Theoretical Insights into Midchain Radicals and Branching Characteristics in Solution Copolymerization of Ethylene and Vinyl Acetate.

The kinetics of intermolecular chain transfer to polymer (CTP) and chain transfer to monomer (CTM), as well as backbiting in solution copolymerization of ethylene and vinyl acetate (VAc), are calculated by density functional theory. An intrinsic rate coefficient for each reaction type, whose Arrhenius parameters are expressed as functions of unreacted monomer composition, is extracted from calculated elementary reactions, and hence it applies to a wide range of fragment compositions of EVA. Backbiting controls the generation of midchain radicals (MCRs) on the backbone, and its rate maximizes at a medium fraction of VAc in the unreacted monomers. CTP plays an insignificant role in MCR generation even at high conversion rates due to its low pre-exponential factor. The concentration of MCRs is quantified and is close to that of ECRs at high conversions and high fractions of VAc in monomers. Additionally, branching characteristics are explored; concentrations of short-chain branching (SCB) and long-chain branching (LCB) are about 0.7-2.5 and 0.1-0.4%, respectively, and drop with VAc fraction rapidly. The role of the migration of MCRs is highlighted, which transforms about 10% of SCB points into LCB points. Disagreeing with insights from laboratory experiments, it is the migration, rather than CTP, which increases the LCB concentration at high conversions.

Al distribution and structural stability of H-BEA zeolites at different Si/Al ratios and temperatures: a first-principles study.

Beta zeolites have been widely used in acid-catalyzed reactions because of their excellent properties. An in-depth study of the position, quantity, and distribution of beta zeolites substituted by Al is significant to understand the catalytic performance of the active site of zeolite catalysts. The distribution of Al in H-BEA and the structure of silanol nests in dealuminated BEA at different Si/Al ratios and synthesis temperatures were studied by the DFT method. T1, T2, T7, and T9 sites were chosen to be simulated. The synthesis temperature can change the distribution of Al and the proportion of T sites at different Si/Al ratios. The proportion of T7 and T9 is more than 70% at different Si/Al ratios of H-BEA and decreases with the synthesis temperature. T1 and T2 sites begin to appear when Si/Al < 20 and the proportion of T1 and T2 sites is less than 20%. When Si/Al < 8, the substitution energy of the AlSiAl structure, which has Si(2Al, 2Si) species, is obviously lower than that of the normal structure, which indicates that the Al-O-Si-O-Al species will appear in H-BEA. The Al(T7)Si(T5)Al(T9)Si(T5)Al(T7) and Al(T1)Si(T1)Al(T9) groups can not only stabilize H-BEA but also play an essential role in the formation of Si(2Al, 2Si) species. For dealuminated BEA zeolites, the silanol nest forms four hydrogen bonds through four silanols. The orientation of silanol groups in the silanol nest formed after dealumination at different T sites is different. The T7 and T9 sites in H-BEA are more likely to undergo dealumination. By contrast, the dealumination of the T1 and T2 sites is a challenge.

Factors Associated with Telemedicine Services Provision for Sexually Transmitted Disease Diagnosis and Treatment Among Dermatologists: Evidence from China.

Background: Telemedicine has experienced rapid growth in China, with wide applications for chronic disease management. Objective: This study examined a unique survey dataset to identify the provision of telemedicine services by dermatologists, and to explore its association with physician characteristics, perception of diagnosis, and physicians' perceptions of the advantages and disadvantages of telemedicine. Materials and Methods: Responses to an anonymous voluntary questionnaire were collected from 238 dermatologists in Zhejiang Province, China, via a mixed mode of online and in-person data collection. Data were analyzed using Stata 16.0. Empirical analyses utilized descriptive statistics and multivariable logistical regression. Results: Among a total of 238 physicians, 34.9% provided telemedicine services. Results from the multivariable logistic regression indicated that, if physicians can use their spare time to help patients, seniority and their perception of the benefit of telemedicine are the two most important factors determining their likelihood of providing telemedicine services among the studied sample. Conclusion: Telemedicine holds great promise, but its practices need to be more efficient to save time and reduce the risk of misdiagnosis so that more physicians may participate.

Insight into the Fischer-Tropsch mechanism on hcp-Fe7C3 (211) by density functional theory: the roles of surface carbon and vacancies.

Iron carbide phases discovered in the spent iron catalysts have proved to be active in the Fischer-Tropsch process. The surface carbon of the iron carbide played a key role in the Fischer-Tropsch mechanism. Since there are two surface carbons, C1 and C2, on the hcp-Fe7C3 (211), which are close to each other, their reaction mechanisms would be significant. Hence, the DFT calculations were performed to investigate the Fischer-Tropsch mechanism involving the surface carbon. It was found that the HC1 + C2 pathway was the major C-C coupling reaction pathway with an effective energy barrier of 0.97 eV. Ethane would be the major C2 product from the HC1C2 species through the stepwise hydrogenation pathway due to the high adsorption energy of ethylene (1.67 eV). After the desorption process of ethane, the carbon vacancy would form. The carbon vacancy was found to be the CO activation site through the CO direct dissociation pathway and the carbon vacancy would recover. It was concluded that the defect-hcp-Fe7C3 (211) is the high active facet of the Fischer-Tropsch synthesis, the carbon vacancy sites are the CO activation sites and the surface carbon sites are the C-C coupling sites. The surface carbons not only act as the chain initiation sites but also act as the chain growth sites in the Fischer-Tropsch mechanism on hcp-Fe7C3 (211).

Mechanistic insight into methane dry reforming over cobalt: a density functional theory study.

Cobalt-based catalysts are a potential candidate among non-noble metal catalysts in dry reformation of methane (DRM), while the detailed mechanism of the DRM reaction is still largely unknown. In this contribution, the rather complicated reaction network for DRM is explored by density functional theory calculations. The most favorable adsorption structures of all species involved in the DRM reaction over Co(0001) have been identified. For CO2 activation, its direct dissociation to generate CO and O is the dominant reaction pathway. For CH4 direct dissociation, CH dehydrogenation into atomic C and H is the rate-determining step (RDS). It is predicted that the CH is the most abundant species among CHx (x = 0-3) over Co(0001). O acts as an oxidant and reacts with CH to produce CHO, and subsequently, CHO decomposes into CO and H. Atomic C may directly react with O to produce CO, or be oxidized by OH to COH, followed by the COH decomposition to CO and H. Thus, three possible pathways for DRM over the Co(0001) surface are proposed in our study, and the oxidation step is suggested as the RDS. The dominant route is identified as CH4 successive dissociation into CH, and CH oxidizing by O to form CHO, then CHO decomposition to CO and H.

Breastfeeding and Atopic Dermatitis Risk: A Systematic Review and Meta-Analysis of Prospective Cohort Studies.

OBJECTIVES: The effect of breastfeeding on atopic dermatitis (AD) remains controversial. To determine the association -between breastfeeding and AD, we conducted an updated meta-analysis of prospective cohort studies. METHODS: A comprehensive search of PubMed, EMBASE, MEDLINE and Cochrane Library was conducted. Studies meeting the predetermined criteria were evaluated by 2 authors independently. The pooled relative risk (RR) adjusted for confounders with its 95% CI was calculated by a random-effects model. Heterogeneity was explored by subgroup analysis and meta-regression. RESULTS: A total of 27 studies were included for meta-analysis. The pooled estimates for the effect of total and exclusive breastfeeding on AD were 1.01 (95% CI 0.93-1.10) and 0.99 (95% CI 0.88-1.11), respectively. Heterogeneity was substantial across studies (total: p < 0.01 or I2 = 65.2%; exclusive: p < 0.01 or I2 = 72.3%). There was a weak evidence for a protective effect of breastfeeding against AD in cohorts with atopic heredity (total: RR 0.85, 95% CI 0.74-0.98; exclusive: RR 0.83, 95% CI 0.70-0.97). In cohorts without atopic heredity, the effect shifted to the risk side when limited to exclusive breastfeeding (RR 1.19, 95% CI 1.02-1.40) while it dropped towards null when limited to total breastfeeding (RR 1.11, 95% CI 0.94-1.31). CONCLUSIONS: There is no association between AD and breastfeeding, regardless of total or exclusive breastfeeding patterns. There is some evidence for a protective function of exclusive and total breastfeeding in a cohort with atopic heredity. The effect shifts to the risk side in cohorts without atopic heredity. However, these findings should be interpreted with caution because heterogeneity is evident.

Comparison of catalytic performance of metal-modified SAPO-34: a molecular simulation study.

Molecular simulation calculation has been performed to investigate the catalytic performance of metal-modified ((Fe, Co, Ni) SAPO-34 in methanol-to-olefins (MTO) process. Adsorption amount and adsorption heats of the reactant, methanol, and the main products, ethylene and propylene, in SAPO-34 and MeAPSO-34 (Me = Fe, Co, Ni) zeolites were analyzed and compared both in single adsorption and co-adsorption process with a Monte Carlo (MC) simulation method. On the other hand, with a molecular dynamics (MD) simulation method, the system energy of the molecules in three different positions was calculated and compared. The simulation results show that modifying SAPO-34 with Fe, Co, and Ni is beneficial to improve the selectivity of light olefins during the MTO process, especially for that of ethylene. And among the three MeAPSO-34 zeolites, the catalytic performance of NiAPSO-34 is the best.

A DFT study on Zr-SBA-15 catalyzed conversion of ethanol to 1,3-butadiene.

Density functional theory (DFT) calculations have been used to elucidate the influence of the surface properties of Zr-SBA-15 on the conversion of ethanol to 1,3-butadiene at the molecular level. To identify the critical reactive intermediates of ethanol catalysis to catalytically form 1,3-butadiene on the Zr-SBA-15 surface, the model of Zr-SBA-15 was first built. The overall enthalpy energy surface was explored for the highly-debated reaction mechanisms, including Toussaint's aldol condensation mechanism and Fripiat's Prins mechanism. It was found that ethanol dehydration to form ethylene possessed a lower energy barrier than dehydrogenation to yield acetaldehyde, which means they are competing reactive pathways. C-C bond coupling to form acetaldol (3-hydroxybutanal) proceeds with a 2.15 eV forward reaction barrier. Direct reaction of ethylene and acetaldehyde proceeds with a free energy barrier of 2.90 eV suggesting that Prins condensation hardly occurs. The results here provide a first glimpse into the overall mechanism of 1,3-butadiene formation on Zr-SBA-15 reactive sites in light of the variety of proposed mechanistic pathways mostly based on conventional homogenous organic chemistry reactions.

DFT study of CO2 conversion on InZr3(110) surface.

Methanol and methane synthesis from CO2 hydrogenation on a InZr3(110) surface has been studied using density functional theory calculations. The CO2 can be chemically adsorbed via a polydentated configuration and the H2 molecule can dissociate to H atoms spontaneously. The methanol is primarily formed via the HCOO route instead of the RWGS route, due to its higher activation barrier of 1.35 eV for HCO hydrogenation. In the HCOO route, the adsorbed CO2 consecutively hydrogenates to form HCOO, H2COO and the H3CO species. The H3COH is produced via the reaction of H3CO with a surface OH group. Furthermore, the C-O bonds of CO, CHO, CH2O and CH3O species prefer to dissociate to C, CH, CH2 CH3 and surface O species. Methane is formed via the hydrogenation of CHx (x = 0-3) monomers with the highest activation barrier of 1.19 eV for CH3 hydrogenation, which is higher than that of the hydrogenation of H2COO in methanol synthesis via the HCOO route. The surface O species formed during CO2 hydrogenation reacts with the adsorbed H2 molecule to produce an OH group which reacts with a surface H atom to form H2O with an activation barrier of 1.13 eV, which then desorbs to the gas phase. Our calculated results indicate that the InZr3 alloy is a potential candidate catalyst for CO2 utilization and conversion.

A DFT study on the aldol condensation reaction on MgO in the process of ethanol to 1,3-butadiene: understanding the structure-activity relationship.

Using periodic density functional theory calculations, the aldol condensation of acetaldehyde to 3-hydroxybutanal over dehydroxylated MgO surfaces with and without structure defects was investigated. Compared with the C-C coupling step, the enolization step via proton transfer of the α-hydrogen of acetaldehyde to the MgO surface or the proton back-transfer step to form the desired 3-hydroxybutanal has a higher energy barrier, indicating that the proton transfer process is the key step for the aldol condensation on MgO. To highlight the effect of water, we also calculated the proton transfer steps in the presence of water and studied the reaction pathways over the partially hydroxylated MgO surface. The results show that water can participate in the proton back-transfer step by donating a proton to the alkoxide anion to form the 3-hydroxybutanal, thus reducing the activation energy; the surface OH groups induce a lowering of the activation energy barriers for the overall reaction. The results of the electronic structure analysis indicate that a strong Lewis acid-weak/medium base pair may have the best performance for aldol condensation, such as Mg3C-O4C-D produced by divacancy defects and Mg4C-O2CH produced by the dissociative adsorption of water. A strong Lewis acid generated by low-coordinated Mg2+ can adsorb and stabilize the acetaldehyde molecule near the catalyst surface which is beneficial for the abstraction of an α-proton from an acetaldehyde molecule, and a medium or weak Brønsted base is favorable for the proton back-transfer step.

Theoretical insights into the effect of terrace width and step edge coverage on CO adsorption and dissociation over stepped Ni surfaces.

Vicinal surfaces of Ni are model catalysts of general interest and great importance in computational catalysis. Here we report a comprehensive study conducted with density functional theory on Ni[n(111) × (100)] (n = 2, 3 and 4) surfaces to explore the effect of terrace width and step edge coverage on CO adsorption and dissociation, a probe reaction relevant to many industrial processes. The coordination numbers (CN), the generalized coordination numbers and the d band partial density of states (d-PDOS) of Ni are identified as descriptors to faithfully reflect the difference of the step edge region for Ni[n(111) × (100)]. Based on analysis of the energy diagrams for CO activation and dissociation as well as the structural features of the Ni(311), Ni(211) and Ni(533) surfaces, Ni(211) (n = 3) is proposed as a model of adequate representativeness for Ni[n(111) × (100)] (n≥ 3) surface groups in investigating small molecule activation over such stepped structures. Further, a series of Ni(211) surfaces with the step edge coverage ranging from 1/4 to 1 monolayer (ML) were utilized to assess their effect on CO activation. The results show that CO adsorption is not sensitive to the step edge coverage, which could readily approach 1 ML under a CO-rich atmosphere. In contrast, CO dissociation manifests strong coverage dependence when the coverage exceeds 1/2 ML, indicating that significant adsorbate-adsorbate interactions emerge. These results are conducive to theoretical studies of metal-catalyzed surface processes where the defects play a vital role.

Investigation on the conversion of ethylene to ethylidyne on Pt(100) and Pd(100) using density functional theory.

The comprehensive formation network of ethylidyne (CH3C) from ethylene (CH2CH2) is investigated on Pt(100) and Pd(100) using the density functional theory method. The structural and energetic features of all intermediate products were considered. We found that the trend of the activation barriers in each pathway on Pt(100) and Pd(100) are the same, whereas the barriers on Pt(100) are higher than that on Pd(100). The activation barriers of 1,2-H shift reactions are relatively high compared with the other reactions. We screened three possible pathways and selected the optimal route as CH2CH2(ethylene) → CH2CH(vinyl) → CH2C(vinylidene) → CH3C(ethylidyne).

Direct versus hydrogen-assisted CO dissociation over stepped Ni and Ni3Fe surfaces: a computational investigation.

The adsorption and dissociation of CO over stepped Ni and Ni3Fe surfaces were systematically studied using density functional theory slab calculations. Both (211)-like surface structure terminations (NiNi step and NiFe step, denoted as Ni3Fe(211)-AA and Ni3Fe(211)-AB) are considered for Ni3Fe. Direct scission of the C-O bond in CO is identified as the least likely one among the three proposed dissociation pathways and CO dissociation via a CHO intermediate appears to be most feasible at low CO coverage on pure and alloyed Ni(211) surfaces. The priority of H-assisted CO dissociation might originate from the more activated C-O bond in COH and CHO. Compared to Ni(211), the Ni3Fe(211)-AB surface could facilitate CO activation especially for the most possible CHO intermediate mechanism, whose rate-limiting step is found to be altered. The d-band center theory and Mulliken charge analysis are also employed to explain the activity difference between Ni3Fe(211)-AB and Ni3Fe(211)-AA. The significant structural sensitivity of CO dissociation highlights the importance of Fe locating in the step edge and the high reactivity of Ni3Fe(211)-AB is largely ascribed to the synergistic effect between Ni and Fe at the step edge.

Self-assembly mechanism of 1,3:2,4-di(3,4-dichlorobenzylidene)-D-sorbitol and control of the supramolecular chirality.

Dibenzylidene-D-sorbitol (DBS) and its derivatives are known to form gels in organic solvents; however, the mechanism of the gel formation has been a subject of much debate. The present work is undertaken to elucidate the organization mechanism of a DBS derivative, 1,3:2,4-di(3,4-dichlorobenzylidene)-D-sorbitol (DCDBS), by taking into account the solvent effects and comparing the experiment data with theoretical calculation. These molecules form smooth nonhelical fibers with a rest circular dichroism (CD) signal in polar solvents, in contrast to rope-liked left-helical fibers with a strong negative CD signal observed in nonpolar solvents. The molecular complexes thus formed were characterized by means of Fourier transform infrared spectra, ultraviolet-visible spectra, X-ray diffraction patterns, static contact angles, and theoretical calculations. It was proposed that the interactions between the gelator and the solvents could subtly change the stacking of the molecules and hence their self-assembled nanostructures. In nonpolar solvents, the gelator molecules appear as a distorted T-shaped structure with the 6-OH forming intermolecular hydrogen bonds with the acetal oxygens of adjacent gelator molecule. In addition, because of differential stacking interactions on both sides of the 10-member ring skeleton of the gelator, the oligomers may assemble in a helix fashion to minimize the energy, leading to helical fibers. In polar solvents, however, the gelator molecules show a rigid planelike structure and thus stack on top of each other because of strong parallel-displaced π interactions. The balanced driving force on both sides of the 10-member ring skeleton made it difficult for the dimers to bend, thus resulting in nonhelical nanostructure. As expected from the mechanisms proposed here, twisted ribbon fibers with a medium strength CD signal were obtained when solvents of different polarities were mixed. Thus, solvent effects revealed in this work represent an effective means of realizing in situ tuning of nanostructures and control of the expression of chirality at supramolecular levels.

Effects of nilotinib on regulatory T cells: the dose matters.

BACKGROUND: Nilotinib is a tyrosine kinase inhibitor with high target specificity. Here, we characterized the effects of nilotinib for the first time on CD4+CD25+ regulatory T cells (Tregs) which regulate anti-tumor/leukemia immune responses. DESIGN AND METHODS: Carboxyfluorescein diacetate succinimidyl ester (CFSE) and 5-bromo-2-deoxy -uridine (BrdU) were used to assess the proliferation and cell cycle distribution of Tregs. The expression of the transcription factor forkhead box P3 (FoxP3) and the glucocorticoid-induced tumor necrosis factor receptor (GITR) were measured by flow cytometry. Western blotting analysis was used to detect the effects of nilotinib on the signal transduction cascade of T-cell receptor (TCR) in Tregs. RESULTS: Nilotinib inhibited the proliferation and suppressive capacity of Tregs in a dose-dependent manner. However, the production of cytokines secreted by Tregs and CD4+CD25- T cells was only inhibited at high concentrations of nilotinib exceeding the mean therapeutic serum concentrations of the drug in patients. Only high doses of nilotinib arrested both Tregs and CD4+CD25- T cells in the G0/G1 phase and down-regulated the expression of FoxP3 and GITR. In western blotting analysis, nilotinib did not show significant inhibitory effects on TCR signaling events in Tregs and CD4+CD25- T cells. CONCLUSIONS: These findings indicate that nilotinib does not hamper the function of Tregs at clinical relevant doses, while long-term administration of nilotinib still needs to be investigated.

Dasatinib inhibits the proliferation and function of CD4+CD25+ regulatory T cells.

CD4+CD25+ regulatory T cells (Tregs) can influence various immune responses. Little is known about the effects of the Abl/Src kinase inhibitor dasatinib on Tregs which regulate anti-tumor/leukaemia immune responses. The present study demonstrated that dasatinib inhibited proliferation of Tregs and CD4+CD25- T cells in a dose-dependent manner, which was associated with the decreased production of corresponding cytokines. Treatment of Tregs with dasatinib inhibited the suppressive capacity of Tregs. The mechanisms of this inhibition included arrest of cells in the G0/G1 phase of cell cycle, down-regulation of the transcription factor forkhead box P3, glucocorticoid-induced tumour necrosis factor receptor and the cytotoxic T lymphocyte associated protein 4 as well as inhibition of signaling events through Src and nuclear factor kappaB. Dasatinib showed an inhibitory effect on the proliferation and function of both Tregs and CD4+CD25- T cells at therapeutically relevant concentrations of the drug. Clinical administration of dasatinib might influence not only the graft-versus-leukaemia effect but also the graft-versus-host-disease in patients receiving dasatinib after allogeneic stem cell transplantation and/or donor lymphocytes infusion as the function of both Tregs and effector T cells are hampered in a similar way by dasatinib.

Dasatinib exerts an immunosuppressive effect on CD8+ T cells specific for viral and leukemia antigens.

OBJECTIVE: To investigate the inhibitory effects of dasatinib on proliferation, function, and signaling events on CD8+T cells. MATERIALS AND METHODS: Carboxyfluorescein diacetate succinimidyl ester and 5-bromo-2-deoxyuridine were used to detect proliferation and cell cycle of CD8+T cells treated with dasatinib, respectively. Frequency and function of viral and leukemia-antigen-specific CD8+T cells from healthy donors were measured by tetramer staining and ELISPOT assay. Western blotting analysis was performed to detect T-cell receptor (TCR), nuclear factor kappa B (NF-kappaB) and Src signaling events in T cells treated with dasatinib or imatinib. RESULTS: Dasatinib inhibited proliferation of CD8+T cells in a dose-dependent manner, which was associated with lower secretion of interferon-gamma and granzyme B, as well as with arrest of CD8+T cells in the G0/G1 phase of cell cycle. Inhibition of CD8+T cells was proven for blood samples from a patient under dasatinib medication when compared with their T-cell status without dasatinib. Western blotting confirmed that these effects were mediated through downregulation of the phosphorylation level of molecules from the TCR and the NF-kappaB signaling transduction cascade. Dasatinib proved to be more potent than imatinib on Src and TCR signaling events in Jurkat T cells. CONCLUSION: Our study demonstrated that dasatinib impaired proliferation and function of CD8+T cells via TCR and NF-kappaB signaling events without inducing apoptosis. Therefore, dasatinib might alter the graft-vs-leukemia effect and the graft-vs-host disease after allogeneic stem cell transplantation sustained by CD8+T cells. Dasatinib might also be used as a novel immunosuppressant agent.

RHAMM-R3 peptide vaccination in patients with acute myeloid leukemia, myelodysplastic syndrome, and multiple myeloma elicits immunologic and clinical responses.

The receptor for hyaluronic acid-mediated motility (RHAMM) is an antigen eliciting both humoral and cellular immune responses in patients with acute myeloid leukemia (AML), myelodysplastic syndrome (MDS), and multiple myeloma (MM). We initiated a phase 1 clinical trial vaccinating 10 patients with R3 (ILSLELMKL), a highly immunogenic CD8(+) T-cell epitope peptide derived from RHAMM. In 7 of 10 patients, we detected an increase of CD8(+)/HLA-A2/RHAMM R3 tetramer(+)/CD45RA(+)/CCR7(-)/CD27(-)/CD28(-) effector T cells in accordance with an increase of R3-specific CD8(+) T cells in enzyme linked immunospot (ELISpot) assays. In chromium release assays, a specific lysis of RHAMM-positive leukemic blasts was shown. Three of 6 patients with myeloid disorders (1/3 AML, 2/3 MDS) achieved clinical responses: one patient with AML and one with MDS showed a significant reduction of blasts in the bone marrow after the last vaccination. One patient with MDS no longer needed erythrocyte transfusions after 4 vaccinations. Two of 4 patients with MM showed a reduction of free light chain serum levels. Taken together, RHAMM-R3 peptide vaccination induced both immunologic and clinical responses, and therefore RHAMM constitutes a promising target for further immunotherapeutic approaches. This study is registered at http://ISRCTN.org as ISRCTN32763606 and is registered with EudraCT as 2005-001706-37.