| 1. |
- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)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. |
- Wang, Zhaoming, et al.
(författare)
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Imputation and subset-based association analysis across different cancer types identifies multiple independent risk loci in the TERT-CLPTM1L region on chromosome 5p15.33
- 2014
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Ingår i: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 23:24, s. 6616-6633
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have mapped risk alleles for at least 10 distinct cancers to a small region of 63 000 bp on chromosome 5p15.33. This region harbors the TERT and CLPTM1L genes; the former encodes the catalytic subunit of telomerase reverse transcriptase and the latter may play a role in apoptosis. To investigate further the genetic architecture of common susceptibility alleles in this region, we conducted an agnostic subset-based meta-analysis (association analysis based on subsets) across six distinct cancers in 34 248 cases and 45 036 controls. Based on sequential conditional analysis, we identified as many as six independent risk loci marked by common single-nucleotide polymorphisms: five in the TERT gene (Region 1: rs7726159, P = 2.10 × 10(-39); Region 3: rs2853677, P = 3.30 × 10(-36) and PConditional = 2.36 × 10(-8); Region 4: rs2736098, P = 3.87 × 10(-12) and PConditional = 5.19 × 10(-6), Region 5: rs13172201, P = 0.041 and PConditional = 2.04 × 10(-6); and Region 6: rs10069690, P = 7.49 × 10(-15) and PConditional = 5.35 × 10(-7)) and one in the neighboring CLPTM1L gene (Region 2: rs451360; P = 1.90 × 10(-18) and PConditional = 7.06 × 10(-16)). Between three and five cancers mapped to each independent locus with both risk-enhancing and protective effects. Allele-specific effects on DNA methylation were seen for a subset of risk loci, indicating that methylation and subsequent effects on gene expression may contribute to the biology of risk variants on 5p15.33. Our results provide strong support for extensive pleiotropy across this region of 5p15.33, to an extent not previously observed in other cancer susceptibility loci.
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| 3. |
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| 4. |
- Cho, Yoon Shin, et al.
(författare)
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Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians.
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:1
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Tidskriftsartikel (refereegranskat)abstract
- We conducted a three-stage genetic study to identify susceptibility loci for type 2 diabetes (T2D) in east Asian populations. We followed our stage 1 meta-analysis of eight T2D genome-wide association studies (6,952 cases with T2D and 11,865 controls) with a stage 2 in silico replication analysis (5,843 cases and 4,574 controls) and a stage 3 de novo replication analysis (12,284 cases and 13,172 controls). The combined analysis identified eight new T2D loci reaching genome-wide significance, which mapped in or near GLIS3, PEPD, FITM2-R3HDML-HNF4A, KCNK16, MAEA, GCC1-PAX4, PSMD6 and ZFAND3. GLIS3, which is involved in pancreatic beta cell development and insulin gene expression, is known for its association with fasting glucose levels. The evidence of an association with T2D for PEPD and HNF4A has been shown in previous studies. KCNK16 may regulate glucose-dependent insulin secretion in the pancreas. These findings, derived from an east Asian population, provide new perspectives on the etiology of T2D.
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| 5. |
- Aaltonen, T., et al.
(författare)
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Combination of Tevatron Searches for the Standard Model Higgs Boson in the W+W- Decay Mode
- 2010
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Ingår i: Physical Review Letters. - 0031-9007 .- 1079-7114. ; 104:6, s. 061802-
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Tidskriftsartikel (refereegranskat)abstract
- We combine searches by the CDF and D0 Collaborations for a Higgs boson decaying to W+W-. The data correspond to an integrated total luminosity of 4.8 (CDF) and 5.4 (D0) fb(-1) of p (p) over bar collisions at root s = 1.96 TeV at the Fermilab Tevatron collider. No excess is observed above background expectation, and resulting limits on Higgs boson production exclude a standard model Higgs boson in the mass range 162-166 GeV at the 95% C.L.
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| 7. |
- Hsu, L. H., et al.
(författare)
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Design, Fabrication, and Reliability of Low-Cost Flip-Chip-On-Board Package for Commercial Applications up to 50 GHz
- 2012
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Ingår i: IEEE Transactions on Components, Packaging and Manufacturing Technology. - 2156-3985 .- 2156-3950. ; 2:3, s. 402-409
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Tidskriftsartikel (refereegranskat)abstract
- This paper presents a flip-chip-on-board (FCOB) packaging technology using a Rogers RO3210 laminate for microwave applications. Compared to the conventional microwave packaging architecture, the proposed FCOB technology skips one level of the ceramic package and thus results in lower reflections and manufacturing costs. To fulfill the small dimension requirement on printed circuit boards, the coplanar waveguide (CPW) transmission line and flip-chip bump were fabricated on a high-k RO3210 board (epsilon(r) = 10.2) with photolithography and electroplating. The GaAs chip patterned with the CPW line was then flip-chip-mounted onto the RO3210 laminate board. This structure displayed excellent performance from dc to 50 GHz with a return loss S-11 greater than 18 dB and insertion loss S-21 less than 0.5 dB. Meanwhile, the flip-chip bonding of the in-house-fabricated In0.52Al0.As-48/In0.6Ga0.4As metamorphic high-electron-mobility transistor devices on RO3210 also displayed excellent gain performance with a small degradation of 1 dB from dc to 40 GHz, showing the potential of implementing microwave integrated circuits on RO3210. To enhance the mechanical reliability, an epoxy-based underfill was injected into the flip-chip assemblies. Thermal cycling tests were performed to test the interconnect reliability, and the results indicated that the samples passed the thermal cycling test at least up to 600 cycles, showing excellent reliability for commercial applications. To the best of the authors' knowledge, this is the first study that evaluates the use of the RO3210 laminate for microwave flip-chip in open literature.
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| 8. |
- Hsu, Li-Han, 1981, et al.
(författare)
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Design of Flip-Chip Interconnect Using Epoxy-Based Underfill Up to V-Band Frequencies With Excellent Reliability
- 2010
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Ingår i: IEEE Transactions on Microwave Theory and Techniques. - 0018-9480 .- 1557-9670. ; 58:8, s. 2244-2250
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- This study demonstrates a flip-chip interconnect with epoxy-based underfill (epsilon(r) = 3.5 and tan delta = 0.02 at 10 MHz) for packaging applications up to V-band frequencies. To achieve the best interconnect performance, both the matching designs on GaAs chip and Al2O3 substrate were adopted with the underfill effects taken into consideration. The optimized flip-chip interconnect showed excellent performance from dc to 67 GHz with return loss below -20 dB and insertion loss less than 0.6 dB. Furthermore, the dielectric loss induced by the underfill was extracted from measurement and compared with the simulation results. The reliability tests including 85 degrees C/85 % relative humidity test, thermal cycling test, and shear force test were performed. For the first time, the S-parameters measurement was performed to check the flip-chip reliability, and no performance decay was observed after 1000 thermal cycles. Moreover, the mechanical strength was improved about 12 times after the underfill was applied. The results show that the proposed flip-chip architecture has excellent reliability and can be applied for commercial applications.
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