Uma Namangalam, Salvi Mohandas, Hemanth Dinesan
et al.
In high-resolution mass spectrometry, an electrospray ionization source is often paired with an ion-funnel to enhance ion transmission. Although it is established that ions experience collision-induced dissociation as they pass through this device, the impact of gas-flow dynamics on ion fragmentation remains unexplored. The present work demonstrates that the gas-flow dynamics from the capillary interface of an electrospray ionization source into an ion-funnel significantly reduces ion fragmentation. This reduction stems from the substantial decrease in the rate of increase in the internal energy of the ions resulting from the collisions with a supersonically expanding gas. The results of this study have significant consequences for systems that employ electrospray mass spectrometry and ion-mobility spectrometry.
Nowdays many factors influence shopper interested in buying merchandise through e-business, such as promotions made by e-business companies, speed and less time, fast payment transactions and low cost, and marketing mix. Most shopper utilize e-business to shop for food products, electronics, logistic (such as gojek/grab/uber, travel) and others. The application of e-business can not be separated from the expertise and knowledge of the public in using the internet and computer systems. However, Indonesian people's awareness of e-business is still low, many people do not know how to utilize it. This is due to low internet infrastructure factors, poor telecommunication facilities. This is still a barrier to the interest of the people of Indonesia to testify online. In addition, shopper confidence and trust in the security of e-business can affect someone to shop online. In explaining the factors that impact on shopper conduct to utilize e-business utilized theory of planned behavior approach. The theory of Planned Behavior (TPB) has supported the prediction of many different conducts of people. TPB shows that determining conduct is one's purpose. This study aims to analyze the impact of perceived behavioral control, subjective norm, and attitude, on purpose to shop online and its impact on online shopping behavior. Exogenous variable research is perceived behavioral control, subjective norm, and attitude. The variables of endogenous research are intended to shop online and online shopping behavior. The research sample of 100 respondents was shopper who shopped in e-business X. Data collection method using questionnaires. Data analysis method using SEM PLS.
Abstract Clusterin (CLU) is a secreted glycoprotein, heterodimeric in nature, and is expressed in a wide variety of tissues and body fluids such as serum and plasma. CLU has also been known to be a promising biomarker for cell death, malignancy, cancer progression, and resistance development. However, the lack of a CLU crystal structure obstructs understanding the possible role of reported mutations on the structure, and the subsequent effects on downstream signaling pathways and cancer progression. Considering the importance of crystal structure, a model structure of the pre-secretory isoform of CLU was built to predict the effect of mutations at the molecular level. Ab initio model was built using RaptorX, and loop refinement and energy minimization were carried out with ModLoop, ModRefiner, and GalaxyWeb servers. The cancer associated mutational spectra of CLU was retrieved from the cBioPortal server and 117 unique missense mutations were identified. Evolutionarily conserved regions and pathogenicity of mutations identified in CLU were analyzed using ConSurf and Rhapsody, respectively. Furthermore, sequence and structure-based mutational analysis were carried out with iSTABLE, DynaMut and PremPS servers. Molecular dynamics simulations were carried out with GROMACS for 50 ns to determine the stability of the wild type and mutant protein structures. A dynamically stable model structure of pre-secretory CLU (psCLU) which has high concurrence with the sequence based secondary structure predictions has been explored. Changes in the intra-atomic interactions and folding pattern between wild type and mutant structures were observed. To our conclusion, eleven mutations with the highest structural and functional significance have been predicted to have pathogenic and deleterious effects. Communicated by Ramaswamy H. Sarma
This article (and all articles in the proceedings volume relating to the same conference) has been retracted by IOP Publishing following an extensive investigation in line with the COPE guidelines. This investigation has uncovered evidence of systematic manipulation of the publication process and considerable citation manipulation. IOP Publishing respectfully requests that readers consider all work within this volume potentially unreliable, as the volume has not been through a credible peer review process. IOP Publishing regrets that our usual quality checks did not identify these issues before publication, and have since put additional measures in place to try to prevent these issues from reoccurring. IOP Publishing wishes to credit anonymous whistleblowers and the Problematic Paper Screener [1] for bringing some of the above issues to our attention, prompting us to investigate further. [1] Cabanac G, Labbé C and Magazinov A 2021 arXiv: 2107.06751v1 Retraction published: 23 February 2022
<p>In ATM network design, self-healing is the ability of the network to continue to provide service in the event of failures, and this compromises both planning and operational aspects. The planning aspect involves optimal/near-optimal network design problems while the operational aspect deals with the implementation of protection schemes using restoration mechanisms, for allocating spare capacity to the network to be used in case of a failure event. This project investigates the survivability (i.e. restoration ratio) - here defined by means of the aggregate restoration ratio - in existing ATM networks based on various spare capacity distribution schemes, with the goal to (1) compare the network survivability for link and path restorations, and (2) determine the effects of various traffic and design related patterns on the restoration ratio.</p>
Background Histologic distinction between well differentiated hepatocellular carcinoma (HCC) and benign hepatocellular mass lesions is a known challenge. Existing biomarkers are of limited diagnostic value. Our previous studies observed an enhanced canalicular expression pattern of clusterin (CLU) in HCC, which was not observed in benign hepatocellular mass lesions such as hepatocellular adenoma. The aim of this study was to further investigate its diagnostic value for HCC by examining the expression pattern of CLU in a large number of non-hepatocellular tumors, and by comparing it with two other commonly used hepatocellular markers pCEA and CD10 that also show a canalicular staining pattern in HCC. Methods Enhanced canalicular staining patterns of CLU, pCEA and CD10 were analyzed on 54 surgically resected well to moderately differentiated HCCs on whole tissue sections, of which 37 had surrounding regenerative nodules while the remaining 17 had a non-cirrhotic background. CLU immunostaining was also performed on tissue microarray sections that contained 74 HCCs (40 of which were also stained for pCEA and CD10), 55 normal liver tissue samples, and 1305 non-hepatocellular tumors from multiple organs. Results Enhanced CLU canalicular staining was observed in 70% (89/128) HCCs but not in regenerative nodules, normal liver tissues or any non-hepatocellular tumors. The sensitivity and specificity for enhanced canalicular staining pattern of CLU in HCCs were 0.70 and 1.00. This enhanced canalicular pattern was observed in only 26 and 23% HCCs for CD10 and pCEA, respectively. These results further demonstrate that the distinctive enhanced canalicular pattern of CLU is unique to HCC. Conclusions CLU is superior to pCEA and CD10 as a diagnostic immunomarker in that it can help distinguish well to moderately differentiated HCC not only from non-HCC malignancies but also from benign hepatocellular mass lesions.
The infrared spectrum of the weakly-bound C2H4-CO2 complex is investigated in the region of the nu3 fundamental band of CO2 (~2350 cm-1), using a tunable OPO laser source to probe a pulsed supersonic slit jet expansion. The spacing of the various K-subbands in this perpendicular spectrum is very irregular, and the pattern of irregularity is quite different from that observed previously in another C2H4-CO2 band by Bemish et al. [J. Chem. Phys. 103, 7788 (1995)]. But by allowing for the different symmetry of the nu3 (CO2) upper vibrational state, both results can be strikingly well explained using the 'double internal rotor' model as described by Bemish et al.
Targeting new molecular pathways leading to Osteoporosis (OP) and Osteoarthritis (OA) is a hot topic for drug discovery. Clusterin (CLU) is a glycoprotein involved in inflammation, proliferation, cell death, neoplastic disease, Alzheimer disease and aging. The present study focuses on the expression and the role of CLU in influencing the decrease of muscle mass and fiber senescence in OP-OA condition. Vastus lateralis muscle biopsies were collected from 20 women with OP undergoing surgery for fragility hip fracture and 20 women undergoing arthroplasty for hip osteoarthritis. We found an overexpression of CLU in degenerated fibers in OP closely correlated with interleukin 6 (IL6) and histone H4 acetylation level. Conversely, in OA muscle tissues we observed a weak expression of CLU but no nuclear histone H4 acetylation. Ex vivo studies on isolated human myoblasts confirmed CLU overexpression in OP as compared to OA (p < 0.001). CLU treatment of isolated OP and OA myoblasts showed: modulation of proliferation, morphological changes, increase of histone H4 acetylation and induction of myogenin (MYOG) activation in OP myoblast only. In OP condition, functional knockdown of CLU by siRNA restores proliferative myoblasts capability and tissue damage repair, carried out by an evident upregulation of Transglutaminase 2 (TGM2). We also observed downmodulation of CX3CR1 expression with consequent impairing of the inflammatory infiltrate recruitment. Results obtained suggest a potential role of CLU in OP by influencing myoblasts terminal differentiation, epigenetic regulation of muscle cell differentiation and senescence. Moreover, CLU silencing points out its role in the modulation of tissue damage repair and inflammation, proposing it as a new diagnostic marker for muscle degeneration and a potential target for specific therapeutic intervention in OP related sarcopenia.
Abstract Introduction: Carotid endarterectomy (CEA) is a surgical procedure used in the prevention of ischemic stroke. However, this procedure can cause complications of ischemia-reperfusion injury to the brain. Clusterin (CLU) is a cytoprotective chaperone protein that is released from neurons in response to various neurological injuries. The objective of the study was to report the changes in serum CLU concentrations of patients undergoing CEA. Materials and methods: The study involved 25 patients with severe internal carotid artery stenosis. Serum samples were taken from patients at three different times: within 24 hours preoperatively to CEA, 12 hours postoperatively, and 48 hours postoperatively. Serum CLU concentrations were measured using a commercially available enzyme-linked immunosorbent assay. Results: When compared to concentrations preoperatively, the serum CLU concentration initially decreased during the 12 hours following CEA. However, 48 hours following the procedure there was an increase in the CLU concentration. After statistical analysis, differences were detected in serum CLU concentration between all three recorded measurements (P < 0.05). Conclusion: Data from our study indicate that serum CLU concentrations are affected after CEA. We hypothesize that serum CLU concentrations may depend on brain ischemia-reperfusion injury following this surgical procedure.
Background Our previous data suggested that three single-nucleotide polymorphisms (SNPs), rs1048661, rs3825942, and rs2165241, of the lysyl oxidase-like 1 gene (LOXL1) are significantly associated with exfoliation syndrome (XFS) and exfoliation glaucoma (XFG). The following study investigated other SNPs that potentially effect XFS/XFG. Methods A total of 216 Uygur patients diagnosed with XFS/XFG, and 297 Uygur volunteers were admitted to the First Affiliated Hospital at Xinjiang Medical University between January 2015 and October 2017. Blood samples were collected by venipuncture. Alleles and genotypes of LOXL1, TBC1D21, ATXN2, APOE, CLU, AFAP1, TXNRD2, CACNA1A, ABCA1, GAS7, and CNTNAP2 were analyzed by direct sequencing. Results The allele G of rs41435250 of LOXL1 was a risk allele for XFS/XFG (P < 0.001), whereas the allele G of rs893818 of LOXL1 was a protective allele for XFS/XFG (P < 0.001). After adjusting all data for age and gender, the following results were obtained: the frequency of genotype CC for rs7137828 of ATXN2 was significantly higher in XFS/XFG patients than in controls (P = 0.027), while no significance was found with reference to the frequency of genotype TT. The frequency of genotype GG for rs893818 of LOXL1 (P < 0.001) and the frequency of genotype AA were both significantly higher in XFS/XFG groups compared to the control group (P < 0.001). In addition, the frequency of genotype TT for rs41435250 of LOXL1 was higher in XFS/XFG patients than in controls (P = 0.003), while no significant difference was found with reference to the frequency of genotype GG after adjusting for age and gender. In addition, the haplotypes G-A/T-G/G-G for rs41435250 and rs893818 were significantly associated with XFS/G. Conclusions With reference to LOXL1, the rs41435250 resulted as a risk factor and rs893818 as a protective factor for XFS/XFG in the Uygur populations. Meanwhile, the rs16958445 of TBC1D21 and the rs7137828 of ATXN2 have also shown to be associated with pathogenesis of XFS/XFG.
Objective To test the association of distinct neuropathologic features of Alzheimer disease (AD) with risk loci identified in genome-wide association studies. Methods Vantaa 85+ is a population-based study that includes 601 participants aged ≥85 years, of which 256 were neuropathologically examined. We analyzed 29 AD risk loci in addition to APOE ε4, which was studied separately and used as a covariate. Genotyping was performed using a single nucleotide polymorphism (SNP) array (341 variants) and imputation (6,038 variants). Participants with Consortium to Establish a Registry for Alzheimer Disease (CERAD) (neuritic Aβ plaques) scores 0 (n = 65) vs score M + F (n = 171) and Braak (neurofibrillary tangle pathology) stages 0–II (n = 74) vs stages IV–VI (n = 119), and with capillary Aβ (CapAβ, n = 77) vs without (n = 179) were compared. Cerebral amyloid angiopathy (CAA) percentage was analyzed as a continuous variable. Results Altogether, 24 of the 29 loci were associated (at p < 0.05) with one or more AD-related neuropathologic features in either SNP array or imputation data. Fifteen loci associated with CERAD score, smallest p = 0.0002122, odds ratio (OR) 2.67 (1.58–4.49) at MEF2C locus. Fifteen loci associated with Braak stage, smallest p = 0.004372, OR 0.31 (0.14–0.69) at GAB2 locus. Twenty loci associated with CAA, smallest p = 7.17E-07, β 14.4 (8.88–20) at CR1 locus. Fifteen loci associated with CapAβ smallest p = 0.002594, OR 0.54 (0.37–0.81) at HLA-DRB1 locus. Certain loci associated with specific neuropathologic features. CASS4, CLU, and ZCWPW1 associated only with CAA, while TREM2 and HLA-DRB5 associated only with CapAβ. Conclusions AD risk loci differ in their association with neuropathologic features, and we show for the first time distinct risk loci for CAA and CapAβ.
AbstractWith the increase in solar activity, the Communication/Outage Forecast System satellite decayed on orbit to below the F peak. As such, we can study the development of convective ionospheric storms and, most importantly, study large‐scale seeding of the responsible instability. For decades, gravity has been suggested as being responsible for the long wavelengths in the range of 200 to 1,000 km, as are commonly observed using airglow and satellite data. Here we suggest that convective thunderstorms are a likely source of gravity waves and point out that recent theoretical analysis has shown this connection to be quite possible.
The photoionization of chiral molecules prepared in a coherent superposition of excited states can give access to the underlying chiral coherent dynamics in a procedure known as photoexcitation induced photoelectron circular dichroism (PXECD). This exclusive dependence on coherence can also be seen in a different part of the angular spectrum, where it is not contingent on the chirality of the molecule, thus allowing extension of PXECD's sensitivity to tracking coherence to non-chiral molecules. Here we present a general theory of PXECD based on angular momentum algebra and derive explicit expressions for all pertinent asymmetry parameters which arise for arbitrary polarisation of pump and probe pulses. The theory is developed in a way that clearly and simply separates chiral and non-chiral contributions to the photoelectron angular distribution, and also demonstrates how PXECD and PECD-type contributions, which may be distinguished by whether pump or ionizing probe enables chiral response, are mixed when arbitrary polarization is used.
Y. Vidal Insua, J. De la camara, Elena Brozos Vázquez
et al.
Colorectal cancer (CRC) is one of the major causes of cancer-related deaths. Early detection of tumor relapse is crucial for determining the most appropriate therapeutic management. In clinical practice, computed tomography (CT) is routinely used, but small tumor changes are difficult to visualize, and reliable blood-based prognostic and monitoring biomarkers are urgently needed. The aim of this study was to prospectively validate a gene expression panel (composed of GAPDH, VIL1, CLU, TIMP1, TLN1, LOXL3 and ZEB2) for detecting circulating tumor cells (CTCs) as prognostic and predictive tool in blood samples from 94 metastatic CRC (mCRC) patients. Patients with higher gene panel expression before treatment had a reduced progression-free survival (PFS) and overall-survival (OS) rates compared with patients with low expression (p = 0.003 and p ≤ 0.001, respectively). Patients with increased expression of CTCs markers during treatment presented PFS and OS times of 8.95 and 11.74 months, respectively, compared with 14.41 and 24.7 for patients presenting decreased expression (PFS; p = 0.020; OS; p ≤ 0.001). Patients classified as non-responders by CTCs with treatment, but classified as responders by CT scan, showed significantly shorter survival times (PFS: 8.53 vs. 11.70; OS: 10.37 vs. 24.13; months). In conclusion, our CTCs detection panel demonstrated efficacy for early treatment response assessment in mCRC patients, and with increased reliability compared to CT scan.
The Clusterin (CLU) gene, also known as apolipoprotein J (ApoJ), is currently the third most associated late-onset Alzheimer’s disease (LOAD) risk gene. However, little was known about the possible effect of CLU genetic variants on AD pathology in brain. Here, we evaluated the interaction between 7 CLU SNPs (covering 95% of genetic variations) and the role of CLU in β-amyloid (Aβ) deposition, AD-related structure atrophy, abnormal glucose metabolism on neuroimaging and CSF markers to clarify the possible approach by that CLU impacts AD. Finally, four loci (rs11136000, rs1532278, rs2279590, rs7982) showed significant associations with the Aβ deposition at the baseline level while genotypes of rs9331888 (P = 0.042) increased Aβ deposition. Besides, rs9331888 was significantly associated with baseline volume of left hippocampus (P = 0.014). We then further validated the association with Aβ deposition in the AD, mild cognitive impairment (MCI), normal control (NC) sub-groups. The results in sub-groups confirmed the association between CLU genotypes and Aβ deposition further. Our findings revealed that CLU genotypes could probably modulate the cerebral the Aβ loads on imaging and volume of hippocampus. These findings raise the possibility that the biological effects of CLU may be relatively confined to neuroimaging trait and hence may offer clues to AD.
Lionel Lacombe, Paul-Gerhard Reinhard, Eric Suraud
et al.
We apply in a schematic model a theory beyond mean-field, namely Stochastic Time-Dependent Hartree-Fock (STDHF), which includes dynamical electron-electron collisions on top of an incoherent ensemble of mean-field states by occasional 2-particle-2-hole ($2p2h$) jumps. The model considered here is inspired by a Lipkin-Meshkov-Glick model of $Ω$ particles distributed into two bands of energy and coupled by a two-body interaction. Such a model can be exactly solved (numerically though) for small $Ω$. It therefore allows a direct comparison of STDHF and the exact propagation. The systematic impact of the model parameters as the density of states, the excitation energy and the bandwidth is presented and discussed. The time evolution of the STDHF compares fairly well with the exact entropy, as soon as the excitation energy is sufficiently large to allow $2p2h$ transitions. Limitations concerning low energy excitations and memory effects are also discussed.