
(author)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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In: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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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.
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| 2. |
- Blunden, Jessica, et al.
(author)
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State of the Climate in 2012
- 2013
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In: Bulletin of The American Meteorological Society - (BAMS). - 0003-0007 .- 1520-0477. ; 94:8, s. S1-S258
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Journal article (peer-reviewed)abstract
- For the first time in serveral years, the El Nino-Southern Oscillation did not dominate regional climate conditions around the globe. A weak La Ni a dissipated to ENSOneutral conditions by spring, and while El Nino appeared to be emerging during summer, this phase never fully developed as sea surface temperatures in the eastern conditions. Nevertheless, other large-scale climate patterns and extreme weather events impacted various regions during the year. A negative phase of the Arctic Oscillation from mid-January to early February contributed to frigid conditions in parts of northern Africa, eastern Europe, and western Asia. A lack of rain during the 2012 wet season led to the worst drought in at least the past three decades for northeastern Brazil. Central North America also experienced one of its most severe droughts on record. The Caribbean observed a very wet dry season and it was the Sahel's wettest rainy season in 50 years. Overall, the 2012 average temperature across global land and ocean surfaces ranked among the 10 warmest years on record. The global land surface temperature alone was also among the 10 warmest on record. In the upper atmosphere, the average stratospheric temperature was record or near-record cold, depending on the dataset. After a 30-year warming trend from 1970 to 1999 for global sea surface temperatures, the period 2000-12 had little further trend. This may be linked to the prevalence of La Ni a-like conditions during the 21st century. Heat content in the upper 700 m of the ocean remained near record high levels in 2012. Net increases from 2011 to 2012 were observed at 700-m to 2000-m depth and even in the abyssal ocean below. Following sharp decreases in to the effects of La Ni a, sea levels rebounded to reach records highs in 2012. The increased hydrological cycle seen in recent years continued, with more evaporation in drier locations and more precipitation in rainy areas. In a pattern that has held since 2004, salty areas of the ocean surfaces and subsurfaces were anomalously salty on average, while fresher areas were anomalously fresh. Global tropical cyclone activity during 2012 was near average, with a total of 84 storms compared with the 1981-2010 average of 89. Similar to 2010 and 2011, the North Atlantic was the only hurricane basin that experienced above-normal activity. In this basin, Sandy brought devastation to Cuba and parts of the eastern North American seaboard. All other basins experienced either near-or below-normal tropical cyclone activity. Only three tropical cyclones reached Category 5 intensity-all in Bopha became the only storm in the historical record to produce winds greater than 130 kt south of 7 N. It was also the costliest storm to affect the Philippines and killed more than 1000 residents. Minimum Arctic sea ice extent in September and Northern Hemisphere snow cover extent in June both reached new record lows. June snow cover extent is now declining at a faster rate (-17.6% per decade) than September sea ice extent (-13.0% per decade). Permafrost temperatures reached record high values in northernmost Alaska. A new melt extent record occurred on 11-12 July on the Greenland ice sheet; 97% of the ice sheet showed some form of melt, four times greater than the average melt for this time of year. The climate in Antarctica was relatively stable overall. The largest maximum sea ice extent since records begain in 1978 was observed in September 2012. In the stratosphere, warm air led to the second smallest ozone hole in the past two decades. Even so, the springtime ozone layer above Antarctica likely will not return to its early 1980s state until about 2060. Following a slight decline associated with the global 2 emissions from fossil fuel combustion and cement production reached a record 9.5 +/- 0.5 Pg C in 2011 and a new record of 9.7 +/- 0.5 Pg C is estimated for 2012. Atmospheric CO2 concentrations increased by 2.1 ppm in 2012, to 392.6 ppm. In spring 2012, 2 concentration exceeded 400 ppm at 7 of the 13 Arctic observation sites. Globally, other greenhouse gases including methane and nitrous oxide also continued to rise in concentration and the combined effect now represents a 32% increase in radiative forcing over a 1990 baseline. Concentrations of most ozone depleting substances continued to fall.
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| 3. |
- Hua, Kuo-Tai, et al.
(author)
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N-α-acetyltransferase 10 protein suppresses cancer cell metastasis by binding PIX proteins and inhibiting Cdc42/Rac1 activity
- 2011
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In: Cancer Cell. - : Cell Press. - 1535-6108 .- 1878-3686. ; 19:2, s. 218-231
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Journal article (peer-reviewed)abstract
- N-α-acetyltransferase 10 protein, Naa10p, is an N-acetyltransferase known to be involved in cell cycle control. We found that Naa10p was expressed lower in varieties of malignancies with lymph node metastasis compared with non-lymph node metastasis. Higher Naa10p expression correlates the survival of lung cancer patients. Naa10p significantly suppressed migration, tumor growth, and metastasis independent of its enzymatic activity. Instead, Naa10p binds to the GIT-binding domain of PIX, thereby preventing the formation of the GIT-PIX-Paxillin complex, resulting in reduced intrinsic Cdc42/Rac1 activity and decreased cell migration. Forced expression of PIX in Naa10-transfected tumor cells restored the migration and metastasis ability. We suggest that Naa10p functions as a tumor metastasis suppressor by disrupting the migratory complex, PIX-GIT- Paxillin, in cancer cells.
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| 4. |
- Rockey, William M., et al.
(author)
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Rational truncation of an RNA aptamer to prostate-specific membrane antigen using computational structural modeling
- 2011
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In: Nucleic Acid Therapeutics. - : Mary Ann Liebert. - 2159-3337 .- 2159-3345. ; 21:5, s. 299-314
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Journal article (peer-reviewed)abstract
- RNA aptamers represent an emerging class of pharmaceuticals with great potential for targeted cancer diagnostics and therapy. Several RNA aptamers that bind cancer cell-surface antigens with high affinity and specificity have been described. However, their clinical potential has yet to be realized. A significant obstacle to the clinical adoption of RNA aptamers is the high cost of manufacturing long RNA sequences through chemical synthesis. Therapeutic aptamers are often truncated postselection by using a trial-and-error process, which is time consuming and inefficient. Here, we used a rational truncation approach guided by RNA structural prediction and protein/RNA docking algorithms that enabled us to substantially truncateA9, an RNA aptamer to prostate-specific membrane antigen (PSMA),with great potential for targeted therapeutics. This truncated PSMA aptamer (A9L; 41mer) retains binding activity, functionality, and is amenable to large-scale chemical synthesis for future clinical applications. In addition, the modeled RNA tertiary structure and protein/RNA docking predictions revealed key nucleotides within the aptamer critical for binding to PSMA and inhibiting its enzymatic activity. Finally, this work highlights the utility of existing RNA structural prediction and protein docking techniques that may be generally applicable to developing RNA aptamers optimized for therapeutic use. © 2011 Mary Ann Liebert, Inc.
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| 5. |
- Sheng, Min, et al.
(author)
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Humidity sensing properties of bismuth phosphates
- 2012
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In: Sensors and Actuators B: Chemical. - : Elsevier BV. - 0925-4005. ; 166, s. 642-649
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Journal article (peer-reviewed)abstract
- Cubic sillenite-type and monoclinic bismuth phosphates were synthesized via hydrothermal methods. Structure and morphology of cubic Bi13.1PO delta and monoclinic BiPO4 were characterized with a variety of analytical methods including powder X-ray diffraction, electron microscopy methods and surface area measurements. The humidity sensing properties of both bismuth phosphate types were investigated with respect to their capacitance characteristics. Sillenite-type cubic bismuth phosphate exhibits better response behavior than monoclinic BiPO4. Cubic bismuth phosphate displays a capacitance change of up to 4 orders of magnitude over a relative humidity (RH) range from 11% to 95% together with a linear adsorption/desorption relationship. This promising humidity sensing behavior is related to the presence of a framework structure containing polarizable Bi3+ cations in combination with moderate phosphate doping. (C) 2012 Elsevier B.V. All rights reserved.
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| 6. |
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| 7. |
- Ying, Yang, 1982-
(author)
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Inclusion Behaviour under a Swirl Flow in a Continuous Casting Process
- 2014
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Licentiate thesis (other academic/artistic)abstract
- A swirl flow generated in a submerged entry nozzle (SEN) can effectively improve a flow pattern and heat transfer in a continuous casting process by using the methods of “swirl blade type” and “electromagnetic type”. In order to obtain a further in-depth understanding with respect to the effect of a swirl flow on a continuous casting process, the inclusion behaviour in a SEN and a mold was studied in the present work. Moreover, the use of electromagnetics was adopted for to generate a rotating electromagnetic field in a continuous casting process of steel. Specifically, an electromagnetic swirl flow generator (EMSFG) was placed around a SEN.First of all, two kinds of a full type EMSFG and a half type EMSFG were designed based on mathematical modeling. Then, distributions of a magnetic flux intensity in an EMSFG as well as distributions of a Lorentz force in molten steel were simulated. It was found that the EMSFG structure and electromagnetic parameters have an important effect on the magnetic flux intensity and Lorentz force distributions. For both a full type and a half type EMSFG, the magnetic flux intensity and Lorentz force increases as the magnetomotive force increases. Especially, for a full type EMSFG, the magnetic flux intensity is distributed evenly in molten steel. Moreover, the Lorentz force increases along a radial direction in the molten steel in the SEN. However, for a half type EMSFG, the magnetic flux intensity and Lorentz force decreases gradually towards the region without an EMSFG. Consequently, a full type EMSFG with a 44000 AT magnetomotive force and a 50 Hz frequency is more suitable to apply in the operation of an EMSFG under actual production conditions.Secondly, the flow field, the temperature field of molten steel and the inclusion behaviour in a SEN and a square bloom mold were simulated under the influence of a rotating electromagnetic field (swirl generator). Also, the influences of different inclusion parameters such as the densities, sizes and boundary conditions, on the inclusion behavior were studied. The results show that a flow pattern in a SEN can be characterized into three distinct flow regions: an accelerating flow of molten steel from an electromagnetic swirl flow generator (EMSFG) inlet to an EMSFG center, a decelerating flow of molten steel from an EMSFG center to an EMSFG outlet, and a recirculation flow of molten steel from an EMSFG outlet to an SEN outlet. In addition, it was found that light Al2O3 inclusion moves towards the rotational center by a centrifugal force, and that a swirl flow prevents nozzle clogging. Moreover, it was also found that the inclusion separation to a mold meniscus increased and that the inclusions trap into a solidified shell wall decreased by using a swirl flow.
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