Hasil untuk "physics.atm-clus"

Soumya Ghosh, Dipayan Chakraborty, Anirban Paul et al.

The fragmentation of 1-propanol resulting from dissociative electron attachment has been explored across an energy range of 3.5 to 16 eV. Four distinct ion species are identified: $\text{H}^{-}$, $\text{O}^{-}$, $\text{OH}^{-}$, and $\text{C}_{3}\text{H}_{7}\text{O}^{-}$. The $\text{OH}^{-}$ ion exhibited a prominent peak near 8.7 eV, along with a small hump near 5.6 eV. Complementary channels led to the formation of the $\text{H}^{-}$ and $\text{C}_{3}\text{H}_{7}\text{O}^{-}$ ions. Both these two ions exhibit a sharp peak near 6 eV and broad overlapping resonances between 7 to 12 eV. The observed ion yields of distinct dissociation fragments in this study, when compared with those from previously studied alcohols, suggest site-specific fragmentation of alcohols during dissociative electron attachment. To gain a deeper understanding of the dissociation pathways, Density Functional Theory~(DFT) calculations were conducted, revealing the threshold energies for each channel. These threshold energies aligned well with the experimental uncertainties.

Jong Chan Lee, Begüm Rukiye Özer, In Heo et al.

Fragment signals in ordinary mass spectra carry no label to identify their parent molecule. By correlating mass signals with rotational Raman spectra, we created a method to label each ion signal with the spectroscopic fingerprint of its neutral parent molecule. In data for a carbon disulfide molecular cluster beam, we assigned 28 distinct ionization and fragmentation channels based on their mass-correlated rotational fingerprints. Unexpected observations included the formation of energetic S2 and SCCS cationic fragments from the CS2-dimer cluster and a significant CS3 signal, uncorrelated to the dimer. The large number of observed channels revealed a surprising complexity that could only be addressed with correlated spectroscopy and computer-aided correlation analysis.

K. Raspe, M. Müller, N. Iwe et al.

Using the example of metal clusters, an experimental setup and procedure is presented, which allows for the generation of size and charge-state selected polyanions from monoanions in a molecular beam. As a characteristic feature of this modular setup, the further charging process via sequential electron attachment within a 3-state digital trap takes place after mass-selection. In contrast to other approaches, the rf based concept permits to access heavy particles. The procedure is highly flexible with respect to the preparation process and potentially suitable for a wide variety of anionic species. By adjusting the storage conditions, i.e., the radio frequency, to the change in the mass-to-charge ratio, we succeeded to produce clusters in highly negative charge states, i.e., Ag$_{800}^{7-}$. The capabilities of the setup are demonstrated by experiments extracting electronic and optical properties of polyanionic metal clusters by analyzing the corresponding photoelectron spectra.

Anirban Paul, Dhananjay Nandi

Complete dissociation dynamics of low-energy electron attachment to carbon disulfide have been studied using the velocity slice imaging (VSI) technique. The ion yields of S- and CS- fragment ions as the function of incident electron energy in the range 5 to 11 eV have been obtained. Two resonances for S- ions at around 6.2 eV and 7.7 eV and only one resonance for CS- ions at around 6.2 eV have been obtained in this energy range. The kinetic energy and the angular distributions of these fragment negative ions at different incident electron energies around these resonances have been measured. From the angular distribution of these fragment anions, we have found that the bending of the temporary negative ions causes a significant change in the angular distribution from the expected one.

Wanli Zhao, Xiu-Li Wang, Yuqing Jiang et al.

Zhiwen Luo, Xiao Chen, Ye‐fan Zhang et al.

Background: Post-surgical recurrence of the metastatic colorectal cancer (mCRC) remains a challenge, even with adjuvant therapy. Moreover, patients show variable outcomes. Here, we set to identify gene models based on the perspectives of intrinsic cell activities and extrinsic immune microenvironment to predict the recurrence of mCRC and guide the adjuvant therapy. Methods: An RNA-based gene expression analysis of CRC samples (total = 998, including mCRCs = 344, non-mCRCs = 654) was performed. A metastasis-evaluation model (MEM) for mCRCs was developed using the Cox survival model based on the prognostic differentially expressed genes between mCRCs and non-mCRCs. This model separated the mCRC samples into high- and low-recurrence risk clusters that were tested using machine learning to predict recurrence. Further, an immune prognostic model (IPM) was built using the COX survival model with the prognostic differentially expressed immune-related genes between the two MEM risk clusters. The ability of MEM and IPM to predict prognosis was analyzed and validated. Moreover, the IPM was utilized to evaluate its relationship with the immune microenvironment and response to immuno-/chemotherapy. Finally, the dysregulation cause of IPM three genes was analyzed in bioinformatics. Results: A high post-operative recurrence risk was observed owing to the downregulation of the immune response, which was influenced by MEM genes (BAMBI, F13A1, LCN2) and their related IPM genes (SLIT2, CDKN2A, CLU). The MEM and IPM were developed and validated through mCRC samples to differentiate between low- and high-recurrence risk in a real-world cohort. The functional enrichment analysis suggested pathways related to immune response and immune system diseases as the major functional pathways related to the IPM genes. The IPM high-risk group (IPM-high) showed higher fractions of regulatory T cells (Tregs) and smaller fractions of resting memory CD4+ T cells than the IPM-low group. Moreover, the stroma and immune cells in the IPM-high samples were scant. Further, the IPM-high group showed downregulation of MHC class II molecules. Additionally, the Tumor Immune Dysfunction and Exclusion (TIDE) algorithm and GDSC analysis suggested the IPM-low as a promising responder to anti-CTLA-4 therapy and the common FDA-targeted drugs, while the IPM-high was non-responsive to these treatments. However, treatment using anti-CDKN2A agents, along with the activation of major histocompatibility complex (MHC) class-II response might sensitize this refractory mCRC subgroup. The dysfunction of MEIS1 might be the reason for the dysregulation of IPM genes. Conclusions: The IPM could identify subgroups of mCRC with a distinct risk of recurrence and stratify the patients sensitive to immuno-/chemotherapy. Further, for the first time, our study highlights the importance of MHC class-II molecules in the treatment of mCRCs using immunotherapy.

Y. Wong, R. Anand, K. M. Yuen et al.

Na An, Yu Fu, Jie Shi et al.

Background: The volume loss of the hippocampus and amygdala in non-demented individuals has been reported to increase the risk of developing Alzheimer’s disease (AD). Many neuroimaging genetics studies mainly focused on the individual effects of APOE and CLU on neuroimaging to understand their neural mechanisms, whereas their synergistic effects have been rarely studied. Objective: To assess whether APOE and CLU have synergetic effects, we investigated the epistatic interaction and combined effects of the two genetic variants on morphological degeneration of hippocampus and amygdala in the non-demented elderly at baseline and 2-year follow-up. Methods: Besides the widely-used volume indicator, the surface-based morphometry method was also adopted in this study to evaluate shape alterations. Results: Our results showed a synergistic effect of homozygosity for the CLU risk allele C in rs11136000 and APOE ɛ4 on the hippocampal and amygdalar volumes during a 2-year follow-up. Moreover, the combined effects of APOE ɛ4 and CLU C were stronger than either of the individual effects in the atrophy progress of the amygdala. Conclusion: These findings indicate that brain morphological changes are caused by more than one gene variant, which may help us to better understand the complex endogenous mechanism of AD.

Shanshui Zeng, Yue Pan, Fei Liu et al.

Preeclampsia (PE) threatens the safety of mothers and fetuses, and its pathogenesis is still unclear. Our previous study has found the relationship between PE and serum Clusterin (CLU). This study aimed to investigate the role of CLU on PE. Firstly, levels of CLU in serum and placental tissue from PE patients and healthy pregnancies were compared. Then, RNA sequencing, cell counting kit-8, matrigel invasion, cell apoptosis, and angiogenesis assay were performed to evaluate the role of CLU on primary isolation trophoblast cells. We found the expression of CLU was increased before the clinical syndrome occurred, whereas its level was positively related to the severity of PE. CLU significantly inhibited the expression of matrix metalloproteinase-9 and Vimentin and enhanced E-cadherin to inhibit epithelial-mesenchymal transition of trophoblast cells, further reducing its migration and invasion. Our results suggested that CLU may play a role in regulating trophoblast invasion and migration during placental development, which may be one of the risk factors for PE.

G. M. Sanda, L. Toma, T. Barbălată et al.

Peripheral artery disease (PAD) is an atherosclerotic disorder affecting arteries of the lower limbs, the major risk factors including dyslipidemia and diabetes mellitus (DM). We aimed to identify alterations of the proteins in high‐density lipoproteins (HDL) associated with HDL dysfunction in PAD patients. HDL2 and HDL3 were isolated from plasma of PAD patients with/without DM (PAD‐DM/PAD) and healthy subjects (N). Apolipoprotein AI (ApoAI), ApoAII, ApoCIII, clusterin (CLU), paraoxonase 1 (PON1), myeloperoxidase (MPO), and ceruloplasmin (CP) were measured in HDL2/HDL3 and plasma. Oxidation and glycation of the analyzed proteins were assessed as malondialdehyde‐protein adducts (MDA) and advanced glycation end‐products (AGE), respectively. The anti‐inflammatory effect of HDL3 was estimated as its potential to reduce monocyte adhesion to tumor necrosis factor α‐activated endothelial cells. We show that in PAD patients compared to N subjects: (i) HDL2 presented increased levels of MDA‐PON1, AGE‐PON1, AGE‐ApoAI, ApoAII, ApoCIII, and CP levels, and decreased PON1 levels; (ii) HDL3 had increased levels of MDA‐ and AGE‐CLU and ‐ApoAI, MDA‐PON1, ApoCIII, CLU, MPO, CP, and reduced PON1 levels. All these alterations were exacerbated by DM. These changes were more pronounced in HDL3, which had reduced anti‐inflammatory potential in PAD and became pro‐inflammatory in PAD‐DM. In PAD patients' plasma, CLU levels and MPO specific activity increased, while PON1 specific activity decreased. In conclusion, HDL function is altered in PAD patients due to multiple modifications of associated proteins that are aggravated by DM. Plasma CLU, MPO, and PON1 could constitute indicators of HDL dysfunction and contribute to risk stratification in PAD patients.

M. Uddin, M. Kabir, Mst. Marium Begum et al.

J. Goldsmith, Nina Spitofsky, Aliyeh Zamani et al.

The intestine is a highly dynamic environment that requires tight control of the various inputs to maintain homeostasis and allow for proper responses to injury. It was recently found that the stem cell niche and epithelium is regenerated after injury by de-differentiated adult cells, through a process that gives rise to Sca1+ fetal-like cells and is driven by a transient population of Clu + revival stem cells (revSCs). However, the molecular mechanisms that regulate this dynamic process have not been fully defined. Here we show that TNFAIP8 (also known as TIPE0) is a regulator of intestinal homeostasis that is vital for proper regeneration. TIPE0 functions through inhibiting basal Akt activation by the commensal microbiota via modulating membrane phospholipid abundance. Loss of TIPE0 in mice results in injury-resistant enterocytes, that are hyperproliferative, yet have regenerative deficits and are shifted towards a de-differentiated state. Tipe0 −/− enterocytes show basal induction of the Clu + regenerative program and a fetal gene expression signature marked by Sca1, but upon injury are unable to generate Sca-1 + /Clu + revSCs and could not regenerate the epithelium. This work demonstrates the role of TIPE0 in regulating the dynamic signaling that determines the injury response and enables intestinal epithelial cell regenerative plasticity. The molecular mechanisms that regulate intestinal Clu+ revival stem cells (revSCs) and their niche to enable regeneration in response to injury are unclear. Here, the authors show that mice without the phospholipid transport protein, TNFAIP8, causes less revSCs to be induced following injury.

M. Ya. Amusia, L. V. Chernysheva

In this Letter, we investigate the time delay of photoelectrons by fullerenes shell in endohedrals. We present general formulas in the frame of the random phase approximation with exchange (RPAE) applied to endohedrals A@CN that consist of an atom A located inside of a fullerenes shell constructed of N carbon atoms C. We calculate the time delay of electrons that leave the inner atom A in course of A@CN photoionization. Our aim is to clarify the role that is played by CN shell. As concrete examples of A we have considered Ne, Fr, Kr and Xe, and as fullerene we consider C60. The presence of the C60 shell manifests itself in powerful oscillations of the time delay of an electron that is ionized from a given subshell nl by a photon with energy. Calculations are performed for outer, subvalent and d-subshells.

B. Abdallah, A. Alzahrani, M. Kassem

Anamika Misra, S. Chakrabarti, I. Gambhir

Late-onset Alzheimer's disease (LOAD) or sporadic AD is the most common form of AD. The precise pathogenetic changes that trigger the development of AD remain largely unknown. Large-scale genome-wide association studies (GWASs) have identified single-nucleotide polymorphisms in multiple genes which are associated with AD; most notably, these are ABCA7, bridging integrator 1 (B1N1), triggering receptor expressed on myeloid cells 2 (TREM2), CD33, clusterin (CLU), complement receptor 1 (CRI), ephrin type-A receptor 1 (EPHA1), membrane-spanning 4-domains, subfamily A (MS4A) and phosphatidylinositol binding clathrin assembly protein (PICALM) genes. The proteins coded by the candidate genes participate in a variety of cellular processes such as oxidative balance, protein metabolism, cholesterol metabolism and synaptic function. This review summarizes the major gene loci affecting LOAD identified by large GWASs. Tentative mechanisms have also been elaborated in various studies by which the proteins coded by these genes may exert a role in AD pathogenesis have also been elaborated. The review suggests that these may together affect LOAD pathogenesis in a complementary fashion.

W. Iskandar, X. Fléchard, J. Matsumoto et al.

We present a combined theoretical and experimental study of primary and post-collision mechanisms involved when colliding low energy multiply charged ions with van der Waals dimers. The collision dynamics is investigated using a classical calculation based on the Coulombic Over-the- Barrier Model adapted to rare-gas dimer targets. Despite its simplicity, the model predictions are found in very good agreement with experimental results obtained using COLd Target Recoil Ion Momentum Spectroscopy (COLTRIMS), both for the relative yields of the different relaxation processes and for the associated transverse momentum exchange distributions between the projectile and the target. This agreement shows to which extent van der Waals dimers can be assimilated to independent atoms.

Rongrong Cai, Jing Han, Jie Sun et al.

Objective: Type 2 diabetes mellitus (T2DM) is related to an elevated risk of mild cognitive impairment (MCI). Plasma clusterin is reported associated with the early pathology of Alzheimer's disease (AD) and longitudinal brain atrophy in subjects with MCI. The rs11136000 single nucleotide polymorphism within the clusterin (CLU) gene is also associated with the risk of AD. We aimed to investigate the associations among plasma clusterin, rs11136000 genotype and T2DM-associated MCI. Methods: A total of 231 T2DM patients, including 126 MCI and 105 cognitively healthy controls were enrolled in this study. Demographic parameters were collected and neuropsychological tests were conducted. Plasma clusterin and CLU rs11136000 genotype were examined. Results: Plasma clusterin was significantly higher in MCI patients than in control group (p = 0.007). In subjects with MCI, plasma clusterin level was negatively correlated with Montreal cognitive assessment and auditory verbal learning test_delayed recall scores (p = 0.027 and p = 0.020, respectively). After adjustment for age, educational attainment, and gender, carriers of rs11136000 TT genotype demonstrated reduced risk for MCI compared with the CC genotype carriers (OR = 0.158, χ2 = 4.113, p = 0.043). Multivariable regression model showed that educational attainment, duration of diabetes, high-density lipoprotein cholesterol (HDL-c), and plasma clusterin levels are associated with MCI in T2DM patients. Conclusions: Plasma clusterin was associated with MCI and may reflect a protective response in T2DM patients. TT genotype exhibited a reduced risk of MCI compared to CC genotype. Further investigations should be conducted to determine the role of clusterin in cognitive decline. Trial registration Advanced Glycation End Products Induced Cognitive Impairment in Diabetes: BDNF Signal Meditated Hippocampal Neurogenesis ChiCTR-OCC-15006060; http://www.chictr.org.cn/showproj.aspx?proj=10536

Hatem A. Alnasser, Q. Guan, Fan Zhang et al.

Mitsuhiko Miyazaki, Ryuhei Ohara, Kota Daigoku et al.

Hydrogen-release by photoexcitation, excited-state- hydrogen-transfer (ESHT), is one of the important photo- chemical processes that occur in aromatic acids and is responsible for photoprotection of biomolecules. The mecha- nism is described by conversion of the initial state to a charge- separated state along the O(N)-H bond elongation, leading to dissociation. Thus ESHT is not a simple H-atom transfer in which a proton and a 1s electron move together. Here we show that the electron-transfer and the proton-motion are decoupled in gas-phase ESHT. We monitor electron and proton transfer independently by picosecond time-resolved near-infrared and infrared spectroscopy for isolated phenol--(ammonia)5, a benchmark molecular cluster. Electron transfer from phenol to ammonia occurred in less than 3 picoseconds, while the overall H-atom transfer took 15 picoseconds. The observed electron-proton decoupling will allow for a deeper understanding and control of of photochemistry in biomolecules

Silvia S Kang, Aishe Kurti, Aleksandra M. Wojtas et al.

Although abundant genetic and biochemical evidence strongly links Clusterin (CLU) to Alzheimer disease (AD) pathogenesis, the receptor for CLU within the adult brain is currently unknown. Using unbiased approaches, we identified Plexin A4 (PLXNA4) as a novel, high-affinity receptor for CLU in the adult brain. PLXNA4 protein expression was high in brain with much lower levels in peripheral organs. CLU protein levels were significantly elevated in the cerebrospinal fluid (CSF) of Plxna4-/- mice and, in humans, CSF levels of CLU were also associated with PLXNA4 genotype. Human AD brains had significantly increased the levels of CLU protein but decreased levels of PLXNA4 by ∼50%. To determine whether PLXNA4 levels influenced cognition, we analyzed the behaviour of Plxna4+/+, Plxna4+/-, and Plxna4-/- mice. In comparison to WT controls, both Plxna4+/- and Plxna4-/- mice were hyperactive in the open field assay while Plxna4-/- mice displayed a hyper-exploratory (low-anxiety phenotype) in the elevated plus maze. Importantly, both Plxna4+/- and Plxna4-/- mice displayed prominent deficits in learning and memory in the contextual fear-conditioning paradigm. Thus, even a 50% reduction in the level of PLXNA4 is sufficient to cause memory impairments, raising the possibility that memory problems seen in AD patients could be due to reductions in the level of PLXNA4. Both CLU and PLXNA4 have been genetically associated with AD risk and our data thus provide a direct relationship between two AD risk genes. Our data suggest that increasing the levels of PLXNA4 or targeting CLU-PLXNA4 interactions may have therapeutic value in AD.