Thermochemistry of the activation of N2 on iron cluster cations: guided ion beam studies of the reactions of Fen+ (n=1-19) with N2

Journal ArticleThe kinetic energy dependences of the reactions of Fen + (n=1-19) with N2 are studied in a guided ion beam tandem mass spectrometer over the energy range of 0-15 eV. In addition to collision-induced dissociation forming Fem + ions, which dominate the product spectra, a variety of FemN2+ and FemN+ product ions, where m<n, is observed

Magnetic field diagnostics and spatio-temporal variability of the solar transition region

Magnetic field diagnostics of the transition region from the chromosphere to the corona faces us with the problem that one has to apply extreme UV spectro-polarimetry. While for coronal diagnostic techniques already exist through infrared coronagraphy above the limb and radio observations on the disk, for the transition region one has to investigate extreme UV observations. However, so far the success of such observations has been limited, but there are various projects to get spectro-polarimetric data in the extreme UV in the near future. Therefore it is timely to study the polarimetric signals we can expect for such observations through realistic forward modeling. We employ a 3D MHD forward model of the solar corona and synthesize the Stokes I and Stokes V profiles of C IV 1548 A. A signal well above 0.001 in Stokes V can be expected, even when integrating for several minutes in order to reach the required signal-to-noise ratio, despite the fact that the intensity in the model is rapidly changing (just as in observations). Often this variability of the intensity is used as an argument against transition region magnetic diagnostics which requires exposure times of minutes. However, the magnetic field is evolving much slower than the intensity, and thus when integrating in time the degree of (circular) polarization remains rather constant. Our study shows the feasibility to measure the transition region magnetic field, if a polarimetric accuracy on the order of 0.001 can be reached, which we can expect from planned instrumentation.Comment: Accepted for publication in Solar Physics (4.Mar.2013), 19 pages, 9 figure

Use of 18O Labels to Monitor Deamidation during Protein and Peptide Sample Processing

Nonenzymatic deamidation of asparagine residues in proteins generates aspartyl (Asp) and isoaspartyl (isoAsp) residues via a succinimide intermediate in a neutral or basic environment. Electron capture dissociation (ECD) can differentiate and quantify the relative abundance of these isomeric products in the deamidated proteins. This method requires the proteins to be digested, usually by trypsin, into peptides that are amenable to ECD. ECD of these peptides can produce diagnostic ions for each isomer; the c· + 58 and z − 57 fragment ions for the isoAsp residue and the fragment ion ((M + nH)(n−1)+· − 60) corresponding to the side-chain loss from the Asp residue. However, deamidation can also occur as an artifact during sample preparation, particularly when using typical tryptic digestion protocols. With 18O labeling, it is possible to differentiate deamidation occurring during trypsin digestion which causes a +3 Da (18O1 + 1D) mass shift from the pre-existing deamidation, which leads to a +1-Da mass shift. This paper demonstrates the use of 18O labeling to monitor three rapidly deamidating peptides released from proteins (calmodulin, ribonuclease A, and lysozyme) during the time course of trypsin digestion processes, and shows that the fast (̃4 h) trypsin digestion process generates no additional detectable peptide deamidations

ELEVATED SERUM LEVELS OF TNF SOLUBLE RECEPTORS IN PATIENTS WITH POSITIVE ANTI-NEUTROPHIL CYTOPLASMIC ANTIBODIES

ANCA are found in various systemic vasculitis and are supposed to play a role in the pathogenesis of the disease, in cooperation with other factors such as cytokines. A total of 36 ANCA-positive and 10 ANCA-negative serum samples were analysed for the presence of TNF soluble receptors (TNF-sR), which are shed from the surface of activated cells and may act as TNF inhibitors. Of the ANCA-positive samples, 67% had elevated TNF-sR75 and 72% had elevated TNF-sR55 compared to ANCA-negative specimens (mean [S.E.] 18.7 [17.3] vs 3.6 [1.5] and 10.5 [9.7] vs 1.9 [0.7] ng/ml, P<0.01). Elevation of TNF-sR in patients with ANCA suggests that cytokines and their inhibitors are involved in the pathogenesis of ANCA-associated autoimmune disease

Endovascular occlusion of right to left arteriovenous shunt associated with persistent left superior vena cava

Left-sided superior vena cava (SVC) as the result of persistence of the left superior cardinal vein in postnatal life is a rare congenital anomaly, is usually associated with other cardiac defects, and can cause symptoms of right to left shunt. We report the case of a 58-year-old Asian man with a history of end-stage renal disease and Ebstein anomaly that was corrected surgically who presented with progressively worsening disabling dyspnea. An echocardiogram with concomitant intravenous saline injection raised the suspicion of right to left shunt, a finding that was confirmed with contrast injection of the left SVC that rapidly filled the left heart chambers and subsequently the aortic arch. To treat this anomaly, we accessed the left basilic vein under ultrasound guidance and inserted a 14F sheath into the left subclavian vein. A covered stent was then prepared at the back table with three Prolene 4-0 sutures that were wrapped around the middle portion of the graft to achieve a controlled area of stenosis after deployment. The stent graft was placed along the proximal innominate vein and the contiguous part of the left SVC. Coil embolization was then performed with coils that were positioned at the stenotic area of the covered stent. An immediate venogram demonstrated residual flow into the left SVC; however, a delayed venogram 2 weeks after the procedure showed occlusion of the left SVC and the development of collaterals to the right innominate vein that was draining to a normal right SVC. The patient remained marginally hypotensive after surgery, but he soon noted a substantial improvement in his symptoms. A repeat echocardiogram with intravenous saline injection confirmed the correction of the right to left shunt. Endovascular repair of persistent left SVC is feasible and safe and can be performed with minimal morbidity

Use of top-down and bottom-up fourier transform ion cyclotron resonance mass spectrometry for mapping calmodulin sites modified by platinum anticancer drugs

Calmodulin (CaM) is a highly conserved, ubiquitous, calcium-binding protein; it binds to and regulates many different protein targets, thereby functioning as a calcium sensor and signal transducer. CaM contains 9 methionine (Met), 1 histidine (His), 17 aspartic acid (Asp), and 23 glutamine acid (Glu) residues, all of which can potentially react with platinum compounds; thus, one-third of the CaM sequence is a possible binding target of platinum anticancer drugs, which represents a major challenge for identification of specific platinum modification sites. Here, top-down electron capture dissociation (ECD) was used to elucidate the transition metal–platinum(II) modification sites. By using a combination of top-down and bottom-up mass spectrometric (MS) approaches, 10 specific binding sites for mononuclear complexes, cisplatin and [Pt(dien)Cl]Cl, and dinuclear complex [{cis-PtCl2(NH3)}2(μ-NH2(CH2)4NH2)] on CaM were identified. High resolution MS of cisplatin-modified CaM revealed that cisplatin mainly targets Met residues in solution at low molar ratios of cisplatin–CaM (2:1), by cross-linking Met residues. At a high molar ratio of cisplatin:CaM (8:1), up to 10 platinum(II) bind to Met, Asp, and Glu residues. [{cis-PtCl2(NH3)}2(μ-NH2(CH2)4NH2)] forms mononuclear adducts with CaM. The alkanediamine linker between the two platinum centers dissociates due to a trans-labilization effect. [Pt(dien)Cl]Cl forms {Pt(dien)}2+ adducts with CaM, and the preferential binding sites were identified as Met51, Met71, Met72, His107, Met109, Met124, Met144, Met145, Glu45 or Glu47, and Asp122 or Glu123. The binding of these complexes to CaM, particularly when binding involves loss of all four original ligands, is largely irreversible which could result in their failure to reach the target DNA or be responsible for unwanted side-effects during chemotherapy. Additionally, the cross-linking of cisplatin to CaM might lead to the loss of the biological function of CaM or CaM–Ca2+ due to limiting the flexibility of the CaM or CaM–Ca2+ complex to recognize target proteins or blocking the binding region of target proteins to CaM

Hybrid approach to complex thoracic aortic aneurysms in high-risk patients: Surgical challenges and clinical outcomes

BackgroundEndovascular therapy is a less invasive alternative treatment for high-risk patients with thoracic aortic aneurysms. However, this technology alone is often not applicable to complex aneurysmal morphology. The purpose of this study was to evaluate the utility of hybrid strategies in high-risk patients who are otherwise unsuitable for endovascular therapy alone.MethodsDuring an 18-month period, 31 high-risk patients (mean age, 69 years; range, 52-89 years) underwent combined open and endovascular approaches for complex aneurysms, including 16 patients with ascending and arch aneurysms and 15 patients with aneurysms involving visceral vessels. Among them, 11 patients had histories of aneurysm repairs. To overcome the anatomic limitations of endovascular repairs, various adjunctive surgical maneuvers were used, including aortic arch reconstruction in 3 patients, supra-aortic trunk debranching in 13 patients (including 8 patients who required aortas as inflow sources), and visceral vessel bypasses in 15 patients (including 10 patients who required bypasses to all 3 visceral branches). Additionally, carotid artery access was obtained in 1 patient, and iliac artery conduits were created in 12 patients.ResultsTechnical success was achieved in all patients. There was one perioperative death (3.2%) due to postoperative bleeding. Two patients (6.4%) had immediate type II endoleaks, which were resolved by the 1-month follow-up. Other procedure-related complications occurred in three patients (9.6%), including renal bypass thromboses in two patients and retroperitoneal hematoma, which was successfully managed conservatively, in one patient. During a mean follow-up of 16 months, two patients died of unrelated causes, whereas the remainder of patients were asymptomatic, without aneurysm enlargement.ConclusionsOur study highlights how hybrid strategies incorporating surgical and endovascular approaches can be used successfully in treating patients with complex thoracic aortic aneurysms. This combined approach potentially expands the field of endovascular stent grafting and is an attractive solution for patients with poor cardiopulmonary reserves

Note on Global Regularity for 2D Oldroyd-B Fluids with Diffusive Stress

We prove global regularity of solutions of Oldroyd-B equations in 2 spatial dimensions with spatial diffusion of the polymeric stresses

The unmet needs of Aboriginal Australians with musculoskeletal pain: A mixed method systematic review

Objective: Musculoskeletal pain (MSP) conditions are the biggest cause of disability and internationally, Indigenous peoples experience a higher burden. There are conflicting reports about Aboriginal Australians and MSP. We conducted a systematic review to describe the prevalence, associated factors, impacts, care access, health care experiences, and factors associated with MSP among Aboriginal Australians. Methods: A systematic search of quantitative and qualitative scientific and grey literature (PROSPERO number: CRD42016038342). Articles were appraised using the Mixed Methods Appraisal Tool. Due to study heterogeneity a narrative synthesis was conducted. Results: Of 536 articles identified, 18 were included (14 quantitative, 4 qualitative), of high (n=11), medium (n=2) and low (n=5) quality. Prevalences of MSP in Aboriginal populations were similar to or slightly higher than the non‐Aboriginal population (prevalence rate ratio 1.1 for back pain, 1.2‐1.5 for osteoarthritis (OA), 1.0‐2.0 for rheumatoid arthritis). Aboriginal people accessed primary care for knee or hip OA at around half the rate of non‐Aboriginal people, and were less than half as likely to have knee or hip replacement surgery. Communication difficulties with health practitioners were the main reason why Aboriginal people with MSP choose not to access care. No articles reported interventions. Conclusions: Findings provide preliminary evidence of an increased MSP burden amongst Aboriginal Australians and, particularly for OA, a mismatch between the disease burden and access to health care. To increase accessibility, health services should initially focus on improving Aboriginal patients’ experiences of care, in particular by improving patient‐practitioner communication. Implications for care and research are outlined