A New Experimental Approach to Evaluate Plasma-induced Damage in Microcantilever

Plasma  etching,  during  micro-fabrication  processing  is  indispensable  for  fabricating  MEMS  structures.  During  the plasma  processes,  two  major matters,  charged  ions  and  vacuum–ultraviolet  (VUV)  irradiation  damage,  take  charge  of reliability  degradation.  The  charged  ions  induce  unwanted  sidewall  etching,  generally  called  as  “notching”,  which causes  degradation  in  brittle  strength.  Furthermore,  the  VUV  irradiation  gives  rise  to  crystal  defects  on  the  etching surface.  To  overcome  the  problem,  neutral  beam  etching  (NBE),  which  use  neutral  particles  without  the  VUV irradiation,  has  been  developed.  In  order  to  evaluate  the  effect  of  the  NBE  quantitatively,  we  measured  the  resonance property of a micro-cantilever before and after NBE treatment. The thickness of damage layer (δ) times the imaginary part  of  the  complex  Young's  modulus  (Eds)  were  then  compared,  which  is  a  parameter  of  surface  damage.  Although plasma processes  make the initial surface of cantilevers damaged during their fabrication, the removal of that damage by NBE was confirmed as the reduction in δEds. NBE will realize a damage-free surface for microstructures

A New Experimental Approach to Evaluate Plasma-induced Damage in Microcantilever

Plasma  etching,  during  micro-fabrication  processing  is  indispensable  for  fabricating  MEMS  structures.  During  the plasma  processes,  two  major matters,  charged  ions  and  vacuum–ultraviolet  (VUV)  irradiation  damage,  take  charge  of reliability  degradation.  The  charged  ions  induce  unwanted  sidewall  etching,  generally  called  as  “notching”,  which causes  degradation  in  brittle  strength.  Furthermore,  the  VUV  irradiation  gives  rise  to  crystal  defects  on  the  etching surface.  To  overcome  the  problem,  neutral  beam  etching  (NBE),  which  use  neutral  particles  without  the  VUV irradiation,  has  been  developed.  In  order  to  evaluate  the  effect  of  the  NBE  quantitatively,  we  measured  the  resonance property of a micro-cantilever before and after NBE treatment. The thickness of damage layer (δ) times the imaginary part  of  the  complex  Young's  modulus  (Eds)  were  then  compared,  which  is  a  parameter  of  surface  damage.  Although plasma processes  make the initial surface of cantilevers damaged during their fabrication, the removal of that damage by NBE was confirmed as the reduction in δEds. NBE will realize a damage-free surface for microstructures.Keywords: cantilever, neutral beam etching, surface los

Structure and Function of the Engineered Multicopper Oxidase CueO from Escherichia coli-Deletion of the Methionine-Rich Helical Region Covering the Substrate-Binding Site

金沢大学大学院自然科学研究科物質創成金沢大学理学部CueO is a multicopper oxidase (MCO) that is involved in the homeostasis of Cu in Escherichia coli and is the sole cuprous oxidase to have ever been found. Differing from other MCOs, the substrate-binding site of CueO is deeply buried under a methionine-rich helical region including α-helices 5, 6, and 7 that interfere with the access of organic substrates. We deleted the region Pro357-His406 and replaced it with a Gly-Gly linker. The crystal structures of a truncated mutant in the presence and in the absence of excess Cu(II) indicated that the scaffold of the CueO molecule and metal-binding sites were reserved in comparison with those of CueO. In addition, the high thermostability of the protein molecule and its spectroscopic and magnetic properties due to four Cu centers were also conserved after truncation. As for functions, the cuprous oxidase activity of the mutant was reduced to ca 10% that of recombinant CueO owing to the decrease in the affinity of the labile Cu site for Cu(I) ions, although activities for laccase substrates such as 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), p-phenylenediamine, and 2,6-dimethoxyphenol increased due to changes in the access of these organic substrates to the type I Cu site. The present engineering of CueO indicates that the methionine-rich α-helices function as a barrier to the access of bulky organic substrates, which provides CueO with specificity as a cuprous oxidase. © 2007 Elsevier Ltd. All rights reserved

Class IA Phosphatidylinositol 3-Kinase in Pancreatic β Cells Controls Insulin Secretion by Multiple Mechanisms

SummaryType 2 diabetes is characterized by insulin resistance and pancreatic β cell dysfunction, the latter possibly caused by a defect in insulin signaling in β cells. Inhibition of class IA phosphatidylinositol 3-kinase (PI3K), using a mouse model lacking the pik3r1 gene specifically in β cells and the pik3r2 gene systemically (βDKO mouse), results in glucose intolerance and reduced insulin secretion in response to glucose. β cells of βDKO mice had defective exocytosis machinery due to decreased expression of soluble N-ethylmaleimide attachment protein receptor (SNARE) complex proteins and loss of cell-cell synchronization in terms of Ca2+ influx. These defects were normalized by expression of a constitutively active form of Akt in the islets of βDKO mice, preserving insulin secretion in response to glucose. The class IA PI3K pathway in β cells in vivo is important in the regulation of insulin secretion and may be a therapeutic target for type 2 diabetes

Optineurin regulates osteoblastogenesis through STAT1

A sophisticated and delicate balance between bone resorption by osteoclasts and bone formation by osteoblasts regulates bone metabolism. Optineurin (OPTN) is a gene involved in primary open-angle glaucoma and amyotrophic lateral sclerosis. Although its function has been widely studied in ophthalmology and neurology, recent reports have shown its possible involvement in bone metabolism through negative regulation of osteoclast differentiation. However, little is known about the role of OPTN in osteoblast function. Here, we demonstrated that OPTN controls not only osteoclast but also osteoblast differentiation. Different parameters involved in osteoblastogenesis and osteoclastogenesis were assessed in Optn−/- mice. The results showed that osteoblasts from Optn−/- mice had impaired alkaline phosphatase activity, defective mineralized nodules, and inability to support osteoclast differentiation. Moreover, OPTN could bind to signal transducer and activator of transcription 1 (STAT1) and regulate runt-related transcription factor 2 (RUNX2) nuclear localization by modulating STAT1 levels in osteoblasts. These data suggest that OPTN is involved in bone metabolism not only by regulating osteoclast function but also by regulating osteoblast function by mediating RUNX2 nuclear translocation via STAT1

Clonal hematopoiesis in adult pure red cell aplasia

Idiopathic pure red cell aplasia (PRCA) and secondary PRCA associated with thymoma and large granular lymphocyte leukemia are generally considered to be immune-mediated. The PRCA2004/2006 study showed that poor responses to immunosuppression and anemia relapse were associated with death. PRCA may represent the prodrome to MDS. Thus, clonal hematopoiesis may be responsible for treatment failure. We investigated gene mutations in myeloid neoplasm-associated genes in acquired PRCA. We identified 21 mutations affecting amino acid sequences in 11 of the 38 adult PRCA patients (28.9%) using stringent filtering of the error-prone sequences and SNPs. Four PRCA patients showed 7 driver mutations in TET2, DNMT3A and KDM6A, and 2 PRCA patients carried multiple mutations in TET2. Five PRCA patients had mutations with high VAFs exceeding 0.3. These results suggest that clonal hematopoiesis by stem/progenitor cells might be related to the pathophysiology of chronic PRCA in certain adult patients

Contrasting Responses of Midlatitude Jets to the North Pacific and North Atlantic Warming

Midlatitude atmospheric circulation is projected to shift poleward, yet the Northern Hemisphere jet shift is absent. Competing thermodynamic responses between tropical and Arctic warming have opposing influences on the jets and increase the uncertainties in future projections. This study shows, however, that sea surface temperature (SST) warming in the midlatitude is a major driver for the future midlatitude jet. Coupled Model Intercomparison Program phase 5 models indicate different SST warming between the midlatitude oceans, which induces a weakening of the North Pacific jet and a poleward shift of the North Atlantic jet. Our atmospheric model experiments enable to quantify the relative roles of Arctic, midlatitude, and tropical warming. The competing effects of midlatitude and tropical warming play a substantial role in the future midlatitude jet, hindering any poleward shift of the North Pacific jet, whereas for the North Atlantic jet, midlatitude SST warming is likely to win the competition. Plain Language Summary Midlatitude weather and climate, including extreme events, are strongly influenced by changes in the jet stream and extratropical cyclones. The future midlatitude circulation in the Northern Hemisphere is considered to depend on the competing effects of tropical and Arctic warming, which have opposing influences on position and intensity of the midlatitude jet and, ultimately, increase the uncertainties in future projections. However, we find that ocean warming in the midlatitudes has a major influence on future midlatitude jet. In the North Pacific, sea surface temperature (SST) warming is the strongest in the north of the strong ocean currents, whereas the North Atlantic SST warming has a peak in the strong ocean currents. This different SST warming leads to the contrasting midlatitude jet responses between the oceans with jet cores. Despite a topic of much debate, the impact of Arctic sea ice loss on the jet is suppressed by midlatitude SST warming. We conclude that the competing effects of midlatitude and tropical SST warming will play a substantial role in the future midlatitude jet. The results here may help decrease the uncertainties in future projections and further our understanding of ongoing midlatitude climate change