- A "flared-end" gradient coil with outer-wall direct cooling for human brain imaging: A feasibility study. [Journal Article]
- MRMagn Reson Imaging 2019 Jul 12
- Optimal gradient performance is arguably a pre-requisite to realize the full potential of ultrahigh field magnetic resonance imaging (MRI). The values of using tailored gradient coils for brain imagi…
Optimal gradient performance is arguably a pre-requisite to realize the full potential of ultrahigh field magnetic resonance imaging (MRI). The values of using tailored gradient coils for brain imaging have been well acknowledged. Unfortunately, conventional head-only gradient coils have two major technical limitations, i.e. limited shoulder clearance and limited cooling capacity. A design, coined "flared-end" gradient coil, combined with a cooling method, named "outer-wall direct cooling", is proposed to address these problems. The "flared-end" design permits brain access to the center of gradient coil. The "flared end" structure is 3D-printed. It has electrical winding patterns (grooves) on one side and evenly spaced cooling channels on the opposite side. Electrical conductor (copper wire) is fixed into the grooves; coolant is in direct contact with the outer surface of the electrical conductor above each cooling channel, eliminating interfacial thermal resistance between coolant and copper wires. Heat transfer area is thus determined by the size and the number of cooling channels. This approach allows high electric current density for high gradient field strength while maintaining high cooling efficiency. Additionally, the symmetric coil geometry guarantees intrinsic torque balance. As a proof of concept, we have made a gradient coil prototype without active shielding. This coil has an inner diameter of 0.3 m, and is capable of generating 0.337, 0.225 and 0.485 mT/m/A along X, Y and Z, respectively. Active shielding was designed theoretically, but not pursued in the construction of this coil prototype. The new coil geometry and cooling method offers a novel avenue for new gradient coils tailored for human brain imaging at ultrahigh field.
- Long-term (52 weeks) safety and efficacy of JR-131, a biosimilar of darbepoetin alfa, in Japanese patients with renal anemia undergoing hemodialysis; Phase 3 prospective study. [Journal Article]
- TATher Apher Dial 2019 Jul 14
- The objective of this study was to evaluate the safety and efficacy of JR-131, a biosimilar of darbepoetin alfa, for long-term treatment of renal anemia patients undergoing hemodialysis. In this mult…
The objective of this study was to evaluate the safety and efficacy of JR-131, a biosimilar of darbepoetin alfa, for long-term treatment of renal anemia patients undergoing hemodialysis. In this multicenter, single-arm, phase 3 study, 159 patients with renal anemia who had been receiving darbepoetin alfa or recombinant human erythropoietins were treated with intravenous JR-131 for 52 weeks. In patients receiving darbepoetin alfa, JR-131 was administered at the same dose, while in patients receiving recombinant human erythropoietin the dose was determined based on the 1:200 conversion ratio following the Japanese darbepoetin alfa package insert. No adverse drug reactions were reported, and no anti-JR-131 antibodies were detected. The hemoglobin levels were maintained in the range of 10.0-12.0 g/dL throughout the study. JR-131 probed to be a useful and lower cost alternative to darbepoetin alfa in the management of renal anemia in patients undergoing hemodialysis. This article is protected by copyright. All rights reserved.
- Structural insight into co-translational membrane protein folding. [Review]
- BBBiochim Biophys Acta Biomembr 2019 Jul 11
- Membrane protein folding studies lag behind those of water-soluble proteins due to immense difficulties of experimental study, resulting from the need to provide a hydrophobic lipid-bilayer environme…
Membrane protein folding studies lag behind those of water-soluble proteins due to immense difficulties of experimental study, resulting from the need to provide a hydrophobic lipid-bilayer environment when investigated in vitro. A sound understanding of folding mechanisms is important for membrane proteins as they contribute to a third of the proteome and are frequently associated with disease when mutated and/or misfolded. Membrane proteins largely consist of α-helical, hydrophobic transmembrane domains, which insert into the membrane, often using the SecYEG/Sec61 translocase system. This mini-review highlights recent advances in techniques that can further our understanding of co-translational folding and notably, the structure and insertion of nascent chains as they emerge from translating ribosomes. This article is part of a Special Issue entitled: Molecular biophysics of membranes and membrane proteins.
- Experience of pediatric urogenital tract inserted objects: 10-year single-center study. [Journal Article]
- JPJ Pediatr Urol 2019 Jun 15
- CONCLUSIONS: Urogenital tract FBs in children is a great challenge. As the vagina is shorter and wider than the urethra, girls with vagina FBs are usually treated by day surgery and adolescent boys of urethra FBs are treated by hospital surgery. Misdiagnosis may occur when patients conceal FBs insert history, have severe urinary tract infections, or have previous surgery history. Ultrasonography helps to reduce misdiagnosis. FBs should be taken into consideration when patients have new symptoms after hypospadias repair, and postoperative changes of hypospadias repair, such as urinary calculi, have been excluded. Appropriate surgery techniques, based on the size, nature, and location of FBs, should be performed for complete removal of FBs with minimal complications to reduce secondary injury. Sharp FBs could be migrated among the digestive system, urogenital system, and deep pelvic. If the procedure is difficult, patients with a stable needle can be conservatively managed with close follow-up. Nevertheless, symptomatic patients should be treated actively.The awareness of potential severity of pediatric urogenital tract FBs should be raised. Appropriate toys and timely sex education help prevent children from urogenital tract FBs insertion. Selecting appropriate techniques for particular situations is the best way to reduce secondary injury, especially for cases with migrated FBs (needles), magnetic FBs, and postoperative FBs.
- Phosphatidylinositol 4,5 Bisphosphate Controls the cis and trans Interactions of Synaptotagmin 1. [Journal Article]
- BJBiophys J 2019 Jun 22
- Synaptotagmin 1 acts as the Ca2+ sensor for synchronous neurotransmitter release; however, the mechanism by which it functions is not understood and is presently a topic of considerable interest. Her…
Synaptotagmin 1 acts as the Ca2+ sensor for synchronous neurotransmitter release; however, the mechanism by which it functions is not understood and is presently a topic of considerable interest. Here, we describe measurements on full-length membrane-reconstituted synaptotagmin 1 using site-directed spin labeling in which we characterize the linker region as well as the cis (vesicle membrane) and trans (cytoplasmic membrane) binding of its two C2 domains. In the full-length protein, the C2A domain does not undergo membrane insertion in the absence of Ca2+; however, the C2B domain will bind to and penetrate in trans to a membrane containing phosphatidylinositol 4,5 bisphosphate, even if phosphatidylserine (PS) is present in the cis membrane. In the presence of Ca2+, the Ca2+ binding loops of C2A and C2B both insert into the membrane interface; moreover, C2A preferentially inserts into PS-containing bilayers and will bind in a cis configuration to membranes containing PS even if a phosphatidylinositol 4,5 bisphosphate membrane is presented in trans. The data are consistent with a bridging activity for synaptotagmin 1 in which the two domains bind to opposing vesicle and plasma membranes. The failure of C2A to bind membranes in the absence of Ca2+ and the long unstructured segment linking C2A to the vesicle membrane indicates that synaptotagmin 1 could act to significantly shorten the vesicle-plasma membrane distance with increasing levels of Ca2+.
- Towards Nonalternant Nanographenes by Self-Promoted Intramolecular Indenoannulation Cascade via C-F bond Activation. [Journal Article]
- CChemistry 2019 Jul 13
- Te development of new synthetic approaches to large PAHs and NGs appears as a matter of great importance. Nevertheless, a serious downside of the bottom-up approach is the necessity of oftentimes met…
Te development of new synthetic approaches to large PAHs and NGs appears as a matter of great importance. Nevertheless, a serious downside of the bottom-up approach is the necessity of oftentimes meticulous multi-step synthesis demanding serious time and financial investments. One of the possibilities to avoid such an unpleasant obstacle is a design of the one-pot procedures, where multiple bonds are formed at once. However, in the general perception, the endeavours to perform several reactions at once lead to the notable drop of the yields with the increase of the number of bonds created. Moreover, the reactions which give an opportunity to form several bonds at once are rather scarce. Scholl reaction, enabling multiple Aryl-Aryl couplings, may serve as an illustrative example of such reactions. Despite its broad applicability, the method allows synthesis only honeycomb like structures and cannot be exploited to insert the pentagons into a PAH's core. Meanwhile, PAHs bearing pentagons within their structure possess an outstanding scope of properties and possible applications e.g. electronics and supramolecular chemistry. Here we report that alumina-mediated HF elimination may be used for the self-promoted multiple indenoannulation yielding useful nonalternant NGs. We demonstrate that the unique nature of the reaction leads to a rather counter-intuitive outcome and allows considering each previous Aryl-Aryl coupling as a promoter of the following ones.
- HLA-I associated adaptation dampens the CD8 T-cell response in HIV Ad5-vectored vaccine recipients. [Journal Article]
- JIJ Infect Dis 2019 Jul 12
- HLA-I associated HIV adaptation is known to negatively impact disease progression and CD8 T-cell responses. We aimed to assess how HLA-I associated adaptation impacts HIV vaccine-induced CD8 T-cell r…
HLA-I associated HIV adaptation is known to negatively impact disease progression and CD8 T-cell responses. We aimed to assess how HLA-I associated adaptation impacts HIV vaccine-induced CD8 T-cell responses in two past vaccine efficacy trials. We found that vaccine-encoded adapted epitopes were less immunogenic than vaccine-encoded non-adapted epitopes, and adapted epitope-specific responses were less polyfunctional than non-adapted epitope-specific responses. Along those lines, vaccine recipients with higher HLA-I adaptation to the Gag vaccine insert mounted less polyfunctional CD8 T-cell responses at the protein-level. Response breadth, which correlated with viral control in recipients who became infected, is also dampened by HLA-I adaptation. These findings suggest that HLA-I associated adaptation is an important consideration for strategies aiming to induce robust CD8 T-cell responses.
- Makkah female teachers' knowledge of seizure first aid. [Journal Article]
- EBEpilepsy Behav 2019 Jul 09; 98(Pt A):10-13
- CONCLUSIONS: Female school teachers in the Makkah region significantly lack adequate training and knowledge of seizure first aid. A health education policy targeting teachers may improve this.
- A modified surgical technique for Descemet's stripping automated endothelial keratoplasty (DSAEK) in altered or abnormal anatomy. [Case Reports]
- AJAm J Ophthalmol Case Rep 2019; 15:100497
- CONCLUSIONS: This technique overcomes the challenges of posterior air bubble migration and posterior dislocation of the donor lenticule in eyes with altered anatomy.
New Search Next
- Crystal structures of Rea1-MIDAS bound to its ribosome assembly factor ligands resembling integrin-ligand-type complexes. [Journal Article]
- NCNat Commun 2019 Jul 11; 10(1):3050
- The Rea1 AAA+-ATPase dislodges assembly factors from pre-60S ribosomes upon ATP hydrolysis, thereby driving ribosome biogenesis. Here, we present crystal structures of Rea1-MIDAS, the conserved domai…
The Rea1 AAA+-ATPase dislodges assembly factors from pre-60S ribosomes upon ATP hydrolysis, thereby driving ribosome biogenesis. Here, we present crystal structures of Rea1-MIDAS, the conserved domain at the tip of the flexible Rea1 tail, alone and in complex with its substrate ligands, the UBL domains of Rsa4 or Ytm1. These complexes have structural similarity to integrin α-subunit domains when bound to extracellular matrix ligands, which for integrin biology is a key determinant for force-bearing cell-cell adhesion. However, the presence of additional motifs equips Rea1-MIDAS for its tasks in ribosome maturation. One loop insert cofunctions as an NLS and to activate the mechanochemical Rea1 cycle, whereas an additional β-hairpin provides an anchor to hold the ligand UBL domains in place. Our data show the versatility of the MIDAS fold for mechanical force transmission in processes as varied as integrin-mediated cell adhesion and mechanochemical removal of assembly factors from pre-ribosomes.